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Updated: 2017-12-11T09:37:04Z

 






(XML) Comparison of Goto-Kakizaki rats and high fat diet-induced obese rats: Are they reliable models to study Type 2 Diabetes mellitus?

2017-12-08T22:00:00Z

by Wilson Mitsuo Tatagiba Kuwabara, Ana Carolina Panveloski-Costa, Caroline Naomi Fukusawa Yokota, Joice Naiara Bertaglia Pereira, Jorge Mancini Filho, Rosangela Pavan Torres, Sandro Massao Hirabara, Rui Curi, Tatiana Carolina Alba-Loureiro

Type 2 Diabetes mellitus (T2DM) is an evident growing disease that affects different cultures throughout the world. T2DM occurs under the influence of three main factors: the genetic background, environmental and behavioral components. Obesity is strongly associated to the development of T2DM in the occident, while in the orient most of the diabetic patients are considered lean. Genetics may be a key factor in the development of T2DM in societies where obesity is not a recurrent public health problem. Herein, two different models of rats were used to understand their differences and reliability as experimental models to study the pathophysiology of T2DM, in two different approaches: the genetic (GK rats) and the environmental (HFD-induced obese rats) influences. GK rats were resistant to weight gain even though food/energy consumption (relative to body weight) was higher in this group. HFD, on the other hand, induced obesity in Wistar rats. White adipose tissue (WAT) expansion in this group was accompanied by immune cells infiltration, inflammation and insulin resistance. GK rats also presented WAT inflammation and insulin resistance; however, no immune cells infiltration was observed in the WAT of this group. Liver of HFD group presented fat accumulation without differences in inflammatory cytokines content, while liver of GK rats didn’t present fat accumulation, but showed an increase of IL-6 and IL-10 content and glycogen. Also, GK rats showed increased plasma GOT and GPT. Soleus muscle of HFD presented normal insulin signaling, contrary to GK rats, which presented higher content of basal phosphorylation of GSK-3β. Our results demonstrated that HFD developed a mild insulin resistance in Wistar rats, but was not sufficient to develop T2DM. In contrast, GK rats presented all the typical hallmarks of T2DM, such as insulin resistance, defective insulin production, fasting hyperglycemia/hyperinsulinemia and lipid plasma alteration. Thus, on the given time point of this study, we may conclude that only GK rats shown to be a reliable model to study T2DM.(image)



(XML) MicroRNA-93 promotes proliferation and metastasis of gastric cancer via targeting TIMP2

2017-12-08T22:00:00Z

by Hao Guan, Weiming Li, Yuanyuan Li, Jichang Wang, Yan Li, Yanan Tang, Shaoying Lu

MicroRNAs (miRNAs) are important regulators of pathobiological processes in various cancer. In the present study, we demonstrated that miR-93 expression was significantly up-regulated in gastric cancer tissues compared with that in matched normal mucosal tissues. High expression of miR-93 was significantly associated with lymph node metastasis and tumor-node-metastasis (TNM) stage. Functionally, ectopic expression of miR-93 promoted cell proliferation, migration, invasion, EMT phenotypes, and repressed apoptosis and G1 cell cycle arrest in vitro, and promoted tumor formation in vivo. We further identified that tissue inhibitor of metalloproteinase 2 (TIMP2) was a direct target of miR-93 by using luciferase reporter assay, qRT-PCR, and immunoblotting assay. Furthermore, knockdown of TIMP2 with specific siRNA showed similar oncogenic effects in gastric cancer cells with that transfected with miR-93 mimics. Our findings indicated that miR-93 serves as a tumor promoter in human gastric carcinogenesis by targeting TIMP2, suggesting that miR-93 might be a promising biomarker and therapeutic target for treatment of gastric cancer.(image)



(XML) Maaqwi cascadensis: A large, marine diving bird (Avialae: Ornithurae) from the Upper Cretaceous of British Columbia, Canada

2017-12-08T22:00:00Z

by Sandy M. S. McLachlan, Gary W. Kaiser, Nicholas R. Longrich

Mesozoic bird fossils from the Pacific Coast of North America are rare, but small numbers are known from the Late Cretaceous aged sediments of Hornby Island, British Columbia. Most are unassociated fragments that offer little information, but additional preparation of a large coracoid has revealed more details of its structure, as well as three associated wing bones. Phylogenetic analysis suggests that Maaqwi cascadensis, gen. et sp. nov. represents a derived crown or near-crown member of Ornithurae, and specifically suggests affinities with Vegaviidae. M. cascadensis is characterized by large size, and regressions based on dimensions of the coracoid suggest a large bird, with an estimated body mass of approximately 1.5 kilograms. The bones are robust, with thick walls, suggesting that M. cascadensis was a bird adapted for diving, similar to modern loons and grebes. The wings are short, while the coracoid is unusually short and broad, similar to modern loons. Along with the Ichthyornithes and Hesperornithes, M. cascadensis and Vegaviidae appear to represent a third clade of bird that evolved to exploit marine habitats in the Late Cretaceous, one specialized for foot-propelled diving and rapid cruising flight over water.(image)



(XML) Desethylamiodarone—A metabolite of amiodarone—Induces apoptosis on T24 human bladder cancer cells via multiple pathways

2017-12-08T22:00:00Z

by Zita Bognar, Katalin Fekete, Csenge Antus, Eniko Hocsak, Rita Bognar, Antal Tapodi, Arpad Boronkai, Nelli Farkas, Ferenc Gallyas Jr., Balazs Sumegi, Arpad Szanto

