bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic review and meta-analysis: influence of smoking cessation on incidence of pneumonia in HIV
Authors: De Preeti , Farley Amanda , Lindson Nicola , Aveyard Paul
Published: January 2013

Background

Smoking is common in people infected with HIV but cessation support is not a routine part of clinical care. The aim was to assess whether smoking is a risk factor for pneumonia in people with HIV and whether smoking cessation ameliorates excess risk.

Methods

We performed MEDLINE and Embase database searches and included cohort or case-control studies conducted in adult patients infected with HIV extracting a hazard ratio (HR) or odds ratio (OR) that compared the incidence of bacterial pneumonia or pneumonia caused byPneumocystis jiroveci(PCP) between two smoking categories. Studies were appraised for quality and combined using inverse variance meta-analysis.

Results

Fourteen cohort and case-control studies were included. Assessment of outcome was good, but assessment of exposure status was poor. Current smokers were at higher risk of bacterial pneumonia than former smokers: HR 1.37 (95% confidence interval (CI): 1.06, 1.78). There was no evidence that former smokers were at higher risk than never smokers: HR 1.24 (95%CI: 0.96, 1.60). Current smokers were at higher risk of bacterial pneumonia than current non-smokers: HR of 1.73 (95%CI: 1.44, 2.06). There was no evidence that smoking increased the incidence of PCP. The HR for current versus non-smokers was 0.94 (95%CI: 0.79, 1.12), but from case-control studies the OR was 1.76 (95%CI: 1.25, 2.48) with heterogeneity. Confined to higher quality studies, the OR was 0.97 (95%CI: 0.81, 1.16). Residual confounding is possible, but available data suggest this is not an adequate explanation.

Conclusions

Smoking is a risk factor for bacterial pneumonia but not PCP and smoking cessation reduces this risk.

See related article:http://www.biomedcentral.com/1741-7015/11/16
Monocyte chemoattractant protein-1 affects migration of hippocampal neural progenitors following status epilepticus in rats
Authors: Hung Yu-Wen , Lai Ming-Tsong , Tseng Yi-Jhan , Chou Chien-Chen , Lin Yung-Yang
Published: January 2013

Background

Epilepsy is a common brain disorder characterized by a chronic predisposition to generate spontaneous seizures. The mechanisms for epilepsy formation remain unknown. A growing body of evidence suggests the involvement of inflammatory processes in epileptogenesis. In the present study, we investigated the involvement of monocyte chemoattractant protein-1 (MCP-1) in aberrant migration of hippocampal progenitors in rats after the insult of status epilepticus (SE).

Methods

SE was induced with pilocarpine in Sprague–Dawley rats. Transcriptional expression of MCP-1 in the dentate gyrus (DG) was measured using quantitative real-time PCR. From 1 to 28 days after SE, the temporal profiles of MCP-1 protein expression in DG were evaluated using enzyme-linked immunosorbent assay. Chemokine (C-C motif) receptor 2 (CCR2) expression in doublecortin-positive neuronal progenitors was examined using double-labeling immunohistochemistry. The involvement of MCP-1/CCR2 signaling in aberrant neuronal progenitor migration in the epileptic hippocampus was assessed in the SE rats using a CCR2 antagonist, RS102895, and the ectopic migration of neuronal progenitors was determined using Prox1/doublecortin double immunostaining.

Results

After SE, MCP-1 gene was significantly upregulated and its corresponding protein expression in the DG was significantly increased on days 1 and 3. Some hilar ectopic progenitor cells of SE rats expressed the MCP-1 receptor, CCR2. Notably, the ectopic migration of neuronal progenitors into hilus was attenuated by a blockade of the MCP-1/CCR2 interaction with a selective CCR2 inhibitor, RS102895.

Conclusions

An increase in dentate MCP-1 is associated with seizure-induced aberrant migration of neuronal progenitors through the interaction with CCR2. The upregulation of MCP-1 after an insult of SE may play a role in the generation of epilepsy.
Characterization of HIV-1 gag and nef in Cameroon: further evidence of extreme diversity at the origin of the HIV-1 group M epidemic
Authors: Tongo Marcel , Martin Darren P , Zembe Lycias , Mpoudi-Ngole Eitel , Williamson Carolyn , Burgers Wendy A
Published: January 2013

Background

Cameroon, in west central Africa, has an extraordinary degree of HIV diversity, presenting a major challenge for the development of an effective HIV vaccine. Given the continuing need to closely monitor the emergence of new HIV variants in the country, we analyzed HIV-1 genetic diversity in 59 plasma samples from HIV-infected Cameroonian blood donors. Full length HIV gag and nef sequences were generated and phylogenetic analyses were performed.

Findings

All gag and nef sequences clustered within HIV-1M. Circulating recombinant form CRF02_AG predominated, accounting for 50% of the studied infections, followed by clade G (11%), clade D and CRF37_cpx (4% each), and clades A, F, CRF01_AE and CRF36_cpx (2% each). In addition, 22% of the studied viruses apparently had nef and gag genes from viruses belonging to different clades, with the majority (8/10) having either a nef or gag gene derived from CRF02_AG. Interestingly, five gag sequences (10%) and three (5%) nef sequences were neither obviously recombinant nor easily classifiable into any of the known HIV-1M clades.

