189 research outputs found
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Low vitamin B12 and lipid metabolism: evidence from pre-clinical and clinical studies
Obesity is a worldwide epidemic responsible for 5% of global mortality. The risks of developing other key metabolic disorders like diabetes, hypertension and cardiovascular diseases (CVDs) are increased by obesity, causing a great public health concern. A series of epidemiological studies and animal models have demonstrated a relationship between the importance of vitamin B12 (B12) and various components of metabolic syndrome. High prevalence of low B12 levels has been shown in European (27%) and South Indian (32%) patients with type 2 diabetes (T2D). A longitudinal prospective study in pregnant women has shown that low B12 status could independently predict the development of T2D five years after delivery. Likewise, children born to mothers with low B12 levels may have excess fat accumulation which in turn can result in higher insulin resistance and risk of T2D and/or CVD in adulthood. However, the independent role of B12 on lipid metabolism, a key risk factor for cardiometabolic disorders, has not been explored to a larger extent. In this review, we provide evidence from pre-clinical and clinical studies on the role of low B12 status on lipid metabolism and insights on the possible epigenetic mechanisms including DNA methylation, micro-RNA and histone modifications. Although, there are only a few association studies of B12 on epigenetic mechanisms, novel approaches to understand the functional changes caused by these epigenetic markers are warranted
The diagnostic accuracy and cost-effectiveness of magnetic resonance spectroscopy and enhanced magnetic resonance imaging techniques in aiding the localisation of prostate abnormalities for biopsy : a systematic review and economic evaluation
Peer reviewedPublisher PD
Systematic review of the clinical effectiveness and cost-effectiveness of rapid point-of-care tests for the detection of genital chlamydia infection in women and men.
Peer reviewedPublisher PD
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Metformin inefficiency to lower lipids in vitamin B12 deficient HepG2 cells is alleviated via adiponectin-AMPK axis
Background: Prolonged metformin treatment decreases vitamin B12 (B12) levels, whereas low B12 is associated with dyslipidaemia. Some studies have reported that metformin has no effect on intrahepatic triglyceride (TG) levels. Although AMP-activated protein kinase (AMPK) activation via adiponectin lowers hepatic TG content, its role in B12 deficiency and metformin has not been explored. We investigated whether low B12 impairs the beneficial effect of metformin on hepatic lipid metabolism via the AMPK-adiponectin axis.
Methods: HepG2 was cultured using custom-made B12-deficient Eagle's Minimal Essential Medium (EMEM) in different B12-medium concentrations, followed by a 24-h metformin/adiponectin treatment. Gene and protein expressions and total intracellular TG were measured, and radiochemical analysis of TG synthesis and seahorse mitochondria stress assay were undertaken.
Results: With low B12, total intracellular TG and synthesized radiolabelled TG were increased. Regulators of lipogenesis, cholesterol and genes regulating fatty acids (FAs; TG; and cholesterol biosynthesis were increased. FA oxidation (FAO) and mitochondrial function were decreased, with decreased pAMPKα and pACC levels. Following metformin treatment in hepatocytes with low B12, the gene and protein expression of the above targets were not alleviated. However, in the presence of adiponectin, intrahepatic lipid levels with low B12 decreased via upregulated pAMPKα and pACC levels. Again, combined adiponectin and metformin treatment ameliorated the low B12 effect and resulted in increased pAMPKα and pACC, with a subsequent reduction in lipogenesis, increased FAO and mitochondrion function.
Conclusions: Adiponectin co-administration with metformin induced a higher intrahepatic lipid-lowering effect. Overall, we emphasize the potential therapeutic implications for hepatic AMPK activation via adiponectin for a clinical condition associated with B12 deficiency and metformin treatment
Prehabilitation is feasible in patients with rectal cancer undergoing neoadjuvant chemoradiotherapy and may minimize physical deterioration:Results from the REx trial
Aim: Rectal cancer patients undergoing neoadjuvant chemoradiotherapy (NACRT) experience physical deterioration and reductions in their quality of life. This feasibility study assessed prehabilitation (a walking intervention) before, during and after NACRT to inform a definitive multi-centred randomized clinical trial (REx trial). Methods: Patients planned for NACRT followed by potentially curative surgery were approached (August 2014–March 2016) (www.isrctn.com; 62859294). Prior to NACRT, baseline physical and psycho-social data were recorded using validated tools. Participants were randomized to either the intervention group (exercise counselling session followed by a 13–17 week telephone-guided walking programme) or a control group (standard care). Follow-up testing was undertaken 1–2 weeks before surgery. Results: Of the 296 screened patients, 78 (26%) were eligible and 48 (61%) were recruited. N = 31 (65%) were men with a mean age of 65.9 years (range 33.7–82.6). Mean intervention duration was 14 weeks with 75% adherence. n = 40 (83%) completed follow-up testing. Both groups recorded reductions in daily walking but the reduction was less in the intervention group although not statistically significant. Participants reported high satisfaction and fidelity to trial procedures. Conclusion: This study demonstrates that prehabilitation is feasible in rectal cancer patients undergoing NACRT. Good recruitment, adherence, retention and patient satisfaction rates support the development of a fully powered trial. The effects of the intervention on physical outcomes were promising
Outcomes of Fusions From the Cervical Spine to the Pelvis.