Bladder cancer (BC) is a common malignancy of the urinary tract that has a higher frequency in men than in women. Cytostatic resistance and metastasis formation are significant risk factors in BC therapy; therefore, there is great interest in overcoming drug resistance and in initiating research for novel chemotherapeutic approaches. Here, we suggest that desethylamiodarone (DEA)–a metabolite of amiodarone—may have cytostatic potential. DEA activates the collapse of mitochondrial membrane potential (detected by JC-1 fluorescence), and induces cell death in T24 human transitional-cell bladder carcinoma cell line at physiologically achievable concentrations. DEA induces cell cycle arrest in the G0/G1 phase, which may contribute to the inhibition of cell proliferation, and shifts the Bax/Bcl-2 ratio to initiate apoptosis, induce AIF nuclear translocation, and activate PARP-1 cleavage and caspase-3 activation. The major cytoprotective kinases—ERK and Akt—are inhibited by DEA, which may contribute to its cell death-inducing effects. DEA also inhibits the expression of B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1) and reduces colony formation of T24 bladder carcinoma cells, indicating its possible inhibitory effect on metastatic potential. These data show that DEA is a novel anti-cancer candidate of multiple cell death-inducing effects and metastatic potential. Our findings recommend further evaluation of its effects in clinical studies.(image)



(XML) The monomeric form of Neisseria DNA mimic protein DMP19 prevents DNA from binding to the histone-like HU protein

2017-12-08T22:00:00Z

by Ming-Fen Huang, Shin-Jen Lin, Tzu-Ping Ko, Yi-Ting Liao, Kai-Cheng Hsu, Hao-Ching Wang

DNA mimicry is a direct and effective strategy by which the mimic competes with DNA for the DNA binding sites on other proteins. Until now, only about a dozen proteins have been shown to function via this strategy, including the DNA mimic protein DMP19 from Neisseria meningitides. We have shown previously that DMP19 dimer prevents the operator DNA from binding to the transcription factor NHTF. Here, we provide new evidence that DMP19 monomer can also interact with the Neisseria nucleoid-associated protein HU. Using BS3 crosslinking, gel filtration and isothermal titration calorimetry assays, we found that DMP19 uses its monomeric form to interact with the Neisseria HU dimer. Crosslinking conjugated mass spectrometry was used to investigate the binding mode of DMP19 monomer and HU dimer. Finally, an electrophoretic mobility shift assay (EMSA) confirmed that the DNA binding affinity of HU is affected by DMP19. These results showed that DMP19 is bifunctional in the gene regulation of Neisseria through its variable oligomeric forms.(image)



(XML) A blaOXA-181-harbouring multi-resistant ST147 Klebsiella pneumoniae isolate from Pakistan that represent an intermediate stage towards pan-drug resistance

2017-12-08T22:00:00Z

by Fouzia Nahid, Rabaab Zahra, Linus Sandegren

Carbapenem resistant Klebsiella pneumoniae (CR-KP) infections are an ever-increasing global issue, especially in the Indian subcontinent. Here we report genetic insight into a blaOXA-181 harbouring Klebsiella pneumoniae, belonging to the pandemic lineage ST147, that represents an intermediate stage towards pan-drug resistance. The CR-KP isolate DA48896 was isolated from a patient from Pakistan and was susceptible only to tigecycline and colistin. It harboured blaOXA-181 and was assigned to sequence type ST147. Analysis from whole genome sequencing revealed a very high sequence similarity to the previously sequenced pan-resistant K. pneumoniae isolate MS6671 from the United Arab Emirates. The two isolates are very closely related with only 46 chromosomal nucleotide differences, 14 indels and differences in plasmid content. Both carry a substantial number of plasmid-borne and chromosomally encoded resistance determinants. Interestingly, the two differences in susceptibility between the isolates could be attributed to DA48896 lacking an insertion of blaOXA-181 into the mgrB gene that results in colistin resistance in MS6671 and SNPs affecting AcrAB efflux pump expression likely to result in tigecycline resistance. These differences between the otherwise very similar isolates indicate that strong selection has occurred for resistance towards these last-resort drugs and illustrates the trajectory of resistance evolution of OXA-181-producing versions of the ST147 international risk clone.(image)



(XML) Contour recognition of complex leaf shapes

2017-12-08T22:00:00Z

by Giacomo Diaz

The leaf shape is an important taxonomic character. Compared to the classic morphological leaf features such as veins, margin indentations, sinuses, etc., the shape is simpler to obtain by using the 'magic wand' or other contouring tools that are available in most of imaging applications. The only exception is when leaves develop large lobes that get in touch or overlap each other, as the presence of hidden or closed portions of the leaf border precludes the application of automatic methods and forces the leaf contour to be traced manually. This is a time consuming and relatively accurate operation that, nevertheless, can not be avoided, as overlapping lobes are characteristic features of the leaves of several plant species and varieties. The method described in the paper overcomes this problem as it allows the leaf contour to be achieved even in the presence of touching or overlapping lobes. The method involves three steps: (1) the acquisition of leaf images using a transilluminator, (2) a two-level image segmentation that allows all leaf components (blade, overlapping lobes and closed sinuses) to be represented in a single binary image, and (3) the contouring and concatenation of all binary outlines in a single, self-intersecting closed contour that reproduces accurately the leaf shape. The method can be extended to acquire the shape of leaves of herbarium specimens, that are often overlapped but can not be easily handled and repositioned because of their extreme fragility and relevant taxonomic value.(image)



(XML) Secreted dual reporter assay with Gaussia luciferase and the red fluorescent protein mCherry

2017-12-08T22:00:00Z

by Diana Wider, Didier Picard

The availability of a wide range of reporter proteins, which can easily be quantitated, has had a major impact on many fields of biomedical research. In some experiments with tissue culture cells, it is necessary to control for differences in transfection efficiency and in other expression parameters. This requirement has been very conveniently met with the popular dual luciferase assay. Its disadvantages are the requirement for cell lysis, the inability to analyze the same cells repeatedly, and the cost, at least in its most commonly used commercial format. Here we describe a novel dual reporter assay with the naturally secreted luciferase from Gaussia princeps as the main reporter protein and a secreted version of the red fluorescent protein mCherry as internal standard. After first measuring mCherry fluorescence in the medium, an enzyme buffer with coelenterazine as substrate is added to the same sample to trigger a glow-type luminescence of the luciferase. The simple and cheap assay can easily be adapted to a variety of experimental situations. As a case in point, we have developed a panel of Gaussia luciferase reporter genes for transcriptional activation assays with estrogen and glucocorticoid response elements, and with response elements for fusion proteins with the Gal4 DNA binding domain for use in mammalian cells. Our secreted dual reporter assay should be an attractive alternative to the currently available commercial kits.(image)



(XML) The meaning of a poor childbirth experience – A qualitative phenomenological study with women in Rwanda

2017-12-08T22:00:00Z

by Judith Mukamurigo, Anna Dencker, Joseph Ntaganira, Marie Berg

Objective

Being pregnant and giving birth is a pivotal life event and one that a woman ordinarily remembers for most of her life. A negative childbirth experience can affect a woman’s health well beyond the episode of the labour and birth itself. This study explored the meaning of a poor childbirth experience, as expressed by women who had given birth in Rwanda.

