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  • BMJ Publishing Group  (33)
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  • 1
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    Higher maternal education is associated with favourable growth of young children in different countries (2013)
    BMJ Publishing Group
    Details
    Publication Date: 2013-06-08
    Description: Background Childhood growth affects long-term health and could contribute to health inequalities that persist throughout life. Methods We compared growth data of 4-year-old to 6-year-old children born 1997–2002 in UK (n=15 168), Sweden (n=6749) and rural China (n=10 327). SD scores (SDS) were calculated against the WHO Growth Standard. Obesity and overweight were defined by the International Obesity Taskforce cut-offs, and stunting, underweight and thinness by height, weight or body mass index (BMI)〈–2 SDS. Associations with maternal education were standardised by calculating the Slope Index of Inequality (SII). Results Mean SDS height, weight and BMI in the UK (–0.01, 0.42, 0.62, respectively) and Sweden (0.45, 0.59, 0.45) were higher than in China (–0.98, –0.82, –0.29). Higher maternal education was consistently associated with taller offspring height SDS (SII: UK 0.25; Sweden 0.17; China 1.06). Underweight and stunting were less common in the UK (prevalence: 0.6% and 2.2%, respectively) and Sweden (0.3% and 0.6%) than in China (9.5% and 16.4%), where these outcomes were inversely associated with maternal education (SII: –25.8% and –12.7%). Obesity prevalence in the UK, Sweden and China was 4.8%, 3.7% and 0.4%, respectively. Maternal education was inversely associated with offspring obesity in the UK (SII: –3.3%) and Sweden (–2.8%), but not in China (+0.3%). Conclusions Higher maternal education was associated with more favourable growth in young children: lower obesity and overweight in the UK and Sweden, and lower stunting and underweight in rural China. Public health strategies to optimise growth in early childhood need to acknowledge socioeconomic factors, but possibly with a different emphasis in different settings.
    Keywords: Health service research, Health education, Obesity (public health), Health promotion
    Print ISSN: 0143-005X
    Electronic ISSN: 1470-2738
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 2
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    Prolonged suppression of HBV in mice by a novel antibody that targets a unique epitope on hepatitis B surface antigen (2016)
    BMJ Publishing Group
    In: Gut
    Details
    Publication Date: 2016-03-10
    Description: Objective This study aimed to investigate the therapeutic potential of monoclonal antibody (mAb) against HBV as a novel treatment approach to chronic hepatitis B (CHB) in mouse models. Methods Therapeutic effects of mAbs against various epitopes on viral surface protein were evaluated in mice mimicking persistent HBV infection. The immunological mechanisms of mAb-mediated viral clearance were systematically investigated. Results Among 11 tested mAbs, a novel mAb E6F6 exhibited the most striking therapeutic effects in several HBV-persistent mice. Single-dose administration of E6F6 could profoundly suppress the levels of hepatitis B surface antigen (HBsAg) and HBV DNA for several weeks in HBV-transgenic mice. E6F6 regimen efficiently prevented initial HBV infection, and reduced viral dissemination from infected hepatocytes in human-liver-chimeric mice. E6F6-based immunotherapy facilitated the restoration of anti-HBV T-cell response in hydrodynamic injection (HDI)-based HBV carrier mice. Immunological analyses suggested that the Fc receptor-dependent phagocytosis plays a predominant role in E6F6-mediated viral suppression. Molecular analyses suggested that E6F6 recognises an evolutionarily conserved epitope (GPCK(R)TCT) and only forms a smaller antibody–viral particle immune complex with limited interparticle crosslinking when it binds to viral particles. This unique binding characteristic of E6F6 to HBV was possibly associated with its effective in vivo opsonophagocytosis for viral clearance. Conclusions These results provided new insight into understanding the therapeutic role and mechanism of antibody against persistent viral infection. The E6F6-like mAbs may provide a novel immunotherapeutic agent against human chronic HBV infection.
