bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional promoter -31G/C variant of Survivin gene predict prostate cancer susceptibility among Chinese: a case control study
Authors: Chen Jiawei , Cui Xinhai , Zhou Hai , Qin Chao , Cao Qiang , Ju Xiaobing , Li Pu , Cai Hongzhou , Zhu Jian , Meng Xiaoxin , Wang Meilin , Zhang Zhengdong , Shao Pengfei , Li Jie , Yin Changjun
Published: July 2013

Background

Abnormal expression of Baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5, also called as survivin), a novel member of the inhibitor of apoptosis protein (IAP) family, has implications in many types of cancer and is considered as a new therapeutic target. We suppose that genetic variant rs9904341 in the 5′ UTR region of survivin gene may be associated with the development and progression of prostate cancer (PCa) in Chinese population.

Methods

TaqMan assay method was used to genotype the polymorphism in the hospital-based case–control analysis of 665 patients with PCa and 710 age-matched cancer-free controls. The genetic associations with the occurrence and progression of PCa were calculated by logistic regression.

Results

Our results indicated that compared with GG genotypes, there was a statistically significant increased risk of PCa associated with those with CC genotypes [odds ratios (ORs) = 1.57, 95%confidence intervals (CIs) = 1.17-2.13, P = 0.004]. Moreover, stratification analysis revealed that the association was more pronounced in subgroups of nondrinkers, nonsmokers and those without a family history of cancer (all P < 0.05). In addition, we observed that PSA ≥ 20 was more frequent in patients carrying GC/CC genotypes than in those with a wild type genotype.

Conclusion

The functional survivin rs9904341 genetic variant may have a substantial influence on the PCa susceptibility and evolution.
Potassium channel openers and prostacyclin play a crucial role in mediating the vasorelaxant activity of Gynura procumbens
Authors: Ng Hien-Kun , Poh Ting-Fung , Lam Sau-Kuen , Hoe See-Ziau
Published: July 2013

Background

Previous studies of Gynura procumbens (G. procumbens) have shown that partially purified fractions of the leaves are capable of lowering the blood pressure of rats by inhibiting angiotensin-converting enzymic activity and causing vasodilatation. The objectives of this study were therefore to further purify the active compounds that exhibited selective effects on blood vessels, determine the mechanism of actions, and to qualitatively analyse the putative compounds present.

Methods

The butanolic fraction (BU) of the crude ethanolic extract was purified using column chromatography to obtain several sub-fractions of different polarities. The in vitro effects of BU and the sub-fractions on vascular tension were subsequently determined using isolated rat thoracic aortic rings. The most potent sub-fraction (F1) alone was then investigated for its mechanisms of the vasorelaxant activity. In another experiment, thin-layer chromatography was used to qualitatively analyse the active compounds found in F1.

Results

The BU and the sub-fractions ranging from 10-7 to 10-2 g/ml significantly (p < 0.05) inhibited the sustained tonic contractions induced by phenylephrine and potassium chloride in a concentration-dependent manner with various degree of potency. The most potent sub-fraction (F1) antagonised the calcium-induced vasocontractions (1 x 10-4 – 1 x 10-2 M) in calcium-free with high concentration of potassium as well as in calcium- and potassium-free Krebs-Henseleit solutions. Contractions induced by noradrenaline and caffeine were not affected by F1. The vasorelaxing effect caused by F1 was significantly attenuated with preincubation of potassium channel blockers (glibenclamide and 4-aminopyridine) and prostacyclin inhibitor (indomethacin) while it was not affected by preincubation with tetraethylammonium, l-nitro-arginine methyl esther, propanolol, atropine, oxadiazolo quinoxalin one and methylene blue. The qualitative phytochemical analysis of F1 indicated the presence of flavonoids.

Conclusion

These results confirm previous findings that G. procumbens causes vasodilatory effects by blocking calcium channels. In addition, the present study further demonstrates that the vasodilatory effect of G. procumbens may also be due to the opening of potassium channels and the stimulation of prostacyclin production. The putative compounds are probably flavonoids in nature.
Particled Mica, STB-HO has chemopreventive potential via G1 arrest, and inhibition of proliferation and vascular endothelial growth factor receptor 2 in HCT colorectal cancer cells
Authors: Cho Sung-Yun , Lee Hyo-Jeong , Cho Sun-Mi , Kim Bonglee , Jung Yeon Kwon , Kim Sung-Hoon
Published: July 2013

Background

Though Mica, a thin and sheet like mineral, has been used as a mineral medicine for treatment of bleeding, dysentery and inflammation in traditional medicine including Ayurveda, the biological evidences of Mica were not clearly elucidated so far. Thus, in the present study, the antitumor mechanism of particled Mica (STB-HO) was examined in colorectal cancers.

Methods

Athymic nude mice were inoculated with HCT116 colon cancer cells and orally administered STB-HO daily for 41 days, and HCT116 and human umbilical vein endothelial cells (HUVECs) were treated with STB-HO for 0 ~ 24 hours to perform immunoblotting, cytotoxicity assay, FACs analysis and measurement of matrix metalloproteinase 9 (MMP-9) secretion and other experiments. Significant differences of all date were evaluated using Student’s t-test and a Turkey-Kramer multiple-comparison post test.