Methods

In a cross-sectional household study conducted in Northern Province and in Kigali City, the capital of Rwanda, a structured questionnaire was answered by women who had given birth one to 13 months earlier. One question, answered by 898 women, asked them to rate their overall experience of childbirth from 0 (very bad) to 10 (very good). Of these, 28 women (3.1%) who had rated their childbirth experience as bad (≤ 4) were contacted for individual interviews. Seventeen of these women agreed to participate in individual in-depth interviews. The texts were analysed with a reflective lifeworld approach.

Results

The essential meaning of a “poor” childbirth experience was that the women had been exposed to disrespectful care, constituted by neglect, verbal or physical abuse, insufficient information, and denial of their husband as a companion. The actions of carers included abandonment, humiliation, shaming and insult, creating feelings of insecurity, fear and distrust in the women. Two of the women did not report any experience of poor care; their low rating was related to having suffered from medical complications.

Conclusion

It is challenging that the main finding is that women are exposed to disrespectful care. In an effort to provide an equitable and high quality maternal health care system in Rwanda, there is a need to focus on activities to implement respectful, evidence-based care for all. One such activity is to develop and provide education programmes for midwives and nurses about professional behaviour when caring for and working with women during labour and birth.

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(XML) Temporal distribution and genetic variants in influenza A(H1N1)pdm09 virus circulating in Mexico, seasons 2012 and 2013

2017-12-08T22:00:00Z

by Jose Reyes Canche-Pech, Laura Conde-Ferraez, Marylin Puerto-Solis, Refugio Gonzalez-Losa, Pilar Granja-Pérez, Salha Villanueva-Jorge, Maria Chan-Gasca, Jesus Gómez-Carballo, Luisa López-Ochoa, Bertha Jiménez-Delgadillo, Iram Rodríguez-Sánchez, Jorge Ramírez-Prado, Guadalupe Ayora-Talavera

The 2012 and 2013 annual influenza epidemics in Mexico were characterized by presenting different seasonal patterns. In 2012 the A(H1N1)pdm09 virus caused a high incidence of influenza infections after a two-year period of low circulation; whereas the 2013 epidemic presented circulation of the A(H1N1)pdm09 virus throughout the year. We have characterized the molecular composition of the Hemagglutinin (HA) and Neuraminidase (NA) genes of the A(H1N1)pdm09 virus from both epidemic seasons, emphasizing the genetic characteristics of viruses isolated from Yucatan in Southern Mexico. The molecular analysis of viruses from the 2012 revealed that all viruses from Mexico were predominantly grouped in clade 7. Strikingly, the molecular characterization of viruses from 2013 revealed that viruses circulating in Yucatan were genetically different to viruses from other regions of Mexico. In fact, we identified the occurrence of two genetic variants containing relevant mutations at both the HA and NA surface antigens. There was a difference on the temporal circulation of each genetic variant, viruses containing the mutations HA-A141T / NA-N341S were detected in May, June and July; whereas viruses containing the mutations HA-S162I / NA-L206S circulated in August and September. We discuss the significance of these novel genetic changes.(image)



(XML) Hexokinase 2 (HK2), the tumor promoter in glioma, is downregulated by miR-218/Bmi1 pathway

2017-12-08T22:00:00Z

by Hui Liu, Nan Liu, Yingduan Cheng, Weilin Jin, Pengxing Zhang, Xin Wang, Hongwei Yang, Xiaoshan Xu, Zhen Wang, Yanyang Tu

In cancer, glycolysis driving enzymes and their regulating microRNAs are one of the key focus of oncology research lately. The glycolytic enzyme hexokinase 2 (HK2) is crucial for the Warburg effect in human glioma, the most common malignant brain tumor. In the present study, we studied the tumorigenic role of HK2 in glioma, and clarified the mechanism of miR-218 induced HK2 regulation in glioma development. The HK2 expression in patient derived glioma and non neoplastic brain tissue was quantified. The HK2 silenced U87 and U251 cell lines were assessed for their proliferation, migration and invasive potential in vitro, while the tumor forming potential of U87 cells was evaluated in vivo. The untreated cell lines served as control. The HK2 expression in (a) lentivirus-infected, miR-218 overexpressing and (b) shRNA mediated Bmi1 silenced U87 and U251 glioma cell lines were quantified. Luciferase reporter assay, qRT-PCR analysis and WB were employed as required. The HK2 expression was significantly increased in glioma tissues comparing with the non neoplastic brain tissues and was positively correlated with the glioma grade. Silencing HK2 in glioma cell lines significantly decreased their proliferation, migration, invasion and tumorigenic abilities. Although, overexpression of miR-218 significantly downregulated the HK2 expression, luciferase reporter assay failed to show HK2 as the direct target of miR-218. A direct correlation, however, was observed between HK2 and Bmi-1, the direct target of miR-218. Taken together, our findings confirmed the tumorigenic activity of HK2 in glioma, and the involvement of the miR218/Bmi1 pathway in the regulation of its expression.(image)



(XML) A three-month longitudinal study of changes in day/night serum total antioxidant capacity in paranoid schizophrenia

2017-12-08T22:00:00Z

by Armando L. Morera-Fumero, Estefanía Díaz-Mesa, Pedro Abreu-Gonzalez, Lourdes Fernandez-Lopez, Fernando Guillen-Pino