Conclusion

This suggests the widespread existence of highly divergent HIV lineages in Cameroon. While the genetic complexity of the Cameroonian HIV-1 epidemic has potentially serious implications for the design of biomedical interventions, detailed analyses of divergent Cameroonian HIV-1M lineages could be crucial for dissecting the earliest evolutionary steps in the emergence of HIV-1M.
Effects of orally applied butyrate bolus on histone acetylation and cytochrome P450 enzyme activity in the liver of chicken – a randomized controlled trial
Authors: Mátis Gábor , Neogrády Zsuzsanna , Csikó György , Kulcsár Anna , Kenéz Ákos , Huber Korinna
Published: January 2013

Background

Butyrate is known as histone deacetylase inhibitor, inducing histone hyperacetylation in vitro and playing a predominant role in the epigenetic regulation of gene expression and cell function. We hypothesized that butyrate, endogenously produced by intestinal microbial fermentation or applied as a nutritional supplement, might cause similar in vivo modifications in the chromatin structure of the hepatocytes, influencing the expression of certain genes and therefore modifying the activity of hepatic microsomal drug-metabolizing cytochrome P450 (CYP) enzymes.

Methods

An animal study was carried out in chicken as a model to investigate the molecular mechanisms of butyrate’s epigenetic actions in the liver. Broiler chicks in the early post-hatch period were treated once daily with orally administered bolus of butyrate following overnight starvation with two different doses (0.25 or 1.25 g/kg body weight per day) for five days. After slaughtering, cell nucleus and microsomal fractions were separated by differential centrifugation from the livers. Histones were isolated from cell nuclei and acetylation of hepatic core histones was screened by western blotting. The activity of CYP2H and CYP3A37, enzymes involved in biotransformation in chicken, was detected by aminopyrine N-demethylation and aniline-hydroxylation assays from the microsomal suspensions.

Results

Orally added butyrate, applied in bolus, had a remarkable impact on nucleosome structure of hepatocytes: independently of the dose, butyrate caused hyperacetylation of histone H2A, but no changes were monitored in the acetylation state of H2B. Intensive hyperacetylation of H3 was induced by the higher administered dose, while the lower dose tended to increase acetylation ratio of H4. In spite of the observed modification in histone acetylation, no significant changes were observed in the hepatic microsomal CYP2H and CYP3A37 activity.

Conclusion

Orally added butyrate in bolus could cause in vivo hyperacetylation of the hepatic core histones, providing modifications in the epigenetic regulation of cell function. However, these changes did not result in alteration of drug-metabolizing hepatic CYP2H and CYP3A37 enzymes, so there might be no relevant pharmacoepigenetic influences of oral application of butyrate under physiological conditions.
Analysis of dosimetric factors associated with temporal lobe necrosis (TLN) in patients with nasopharyngeal carcinoma (NPC) after intensity modulated radiotherapy
Authors: Su Sheng-Fa , Huang Shao-Ming , Han Fei , Huang Ying , Chen Chun-Yan , Xiao Wei-Wei , Sun Xue-Ming , Lu Tai-Xiang
Published: January 2013

Background

The radiation tolerance dose-volume in brain remains unclear for nasopharyngeal carcinoma (NPC) patients treated with intensity modulated radiotherapy (IMRT). We performed this study to investigate dosimetric factors associated with temporal lobe necrosis (TLN) in NPC patients treated with IMRT.

Methods

From 2001 to 2008, 870 NPC patients were treated with IMRT. For the whole group, 40 patients have developed MRI-diagnosed TLN, and 219 patients were followed-up more than 60 months. Predictive dosimetric factors for TLN were identified by using univariate and multivariate analysis in these 259 patients.

Results

By univariate analyses, rVX ( percent of temporal lobes receiving ≥ X Gy) and aVX ( absolute volumes of temporal lobes receiving ≥ X Gy, values of X considered were 10, 20, 30, 40, 50, 60, 66 and 70) were all significantly associated with TLN. Multivariate analysis by logistic regression showed that rV40 and aV40 were significant factors for TLN. All dosimetric factors in current serials were highly correlated one another (p < 0.001). The 5-year incidence of TLN for rV40 <10% or aV40 <5 cc is less than 5%. The incidence for rV40 ≥ 15% or aV40c ≥ 10c is increased significantly and more than 20%.

Conclusions

In this study, all dosimetric factors were highly correlated, rV40 and aV40 were independent predictive factors for TLN, IMRT with rV40 <10% or aV40 <5 cc in temporal lobe is relatively safe.
Specific combination of compound heterozygous mutations in 17β-hydroxysteroid dehydrogenase type 4 (HSD17B4) defines a new subtype of D-bifunctional protein deficiency
Authors: McMillan Hugh J , Worthylake Thea , Schwartzentruber Jeremy , Gottlieb Chloe C , Lawrence Sarah E , MacKenzie Alex , Beaulieu Chandree L , Mooyer Petra A W ,   FORGE Canada Consortium, Wanders Ronald J A , Majewski Jacek , Bulman Dennis E , Geraghty Michael T , Ferdinandusse Sacha , Boycott Kym M
Published: January 2013

Background

D-bifunctional protein (DBP) deficiency is typically apparent within the first month of life with most infants demonstrating hypotonia, psychomotor delay and seizures. Few children survive beyond two years of age. Among patients with prolonged survival all demonstrate severe gross motor delay, absent language development, and severe hearing and visual impairment. DBP contains three catalytically active domains; an N-terminal dehydrogenase, a central hydratase and a C-terminal sterol carrier protein-2-like domain. Three subtypes of the disease are identified based upon the domain affected; DBP type I results from a combined deficiency of dehydrogenase and hydratase activity; DBP type II from isolated hydratase deficiency and DBP type III from isolated dehydrogenase deficiency. Here we report two brothers (16½ and 14 years old) with DBP deficiency characterized by normal early childhood followed by sensorineural hearing loss, progressive cerebellar and sensory ataxia and subclinical retinitis pigmentosa.