Results

STB-HO significantly suppressed the tumor volume and weight in athymic nude mice inoculated with HCT116 cells at a dose of 100 mg/kg. Thus, the in vivo antitumor mechanism of STB-HO was to elucidated in vitro as well. STB-HO exerted cytotoxicity in HCT116, SW620 and HCT15 colorectal cancer cells. Also, STB-HO increased G1 cell population in a time and concentration dependent manner, enhanced the expression of p21, p27, p53 as cyclin dependent kinase (CDK) inhibitors, attenuated the expression of proliferating cell nuclear antigen (PCNA) and cyclin D1 and also reduced the production of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP-9) in HCT116 cells. Consistently, STB-HO suppressed the phosphorylation of VEGFR2 in HCT116, SW620 and HCT15 cells. Also, STB-HO inhibited the VEGF mediated proliferation and also attenuated the phosphorylation of VEGFR2 and Akt in human umbilical vein endothelial cells (HUVECs).

Conclusions

Collectively, these findings suggest that STB-HO has chemopreventive potential via G1 arrest and inhibition of proliferation and VEGFR2 in HCT116 colorectal cancer cells.
Influence on the behavior of lung cancer H1299 cells by silencing SLC35F2 expression
Authors: Li Xiao , Li Jilun , Jiang Guanchao , Bu Liang , Yang Fan , Liu Jun , Wang Jun
Published: July 2013

Background

To investigate the effects of RNA interference-mediated downregulation of Human Solute Carrier Family 35 member F2 (SLC35F2) expression on the biological behavior of lung cancer H1299 cells.

Methods

The lentiviral vector of small interfering RNA targeting SLC35F2 was introduced into H1299 cells by liposome-mediated transfection. Expression of the SLC35F2 protein was measured by western blot. The proliferation of H1299 cells was determined by Cell Counting Kit-8 assay. The migration of H1299 cells was measured by Transwell migration assay. Cell cycle analysis used fluorescence-activated cell sorting.

Results

SLC35F2 expression was markedly downregulated in H1299 cell clone (transfected with the lentiviral vector harboring small interfering RNA targeting SLC35F2). Proliferation decreased significantly compared with that of non-transfected H1299 cells. Transwell migration assay showed that fewer cells moved through the artificial basement membrane compared with untransfected H1299 cells (38.3 ± 5.7 vs. 113.5 ± 8.5, P < 0.05). The cell cycle of H1299 cells was changed, the percentage of H1299 cells in S and G2/M phases being significantly decreased compared with untransfected H1299 cells (S phase: 15.3% ± 3.0% vs. 27.0% ± 5.4%, P > 0.05; G2/M phase; 3.0% ± 1.1% vs. 10.5% ± 1.7%, P < 0.05), whereas the percentage of H1299 cells in G0/G1 phase increased markedly (81.7% ± 4.0% vs. 62.5% ± 1.9%, P < 0.05).

Conclusion

RNA interference-mediated downregulation of SLC35F2 expression by lentiviral vector can attenuate the proliferation, migration and invasion of H1299 cells.
Vertical platysma myocutaneous flap that sacrifices the facial artery and vein
Authors: Li Zhen-ning , Li Rui-wu , Liu Fa-yu , Fang Qi-gen , Zhang Xu , Sun Chang-fu
Published: July 2013

Background

Platysma myocutaneous flap (PMF) is a generally used technique for defect reconstruction after an oral cancer resection. The aim of the study is to present our experience using vertical PMF that sacrificed the facial artery and vein for intraoral reconstruction.

Methods

A retrospective review of the medical records of 54 patients who underwent vertical PMF that sacrificed the facial artery and vein for intraoral reconstruction was performed. A comparison between PMF that sacrificed and that preserved the facial vessels was made, and we also compared PMF that sacrificed the facial vessels with radial forearm free flap (RFFF). Statistics concerning the patients’ clinical factors were gathered.

Results

The mean age of the 54 patients who underwent PMF that sacrificed the facial artery and vein was 62.0 ± 10.98 years. The co-morbid disease rate of PMF was 53.7%. The flap size ranged from 12 × 5.5 cm to 7 × 5 cm. Survival of the flap was found in all of the cases, with partial necrosis in four cases (7.4%) and total loss in none of the cases. The operation time was 5.7 ± 1.17 h. The complication and success rates were 27.8% and 92.6%, respectively. The 3-year and 5-year survival rates were 77.8% (21/27) and 69.23% (9/13), respectively. The majority of the patients (87.0%) in our series were satisfied with the results of the surgery. There was no significant difference between PMF that sacrificed or that preserved the facial vessels, both in success rate (P = 1) or complication rate (P = 0.72). The patients in the PMF group were older than the patients in the RFFF group (P = 0.011), the operation time was shorter (P < 0.001), and the co-morbid disease rate was higher (P = 0.002). Although the complication rate of PMF (15/54, 27.8%) was higher than that of RFFF (2/34, 5.9%) (P = 0.011), their success rates were similar (92.6%, 94.1%) (P = 1.00).

Conclusions

Vertical PMF that sacrifices the facial artery and vein has specific advantages including in ease preparation and limitations. This technique may provide an effective method for intraoral reconstruction. Our experience in handling the flap may contribute to the success rate.
ToF-SIMS analysis of osteoblast-like cells and their mineralized extracellular matrix on strontium enriched bone cements
Authors: Kokesch-Himmelreich Julia , Schumacher Matthias , Rohnke Marcus , Gelinsky Michael , Janek Jürgen
Published: July 2013