Free radicals and an oxidant/antioxidant imbalance have been involved in the schizophrenia pathophysiology. The total antioxidant capacity (TAC) is a measure of the antioxidant capacity of a system. Day/night changes are a biological characteristic of hormones such as melatonin or cortisol. There is little information about TAC day/night changes in schizophrenia patients. The aim of this research is to study if there are day/night changes in serum TAC levels of schizophrenia patients. Thirty-two DSM-IV schizophrenia paranoid patients were studied. Blood was sampled at 12:00 and 00:00 h at admission, discharge and three months after hospital discharge (TMAHD). TAC results are expressed as mmol of Trolox/L. Patients did not have day/night TAC differences at admission (12:00: 0.67±0.12 vs. 00:00: 0.61±0.14, p>0.14) or discharge (12:00: 0.65±0.15 vs. 00:00: 0.65±0.12, p>0.99). At TMHD, patients had significantly higher TAC levels at midday than midnight (12:00: 0.83±0.10 vs. 00:00: 0.74±0.12, p<0.006) as it has been reported in healthy subjects. There were no significant TAC differences at 12.00 and 00:00 between admission and discharge. At TMAHD, patients had significantly higher TAC levels than at admission and discharge, both at 12:00 and 00:00 h. In conclusion, the absence of day/night serum TAC changes when clinically relapsed and the normalization of day/night serum TAC changes at TMHD can be considered as a biological marker of schizophrenia evolution.(image)



(XML) Does cognitive impairment impact adherence? A systematic review and meta-analysis of the association between cognitive impairment and medication non-adherence in stroke

2017-12-08T22:00:00Z

by Daniela Rohde, Niamh A. Merriman, Frank Doyle, Kathleen Bennett, David Williams, Anne Hickey

Background

While medication adherence is essential for the secondary prevention of stroke, it is often sub-optimal, and can be compromised by cognitive impairment. This study aimed to systematically review and meta-analyse the association between cognitive impairment and medication non-adherence in stroke.

Methods

A systematic literature search of longitudinal and cross-sectional studies of adults with any stroke type, which reported on the association between any measure of non-adherence and cognitive impairment, was carried out according to PRISMA guidelines. Odds ratios and 95% confidence intervals were the primary measure of effect. Risk of bias was assessed using the Cochrane Bias Methods Group's Tool to Assess Risk of Bias in Cohort Studies, with evidence quality assessed according to the GRADE approach. We conducted sensitivity analyses according to measure of cognitive impairment, measure of medication adherence, population, risk of bias and adjustment for covariates. The protocol was registered with PROSPERO.

Results

From 1,760 titles and abstracts, we identified 9 studies for inclusion. Measures of cognitive impairment varied from dementia diagnosis to standardised cognitive assessments. Medication adherence was assessed through self-report or administrative databases. The majority of studies were of medium risk of bias (n = 6); two studies had low risk of bias. Findings were mixed; when all studies were pooled, there was no evidence of an association between cognitive impairment and medication non-adherence post-stroke [OR (95% CI): 0.85 (0.66, 1.03)]. However, heterogeneity was substantial [I2 = 90.9%, p < .001], and the overall evidence quality was low.

Conclusions

Few studies have explored associations between cognitive impairment and medication adherence post-stroke, with substantial heterogeneity in study populations, and definitions and assessments of non-adherence and cognitive impairment. Further research using clear, standardised and objective assessments is needed to clarify the association between cognitive impairment and medication non-adherence in stroke.

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(XML) Characterization of the CCT family and analysis of gene expression in Aegilops tauschii

2017-12-08T22:00:00Z

by Xingwei Zheng, Xiaohua Li, Chuan Ge, Jianzhong Chang, Mengmeng Shi, Jianli Chen, Linyi Qiao, Zhijian Chang, Jun Zheng, Jiancheng Zhang

Flowering is crucial for reproductive success in flowering plant. The CCT domain-containing genes widely participate in the regulation of flowering process in various plant species. So far, the CCT family in common wheat is largely unknown. Here, we characterized the structure, organization, molecular evolution and expression of the CCT genes in Aegilops tauschii, which is the D genome donor of hexaploid wheat. Twenty-six CCT genes (AetCCT) were identified from the full genome of A. tauschii and these genes were distributed on all 7 chromosomes. Phylogenetic analysis classified these AetCCT genes into 10 subgroups. Thirteen AetCCT members in group A, C, H and G achieved rapid evolution based on evolutionary rate analysis. The AetCCT genes respond to different exogenous hormones and abiotic treatments, the expression of AetCCT4, 7, 8, 11, 12, 16, 17, 19, 21 and 22 showed a significant 24 h rhythm. This study may provide a reference for common wheat's evolution, domestication and evolvement rules, and also help us to understand the ecological adaptability of A. tauschii.(image)



(XML) PsrA controls the synthesis of the Pseudomonas aeruginosa quinolone signal via repression of the FadE homolog, PA0506

2017-12-08T22:00:00Z

by Greg Wells, Samantha Palethorpe, Everett C. Pesci

Pseudomonas aeruginosa is a ubiquitous, Gram-negative opportunistic pathogen that can cause disease in various sites within the human body. This bacterium is a major source of nosocomial infections that are often difficult to treat due to high intrinsic antibiotic resistance and coordinated virulence factor production. P. aeruginosa utilizes three cell-to-cell signaling systems to regulate numerous genes in response to cell density. One of these systems utilizes the small molecule 2-heptyl-3-hydroxy-4-quinolone (Pseudomonas quinolone signal [PQS]) as a signal that acts as a co-inducer for the transcriptional regulator PqsR. Quinolone signaling is required for virulence in multiple infection models, and PQS is produced during human infections, making this system an attractive target for potential drug development. In this study we have examined the role of a TetR-type transcriptional regulator, PsrA, in the regulation of PQS production by P. aeruginosa. Previous studies showed that PsrA regulates genes of the fatty acid β-oxidation pathway, including PA0506, which encodes a FadE homolog. In this report, we show that deletion of psrA resulted in a large decrease in PQS production and that co-deletion of PA0506 allowed PQS production to be restored to a wild type level. We also found that PQS production could be restored to the psrA mutant by the addition of oleic or octanoic acid. Taken together, our data suggest that psrA positively affects PQS production by repressing the transcription of PA0506, which leads to a decrease in the conversion of acyl-CoA compounds to enoyl-CoA compounds, thereby allowing some octanoyl-CoA to escape the ß-oxidation pathway and serve as a PQS precursor.(image)



