BMQ

BMQ: Boston Medical Quarterly was published from 1950-1966 by the Boston University School of Medicine and the Massachusetts Memorial Hospitals

Association between Variations in Cell Cycle Genes and Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a devastating and progressive lung disease. Its aetiology is thought to involve damage to the epithelium and abnormal repair. Alveolar epithelial cells near areas of remodelling show an increased expression of proapoptotic molecules. Therefore, we investigated the role of genes involved in cell cycle control in IPF. Genotypes for five single nucleotide polymorphisms (SNPs) in the tumour protein 53 (TP53) gene and four SNPs in cyclin-dependent kinase inhibitor 1A (CDKN1A), the gene encoding p21, were determined in 77 IPF patients and 353 controls. In peripheral blood mononuclear cells (PBMC) from 16 healthy controls mRNA expression of TP53 and CDKN1A was determined

IL1RN genetic variations and risk of IPF: a meta-analysis and mRNA expression study

Idiopathic pulmonary fibrosis (IPF) is a rare and devastating lung disease of unknown aetiology. Genetic variations in the IL1RN gene, encoding the interleukin-1 receptor antagonist (IL-1Ra), have been associated with IPF susceptibility. Several studies investigated the variable number tandem repeat (VNTR) or single nucleotide polymorphisms rs408392, rs419598 and rs2637988, with variable results. The aim of this study was to elucidate the influence of polymorphisms in IL1RN on IPF susceptibility and mRNA expression. We performed a meta-analysis of the five case–control studies that investigated an IL1RN polymorphism in IPF in a Caucasian population. In addition, we investigated whether IL1RN mRNA expression was influenced by IL1RN polymorphisms. The VNTR, rs408392 and rs419598 were in tight linkage disequilibrium, with D′ > 0.99. Furthermore, rs2637988 was in linkage disequilibrium with the VNTR (D′ = 0.90). A haploblock of VNTR*2 and the minor alleles of rs408392and rs419598 was constructed. Meta-analysis revealed that this VNTR*2 haploblock is associated with IPF susceptibility both with an allelic model (odds ratio = 1.42, p = 0.002) and a carriership model (odds ratio = 1.60, p = 0.002). IL1RN mRNA expression was significantly influenced by rs2637988, with lower levels found in carriers of the (minor) GG genotype (p < 0.001). From this meta-analysis, we conclude that the VNTR*2 haploblock is associated with susceptibility to IPF. In addition, polymorphisms in IL1RN influence IL-1Ra mRNA expression, suggesting that lower levels of IL-1Ra predispose to developing IPF. Together these findings demonstrate that the cytokine IL-1Ra plays a role in IPF pathogenesis

Magnetic resonance imaging for detecting root avulsions in traumatic adult brachial plexus injuries: protocol for a systematic review of diagnostic accuracy

Background Adult brachial plexus injuries (BPI) are becoming more common. The reconstruction and prognosis of pre-ganglionic injuries (root avulsions) are different to other types of BPI injury. Preoperative magnetic resonance imaging (MRI) is being used to identify root avulsions, but the evidence from studies of its diagnostic accuracy are conflicting. Therefore, a systematic review is needed to address uncertainty about the accuracy of MRI and to guide future research. Methods We will conduct a systematic search of electronic databases alongside reference tracking. We will include studies of adults with traumatic BPI which report the accuracy of preoperative MRI (index test) against surgical exploration of the roots of the brachial plexus (reference standard) for detecting either of the two target conditions (any root avulsion or any pseudomeningocoele as a surrogate marker of root avulsion). We will exclude case reports, articles considering bilateral injuries and studies where the number of true positives, false positives, false negatives and true negatives cannot be derived. The methodological quality of the included studies will be assessed using a tailored version of the QUADAS-2 tool. Where possible, a bivariate model will be used for meta-analysis to obtain summary sensitivities and specificities for both target conditions. We will investigate heterogeneity in the performance of MRI according to field strength and the risk of bias if data permits. Discussion This review will summarise the current diagnostic accuracy of MRI for adult BPI, identify shortcomings and gaps in the literature and so help to guide future research

Transplantation of embryonic spinal cord derived cells to prevent muscle atrophy after various peripheral nerve injuries

Poster Presentation: no. P53Every human has 45 miles long nerve network that together with the spinal cord is susceptible to traumatic injuries, leading to a loss of motor and sensory functions. Different surgical repairs are available for peripheral nerve injuries happening on either distal or proximal site. However, the speed of axonal regeneration after the repair is limited and therefore, target muscles atrophy severely during that time, making them incapable of receiving axons after too long time. Neuronal replacement strategy through cell transplantation is a potential method to prevent muscle atrophy. In our study, we tested E14.5 rat embryonic spinal cord derived fetal cells versus neural progenitor cells (NPCs), as well as cells from 3 different spinal cord segments, for their ability to reduce the muscle atrophy after the complete musculocutaneous nerve transection. We showed that fetal cells were more efficient compared to the NPCs, whereas lumbar cells were slightly better compared to thoracic and cervical cells. Therefore, fetal lumbar cells were next used in clinically more relevant injury models that included delayed surgical repair. After long-term crush injury, these cells helped to preserve the muscles, resulting in an earlier functional recovery, while no effect was seen after the nerve transection with delayed end-to-end repair. Next, spinal root avulsion injury that includes the damage to both PNS and CNS, was used. Here, these cells slightly prevented the muscle atrophy, resulting in earlier and better functional recovery after the delayed ventral root reimplantation, while GDNF treatment helped the host motoneuron cell bodies to survive

There and Back Again: The Dutch Energy Sector from Privatisation to New Public Energy Companies

The public energy company might experience a serious come-back in the Dutch energy sector. The ideas that drove (local) governments to privatise a few decades ago now seem to have been replaced by the idea that public energy companies could fulfil a role in the energy transition. Public energy companies can take into account social or community interests that commercial companies not always do and they allow local governments the opportunity to exert influence, for instance when developing renewable energy projects or when rolling out heat networks. however, they do not always operate at the lowest societal cost. Therefore, each time when a public energy company is founded or expanded, it should be reflected whether this serves the public interest and how the risks of the project can be mitigated

Evaluation of circulating YKL-40 levels in idiopathic interstitial pneumonias

INTRODUCTION: YKL-40 is a novel biomarker in diseases with inflammation, fibrosis and tissue remodelling. Previously, circulating YKL-40 was shown to be elevated in patients with idiopathic pulmonary fibrosis (IPF) and was associated with survival. OBJECTIVE: To compare YKL-40 serum levels between IPF and other interstitial pneumonias such as non-specific interstitial pneumonia (NSIP), smoking-related interstitial lung disease (SR-ILD) and cryptogenic organising pneumonia (COP). MATERIALS AND METHODS: Serum YKL-40 levels were measured in 124 healthy controls and 315 patients. Serial measurements were available in 36 patients with IPF and 6 patients with COP. RESULTS: Serum YKL-40 levels were elevated in all patient groups compared to controls (p < 0.0001), and highest levels were found in the most fibrotic diseases, which showed worst prognosis. CONCLUSION: YKL-40 is highly elevated in fibrotic interstitial pneumonias and may reflect the degree of activity of the fibrogenic process. Remarkably, levels remain high in IPF, but can decrease in other interstitial pneumonias, which appears to be related to a better prognosis