Commonly used implants for therapeutic approaches of non-systemically impaired bone do not sufficiently support the healing process of osteoporotic bone. Since strontium (II) has been proven as an effective anti-osteoporotic drug new types of strontium enriched calcium phosphate bone cements were developed. As osteoporosis is characterized by an imbalance of osteoblast and osteoclast activity the influence of this newly generated strontium enriched biomaterials on the cellular behavior of osteoblast-like cells was investigated by time of flight secondary ion mass spectrometry (ToF-SIMS). ToF-SIMS is used to analyze whether strontium is incorporated in the mineralized extracellular matrix (mECM) and whether there is strontium uptake by osteogenically differentiated human mesenchymal stem cells (hMSCs). Therefore hMSCs were cultured in osteogenic differentiation medium for 21 days on two different strontium enriched bone cements (S100 and A10) and for reference also on the pure calcium phosphate cement (CPC) and on a silicon wafer. The distribution of strontium in the osteoblast-like cells and within their mineralized extracellular matrix was analyzed. A higher intensity of the strontium signal could be detected in the region of the mECM, synthesized by cells cultivated on the Sr- substituted bone cement (S100) in comparison to the reference groups. The osteoblast-like cells used the released strontium from the biomaterial to synthesize their mECM. Apart from that a uniform strontium distribution was measured within all investigated cells. However, different amounts of strontium were found in cells cultured on different biomaterials and substrates. Compared to the negative controls the strontium content in the cells on the strontium enriched biomaterials was much higher. A higher concentration of strontium inside the cells means that more strontium can take part in signaling pathways. As strontium is known for its beneficial effects on osteoblasts by promoting osteoblastic cell replication and differentiation, and reducing apoptosis, the newly developed strontium enriched calcium phosphate cements are promising implant materials for osteoporotic bone.
3H-Deprenyl and 3H-PIB autoradiography show different laminar distributions of astroglia and fibrillar β-amyloid in Alzheimer brain
Authors: Marutle Amelia , Gillberg Per-Göran , Bergfors Assar , Yu Wenfeng , Ni Ruiqing , Nennesmo Inger , Voytenko Larysa , Nordberg Agneta
Published: July 2013

Background

The pathological features in Alzheimer’s disease (AD) brain include the accumulation and deposition of β-amyloid (Aβ), activation of astrocytes and microglia and disruption of cholinergic neurotransmission. Since the topographical characteristics of these different pathological processes in AD brain and how these relate to each other is not clear, this motivated further exploration using binding studies in postmortem brain with molecular imaging tracers. This information could aid the development of specific biomarkers to accurately chart disease progression.

Results

In vitro binding assays demonstrated increased [3H]-PIB (fibrillar Aβ) and [3H]-PK11195 (activated microglia) binding in the frontal cortex (FC) and hippocampus (HIP), as well as increased binding of [3H]-l-deprenyl (activated astrocytes) in the HIP, but a decreased [3H]-nicotine (α4β2 nicotinic acetylcholine receptor (nAChR)) binding in the FC of AD cases compared to age-matched controls. Quantitative autoradiography binding studies were also performed to investigate the regional laminar distributions of [3H]-l-deprenyl, [3H]-PIB as well as [125I]-α-bungarotoxin (α7 nAChRs) and [3H]-nicotine in hemisphere brain of a typical AD case. A clear lamination pattern was observed with high [3H]-PIB binding in all layers and [3H]-deprenyl in superficial layers of the FC. In contrast, [3H]-PIB showed low binding to fibrillar Aβ, but [3H]-deprenyl high binding to activated astrocytes throughout the HIP. The [3H]-PIB binding was also low and the [3H]-deprenyl binding high in all layers of the medial temporal gyrus and insular cortex in comparison to the frontal cortex. Low [3H]-nicotine binding was observed in all layers of the frontal cortex in comparison to layers in the medial temporal gyrus, insular cortex and hippocampus. Immunohistochemical detection in the AD case revealed abundant glial fibrillary acidic protein positive (GFAP+) reactive astrocytes and α7 nAChR expressing GFAP+ astrocytes both in the vicinity and surrounding Aβ neuritic plaques in the FC and HIP. Although fewer Aβ plaques were observed in the HIP, some hippocampal GFAP+ astrocytes contained Aβ-positive (6 F/3D) granules within their somata.

Conclusions

Astrocytosis shows a distinct regional pattern in AD brain compared to fibrillar Aβ, suggesting that different types of astrocytes may be associated with the pathophysiological processes in AD.
Sunitinib enhances neuronal survival in vitro via NF-κB-mediated signaling and expression of cyclooxygenase-2 and inducible nitric oxide synthase
Authors: Sanchez Alma , Tripathy Debjani , Yin Xiangling , Luo Jinhua , Martinez Joseph M , Grammas Paula
Published: July 2013

Background

Angiogenesis is tightly linked to inflammation and cancer. Regulation of angiogenesis is mediated primarily through activation of receptor tyrosine kinases, thus kinase inhibitors represent a new paradigm in anti-cancer therapy. However, these inhibitors have broad effects on inflammatory processes and multiple cell types. Sunitinib is a multitarget receptor tyrosine kinase inhibitor, which has shown promise for the treatment of glioblastoma, a highly vascularized tumor. However, there is little information as to the direct effects of sunitinib on brain-derived neurons. The objective of this study is to explore the effects of sunitinib on neuronal survival as well as on the expression of inflammatory protein mediators in primary cerebral neuronal cultures.

Methods

Primary cortical neurons were exposed to various doses of sunitinib. The drug-treated cultures were assessed for survival by MTT assay and cell death by lactate dehydrogenase release. The ability of sunitinib to affect NF-κB, COX2 and NOS2 expression was determined by western blot. The NF-κB inhibitors dicoumarol, SN50 and BAY11-7085 were employed to assess the role of NF-κB in sunitinib-mediated effects on neuronal survival as well as COX2 and NOS2 expression.