Methods and results

Biochemical analysis revealed normal levels of plasma VLCFA, phytanic acid and pristanic acid, and normal bile acids in urine; based on these results no diagnosis was made. Exome analysis was performed using the Agilent SureSelect 50Mb All Exon Kit and the Illumina HiSeq 2000 next-generation-sequencing (NGS) platform. Compound heterozygous mutations were identified by exome sequencing and confirmed by Sanger sequencing within the dehydrogenase domain (c.101C>T; p.Ala34Val) and hydratase domain (c.1547T>C; p.Ile516Thr) of the 17β-hydroxysteroid dehydrogenase type 4 gene (HSD17B4). These mutations have been previously reported in patients with severe-forms of DBP deficiency, however each mutation was reported in combination with another mutation affecting the same domain. Subsequent studies in fibroblasts revealed normal VLCFA levels, normal C26:0 but reduced pristanic acid beta-oxidation activity. Both DBP hydratase and dehydrogenase activity were markedly decreased but detectable.

Conclusions

We propose that the DBP phenotype seen in this family represents a distinct and novel subtype of DBP deficiency, which we have termed type IV based on the presence of a missense mutation in each of the domains of DBP resulting in markedly reduced but detectable hydratase and dehydrogenase activity of DBP. Given that the biochemical testing in plasma was normal in these patients, this is likely an underdiagnosed form of DBP deficiency.
Aggregation and neurotoxicity of recombinant α-synuclein aggregates initiated by dimerization
Authors: Roostaee Alireza , Beaudoin Simon , Staskevicius Antanas , Roucou Xavier
Published: January 2013

Background

Aggregation of the α-Synuclein (α-Syn) protein, amyloid fibril formation and progressive neurodegeneration are the neuropathological hallmarks of Parkinson's Disease (PD). However, a detailed mechanism of α-Syn aggregation/fibrillogenesis and the exact nature of toxic oligomeric species produced during amyloid formation process are still unknown.

Results

In this study, the rates of α-Syn aggregation were compared for the recombinant wild-type (WT) α-Syn and a structurally relevant chimeric homologous protein containing an inducible Fv dimerizing domain (α-SynFv), capable to form dimers in the presence of a divalent ligand (AP20187). In the presence of AP20187, we report a rapid random coil into β-sheet conformational transformation of α-SynFv within 24 h, whereas WT α-Syn showed 24 h delay to achieve β-sheet structure after 48 h. Fluorescence ANS and ThT binding experiments demonstrate an accelerated oligomer/amyloid formation of dimerized α-SynFv, compared to the slower oligomerization and amyloidogenesis of WT α-Syn or α-SynFv without dimerizer AP20187. Both α-SynFv and α-Syn pre-fibrillar aggregates internalized cells and induced neurotoxicity when injected into the hippocampus of wild-type mice. These recombinant toxic aggregates further converted into non-toxic amyloids which were successfully amplified by protein misfolding cyclic amplification method, providing the first evidence for the in vitro propagation of synthetic α-Syn aggregates.

Conclusions

Together, we show that dimerization is important for α-Syn conformational transition and aggregation. In addition, α-Syn dimerization can accelerate the formation of neurotoxic aggregates and amyloid fibrils which can be amplified in vitro. A detailed characterization of the mechanism of α-Syn aggregation/amyloidogenesis and toxicity is crucial to comprehend Parkinson's disease pathology at the molecular level.
Her-2/neu expression is a negative prognosticator in ovarian cancer cases that do not express the follicle stimulating hormone receptor (FSHR)
Authors: Heublein Sabine , Vrekoussis Thomas , Mayr Doris , Friese Klaus , Lenhard Miriam , Jeschke Udo , Dian Darius
Published: January 2013

Background

Anti-Her-2 treatment is successfully administered to Her-2 overexpressing breast cancer patients and significantly implicates upon their survival. Building on these promising results, anti-Her-2 treatment protocols were tested as an option for epithelial ovarian cancer (EOC) as well. However Her-2 signalling is known to be modulated by G-protein coupled receptors (GPCR). Since a common GPCR in ovarian cancer is the FSH receptor (FSHR), we investigated the prognostic significance of Her-2 in patients that had been stratified according to their FSHR status.

Findings

A total number of 153 EOC patients were included in this study. Her-2 positivity was assessed using a standard protocol. Intriguingly Her-2 turned out to be an independent prognostic marker for poor overall survival only in those patients that did not express FSHR. This did neither apply for the whole panel nor in case of FSHR co-expression.

Conclusions

We thus conclude that Her-2 can be a negative prognosticator only in FSHR negative EOC cases. Hence by stratifying EOC patients according to their FSHR expression status, we introduce a diagnostic protocol to effectively select EOC patients that would most probably respond to anti-Her-2 treatment. This observation could be of clinical importance in terms of selecting the patient that would most likely benefit from anti-Her-2 treatment.
Multi-parameter systematic strategies for predictive, preventive and personalised medicine in cancer
Authors: Hu Rong , Wang Xiaowei , Zhan Xianquan
Published: January 2013

Cancer is a complex disease that causes the alterations in the levels of gene, RNA, protein and metabolite. With the development of genomics, transcriptomics, proteomics and metabolomic techniques, the characterisation of key mutations and molecular pathways responsible for tumour progression has led to the identification of a large number of potential targets. The increasing understanding of molecular carcinogenesis has begun to change paradigms in oncology from traditional single-factor strategy to multi-parameter systematic strategy. The therapeutic model of cancer has changed from adopting the general radiotherapy and chemotherapy to personalised strategy. The development of predictive, preventive and personalised medicine (PPPM) will allow prediction of response with substantially increased accuracy, stratification of particular patient groups and eventual personalisation of medicine. The PPPM will change the approach to tumour diseases from a systematic and comprehensive point of view in the future. Patients will be treated according to the specific molecular profiles that are found in the individual tumour tissue and preferentially with targeted substances, if available.
Incretin secretion stimulated by ursodeoxycholic acid in healthy subjects
Authors: Murakami Masanori , Une Naoko , Nishizawa Maiko , Suzuki Sayaka , Ito Hideki , Horiuchi Toshiyuki
Published: January 2013