(XML) Anatomical relationships between serotonin 5-HT2A and dopamine D2 receptors in living human brain

2017-12-08T22:00:00Z

by Tatsuya Ishii, Yasuyuki Kimura, Masanori Ichise, Keisuke Takahata, Soichiro Kitamura, Sho Moriguchi, Manabu Kubota, Ming-Rong Zhang, Makiko Yamada, Makoto Higuchi, Yoshinori Okubo, Tetsuya Suhara

Methods

Seven healthy volunteers underwent PET scans with [18F]altanserin and [11C]FLB 457 for 5-HT2A and D2 receptors, respectively. As a measure of receptor density, a binding potential (BP) was calculated from PET data for 76 cerebral cortical regions. A correlation matrix was calculated between the binding potentials of [18F]altanserin and [11C]FLB 457 for those regions. The regional relationships were investigated using a bicluster analysis of the correlation matrix with an iterative signature algorithm.

Results

We identified two clusters of regions. The first cluster identified a distinct profile of correlation coefficients between 5-HT2A and D2 receptors, with the former in regions related to sensorimotor integration (supplementary motor area, superior parietal gyrus, and paracentral lobule) and the latter in most cortical regions. The second cluster identified another distinct profile of correlation coefficients between 5-HT2A receptors in the bilateral hippocampi and D2 receptors in most cortical regions.

Conclusions

The observation of two distinct clusters in the correlation matrix suggests regional interactions between 5-HT2A and D2 receptors in sensorimotor integration and hippocampal function. A bicluster analysis of the correlation matrix of these neuroreceptors may be beneficial in understanding molecular networks in the human brain.

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(XML) Construction and validation of a psychometric scale to measure awareness on consumption of irradiated foods

2017-12-08T22:00:00Z

by Tiago Rusin, Wilma Maria Coelho Araújo, Cristiane Faiad, Helio de Carvalho Vital

Although food irradiation has been used to ensure food safety, most consumers are unaware of the basic concepts of irradiation, misinterpreting information and demonstrating a negative attitude toward food items treated with ionizing radiation. This research is aimed at developing a tool to assess the awareness on the consumption of irradiated food. The sample was composed by employees from different social classes and school levels of Brazilian universities, who reflect the end-users of the irradiated foods, representative of the views of lay consumers. The total number of respondents was 614. In order to assess the Awareness Scale on Consumption of Irradiated Foods (ASCIF), an instrument has been developed and submitted to semantic tests and judge’s validation. The instrument, that included 32 items, contemplated four construct factors: concepts (6 items), awareness (10 items), labeling (7 items) and safety of Irradiated foods (9 items). The data were collected by electronic means, through the site . By using exploratory factorial analysis (EFA) 4 factors have been found. They summarize the 31 items included. These factors account for 64.32% of the variance of the items and the internal consistency of the factors has been deemed good. An Exploratory Structural Equation Modeling (ESEM) was conducted to evaluate the factor structure of the instrument. The proposed instrument has been found to meet consistency criteria as an efficient tool for indicating assessing potential challenges and opportunities for the irradiated food markets.(image)



(XML) MALDI MSI of MeLiM melanoma: Searching for differences in protein profiles

2017-12-08T22:00:00Z

by Roman Guran, Lucie Vanickova, Vratislav Horak, Sona Krizkova, Petr Michalek, Zbynek Heger, Ondrej Zitka, Vojtech Adam

Background

Treatment of advanced cutaneous melanoma remains challenging, and new data on melanoma biology are required. The most widely accepted criteria for the prognostic evaluation of melanoma are histopathological and clinical parameters, and the identification of additional tumor markers is thus of paramount importance. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI), an important tool in cancer research, is useful for unraveling the molecular profile of melanoma.

Methodology/Principal findings

In this report, we used the melanoma-bearing Libechov minipig (MeLiM), a unique animal model that allows observation of the complete spontaneous regression of invasive cutaneous melanoma, to investigate i) the differences between melanoma and healthy skin protein profiles and ii) the proteins potentially involved in spontaneous regression. The MeLiM tissues were cryosected, histologically characterized, analyzed by MALDI MSI, and immunohistologically stained. Multivariate statistical analyses of the MALDI MSI data revealed ten relevant m/z ions, of which the expression levels varied significantly among the studied MeLiM tissues. These ion peaks were used to create mass ion images/maps and visualize the differences between tumor and healthy skin specimens, as well as among histologically characterized tissue regions.

Conclusions/Significance

Protein profiles comprising ten statistically significant mass ion peaks useful for differentiating cutaneous melanoma and healthy skin tissues were determined. Peaks at m/z 3044, 6011, 6140 and 10180 were overexpressed in melanoma compared with healthy skin tissue. More specifically, m/z 6140 was expressed at significantly (p < 0.05) higher levels in normally growing melanoma regions than in regions with early and late spontaneous regression. This study demonstrates the clinical utility of MALDI MSI for the analysis of tissue cryosections at a molecular level.

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(XML) Can nerve regeneration on an artificial nerve conduit be enhanced by ethanol-induced cervical sympathetic ganglion block?