Results

Treatment of neuronal cultures with sunitinib caused a dose-dependent increase in cell survival and decrease in neuronal cell death. Exposure of neurons to sunitinib also induced an increase in the expression of NF-κB, COX2 and NOS2. Inhibiting NF-κB blunted the increase in cell survival and decrease in cell death evoked by sunitinib. Treatment of cell cultures with both sunitinib and NF-κB inhibitors mitigated the increase in COX2 and NOS2 caused by sunitinib.

Conclusions

Sunitinib increases neuronal survival and this neurotrophic effect is mediated by NF-κB. Also, the inflammatory proteins COX2 and NOS2 are upregulated by sunitinib in an NF-κB-dependent manner. These data are in agreement with a growing literature suggesting beneficial effects for inflammatory mediators such as NF-κB, COX2 and NOS2 in neurons. Further work is needed to fully explore the effects of sunitinib in the brain and its possible use as a treatment for glioblastoma. Finally, sunitinib may be useful for the treatment of a range of central nervous system diseases where neuronal injury is prominent.
Shifted termination assay (STA) fragment analysis to detect BRAF V600 mutations in papillary thyroid carcinomas
Authors: Kang So Young , Ahn Soomin , Lee Sun-Mi , Jeong Ji Yun , Sung Ji-Youn , Oh Young Lyun , Kim Kyoung-Mee
Published: July 2013

Background

BRAF mutation is an important diagnostic and prognostic marker in patients with papillary thyroid carcinoma (PTC). To be applicable in clinical laboratories with limited equipment, diverse testing methods are required to detect BRAF mutation.

Methods

A shifted termination assay (STA) fragment analysis was used to detect common V600 BRAF mutations in 159 PTCs with DNAs extracted from formalin-fixed paraffin-embedded tumor tissue. The results of STA fragment analysis were compared to those of direct sequencing. Serial dilutions of BRAF mutant cell line (SNU-790) were used to calculate limit of detection (LOD).

Results

BRAF mutations were detected in 119 (74.8%) PTCs by STA fragment analysis. In direct sequencing, BRAF mutations were observed in 118 (74.2%) cases. The results of STA fragment analysis had high correlation with those of direct sequencing (p < 0.00001, κ = 0.98). The LOD of STA fragment analysis and direct sequencing was 6% and 12.5%, respectively. In PTCs with pT3/T4 stages, BRAF mutation was observed in 83.8% of cases. In pT1/T2 carcinomas, BRAF mutation was detected in 65.9% and this difference was statistically significant (p = 0.007). Moreover, BRAF mutation was more frequent in PTCs with extrathyroidal invasion than tumors without extrathyroidal invasion (84.7% versus 62.2%, p = 0.001). To prepare and run the reactions, direct sequencing required 450 minutes while STA fragment analysis needed 290 minutes.

Conclusions

STA fragment analysis is a simple and sensitive method to detect BRAF V600 mutations in formalin-fixed paraffin-embedded clinical samples.

Virtual Slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5684057089135749
“Tertius gaudens”: germplasm exchange networks and agroecological knowledge among home gardeners in the Iberian Peninsula
Authors: Reyes-García Victoria , Molina José Luis , Calvet-Mir Laura , Aceituno-Mata Laura , Lastra Juan J , Ontillera Ricardo , Parada Montse , Pardo-de-Santayana Manuel , Rigat Montse , Vallès Joan , Garnatje Teresa
Published: July 2013

Background

The idea that knowledge flows through social networks is implicit in research on traditional knowledge, but researchers have paid scant attention to the role of social networks in shaping its distribution. We bridge those two bodies of research and investigate a) the structure of network of exchange of plant propagation material (germplasm) and b) the relation between a person’s centrality in such network and his/her agroecological knowledge.

Methods

We study 10 networks of germplasm exchange (n = 363) in mountain regions of the Iberian Peninsula. Data were collected through participant observation, semi-structured interviews, and a survey.

Results

The networks display some structural characteristics (i.e., decentralization, presence of external actors) that could enhance the flow of knowledge and germplasm but also some characteristics that do not favor such flow (i.e., low density and fragmentation). We also find that a measure that captures the number of contacts of an individual in the germplasm exchange network is associated with the person’s agroecological knowledge.

Conclusion

Our findings highlight the importance of social relations in the construction of traditional knowledge.
Evaluation of inter-observer variability of bladder boundary delineation on cone-beam CT
Authors: Nishioka Kentaro , Shimizu Shinichi , Kinoshita Rumiko , Inoue Tetsuya , Onodera Shunsuke , Yasuda Koichi , Harada Keiichi , Nishikawa Yukiko , Onimaru Rikiya , Shirato Hiroki
Published: July 2013

Background

In-room cone-beam computerized tomography (CBCT) imaging is a promising method to reduce setup errors, especially in organs such as the bladder that often have large intrafractional variations due to organ movement. CBCT image quality is limited by low contrast and imaging artifacts, but few data have been reported about inter-observer variability of bladder boundary delineation on CBCT. The aim of this work was to analyze and evaluate the inter-observer contouring uncertainties of bladder boundary delineation on CBCT images in a prospective fashion.

Methods

Five radiation oncologists contoured 10 bladders using the CBCT datasets of consecutive 10 patients (including 4 females) who were irradiated to the pelvic region. Prostates were also contoured in male patients. Patients who had had prostatectomy were excluded. The coefficient of variation (COV), conformity index (CIgen), and coordinates of center-of-mass (COM) of the bladder and prostate were calculated for each patient.