Bile acids play an important role in post-prandial glucose metabolism by stimulating release of glucagon-like peptide-1 (GLP-1) via the G-protein-coupled receptor TGR5, which is expressed in intestinal L cells. Thus, bile acid sequestrants are expected to stimulate secretion of endogenous GLP-1 through TGR5. We investigated incretin and insulin secretion after a meal with and without ursodeoxycholic acid (UDCA), a widely used therapeutic agent in liver diseases, in 7 non-diabetic Japanese subjects. We found that UDCA intake resulted in higher GLP-1 secretion (area under the curve [AUC] of 0–60 min after meal without UDCA, 450 ± 162 mmol·min/l; with UDCA, 649 ± 232 mmol·min/l, P = 0.046) and lower blood glucose (AUC of 0–60 min without UDCA, 7191 ± 250 mg·min/dl; with UDCA, 6716 ± 189 mg·min/dl, P = 0.001) , although we did not find statistically significant insulin increase by UDCA intake (AUC of 0–60 min without UDCA, 1551 ± 418 μU·min/ml; with UDCA, 1941 ± 246 μU·min/ml, P = 0.065). These results suggest that UDCA increases bile-induced GLP-1 secretion. Ours is the first report showing increased GLP-1 secretion and decreased blood glucose in response to UDCA.
Duality for multiobjective fractional programming problem using convexifactors
Authors: Suneja Surjeet Kaur , Kohli Bhawna
Published: January 2013

In this paper, the concept of ∂*-quasiconvexity is introduced by using convexifactors. Mond-Weir-type and Schaible-type duals are associated with a multiobjective fractional programming problem, and various duality results are established under the assumptions of ∂*-pseudoconvexity and ∂*-quasiconvexity.
RhoB modifies estrogen responses in breast cancer cells by influencing expression of the estrogen receptor
Authors: Médale-Giamarchi Claire , Lajoie-Mazenc Isabelle , Malissein Emilie , Meunier Elise , Couderc Bettina , Bergé Yann , Filleron Thomas , Keller Laura , Marty Claudine , Lacroix-Triki Magali , Dalenc Florence , Doisneau-Sixou Sophie F , Favre Gilles
Published: January 2013

Introduction

RhoB has been reported to exert positive and negative effects on cancer pathophysiology but an understanding of its role in breast cancer remains incomplete. Analysis of data from the Oncomine database showed a positive correlation between RhoB expression and positivity for both estrogen receptor alpha (ERα) and progesterone receptor (PR).

Methods

This finding was validated by our analysis of a tissue microarray constructed from a cohort of 113 patients and then investigated in human cell models.

Results

We found that RhoB expression in tissue was strongly correlated with ERα and PR expression and inversely correlated with tumor grade, tumor size and count of mitosis. In human breast cancer cell lines, RhoB attenuation was associated with reduced expression of both ERα and PR, whereas elevation of RhoB was found to be associated with ERα overexpression. Mechanistic investigations suggested that RhoB modulates ERα expression, controlling both its protein and mRNA levels, and that RhoB modulates PR expression by accentuating the recruitment of ERα and other major co-regulators to the promoter of PR gene. A major consequence of RhoB modulation was that RhoB differentially regulated the proliferation of breast cancer cell lines. Interestingly, we documented crosstalk between RhoB and ERα, with estrogen treatment leading to RhoB activation.

Conclusion

Taken together, our findings offer evidence that in human breast cancer RhoB acts as a positive function to promote expression of ERα and PR in a manner correlated with cell proliferation.
Anagliptin, a DPP-4 Inhibitor, Suppresses Proliferation of Vascular Smooth Muscles and Monocyte Inflammatory Reaction and Attenuates Atherosclerosis in Male apo E-Deficient Mice
Authors: Ervinna Nasib , Mita Tomoya , Yasunari Eisuke , Azuma Kosuke , Tanaka Rica , Fujimura Satoshi , Sukmawati Dewi , Nomiyama Takashi , Kanazawa Akio , Kawamori Ryuzo , Fujitani Yoshio , Watada Hirotaka
Published: January 2013

Dipeptyl peptidase-4 (DPP-4) inhibitors modulate the progression of atherosclerosis. To gain insights into their mechanism of action, 9-wk-old male apolipoprotein E (apoE)-deficient mice were fed a DPP-4 inhibitor, anagliptin-containing diet. The effects of anagliptin were investigated in, a monocyte cell line, human THP-1 cells, and rat smooth muscle cells (SMCs). Treatment with anagliptin for 16 wk significantly reduced accumulation of monocytes and macrophages in the vascular wall, SMC content in plaque areas, and oil red O-stained area around the aortic valve without affecting glucose tolerance or body weight. Serum DPP-4 concentrations were significantly higher in apoE-deficient mice than control mice, and the levels increased with aging, suggesting the involvement of DPP-4 in the progression of atherosclerosis. Indeed, soluble DPP-4 augmented cultured SMC proliferation, and anagliptin suppressed the proliferation by inhibiting ERK phosphorylation. In THP-1 cells, anagliptin reduced lipopolysaccharide-induced TNF-α production with inhibiting ERK phosphorylation and nuclear translocation of nuclear factor-κB. Quantitative analysis also showed that anagliptin reduced the area of atherosclerotic lesion in apoE-deficient mice. These results indicated that the anti-atherosclerotic effect of anagliptin is mediated, at least in part, through its direct inhibition of SMC proliferation and inflammatory reaction of monocytes.
Analysis of Body Composition in Individuals With High Bone Mass Reveals a Marked Increase in Fat Mass in Women But Not Men
Authors: Gregson Celia L. , Paggiosi Margaret A. , Crabtree Nicola , Steel Sue A. , McCloskey Eugene , Duncan Emma L. , Fan Bo , Shepherd John A. , Fraser William D. , Smith George Davey , Tobias Jon H.
Published: January 2013

Context:

High bone mass (HBM), detected in 0.2% of dual-energy x-ray absorptiometry (DXA) scans, is characterized by raised body mass index, the basis for which is unclear.