    Keywords: Hepatitis B
    Print ISSN: 0017-5749
    Electronic ISSN: 1468-3288
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 3
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    Progressive genomic convergence of two Helicobacter pylori strains during mixed infection of a patient with chronic gastritis (2015)
    BMJ Publishing Group
    In: Gut
    Details
    Publication Date: 2015-03-07
    Description: Objective To study the detailed nature of genomic microevolution during mixed infection with multiple Helicobacter pylori strains in an individual. Design We sampled 18 isolates from a single biopsy from a patient with chronic gastritis and nephritis. Whole-genome sequencing was applied to these isolates, and statistical genetic tools were used to investigate their evolutionary history. Results The genomes fall into two clades, reflecting colonisation of the stomach by two distinct strains, and these lineages have accumulated diversity during an estimated 2.8 and 4.2 years of evolution. We detected about 150 clear recombination events between the two clades. Recombination between the lineages is a continuous ongoing process and was detected on both clades, but the effect of recombination in one clade was nearly an order of magnitude higher than in the other. Imputed ancestral sequences also showed evidence of recombination between the two strains prior to their diversification, and we estimate that they have both been infecting the same host for at least 12 years. Recombination tracts between the lineages were, on average, 895 bp in length, and showed evidence for the interspersion of recipient sequences that has been observed in in vitro experiments. The complex evolutionary history of a phage-related protein provided evidence for frequent reinfection of both clades by a single phage lineage during the past 4 years. Conclusions Whole genome sequencing can be used to make detailed conclusions about the mechanisms of genetic change of H. pylori based on sampling bacteria from a single gastric biopsy.
    Keywords: Open access, Stomach and duodenum
    Print ISSN: 0017-5749
    Electronic ISSN: 1468-3288
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 4
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    Pericardial effusion (2015)
    BMJ Publishing Group
    Details
    Publication Date: 2015-06-19
    Description: bmj;350/jun17_11/h2893/FIG1F1fig1A 54 year old man presented with a three week history of cough, breathlessness, chest pain, and peripheral oedema; he had lost 38 kg in weight over six months....
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 5
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    Asia-Pacific consensus on the management of gastro-oesophageal reflux disease: an update focusing on refractory reflux disease and Barrett's oesophagus (2016)
    BMJ Publishing Group
    In: Gut
    Details
    Publication Date: 2016-08-10
    Description: Objective Since the publication of the Asia-Pacific consensus on gastro-oesophageal reflux disease in 2008, there has been further scientific advancement in this field. This updated consensus focuses on proton pump inhibitor-refractory reflux disease and Barrett's oesophagus. Methods A steering committee identified three areas to address: (1) burden of disease and diagnosis of reflux disease; (2) proton pump inhibitor-refractory reflux disease; (3) Barrett's oesophagus. Three working groups formulated draft statements with supporting evidence. Discussions were done via email before a final face-to-face discussion. We used a Delphi consensus process, with a 70% agreement threshold, using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria to categorise the quality of evidence and strength of recommendations. Results A total of 32 statements were proposed and 31 were accepted by consensus. A rise in the prevalence rates of gastro-oesophageal reflux disease in Asia was noted, with the majority being non-erosive reflux disease. Overweight and obesity contributed to the rise. Proton pump inhibitor-refractory reflux disease was recognised to be common. A distinction was made between refractory symptoms and refractory reflux disease, with clarification of the roles of endoscopy and functional testing summarised in two algorithms. The definition of Barrett's oesophagus was revised such that a minimum length of 1 cm was required and the presence of intestinal metaplasia no longer necessary. We recommended the use of standardised endoscopic reporting and advocated endoscopic therapy for confirmed dysplasia and early cancer. Conclusions These guidelines standardise the management of patients with refractory gastro-oesophageal reflux disease and Barrett's oesophagus in the Asia-Pacific region.