Results

The mean COV for the bladder and prostate was 0.08 and 0.20, respectively. The mean CIgen of the bladder and prostate was 0.81 and 0.66, respectively. The root mean square (RMS) of the inter-observer standard deviation (σ) of the COM displacement in the left-right (LR) and anterior-posterior (AP) direction was 0.79, 0.87 and 0.54 for the bladder and 0.63, 0.99 and 1.72 for the prostate. Regarding the mean COV and CIgen for the bladder, the differences between males and females were not significant.

Conclusions

Inter-observer variability for bladder delineation on CBCT images was substantially small regardless of gender. We believe that our results support the applicability of CBCT in adaptive radiotherapy for bladder cancer.
Oto-facial syndrome and esophageal atresia, intellectual disability and zygomatic anomalies - expanding the phenotypes associated with EFTUD2 mutations
Authors: Voigt Claudia , Mégarbané André , Neveling Kornelia , Czeschik Johanna Christina , Albrecht Beate , Callewaert Bert , von Deimling Florian , Hehr Andreas , Falkenberg Smeland Marie , König Rainer , Kuechler Alma , Marcelis Carlo , Puiu Maria , Reardon Willie , Riise Stensland Hilde Monica Frostad , Schweiger Bernd , Steehouwer Marloes , Teller Christopher , Martin Marcel , Rahmann Sven , Hehr Ute , Brunner Han G , Lüdecke Hermann-Josef , Wieczorek Dagmar
Published: July 2013

Background

Mutations in EFTUD2 were proven to cause a very distinct mandibulofacial dysostosis type Guion-Almeida (MFDGA, OMIM #610536). Recently, gross deletions and mutations in EFTUD2 were determined to cause syndromic esophageal atresia (EA), as well. We set forth to find further conditions caused by mutations in the EFTUD2 gene (OMIM *603892).

Methods and results

We performed exome sequencing in two familial cases with clinical features overlapping with MFDGA and EA, but which were previously assumed to represent distinct entities, a syndrome with esophageal atresia, hypoplasia of zygomatic complex, microcephaly, cup-shaped ears, congenital heart defect, and intellectual disability in a mother and her two children [AJMG 143A(11):1135-1142, 2007] and a supposedly autosomal recessive oto-facial syndrome with midline malformations in two sisters [AJMG 132(4):398-401, 2005]. While the analysis of our exome data was in progress, a recent publication made EFTUD2 mutations highly likely in these families. This hypothesis could be confirmed with exome as well as with Sanger sequencing. Also, in three further sporadic patients, clinically overlapping to these two families, de novo mutations within EFTUD2 were identified by Sanger sequencing. Our clinical and molecular workup of the patients discloses a broad phenotypic spectrum, and describes for the first time an instance of germline mosaicism for an EFTUD2 mutation.

Conclusions

The clinical features of the eight patients described here further broaden the phenotypic spectrum caused by EFTUD2 mutations or deletions. We here show, that it not only includes mandibulofacial dysostosis type Guion-Almeida, which should be reclassified as an acrofacial dysostosis because of thumb anomalies (present in 12/35 or 34% of patients) and syndromic esophageal atresia [JMG 49(12). 737-746, 2012], but also the two new syndromes, namely oto-facial syndrome with midline malformations published by Mégarbané et al. [AJMG 132(4): 398-401, 2005] and the syndrome published by Wieczorek et al. [AJMG 143A(11): 1135-1142, 2007] The finding of mild phenotypic features in the mother of one family that could have been overlooked and the possibility of germline mosaicism in apparently healthy parents in the other family should be taken into account when counseling such families.
Fabry_CEP: a tool to identify Fabry mutations responsive to pharmacological chaperones
Authors: Cammisa Marco , Correra Antonella , Andreotti Giuseppina , Cubellis Maria Vittoria
Published: July 2013

Fabry_CEP is a user-friendly web-application designed to help clinicians Choose Eligible Patients for the therapy with pharmacological chaperones. It provides a database and a predictive tool to evaluate the responsiveness of lysosomal alpha-galactosidase mutants to a small molecule drug, namely 1-Deoxy-galactonojirimycin. The user can introduce any missense/nonsense mutation in the coding sequence, learn whether it is has been tested and gain access to appropriate reference literature. In the absence of experimental data structural, functional and evolutionary analysis provides a prediction and the probability that a given mutation is responsive to the drug.
Systematic review and meta-analysis of the effectiveness of continuous glucose monitoring (CGM) on glucose control in diabetes
Authors: Poolsup Nalinee , Suksomboon Naeti , Kyaw Aye Mon
Published: July 2013

Diabetes mellitus is a chronic disease that necessitates continuing treatment and patient self-care education. Monitoring of blood glucose to near normal level without hypoglycemia becomes a challenge in the management of diabetes. Although self monitoring of blood glucose (SMBG) can provide daily monitoring of blood glucose level and help to adjust therapy, it cannot detect hypoglycemic unawareness and nocturnal hypoglycemia which occurred mostly in T1DM pediatrics. Continuous glucose monitoring (CGM) offers continuous glucose data every 5 minutes to adjust insulin therapy especially for T1DM patients and to monitor lifestyle intervention especially for T2DM patients by care providers or even patients themselves. The main objective of this study was to assess the effects of continuous glucose monitoring (CGM) on glycemic control in Type 1 diabetic pediatrics and Type 2 diabetic adults by collecting randomized controlled trials from MEDLINE (pubmed), SCOPUS, CINAHL, Web of Science and The Cochrane Library up to May 2013 and historical search through the reference lists of relevant articles. There are two types of CGM device: real-time CGM and retrospective CGM and both types of the device were included in the analysis. In T1DM pediatrics, CGM use was no more effective than SMBG in reducing HbA1c [mean difference – 0.13% (95% CI -0.38% to 0.11%,]. This effect was independent of HbA1c level at baseline. Subgroup analysis indicated that retrospective CGM was not superior to SMBG [mean difference -0.05% (95% CI -0.46% to 0.35%)]. In contrast, real-time CGM revealed better effect in lowering HbA1c level compared with SMBG [mean difference -0.18% (95% CI -0.35% to -0.02%, p = 0.02)]. In T2DM adults, significant reduction in HbA1c level was detected with CGM compared with SMBG [mean difference – 0.31% (95% CI -0.6% to -0.02%, p = 0.04)].