Study designRetrospective cohort study.ObjectiveDetermine the indications, complications, and clinical outcomes in patients requiring fusions from the cervical spine to the pelvis. Several investigators have examined fusions from the thoracic spine to the sacrum, but no similar study has been performed for cervical-to-pelvis fusions.MethodsPatients from 2003 to 2014 with an upper instrumented vertebrae (UIV) in the cervical spine (any level) and a lower instrumented vertebrae (LIV) in the sacrum or pelvis were included in the study. Those with infectious or acute trauma-related deformities were excluded. Patient demographics, medical history, diagnosis, operative procedure, and health-related quality of life measures were analyzed. Student's t test, Kruskal-Wallis test, and χ2 test were used as appropriate; significance was set at P < .05 for all tests.ResultsFifty-five patients met inclusion criteria for the study. Average follow-up was 2.8 years. Proximal junctional kyphosis was the most common indication for cervical-to-pelvis fusions (36%). The most common UIV was C2 (29%) followed by C7 (24%). There was an average 31° correction in maximum kyphosis and a 3.3 cm improvement in sagittal vertical axis. In adults, the rate of complication was 71.4%, with a major complication rate of 39.3% and reoperation rate of 53.6%. There was significant improvement in the Scoliosis Research Society (SRS-22r) score (3.0 to 3.5; P < .01).ConclusionProximal junctional kyphosis is the most common indication for patients requiring fusion to the cervical spine. Adult patients incur a significant risk of major complications and reoperations. However, significant improvement in SRS-22r outcomes are noted in these patients
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Intracellular and tissue levels of vitamin B12 in hepatocytes are modulated by CD320 receptor and TCN2 transporter
The liver mass constitutes hepatocytes expressing receptors for vitamin B12 (B12)-bound transporters in circulation. However, intrahepatic and circulating B12 interrelationship levels remain unclear. We assessed the intracellular B12 levels at various circulating B12 concentrations in human HepG2 cell-line and liver tissue levels of B12 in the C57BL/6 mouse model. In HepG2 cells treated with a range of B12 concentrations, the intracellular and circulatory B12 levels, transcript and protein levels of B12 receptor (CD320) and transporter (TCN2) were determined using immu-noassays, qRT-PCR and Western blot, respectively. Similar assessments were done in plasma and liver tissue of C57BL/6 mice, previously fed a diet of either a high or low B12 (30.82 μg B12/kg and 7.49 μg B12/kg, respectively) for 8-10 weeks. The physiological B12 status (0.15-1 nM) resulted in increased levels of intracellular B12 in HepG2 cells compared to supraphysiological levels of B12 (>1 nM). Gene and protein expression of CD320 and TCN2 were also higher at physiological levels of B12. Progressively increasing extracellular B12 to supraphysiological levels led to relative decreased levels of intracellular B12, lower expression of gene and protein levels of CD320 and TCN2. Similar results were observed in liver tissue from mice fed on a low B12 diet verses high B12 diet. These findings suggest that unlike supraphysiological B12, physiological levels of B12 in the extra-cellular media or circulation accelerates active transport of B12, and expression of CD320 and TCN2, resulting in higher relative uptake of B12 in hepatocytes
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Vitamin B12 induces hepatic fatty infiltration through altered fatty acid metabolism
Background/Aims: Rise in global incidence of obesity impacts metabolic health. Evidence from human and animal models show association of vitamin B12 (B12) deficiency with elevated BMI and lipids. Human adipocytes demonstrated dysregulation of lipogenesis by low B12 via hypomethylation and altered microRNAs. It is known de novo hepatic lipogenesis plays a key role towards dyslipidaemia, however, whether low B12 affects hepatic metabolism of lipids is not explored.
Methods: HepG2 was cultured in B12-deficient EMEM medium and seeded in different B12 media: 500nM(control), 1000pM(1nM), 100pM and 25pM(low) B12. Lipid droplets were examined by Oil Red O (ORO) staining using microscopy and then quantified by elution assay. Gene expression were assessed with real-time quantitative polymerase chain reaction (qRT-PCR) and intracellular triglycerides were quantified using commercial kit (Abcam, UK) and radiochemical assay. Fatty acid composition was measured by gas chromatography and mitochondrial function by seahorse XF24 flux assay.
Results: HepG2 cells in low B12 had more lipid droplets that were intensely stained with ORO compared with control. The total intracellular triglyceride and incorporation of radio-labelled-fatty acid in triglyceride synthesis were increased. Expression of genes regulating fatty acid, triglyceride and cholesterol biosynthesis were upregulated. Absolute concentrations of total fatty acids, saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), trans-fatty acids and individual even-chain and odd-chain fatty acids were significantly increased. Also, low B12 impaired fatty acid oxidation and mitochondrial functional integrity in HepG2 compared with control.
Conclusion: Our data provide novel evidence that low B12 increases fatty acid synthesis and levels of individual fatty acids, and decreases fatty acid oxidation and mitochondrial respiration, thus resulting in dysregulation of lipid metabolism in HepG2. This highlights the potential significance of de novo lipogenesis and warrants possible epigenetic mechanisms of low B12
Surveillance mammography for detecting ipsilateral breast tumour recurrence and metachronous contralateral breast cancer: a systematic review
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Conservative treatment for urinary incontinence in Men After Prostate Surgery (MAPS) : two parallel randomised controlled trials
Final Report Submitted to NIHR HTA ProgrammePeer reviewedPublisher PD
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