    Keywords: Gastro-oesophageal reflux, Editor's choice, Oesophageal cancer
    Print ISSN: 0017-5749
    Electronic ISSN: 1468-3288
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 6
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    Carbonic anhydrase IV inhibits colon cancer development by inhibiting the Wnt signalling pathway through targeting the WTAP-WT1-TBL1 axis (2016)
    BMJ Publishing Group
    In: Gut
    Details
    Publication Date: 2016-08-10
    Description: Objective We found that carbonic anhydrase IV (CA4), a member of the carbonic anhydrases, is silenced in colorectal cancer (CRC). We analysed its epigenetic inactivation, biological effects and prognostic significance in CRC. Design The biological functions of CA4 were determined by in vitro and in vivo tumorigenicity assays. The CA4 co-operator was identified by immunoprecipitation and mass spectrometry. CA4 downstream effectors and signalling pathways were elucidated by promoter luciferase assay, electrophoretic mobility shift assay and chromatin immunoprecipitation. The clinical impact of CA4 was assessed in 115 patients with CRC. Results CA4 was silenced in all nine CRC cell lines and 92.6% of CRC tumours. The promoter hypermethylation contributed to the inactivation of CA4 , and it was detected in 75.7% of the patients with CRC. After a median follow-up of 49.3 months, multivariate analysis showed that the patients with CA4 hypermethylation had a recurrence of Stage II/III CRC. The re-expression of CA4 inhibited cell proliferation, induced apoptosis and cell cycle arrest in the G1 phase. CA4 inhibited the activity of the Wnt signalling pathway and mediated the degradation of β-catenin . CA4 interacted with Wilms’ tumour 1-associating protein (WTAP) and induced WTAP protein degradation through polyubiquitination. Moreover, CA4 promoted the transcriptional activity of Wilms’ tumour 1 (WT1), an antagonist of the Wnt pathway, which resulted in the induction of transducin β-like protein 1 ( TBL1 ) and the degradation of β-catenin. Conclusions CA4 is a novel tumour suppressor in CRC through the inhibition of the Wnt signalling pathway by targeting the WTAP–WT1–TBL1 axis. CA4 methylation may serve as an independent biomarker for the recurrence of CRC.
    Keywords: Open access, Colon cancer
    Print ISSN: 0017-5749
    Electronic ISSN: 1468-3288
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 7
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    Gain-of-function mutation in TRPV4 identified in patients with osteonecrosis of the femoral head (2016)
    BMJ Publishing Group
    Details
    Publication Date: 2016-09-23
    Description: Background Osteonecrosis of the femoral head is a debilitating disease that involves impaired blood supply to the femoral head and leads to femoral head collapse. Methods We use whole-exome sequencing and Sanger sequencing to analyse a family with inherited osteonecrosis of the femoral head and fluorescent Ca 2+ imaging to functionally characterise the variant protein. Results We report a family with four siblings affected with inherited osteonecrosis of the femoral head and the identification of a c.2480_2483delCCCG frameshift deletion followed by a c.2486T〉A substitution in one allele of the transient receptor potential vanilloid 4 (TRPV4) gene. TRPV4 encodes a Ca 2+ -permeable cation channel known to play a role in vasoregulation and osteoclast differentiation. While pathogenic TRPV4 mutations affect the skeletal or nervous systems, association with osteonecrosis of the femoral head is novel. Functional measurements of Ca 2+ influx through mutant TRPV4 channels in HEK293 cells and patient-derived dermal fibroblasts identified a TRPV4 gain of function. Analysis of channel open times, determined indirectly from measurement of TRPV4 activity within a cluster of TRPV4 channels, revealed that the TRPV4 gain of function was caused by longer channel openings. Conclusions These findings identify a novel TRPV4 mutation implicating TRPV4 and altered calcium homeostasis in the pathogenesis of osteonecrosis while reinforcing the importance of TRPV4 in bone diseases and vascular endothelium.
    Keywords: Open access, Molecular genetics, Calcium and bone
    Print ISSN: 0022-2593
    Electronic ISSN: 1468-6244
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 8
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    Chronic low level trimethyltin exposure and the risk of developing nephrolithiasis (2013)
    BMJ Publishing Group
    Details
    Publication Date: 2013-07-11
    Description: Objectives Nephrolithiasis (kidney stones) is a common disease with the prevalence that is increasing globally. We previously found that trimethyltin (TMT), a by-product of plastic stabilisers, can inhibit the H + /K + ATPase activity in renal intercalated cells and alter urinary pH, which is a known risk factor for nephrolithiasis. In this study, we conducted a cross-sectional analysis to evaluate the impact of chronic low level occupational TMT exposure on nephrolithiasis. Methods This study included 216 healthy workers with TMT exposure and 119 workers as controls with no TMT exposure. All study participants were administered a questionnaire and underwent a routine clinical examination including an ultrasonographic screening for kidney stones. Exposures were assessed by measuring TMT concentrations in personal air samples, blood and urine. Logistic regression analysis was used to estimate the ORs and 95% CIs for the risk of kidney stones. Results TMT exposed workers had a higher prevalence of kidney stones (18.06%) in comparison with control workers (5.88%). High TMT concentrations in personal air samples, blood and urines were positively associated with increased prevalence of kidney stones in workers exposed to TMT compared with controls workers (p-trend values=0.005, 0.008 and 0.002, respectively). The length of employment in plants with elevated TMT levels (duration of the exposure) was significantly associated with the increased prevalence of kidney stones (p trend=0.001). The ORs were 2.66 for 〈3 years, 3.73 for 3–〈10 years and 7.89 for 10+ years of employment compared with control workers. Conclusions To our knowledge, this is the first report to demonstrate that occupational exposure to TMT is a potential risk factor for nephrolithiasis.