This systematic review and meta-analysis suggested that real-time CGM can be more effective than SMBG in T1DM pediatrics, though retrospective CGM was not. CGM provided better glycemic control in T2DM adults compared with SMBG.
Bottom-up Synthesis of Titania and Zirconia Nanosheets and Their Composites with Graphene
Authors: Takenaka Sakae , Uwai Shunsuke , Ida Shintaro , Matsune Hideki , Kishida Masahiro
Published: July 2013

Simple impregnation of graphene oxide (GO) in cyclohexane containing Ti(OC4H9)4 or Zr(OC4H9)4, followed by a solvothermal reaction, resulted in the deposition of nanosheets of TiO2 or ZrO2 a few nanometers thick on the reduced GO. In addition, free-standing nanosheets of TiO2 or ZrO2 were formed by calcination of these composites in air.
Systematic assessment of benefits and risks: study protocol for a multi-criteria decision analysis using the Analytic Hierarchy Process for comparative effectiveness research
Authors: Maruthur Nisa M , Joy Susan , Dolan James , Segal Jodi B , Shihab Hasan M , Singh Sonal
Published: July 2013

Background: Regulatory decision-making involves assessment of risks and benefits of medications at the time of approval or when relevant safety concerns arise with a medication. The Analytic Hierarchy Process (AHP) facilitates decision-making in complex situations involving tradeoffs by considering risks and benefits of alternatives. The AHP allows a more structured method of synthesizing and understanding evidence in the context of importance assigned to outcomes. Our objective is to evaluate the use of an AHP in a simulated committee setting selecting oral medications for type 2 diabetes. 

Methods:This study protocol describes the AHP in five sequential steps using a small group of diabetes experts representing various clinical disciplines. The first step will involve defining the goal of the decision and developing the AHP model. In the next step, we will collect information about how well alternatives are expected to fulfill the decision criteria. In the third step, we will compare the ability of the alternatives to fulfill the criteria and judge the importance of eight criteria relative to the decision goal of the optimal medication choice for type 2 diabetes. We will use pairwise comparisons to sequentially compare the pairs of alternative options regarding their ability to fulfill the criteria. In the fourth step, the scales created in the third step will be combined to create a summary score indicating how well the alternatives met the decision goal. The resulting scores will be expressed as percentages and will indicate the alternative medications' relative abilities to fulfill the decision goal. The fifth step will consist of sensitivity analyses to explore the effects of changing the estimates. We will also conduct a cognitive interview and process evaluation. 

Discussion: Multi-criteria decision analysis using the AHP will aid, support and enhance the ability of decision makers to make evidence-based informed decisions consistent with their values and preferences.
Work Flow Analysis of Around-the-clock Processing of Blood Culture Samples and Integrated MALDI-TOF Mass Spectrometry Analysis for the Diagnosis of Bloodstream Infections
Authors: Schneiderhan Wilhelm , Grundt Alexander , Wörner Stefan , Findeisen Peter , Neumaier Michael
Published: July 2013

BACKGROUND

Because sepsis has a high mortality rate, rapid microbiological diagnosis is required to enable efficient therapy. The effectiveness of MALDI-TOF mass spectrometry (MALDI-TOF MS) analysis in reducing turnaround times (TATs) for blood culture (BC) pathogen identification when available in a 24-h hospital setting has not been determined.

METHODS

On the basis of data from a total number of 912 positive BCs collected within 140 consecutive days and work flow analyses of laboratory diagnostics, we evaluated different models to assess the TATs for batch-wise and for immediate response (real-time) MALDI-TOF MS pathogen identification of positive BC results during the night shifts. The results were compared to TATs from routine BC processing and biochemical identification performed during regular working hours.

RESULTS

Continuous BC incubation together with batch-wise MALDI-TOF MS analysis enabled significant reductions of up to 58.7 h in the mean TATs for the reporting of the bacterial species. The TAT of batch-wise MALDI-TOF MS analysis was inferior by a mean of 4.9 h when compared to the model of the immediate work flow under ideal conditions with no constraints in staff availability.