Objective:

To investigate why body mass index is elevated in individuals with HBM, we characterized body composition and examined whether differences could be explained by bone phenotypes, eg, bone mass and/or bone turnover.

Design, Setting, and Participants:

We conducted a case-control study of 153 cases with unexplained HBM recruited from 4 UK centers by screening 219 088 DXA scans. A total of 138 first-degree relatives (of whom 51 had HBM) and 39 spouses were also recruited. Unaffected individuals served as controls.

Main Outcome Measures:

We measured fat mass, by DXA, and bone turnover markers.

Results:

Among women, fat mass was inversely related to age in controls (P = .01), but not in HBM cases (P = .96) in whom mean fat mass was 8.9 [95% CI 4.7, 13.0] kg higher compared with controls (fully adjusted mean difference, P < .001). Increased fat mass in male HBM cases was less marked (gender interaction P = .03). Compared with controls, lean mass was also increased in female HBM cases (by 3.3 [1.2, 5.4] kg; P < .002); however, lean mass increases were less marked than fat mass increases, resulting in 4.5% lower percentage lean mass in HBM cases (P < .001). Osteocalcin was also lower in female HBM cases compared with controls (by 2.8 [0.1, 5.5] μg/L; P = .04). Differences in fat mass were fully attenuated after hip bone mineral density (BMD) adjustment (P = .52) but unchanged after adjustment for bone turnover (P < .001), whereas the greater hip BMD in female HBM cases was minimally attenuated by fat mass adjustment (P < .001).

Conclusions:

HBM is characterized by a marked increase in fat mass in females, statistically explained by their greater BMD, but not by markers of bone turnover.
Genotype-Phenotype Correlation in 153 Adult Patients With Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency: Analysis of the United Kingdom Congenital Adrenal Hyperplasia Adult Study Executive (CaHASE) Cohort
Authors: Krone Nils , Rose Ian T. , Willis Debbie S. , Hodson James , Wild Sarah H. , Doherty Emma J. , Hahner Stefanie , Parajes Silvia , Stimson Roland H. , Han Thang S. , Carroll Paul V. , Conway Gerry S. , Walker Brian R. , MacDonald Fiona , Ross Richard J. , Arlt Wiebke ,   for the United Kingdom Congenital adrenal Hyperplasia Adult Study Executive (CaHASE)
Published: January 2013

Context:

In congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, a strong genotype-phenotype correlation exists in childhood. However, similar data in adults are lacking.

Objective:

The objective of the study was to test whether the severity of disease-causing CYP21A2 mutations influences the treatment and health status in adults with CAH.

Research Design and Methods:

We analyzed the genotype in correlation with treatment and health status in 153 adults with CAH from the United Kingdom Congenital adrenal Hyperplasia Adult Study Executive cohort.

Results:

CYP21A2 mutations were distributed similarly to previously reported case series. In 7 patients a mutation was identified on only 1 allele. Novel mutations were detected on 1.7% of alleles (5 of 306). Rare mutations were found on 2.3% of alleles (7 of 306). For further analysis, patients were categorized into CYP21A2 mutation groups according to predicted residual enzyme function: null (n = 34), A (n = 42), B (n = 36), C (n = 34), and D (n = 7). Daily glucocorticoid dose was highest in group null and lowest in group C. Fludrocortisone was used more frequently in patients with more severe genotypes. Except for lower female height in group B, no statistically significant associations between genotype and clinical parameters were found. Androgens, blood pressure, lipids, blood glucose, and homeostasis model assessment of insulin resistance were not different between groups. Subjective health status was similarly impaired across groups.

Conclusions:

In adults with classic CAH and women with nonclassic CAH, there was a weak association between genotype and treatment, but health outcomes were not associated with genotype. The underrepresentation of males with nonclassic CAH may reflect that milder genotypes result in a milder condition that is neither diagnosed nor followed up in adulthood. Overall, our results suggest that the impaired health status of adults with CAH coming to medical attention is acquired rather than genetically determined and therefore could potentially be improved through modification of treatment.
Effects of Simvastatin on Retinoic Acid System in Primary Human Endometrial Stromal Cells and in a Chimeric Model of Human Endometriosis
Authors: Sokalska Anna , Anderson MariaPia , Villanueva Jesus , Ortega Israel , Bruner-Tran Kaylon L. , Osteen Kevin G. , Duleba Antoni J.
Published: January 2013

Context:

Retinoic acid (RA) may promote survival or apoptosis of cells, depending on the levels of binding proteins: apoptosis-inducing cellular RA binding protein 2 (CRABP2), and cell survival-promoting fatty acid binding protein 5 (FABP5). Increased cellular uptake of retinol and altered actions of RA related to reduced expression of CRABP2 may contribute to the development of endometriosis. Recently statins have been shown to inhibit growth of human endometrial stromal (HES) cells and to reduce the number and size of endometriotic implants in experimental models of this disorder.