2017-12-08T22:00:00Z

by Yoshiki Shionoya, Katsuhisa Sunada, Keiji Shigeno, Akira Nakada, Michitaka Honda, Tatsuo Nakamura

This study aimed to determine whether nerve regeneration by means of an artificial nerve conduit is promoted by ethanol-induced cervical sympathetic ganglion block (CSGB) in a canine model. This study involved two experiments—in part I, the authors examined the effect of CSGB by ethanol injection on long-term blood flow to the orofacial region; part II involved evaluation of the effect of CSGB by ethanol injection on inferior alveolar nerve (IAN) repair using polyglycolic acid-collagen tubes. In part I, seven Beagles were administered left CSGB by injection of 99.5% ethanol under direct visualization by means of thoracotomy, and changes in oral mucosal blood flow in the mental region and nasal skin temperature were evaluated. The increase in blood flow on the left side lasted for 7 weeks, while the increase in average skin temperature lasted 10 weeks on the left side and 3 weeks on the right. In part II, fourteen Beagles were each implanted with a polyglycolic acid-collagen tube across a 10-mm gap in the left IAN. A week after surgery, seven of these dogs were administered CSGB by injection of ethanol. Electrophysiological findings at 3 months after surgery revealed significantly higher sensory nerve conduction velocity and recovery index (ratio of left and right IAN peak amplitudes) after nerve regeneration in the reconstruction+CSGB group than in the reconstruction-only group. Myelinated axons in the reconstruction+CSGB group were greater in diameter than those in the reconstruction-only group. Administration of CSGB with ethanol resulted in improved nerve regeneration in some IAN defects. However, CSGB has several physiological effects, one of which could possibly be the long-term increase in adjacent blood flow.(image)



(XML) Effect of 3D microstructure of dermal papillae on SED concentration at a mechanoreceptor location

2017-12-08T22:00:00Z

by Trung Quang Pham, Takayuki Hoshi, Yoshihiro Tanaka, Akihito Sano

The feeling of touch is an essential human sensation. Four types of mechanoreceptors (i.e., FA-I, SA-I, FA-II, and SA-II) in human skin signalize physical properties, such as shape, size, and texture, of an object that is touched and transmit the signal to the brain. Previous studies attempted to investigate the mechanical properties of skin microstructure and their effect on mechanoreceptors by using finite element modeling. However, very few studies have focused on the three-dimensional microstructure of dermal papillae, and this is related to that of FA-I receptors. A gap exists between conventional 2D models of dermal papillae and the natural configuration, which corresponds to a complex and uneven structure with depth. In this study, the three-dimensional microstructure of dermal papillae is modeled, and the differences between two-dimensional and three-dimensional aspects of dermal papillae on the strain energy density at receptor positions are examined. The three-dimensional microstructure has a focalizing effect and a localizing effect. Results also reveal the potential usefulness of these effects for tactile sensor design, and this may improve edge discrimination.(image)



(XML) Do managed bees have negative effects on wild bees?: A systematic review of the literature

2017-12-08T22:00:00Z

by Rachel E. Mallinger, Hannah R. Gaines-Day, Claudio Gratton

Managed bees are critical for crop pollination worldwide. As the demand for pollinator-dependent crops increases, so does the use of managed bees. Concern has arisen that managed bees may have unintended negative impacts on native wild bees, which are important pollinators in both agricultural and natural ecosystems. The goal of this study was to synthesize the literature documenting the effects of managed honey bees and bumble bees on wild bees in three areas: (1) competition for floral and nesting resources, (2) indirect effects via changes in plant communities, including the spread of exotic plants and decline of native plants, and (3) transmission of pathogens. The majority of reviewed studies reported negative effects of managed bees, but trends differed across topical areas. Of studies examining competition, results were highly variable with 53% reporting negative effects on wild bees, while 28% reported no effects and 19% reported mixed effects (varying with the bee species or variables examined). Equal numbers of studies examining plant communities reported positive (36%) and negative (36%) effects, with the remainder reporting no or mixed effects. Finally, the majority of studies on pathogen transmission (70%) reported potential negative effects of managed bees on wild bees. However, most studies across all topical areas documented the potential for impact (e.g. reporting the occurrence of competition or pathogens), but did not measure direct effects on wild bee fitness, abundance, or diversity. Furthermore, we found that results varied depending on whether managed bees were in their native or non-native range; managed bees within their native range had lesser competitive effects, but potentially greater effects on wild bees via pathogen transmission. We conclude that while this field has expanded considerably in recent decades, additional research measuring direct, long-term, and population-level effects of managed bees is needed to understand their potential impact on wild bees.(image)



(XML) Reinforcement learning account of network reciprocity

2017-12-08T22:00:00Z

by Takahiro Ezaki, Naoki Masuda

Evolutionary game theory predicts that cooperation in social dilemma games is promoted when agents are connected as a network. However, when networks are fixed over time, humans do not necessarily show enhanced mutual cooperation. Here we show that reinforcement learning (specifically, the so-called Bush-Mosteller model) approximately explains the experimentally observed network reciprocity and the lack thereof in a parameter region spanned by the benefit-to-cost ratio and the node’s degree. Thus, we significantly extend previously obtained numerical results.(image)



(XML) Detection of spontaneous pulse using the acceleration signals acquired from CPR feedback sensor in a porcine model of cardiac arrest

2017-12-08T22:00:00Z

by Liang Wei, Gang Chen, Zhengfei Yang, Tao Yu, Weilun Quan, Yongqin Li

Background

Reliable detection of return of spontaneous circulation with minimal interruptions of chest compressions is part of high-quality cardiopulmonary resuscitation (CPR) and routinely done by checking pulsation of carotid arteries. However, manual palpation was time-consuming and unreliable even if performed by expert clinicians. Therefore, automated accurate pulse detection with minimal interruptions of chest compression is highly desirable during cardiac arrest especially in out-of-hospital settings.

Objective

To investigate whether the acceleration (ACC) signals acquired from accelerometer-based CPR feedback sensor can be used to distinguish perfusing rhythm (PR) from pulseless electrical activity (PEA) in a porcine model of cardiac arrest.

Methods

Cardiac arrest was induced in 49 male adult pigs. ECG, arterial blood pressure (ABP) and ACC waveforms were simultaneously recorded during CPR. 3-second segments containing compression-free signals during chest compression pauses were extracted and only those segments with organized rhythm were used for analysis. PR was defined as systolic arterial pressure >60 mmHg and pulse pressure >10 mmHg, while PEA was defined as an organized rhythm that does not meet the above criteria for PR. Peak correlation coefficient (CCp) of the cross-correlation function between pre-processed ECG and ACC, was used to discriminate PR and PEA.