CONCLUSIONS

Together with continuous cultivation of BC, the 24-h availability of MALDI-TOF MS can reduce the TAT for microbial pathogen identification within a routine clinical laboratory setting. Batch-wise testing of positive BC loses a few hours compared to real-time identification but is still far superior to classical BC processing. Larger prospective studies are required to evaluate the contribution of rapid around-the-clock pathogen identification to medical decision-making for septicemic patients.
Prediction of Egyptian 500-kV Overhead Transmission Line’s Radio Interference by Using the Excitation Function
Authors: El Dein Adel Z.
Published: July 2013

This article presents applications of the excitation function on the prediction of the radio interference (RI) of overhead transmission line (OHTL), due to corona effect. These applications are done under different weather conditions such as heavy rain, wet conductor, and fair weather.Also, this article investigates the factors influencing the RI level, namely, the height of conductors, phase spacing, number of subconductors in the bundle, diameter of subconductor, and subconductor spacing in the bundle.In this article, it is shown that the RI level is dependent on the weather conditions. Where the RI level under heavy rain has the maximum level, hence, it should be considered as a basic level of any OHTL.
Power Management Based Current Control Technique for Photovoltaic-Battery Assisted Wind–Hydro Hybrid System
Authors: Ram Prabhakar J. , Ragavan K.
Published: July 2013

This article proposes new power management based current control strategy for integrated wind–solar–hydro system equipped with battery storage mechanism. In this control technique, an indirect estimation of load current is done, through energy balance model, DC-link voltage control and droop control. This system features simpler energy management strategy and necessitates few power electronic converters, thereby minimizing the cost of the system. The generation–demand (G–D) management diagram is formulated based on the stochastic weather conditions and demand, which would likely moderate the gap between both. The features of management strategy deploying energy balance model include (1) regulating DC-link voltage within specified tolerances, (2) isolated operation without relying on external electric power transmission network, (3) indirect current control of hydro turbine driven induction generator and (4) seamless transition between grid-connected and off-grid operation modes. Furthermore, structuring of the hybrid system with appropriate selection of control variables enables power sharing among each energy conversion systems and battery storage mechanism. By addressing these intricacies, it is viable to regulate the frequency and voltage of the remote network at load end. The performance of the proposed composite scheme is demonstrated through time-domain simulation in MATLAB/Simulink environment.
Zur Stellung des Antisemitismus im Denken Carl Schmitts
Authors: Egner David
Published: July 2013

Vorspann

Die Zeiten, in denen Bewunderer Carl Schmitts dessen antisemitische Äußerungen und Handlungen unter dem NS-Regime als Opportunismus oder gar als überlebensnotwendige Anpassung verharmlosen konnten, sind längst vorbei, enthalten doch seine mittlerweile veröffentlichten Tagebücher aus der Zeit vor der NS-Diktatur ebenso wie seine Nachkriegsaufzeichnungen zahlreiche antijüdische Statements. Doch welche Bedeutung hat der Antisemitismus für Schmitts wissenschaftliches Werk? In die anhaltende Debatte darüber greift David Egner mit seinem folgenden Beitrag ein, bei dem es ihm besonders um die Präzisierung der Analyse Schmitt’scher Denkfiguren geht.
How “Discover the COSMOS” and “PATHWAY” are changing the science education in European high schools.
Authors: Kourkoumelis Christine
Published: July 2013

It has been noted by various reports that during recent years, there has been an alarming decline in young people’s interest for science studies and mathematics. Since it is believed that the traditional teaching methods often fail to foster positive attitudes towards learning science, the European Commission has made intensive efforts to promote science education in schools though new methods based on the inquiry based techniques: questions, search and answers. This is coupled to hands-on experience, playful learning accompanied by laboratory exercises and examples.

“Discover the COSMOS” is such a project which brings into synergy resources from high energy, astronomy and space physics to promote e-Science in Europe. Event analysis tools from the ATLAS experiments at the Large Hadron Collider of CERN -such as the “hunt for the Higgs” application- as well as time slices in various robotic telescopes around the world and the related software to process the images, are all available as educational scenaria for both the students and the educators. Moreover, the best practices are presented in a more theoretical for the teachers in the “Pathway” project. Examples of the available resources as well as first results from the evaluation of the programs are presented.
Recipient gaze and the resolution of overlapping talk in hearing impaired interaction
Authors: Skelt Louise
Published: July 2013

This paper presents findings from a larger conversation analysis study of interactional management by adults with severe or profound acquired hearing impairment and their experienced communication partners. As in most interaction, overlapping talk occurs in interactions involving people with hearing impairment. However, both the initiation and the resolution of overlapping talk in these interactions may be determined by the availability (or non-availability) of the gaze and potential recipiency of the hearing-impaired co-participant. Experienced non-hearing-impaired interactional partners can be seen to drop quickly out of problematic overlap in the absence of their hearing impaired co-participant's gaze. Only in the presence of co-participant gaze will these partners compete for the turn. Similarly, collaborative overlapping talk by these partners is initiated only in the presence of the co-participant's gaze and potential recipiency. By responding in this way to the presence and absence of their hearing-impaired co-participants’ gaze, these partners maximise recipiency for their own talk and thereby minimise repairable problems of understanding, even if this means risking the loss of their own contributions.
Acetone extract from Streptoverticillium sp., a bacterium isolated from Brazilian Cerrado soil, induces anti-inflammatory activity in mice
Authors: CRUZ RODRIGO B. DA , GALDINO PABLINNY M. , PENNA KARLLA G.B.D. , HOFFMANN KAREN , COSTA ELSON A. , BATAUS LUIZ A.M.
Published: July 2013