Objective:

The objective of the study was to determine whether effects of simvastatin on HES cells and experimental endometriotic implants are related to the modulation of the RA system.

Methods:

Effects of simvastatin and RA on proliferation and apoptosis of HES cells were evaluated. Expression of stimulated by RA 6 (STRA6), CRABP2, and FABP5 was determined by real-time PCR and Western blotting. Effects of simvastatin were also evaluated in a nude mouse model of human endometriosis.

Results:

Simvastatin potentiated an inhibitory effect of RA on growth of HES cells. In HES cells, simvastatin induced expression of STRA6 and CRABP2 but not FABP5. Similarly, simvastatin treatment of nude mice bearing human endometrial xenografts led to an increased expression of CRABP2 and STRA6 proteins in ectopic lesions.

Conclusions:

Simvastatin interacts with the RA system, inducing the expression of the key protein regulating the uptake of retinol (STRA6) and the expression of apoptosis-promoting CRABP2. These effects may contribute to cooperative apoptosis-inducing effects of simvastatin and RA and support the examination of these compounds in the treatment of endometriosis.
Review on Savonius Rotor for Harnessing Wind Energy
Authors: Golecha K. , Kamoji M. A. , Kedare S. B. , Prabhu S. V.
Published: January 2013

Wind machines convert kinetic energy of the wind into usable form of mechanical energy or electrical energy. The Savonius rotor is a vertical axis wind machine which is simple in design. High starting torque characteristics make it suitable for standalone power generation as well as water pumping applications. This paper reviews the literature on the performance characteristics of the Savonius rotor. Multi-bladed rotor, multistage rotor, shape of the blade, use of deflecting plate, guide vanes and nozzle augmentation are several ways to enhance the performance characteristics. This review would help an engineer in building an improved Savonius rotor for a given application.
Recent Advances in Rotor Design of Vertical Axis Wind Turbines
Authors: MacPhee David , Beyene Asfaw
Published: January 2013

The following work represents the most recent advances in design and testing of vertical axis wind turbines (VAWT) rotors. VAWTs have received much attention as of late due to proposed advantages in small scale and off grid wind power generation. Thus, many recent works have surfaced involving analysis, design and optimization of VAWT rotors in order to more efficiently convert wind energy to electricity or other readily usable means. This paper is a collection of most of the recent literature works involving VAWT rotor design and testing, the majority of which published after 2005. We discuss research in the designing of various lift based rotors as well as some drag based rotors, hybrids, and various others. The recent work in this area suggests VAWT capacity could dramatically increase in the near future, and play a vital role in obtaining cleaner, more sustainable energy when global energy demand is increasing at an unprecedented rate.

HIGHLIGHTS

A review of various works involving rotor design and testing of both lift and drag Vertical Axis Wind Turbines (VAWTs) is presented; Benefits of vertical axis wind turbines in small scale and off grid wind power generation is summarized; Much of the recent work, published after 2005, has been directed towards analyzing, designing, and optimizing rotor shapes.

The body of this recent work suggests that research on VAWT rotor design continues to flourish and could make VAWTs a viable competitor to more traditional Horizontal Axis Wind Turbines (HAWTs) worldwide.
Wind-Driven SEIGs for Supplying Isolated Loads Employing DSP Based Power Electronic Controllers
Authors: Senthilkumar S. , Kumaresan N. , Rakesh N. , Vijayakumar K. , Subbiah M.
Published: January 2013

A DSP based closed-loop system has been developed for wind-driven three-phase Self-Excited Induction Generators (SEIGs) using a diode bridge rectifier (DBR) followed by an IGBT inverter. This system is meant for supplying isolated ac loads with a voltage of constant magnitude and frequency, for any operating condition of varying nature of wind speed and consumer load. The configuration and implementation of this proposed system have been fully described. The detailed method of analysing and predetermining the performance characteristics of such stand-alone systems has also been explained. Test results obtained on an SEIG operated with the controller built in the laboratory, demonstrate the successful working of both the hardware and software of the control scheme and the usefulness of the set-up as a whole for supplying isolated ac loads. With the varying nature of wind speed, a method of meeting the power balance between the wind power available and the load power requirement has also been explained with extensive Simulation studies.
Multiwalled carbon nanotubes-magnetite reinforced thermoplastic polypropylene-natural rubber blends
Authors: Kong Ing , Shanks Robert , Ahmad Sahrim , Yu Lih-Jiun
Published: January 2013

The effect of multiwalled carbon nanotubes (MWCNTs)-magnetite (Fe3O4) hybrid content on the magnetic and dynamic mechanical properties of thermoplastic polypropylene-natural rubber (TPNR) nanocomposites was evaluated. The effect of acid treatment of MWCNTs on the properties of nanocomposites has also been examined. TPNR/fillers nanocomposites were prepared via a Thermo Haake internal mixer using melt blending method with ball-milling technique as a pre-mixed process. The acid treatment successfully shortened the lengths and disentangled the crowds of MWCNTs. The improved dispersion of acid-treated MWCNTs-Fe3O4 in TPNR matrix and the enhanced interfacial adhesion between acid-treated MWCNTs-Fe3O4 and TPNR matrix increased the magnetic and dynamic mechanical properties. Acid-treated MWCNTs-Fe3O4 filled TPNR shows 10% improvement in storage modulus over neat TPNR due to the fine dispersion of MWCNTs in the TPNR matrix.
Characteristics of nickel tip carbon nanorod growth by pulsed plasma chemical vapor deposition
Authors: Yooyen S. , Kawamura T. , Kotake S. , Suzuki Y.
Published: January 2013