    Print ISSN: 1351-0711
    Electronic ISSN: 1470-7926
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 9
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    Comparison of MRI with liver-specific contrast agents and multidetector row CT for the detection of hepatocellular carcinoma: a meta-analysis of 15 direct comparative studies (2013)
    BMJ Publishing Group
    In: Gut
    Details
    Publication Date: 2013-09-15
    Description: We read with great interest the paper by Tremosini et al 1 which prospectively assessed the diagnostic performance of a panel of markers (glypican 3, heat shock protein 70, and glutamine synthetase) for small (〈20 mm) hepatocellular carcinoma (HCC) in patients with cirrhosis. This study showed that the panel of markers is a useful diagnostic approach for the diagnosis of small HCC. It had a high specificity (100%) but a relatively low sensitivity (60%) when at least two of the markers (regardless of which) were positive. To diagnose HCC, some useful, non-invasive imaging tests, such as CT and MRI, can also be used. The guidelines recently updated by the American Association for the Study of Liver Diseases (AASLD) state that a non-invasive diagnosis of HCC can be made if a lesion 〉10 mm has a typical vascular enhancement pattern in 4-phase multidetector row CT (MDCT) or dynamic contrast enhanced...
    Print ISSN: 0017-5749
    Electronic ISSN: 1468-3288
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 10
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    miR-574-5p negatively regulates Qki6/7 to impact {beta}-catenin/Wnt signalling and the development of colorectal cancer (2013)
    BMJ Publishing Group
    In: Gut
    Details
    Publication Date: 2013-04-03
    Description: Objective Deficiency or reduced expression of signal transduction and activation of RNA family protein Quaking ( Qki ) is associated with developmental defects in neural and vascular tissues and the development of debilitating human diseases including colorectal cancer (CRC). However, the mechanisms underlying the aberrant downregulation or deficiency of Qki were uncertain. Design Expression of miR-574-5p, Qki5/6/7/7b splicing variants, β-catenin and p27 Kip1 was determined in mouse and human CRC cells and tissues to investigate the post-transcriptional regulation of Qki isoforms by miR-574-5p and its impact on β-catenin / p27 Kip1 signalling, cell cycle progression, proliferation, migration, invasion and tumour growth. Results In the CRC tissues of C57BL/6- Apc min/+ mice, miR-574-5p was found to be significantly upregulated and negatively correlated with the expression of Qki but positively correlated with the expression of β-catenin . In mouse and human CRC cells, miR-574-5p was shown to regulate Qki isoforms ( Qki6/7 in particular) post-transcriptionally and caused altered expression in β-catenin and p27 Kip1 , increased proliferation, migration and invasion and decreased differentiation and cell cycle exit. Furthermore, in clinical CRC tissues, miR-574-5p was shown to be greatly upregulated and inversely correlated with the expression of Qki s. Finally, inhibition of miR-574-5p was shown to suppress the growth of tumours in the nude mice. Conclusions Together, these novel findings suggest that miR-574-5p is a potent ribo-regulator for Qkis and that aberrant miR-574-5p upregulation can be oncogenic.
    Keywords: Open access, Colon cancer
    Print ISSN: 0017-5749
    Electronic ISSN: 1468-3288
    Topics: Medicine
    Published by BMJ Publishing Group
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