The Streptoverticillium sp. Z1 is an actinomycete isolated from the soil under Cerrado vegetation, the extract of this strain was investigated in nociceptive and inflammatory models. The Streptoverticillium extract (ExS) 50 and 100 mg/kg (s.c.) produced a significant inhibition of acetic acid-induced abdominal writhings thereby demonstrating an anti-nociceptive effect. In the tail flick test the ExS (s.c.) was inactive. This result implited that ExS does not contain opioid-like compounds with central analgesic properties. In the inflammatory models, ExS 100 and 200 mg/kg (s.c.) were able to inhibit the croton oil-induced ear edema and, ExS 200 and 500 mg/kg (s.c.) inhibited the leukocyte migration on the carrageenan-induced peritonitis. The phospholipase A2 enzymatic assay showed that the anti-inflammatory activity of ExS was not due to direct effect on phospholipase A2 activity. These data suggest that Streptoverticillium sp. produces metabolites with anti-inflammatory effect and that these metabolites are unable to directly inhibit phospholipase A2 enzyme.
The effect of temperature on the germination of Melocactus violaceus Pfeiff. (Cactaceae), a threatened species in restinga sandy coastal plain of Brazil
Authors: ZAMITH LUIZ R. , CRUZ DENISE D. , RICHERS BARBARA T.T.
Published: July 2013

Melocactus violaceus is an endangered species due to habitat destruction and the overcollection of this species for ornamental use. The aim of this study was to test the effect of different temperatures on the germination of M. violaceus. Three treatments were conducted: a constant temperature of 25ºC, a 20-35ºC alternating temperature, both inside germination chamber, and an alternating temperature under room temperature (mean temperature ranged from 25-37ºC). The final seed germination rates at the alternating temperature treatments were not significantly different (65% in the seed germinator and 62.5% at room condition). However, both treatments with alternating temperatures had significantly higher germination rates compared to the treatment kept at the constant temperature (8%). Our study showed that alternating temperatures between 20 and 37ºC provides satisfactory conditions to induce a high percentage of seed germination of M. violaceus, without the passage of seeds through the digestive tract of its natural disperser, the lizard Tropidurus torquatus. This condition contributes to efficiently producing seedlings that can be reintroduced into conservation areas or used as ornamentals that may help reduce the overcollection of the remaining native populations.
Phytogeographical patterns of dry forests sensu stricto in northern Minas Gerais State, Brazil
Authors: ARRUDA DANIEL M. , FERREIRA-JUNIOR WALNIR G. , DUQUE-BRASIL REINALDO , SCHAEFER CARLOS E.R.
Published: July 2013

The Deciduous Complex that occurs in northern Minas Gerais State, Brazil, raises questions about the floristic affinities of these formations in relation to neighboring phytogeographical domains. Little is known about the identity of the seasonal forest formations that comprise this complex, or about its relationships to abiotic components, such as soils, topography and climate. This study aimed to recognize the patterns of floristic similarity of all studied fragments of dry forest of northern Minas Gerais with soil and climate attributes, based on the available database. Cluster analysis indicated the existence of two floristic groups that had clear associations with either the Koppen's BSh (semi-arid) or Aw (seasonal tropical) climates. Likewise, the subdivisions of these groups showed clear associations with the dominant soil classes in the region. The Red-Yellow Latosol is the dominant soil classes in the BSh climatic domain, seconded by alluvial areas associated with Fluvic Neosols. The Aw domain comprised a much varied set of soils: Nitosols, Argisols, Cambisols and Litholic Neosols, most derived from the Bambuí limestone/slate formation. The ecotonal nature of northern Minas Gerais State provides a complex interaction between the flora of neighboring phytogeographical domains. This, allied to pedogeomorphological factors, allowed a better understanding of the effects of late Quaternary climate changes for the Deciduous Complex evolution. We conclude that the Latosols under present-day semi-arid climates (BSh) are relicts of former wetter climates, during which humid forest (semideciduous) expansion took place. Later, these semideciduous forests were subjected to a much drier climate, when selection for deciduousness led to the present-days Deciduous Complex scenario.
Hormesis with glyphosate depends on coffee growth stage
Authors: CARVALHO LEONARDO B. DE , ALVES PEDRO L.C.A. , DUKE STEPHEN O.
Published: July 2013

Weed management systems in almost all Brazilian coffee plantations allow herbicide spray to drift on crop plants. In order to evaluate if there is any effect of the most commonly used herbicide in coffee production, glyphosate, on coffee plants, a range of glyphosate doses were applied directly on coffee plants at two distinct plant growth stages. Although growth of both young and old plants was reduced at higher glyphosate doses, low doses caused no effects on growth characteristics of young plants and stimulated growth of older plants. Therefore, hormesis with glyphosate is dependent on coffee plant growth stage at the time of herbicide application.
Are sun- and shade-type anatomy required for the acclimation of Neoregelia cruenta?
Authors: REINERT FERNANDA , LEAL-COSTA MARCOS V. , JUNQUEIRA NICIA E. , TAVARES ELIANA S.
Published: July 2013

Sun and shade plants are often discriminated by a number of sun- and shade-type anatomies. Nonetheless, we propose that among tank-bromeliads, changes in rosette architecture satisfy the requirements for coping with contrasting light levels. The tank-bromeliad Neoregelia cruenta naturally colonises sub-habitats ranging from full exposure to direct sunlight, to shaded environments in sand ridge plains. We quantified anatomical and morphological traits of leaves and rosettes of N. cruenta grown under sun and shade conditions. Cells with undulated lateral walls within the water parenchyma are for the first time described for the family. Under high light, leaf blades were wider, shorter, and yellowish. The rosette diameter of sun plants was less than half that of shade plants. Sun leaves overlapped with neighbouring leaves for most of their length, forming a cylindrical rosette where water accumulates. Shade leaves only overlapped in the centre of the rosette. Most anatomical traits were similar under both growth conditions. Stomata were absent from the base of sun leaves, which is probably explained by limited gas exchange at the base of the tight sun-type rosette. Data suggest that the ability of N. cruenta to acclimate to sun and shade is better explained by changes in rosette architecture than by leaf anatomy.