Growth of nickel tip carbon nanorod by means of pulsed plasma chemical vapor deposition (PPCVD) was carried out at different deposition time. Effects of deposition time under the methane plasma on the growth of carbon nanorod were investigated. The nucleation and growth mechanism of nickel tip carbon nanorod were also discussed. Nanoparticles were formed on substrate to introduce more nucleation sites at an elevated deposition time, and the density of nanorod on the surface of the substrate was greatly increased until the proper methane plasma deposition time. The longest nanorods and the highest nanorods density were found after methane plasma treatment of 3 min and 10 min respectively. Nanorod was about 60 nanometers in diameter and about 550 nanometers in length. Nanorods had onion and V-shape with Ni tip.
Residual stresses measurement with hole-drilling method on 6,061 aluminum under SMAT treatment
Authors: Jiang Hao , Liu Long , Zhou L. , Lu J.
Published: January 2013

Large compressive residual stress is induced on the aluminum 6,061 sheets by application of typical processing named SMAT (Surface Mechanical Attrition Treatment). The incremental hole-drilling method is applied to assess the thickness-through distribution of residual stress associated with traditional rosette strain gauges and non contact optical method. The results obtained by these two technologies exhibit good agreement, which verifies the reliability of the optical setup. On the other hand, the effect of induced topography on the surface of aluminum sheets is discussed to collate the initial position of drilling process.
Synthesis of au/co hollow microspheres via galvanic replacement reaction in organic solvent
Authors: Khe Cheng-Seong , Aziz Azizan , Lockman Zainovia
Published: January 2013

Cobalt/gold hollow microspheres were successfully prepared through galvanic replacement in an organic solvent. The diameters of these hollow microspheres ranged from 800 nm to 1 μm. However, the surface of the hollow microsphere was very rough. Nanospikes of various lengths from about 40 to 100 nm were grown on the surface of these spheres. Initially, particles with "island-like" rough surfaces were found with the addition of 4 ml chloroauric acid (HAuCl4). When the volume of HAuCl4 increased from 4 to 5 ml, microspheres with a hollow structure were formed. Some broken microspheres were observed when HAuCl4 was further increased to 6 ml. X-ray diffraction results showed a high-intensity sharp peak of gold when the HAuCl4 in the sample increased. After the galvanic replacement reaction, the cobalt content in the sample decreased meanwhile the gold content increased. This can be seen from energy dispersive X-ray analysis spectroscopy and also evident from the thermo gravimetric analysis result. The hollow Au/Co microspheres showed two broad plasmonic peaks in the ultraviolet-visible measurement. The plasmonic peaks at longer wavelengths shifted to the near-infrared region with the addition of HAuCl4.
Utilizing artificial neural network for forecasting groundwater table depths fluctuations
Authors: Mardookhpour A.
Published: January 2013

This study presented the model of predicting the water table fluctuation in flood plain of Sepidroud watershed (North of Iran-Gilan). The model for prediction of water table depth was developed leaning on artificial neural network. The neural network with different numbers of hidden layer neurons was developed by using 4 years (2004-2007) monthly rainfall, potential evapotranspiration and influencing wells as input and water table depth as output. The best model was selected based on mean square error. The results showed that artificial neural network could be used to predict water table depth in aquifer with good convergence and maximum error was 5% approximately.
Kinetics of Reduction of Titano-magnetite Powder by H2
Authors: Dang Jie , Hu Xiaojun , Zhang Guohua , Hou Xinmei , Yang Xiaobo , Chou Kuochih
Published: January 2013

Reduction of titano-magnetite powder containing 56.9 mass% of iron and 9.01 mass% of TiO2 with H2-Ar gas mixtures was investigated in isothermal experiments using thermo-gravimetric analyzer (TGA), X-ray diffraction (XRD) and scanning electron microscopy (SEM). The reduction of titano-magnetite was proved to proceed via a dual reactions mechanism. The first reaction is reduction of titano-magnetite to wüstite and ilmenite and the second one is reduction of wüstite and ilmenite to iron and titanium-containing phase. It was found that the dual reactions occurred simultaneously during the reduction. The reduction kinetics of titano-magnetite was analyzed according to a dual reactions kinetic model and the results indicated that the gaseous species diffusion in product layer was the rate controlling step for the first reaction, and interfacial chemical reaction was that for the second reaction. The apparent activation energies were extracted to be 98 kJ/mol and 115 kJ/mol for the first and second reaction, respectively.
Von der „Tendenzwende“ zur „geistig-moralischen Wende“. Konstruktion und Kritik konservativer Signaturen in den 1970er und 1980er Jahren
Authors: Hoeres Peter
Published: January 2013

Vorspann

Am 1. Oktober 2012 jährten sich die Ablösung der sozialliberalen Koalition und der Amtsantritt von Helmut Kohl zum 30. Mal. Untrennbar mit diesem Regierungswechsel verbunden war die Rede von der „geistig-moralischen Wende“, die die politische Auseinandersetzung in den ersten Jahren der Ära Kohl prägte. Peter Hoeres, Historiker aus Gießen, zeichnet die Entstehung des Diskurses über die „Wende“ und ihre Volten in den 1970er und 1980er Jahren nach. Er zeigt auf, welche Hoffnungen und welche Ängste damit verbunden waren – und er klärt, was Helmut Kohl tatsächlich zur „Wende“ gesagt hat und was nicht.
Recurrence of differentiated thyroid cancer in the elderly
Authors: Hollenbeak Christopher S , Boltz Melissa M , Schaefer Eric W , Saunders Brian D , Goldenberg David
Published: January 2013

Objective

Data from the Surveillance Epidemiology and End Results Medicare-linked database were used to estimate the incidence of and risk factors associated with recurrent thyroid cancer, and to assess the impact of recurrence on mortality following diagnosis, controlling for mortality as a competing risk.