Results

63 PR and 153 PEA were identified from the total of 1025 extracted segments. CCp was significantly higher for PR as compared to PEA (0.440±0.176 vs. 0.067±0.042, p<0.01) and highly correlated with ABP (r = 0.848, p<0.001). The area under the receiver operating characteristic curve, sensitivity, specificity and accuracy were 0.965, 93.6%, 97.5% and 96.7% for the ACC-based automatic spontaneous pulse detection.

Conclusions

In this animal model, the ACC signals acquired from an accelerometer-based CPR feedback sensor can be used to detect the presence of spontaneous pulse with high accuracy.

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(XML) Hexahydrocurcumin protects against cerebral ischemia/reperfusion injury, attenuates inflammation, and improves antioxidant defenses in a rat stroke model

2017-12-08T22:00:00Z

by Piyawadee Wicha, Jiraporn Tocharus, Adchara Janyou, Jinatta Jittiwat, Chatchawan Changtam, Apichart Suksamrarn, Chainarong Tocharus

The purpose of the present experiment was to investigate whether hexahydrocurcumin (HHC) attenuates brain damage and improves functional outcome via the activation of antioxidative activities, anti-inflammation, and anti-apoptosis following cerebral ischemia/reperfusion (I/R). In this study, rats with cerebral I/R injury were induced by a transient middle cerebral artery occlusion (MCAO) for 2 h, followed by reperfusion. The male Wistar rats were randomly divided into five groups, including the sham-operated, vehicle-treated, 10 mg/kg HHC-treated, 20 mg/kg HHC-treated, and 40 mg/kg HHC-treated I/R groups. The animals were immediately injected with HHC by an intraperitoneal administration at the onset of cerebral reperfusion. After 24 h of reperfusion, the rats were tested for neurological deficits, and the pathology of the brain was studied by 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin (H&E) staining, and terminal deoxynucleotidyltransferase UTP nick end labeling (TUNEL) staining. In addition, the brain tissues were prepared for protein extraction for Western blot analysis, a malondialdehyde (MDA) assay, a nitric oxide (NO) assay, a superoxide dismutase (SOD) assay, a glutathione (GSH) assay, and a glutathione peroxidase (GSH-Px) assay. The data revealed that the neurological deficit scores and the infarct volume were significantly reduced in the HHC-treated rats at all doses compared to the vehicle group. Treatment with HHC significantly attenuated oxidative stress and inflammation, with a decreased level of MDA and NO and a decreased expression of NF-κB (p65) and cyclooxygenase-2 (COX-2) in the I/R rats. HHC also evidently increased Nrf2 (nucleus) protein expression, heme oxygenase-1 (HO-1) protein expression, the antioxidative enzymes, and the superoxide dismutase (SOD) activity. Moreover, the HHC treatment also significantly decreased apoptosis, with a decrease in Bax and cleaved caspase-3 and an increase in Bcl-XL, which was in accordance with a decrease in the apoptotic neuronal cells. Therefore, the HHC treatment protects the brain from cerebral I/R injury by diminishing oxidative stress, inflammation, and apoptosis. The antioxidant properties of HHC may play an important role in improving functional outcomes and may offer significant neuroprotection against I/R damage.(image)



(XML) The effectiveness and limitation of the national childhood hepatitis A vaccination program in the Republic of Korea: Findings from the Korean National Health and Nutrition Examination Survey (KNHANES), 2015

2017-12-08T22:00:00Z

by Juwon Lim, Kyuwoong Kim, Seulggie Choi, Sang Min Park

Background

Vaccination for hepatitis A virus (HAV) has been implemented as one of the national vaccination programs despite the epidemiological transition of HAV in the Republic of Korea. While the national HAV vaccination program is largely associated with the shift of socioeconomic trend in the country, concerns have been raised on the effectiveness of the HAV immunization. The objective of this study was to examine the epidemiological trend of HAV and assess the effectiveness of the nationwide HAV vaccination policy based on a nationally representative sample of the Korean population collected in 2015.

Methods

We analyzed anti-HAV of 5,856 respondents aged ≥10 years collected from Korean National Health and Nutrition Examination Survey (KNHANES) data in 2015. We estimated age-adjusted anti-HAV prevalence by sociodemographic and other characteristics. We evaluated the factors associated with anti-HAV positivity among each age group (10–19, 20–29, 30–45 and over 45 years old).

Results

The prevalence of anti-HAV among adults aged ≥10 years was 72.5% (95% confidence interval, CI, 73.7–71.4) in 2015. The lowest age-specific prevalence was among adults aged 20–29 years with 11.9% (95% CI 9.3–15.1%). The prevalence of anti-HAV among those aged 10–14 and 15–19 years was 59.7% (95% CI 52.7–66.4) and 24.0% (95% CI 19.5–29.3), respectively. The prevalence of anti-HAV among adults aged between 30 and 44 years rapidly increased from below 20% to above 90%. The prevalence of anti-HAV among adults aged ≥45 years was 97.8% (95% CI 96.0–97.6). Factors significantly associated with anti-HAV positivity among those aged 10–19 years old were young age, higher house income and high influenza vaccination rate. Compared to the respondents aged 10–19 years (those who were subject to the national childhood vaccine recommendation), those aged 20–29 years (those who were not subject to the recommendation) had low adjusted odds ratio (OR, 0.52 95% CI 0.34–.81 P-value = 0.004) for anti-HAV positivity.

Conclusions

The age-adjusted anti-HAV prevalence showed a U-shaped association, implying the high dependence of anti-HAV prevalence on age and the epidemiological shift. The inclusion of the hepatitis A vaccine into the national immunization recommendation was effective shown by the increase of immunity in the general population. However, the vaccination rate was low in the low-income group. Young adults aged 20–39 years may benefit from inclusion in the HAV vaccination program due to the significantly low vaccination rate.