Design

We identified 2883 patients over 65 years of age diagnosed with a single, primary well-differentiated thyroid cancer between 1995 and 2007. A recurrence was considered if the patient had evidence of I-131 therapy, imaging for metastatic thyroid carcinoma, or complete thyroidectomy beyond 6 months of diagnosis. Competing risk regressions were performed using Cox proportional hazards models with 1- and 2-year landmarks.

Results

Recurrence was observed in 1117 (39%) of the 2883 patients in the cohort. Age, stage, and treatment status were significant risk factors for developing recurrent disease (P<0.0001). Patients with recurrent disease had a higher risk of all-cause mortality within 10 years of diagnosis than patients with no recurrence at 1- and 2-year landmarks. Patients with follicular histology and a recurrence were less likely to die from cancer (hazard ratio 0.54; P=0.03) than patients with no recurrence.

Conclusions

The rate of recurrence of well-differentiated thyroid carcinomas in this sample of elderly patients was 39%. Extent of disease and older age negatively impacted the risk of recurrence from differentiated thyroid cancer. In these data, patients with follicular histology and a recurrence were less likely to die, suggesting that mortality and recurrence are competing risks. These data should be taken into account with individualized treatment strategies for elderly patients with recurrent malignant thyroid disease.
Effects of a New Implant Abutment Design on Peri-Implant Soft Tissues
Authors: Chien Hua-Hong , Schroering Robert L. , Prasad Hari S. , Tatakis Dimitris N.
Published: January 2013

The purpose of this study was to assess the effects of a modified implant abutment design on peri-implant soft and hard tissues in dogs. Three months after extraction of mandibular premolar teeth, 3 dental implants were placed in each side of the jaw using a 1-stage approach. Implants on one side of the mandible received standard abutments (control), and implants on the contralateral side received modified, patented, grooved abutments (test). Two months after implant placement, animals were euthanized and specimens were prepared for histologic and histomorphometric assessment. The linear distance (in micrometers) was measured from the implant shoulder (IS) to the following landmarks: gingival margin (GM; distance IS-GM), most apical position of the junctional epithelium (JE; distance IS-JE), and bone crest (BC; distance IS-BC). Percent of bone-to-implant contact was also measured. Histologic assessment revealed that all implants were osseointegrated and that interimplant gingival fibers between test abutments appeared to be more numerous and organized than control abutments. The IS-GM and IS-JE distances in test implants were greater than the corresponding distances in control implants (P = .024 and P = .015, respectively), whereas crestal bone loss (IS-BC) was greater for control implants than test implants (P = .037). There were no differences between control and test implants in bone-to-implant contact (P = .69), which averaged close to 50%. These results suggest that the modified groove design incorporated in standard abutments confers both soft and hard tissue benefits.
Polycarbonates from biorenewable diols via carbonate metathesis polymerization
Authors: Vanderhenst Rob , Miller Stephen A.
Published: January 2013

Carbonate metathesis polymerization (CaMP), an application of the carbonate interchange reaction, is developed and applied to form high-molecular-weight polycarbonates (Mn up to 49 400) from renewable diols and dimethyl carbonate. The CaMP methodology can be applied in a stepwise fashion that first iso-lates bis-carbonates or it can be applied directly to diols. A survey of twenty catalysts is conducted and K2CO3 is identified as competent for the direct method since it catalyzes both carbonate for-mation from alcohols and carbonate interchange. Diol selection and copolymerization strategies – including the incorporation of aromatic diols – allow for precise tuning of polymeric thermal properties. Furthermore, supplementary information is available at http://www.icevirtuallibrary.com/upload/10.1680gmat.12.00022_SupplementaryInformation.pdf
Importance of terrestrial subsidies for estuarine food webs in contrasting East African catchments
Authors: Abrantes Kátya G. , Barnett Adam , Marwick Trent R. , Bouillon Steven
Published: January 2013

Little is known on the degree to which terrestrial organic matter delivered to tropical estuaries contributes to estuarine consumers. Here, stable isotope analysis is used to constrain this contribution for contrasting east African estuaries whose catchments differ in relative C3/C4 vegetation cover. As these two types of vegetation differ strongly in δ13C, we anticipated that terrestrial subsidies would be reflected in a gradient in estuarine consumer δ13C values, following the relative importance of C3 (characterised by low δ13C) vs. C4 (characterised by high δ13C) cover. Five estuaries were sampled for aquatic biogeochemical parameters, primary producers and consumers of different trophic ecologies: the Zambezi (catchment with a C3/C4 cover of 61/39%) in Mozambique, the Tana in Kenya (36/64%) and the Betsiboka (42/58%), Rianila (85/15%) and Canal des Pangalanes (C3‐dominated) in Madagascar. Sampling was done before and after the 2010/2011 wet season. There were positive relationships between the proportion of C4 cover in the catchment and turbidity, δ13CDIC, δ13CDOC, δ13CPOC and δ15NPN. There were also significant positive relationships between δ13CPOC and consumer δ13C and between δ15NPN and consumer δ15N for all consumer trophic guilds, confirming the incorporation of organic material transported from the catchments by estuarine consumers, and implying that this material is transported up to high trophic level fish. Bayesian mixing models confirmed that C4 material was the most important source for the highly turbid, C4‐dominated estuaries, contributing up to 61–91% (95% CI) to phytodetritivorous fish in the Betsiboka, whereas for the less turbid C3‐dominated estuaries terrestrial subsidies were not as important and consumers relied on a combination of terrestrial and aquatic sources. This shows that the ecology of the overall catchment affects the estuaries at the most basic, energetic level, and activities that alter the turbidity and productivity of rivers and estuaries can affect food webs well beyond the area of impact.