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(XML) Process service quality evaluation based on Dempster-Shafer theory and support vector machine

2017-12-08T22:00:00Z

by Feng-Que Pei, Dong-Bo Li, Yi-Fei Tong, Fei He

Human involvement influences traditional service quality evaluations, which triggers an evaluation’s low accuracy, poor reliability and less impressive predictability. This paper proposes a method by employing a support vector machine (SVM) and Dempster-Shafer evidence theory to evaluate the service quality of a production process by handling a high number of input features with a low sampling data set, which is called SVMs-DS. Features that can affect production quality are extracted by a large number of sensors. Preprocessing steps such as feature simplification and normalization are reduced. Based on three individual SVM models, the basic probability assignments (BPAs) are constructed, which can help the evaluation in a qualitative and quantitative way. The process service quality evaluation results are validated by the Dempster rules; the decision threshold to resolve conflicting results is generated from three SVM models. A case study is presented to demonstrate the effectiveness of the SVMs-DS method.(image)



(XML) Association of genetic variations in FOXO3 gene with susceptibility to noise induced hearing loss in a Chinese population

2017-12-08T22:00:00Z

by Haoran Guo, Enmin Ding, Ying Bai, Hengdong Zhang, Huanxi Shen, Jun Wang, Xianping Song, Wenyan Cai, Jiadi Guo, Baoli Zhu

Noise induced hearing loss (NIHL), a multifactorial disease involving both genetic and environmental factors, is one of the most important occupational health hazards. Nonetheless, the influence of FOXO3 variants on NIHL risk have not been illuminated. This research was conducted to explore the effects of FOXO3 polymorphisms on individual susceptibility to NIHL. A total of 2689 industrial workers from one textile factory of east China were recruited to participate in the current research. Venous blood was collected, questionnaire and pure-tone audiometry (PTA) was conducted by specialist physicians. Then, we performed genotyping of three selected SNPs (rs2802292, rs10457180, and rs12206094) in FOXO3 gene in 566 NIHL patients and 566 controls. Subsequently, the main effects of genotype and its interactions were evaluated. Our results revealed that individuals with the G allele of rs2802292, G allele of rs10457180, T allele of rs12206094 (OR = 1.43, 1.43, and 1.31 respectively) and the haplotype GAC and others (TGT/GGT/GGC/GAT) (rs2802292-rs10457180-rs12206094) (OR = 1.49 and 2.09 respectively) are associated with an increased risk of NIHL in a Chinese population. Stratified analysis showed that an increased NIHL risk was found in the subjects who exposed to noise >16 years with rs2802292 GG/GT and rs10457180 AG/GG genotype with an OR of 1.62 and 1.66 respectively. Multifactor dimensionality reduction analysis indicated that rs10457180, rs2802292, and rs12206094 have interactions and are related to increased NIHL risk (OR = 1.53). The genetic polymorphism rs2802292, rs10457180, and rs12206094 within FOXO3 gene are associated with an increased risk of NIHL in a Chinese population and have potential to be biomarkers for noise exposed workers.(image)



(XML) Improved approach for electric vehicle rapid charging station placement and sizing using Google maps and binary lightning search algorithm

2017-12-08T22:00:00Z

by Md. Mainul Islam, Hussain Shareef, Azah Mohamed

The electric vehicle (EV) is considered a premium solution to global warming and various types of pollution. Nonetheless, a key concern is the recharging of EV batteries. Therefore, this study proposes a novel approach that considers the costs of transportation loss, buildup, and substation energy loss and that incorporates harmonic power loss into optimal rapid charging station (RCS) planning. A novel optimization technique, called binary lightning search algorithm (BLSA), is proposed to solve the optimization problem. BLSA is also applied to a conventional RCS planning method. A comprehensive analysis is conducted to assess the performance of the two RCS planning methods by using the IEEE 34-bus test system as the power grid. The comparative studies show that the proposed BLSA is better than other optimization techniques. The daily total cost in RCS planning of the proposed method, including harmonic power loss, decreases by 10% compared with that of the conventional method.(image)



(XML) Safety and efficacy of the PrePex device in HIV-positive men: A single-arm study in Zimbabwe

2017-12-08T22:00:00Z

by Mufuta Tshimanga, Batsirai Makunike-Chikwinya, Tonderayi Mangwiro, Patricia Tapiwa Gundidza, Pesanai Chatikobo, Vernon Murenje, Amy Herman-Roloff, Peter H. Kilmarx, Marrianne Holec, Gerald Gwinji, Owen Mugurungi, Munyaradzi Murwira, Sinokuthemba Xaba, Scott Barnhart, Caryl Feldacker

Methods

We aimed to determine if the adverse event (AE) rate was non-inferior to an AE rate of 2%, a rate considered the global standard of MC safety. Study procedures, AE definitions, and study staff were unchanged from previous PrePex Zimbabwe trials. After PrePex placement and removal, weekly visits assessed wound healing. Men returned on Day 90. Safety was defined as occurrence of moderate and serious clinical AEs. Efficacy was defined as ability to reach the endpoint of complete circumcision.

Results

Among 400 healthy, HIV-positive, consenting adults, median age was 40 years (IQR: 34, 46); 79.5% in WHO stage 2; median CD4 was 336.5c/μl (IQR: 232, 459); 337 (85%) on anti-retroviral therapy. Among 385 (96%) observed completely healed, median days to complete healing was 42 (IQR: 35–49). There was no association between time to healing and CD4 (p = 0.66). Four study-related severe AEs and no moderate AEs were reported: severe/moderate AE rate of 1.0% (95% CI: 0.27% to 2.5). This was non-inferior to 2% AEs (p = 0.0003). All AEs were device displacements resulting in surgical MC and, subsequently, complete healing.

Conclusion

Male circumcision among healthy, HIV-positive men using PrePex is safe and effective. Reducing the barrier of HIV testing while improving counseling for safer sex practices among all MC clients could increase MC uptake and avert more HIV infections.

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