Simple biliary cysts of the liver can be lined by mucinous epithelium.

Aims & Methods: Simple biliary cysts of the liver are described to be lined by biliary epithelium and may be managed nonsurgically or by deroofing only. By contrast, its important differential diagnosis-mucinous cystic neoplasm (MCN)-is at least focally lined by mucinous epithelium, has malignant potential, and therefore should be resected. Following anecdotal observations in routine diagnostic practice, the following case series was assembled to confirm whether simple biliary cysts of the liver can be lined by mucinous epithelium.

Synthesis of scaffold-free, three dimensional, osteogenic constructs following culture of skeletal osteoprogenitor cells on glass surfaces.

Background: Efficient differentiation of stem cells into three-dimensional (3D) osteogenic construct is still an unmet challenge. These constructs can be crucial for patients with bone defects due to congenital or traumatic reasons. The modulation of cell fate and function as a consequence of interaction with the physical and chemical properties of materials is well known.

Periprosthetic seroma occurrence after femoropopliteal bypass grafting: Surgical management after failure of non-surgical measures in relieving symptoms.

Objective: Periprosthetic seroma is a rare complication of femoropopliteal bypass grafting. Periprosthetic seroma can be defined as the collection of non-infected serous fluid around a prosthetic arterial graft. There is a dearth of literature on how to manage periprosthetic seroma occurrence after femoropopliteal bypass especially in patients whose symptoms do not improve with typical conservative measures.

Short communication: Effect of granulocyte-macrophage colony-stimulating factor on neonatal calf peripheral blood neutrophil function in vitro.

Neutrophils are innate immunity cells that represent the first line of cellular defense against invading pathogens. Dairy calves, however, experience neutrophil dysfunction during the first weeks of age, contributing to increased disease susceptibility during this period. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine that improves neutrophil function in neonates of other species and mature cows.

Surgical timing after chemoradiotherapy for rectal cancer, analysis of technique (STARRCAT): results of a feasibility multi-centre randomized controlled trial.

Background: The optimal time of rectal resection after long-course chemoradiotherapy (CRT) remains unclear. A feasibility study was undertaken for a multi-centre randomized controlled trial evaluating the impact of the interval after chemoradiotherapy on the technical complexity of surgery.

Methods: Patients with rectal cancer were randomized to either a 6- or 12-week interval between CRT and surgery between June 2012 and May 2014 (ISRCTN registration number: 88843062).

Association of reduced type IX collagen gene expression in human osteoarthritic chondrocytes with epigenetic silencing by DNA hypermethylation.

Objective: To investigate whether the changes in collagen gene expression in osteoarthritic (OA) human chondrocytes are associated with changes in the DNA methylation status in the COL2A1 enhancer and COL9A1 promoter.

Methods: Expression levels were determined using quantitative reverse transcription-polymerase chain reaction, and the percentage of DNA methylation was quantified by pyrosequencing. The effect of CpG methylation on COL9A1 promoter activity was determined using a CpG-free vector; cotransfections with expression vectors encoding SOX9, hypoxia-inducible factor 1α (HIF-1α), and HIF-2α were carried out to analyze COL9A1 promoter activities in response to changes in the methylation status.

Evaluating the role of fluorodeoxyglucose positron emission tomography-computed tomography in multi-disciplinary team recommendations for oesophago-gastric cancer.

Background: National guidelines recommend that fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) is performed in all patients being considered for radical treatment of oesophageal or oesophago-gastric cancer without computerised tomography scan (CTS) evidence of metastasis. Guidance also mandates that all patients with cancer have treatment decisions made within the context of a multi-disciplinary team (MDT) meeting. Little is known, however, about the influence of PET-CT on decision making within MDTs.

Regulated transcription of human matrix metalloproteinase 13 (MMP13) and interleukin-1β (IL1B) genes in chondrocytes depends on methylation of specific proximal promoter CpG sites.

The role of DNA methylation in the regulation of catabolic genes such as MMP13 and IL1B, which have sparse CpG islands, is poorly understood in the context of musculoskeletal diseases. We report that demethylation of specific CpG sites at -110 bp and -299 bp of the proximal MMP13 and IL1B promoters, respectively, detected by in situ methylation analysis of chondrocytes obtained directly from human cartilage, strongly correlated with higher levels of gene expression. The methylation status of these sites had a significant impact on promoter activities in chondrocytes, as revealed in transfection experiments with site-directed CpG mutants in a CpG-free luciferase reporter.

Epigenetic regulation during fetal femur development: DNA methylation matters.

Epigenetic modifications are heritable changes in gene expression without changes in DNA sequence. DNA methylation has been implicated in the control of several cellular processes including differentiation, gene regulation, development, genomic imprinting and X-chromosome inactivation. Methylated cytosine residues at CpG dinucleotides are commonly associated with gene repression; conversely, strategic loss of methylation during development could lead to activation of lineage-specific genes.

Loss of methylation in CpG sites in the NF-κB enhancer elements of inducible nitric oxide synthase is responsible for gene induction in human articular chondrocytes.

Objective: To investigate whether the abnormal expression of inducible nitric oxide synthase (iNOS) by osteoarthritic (OA) human chondrocytes is associated with changes in the DNA methylation status in the promoter and/or enhancer elements of iNOS.

Methods: Expression of iNOS was quantified by quantitative reverse transcriptase-polymerase chain reaction. The DNA methylation status of the iNOS promoter and enhancer regions was determined by bisulfite sequencing or pyrosequencing.

Developmental plasticity of human foetal femur-derived cells in pellet culture: self assembly of an osteoid shell around a cartilaginous core.

This study has examined the osteogenic and chondrogenic differentiation of human foetal femur-derived cells in 3-dimensional pellet cultures. After culture for 21-28 days in osteogenic media, the pellets acquired a unique configuration that consisted of an outer fibrous layer, an osteoid-like shell surrounding a cellular and cartilaginous region. This configuration is typical to the cross section of the foetal femurs at the same age and was not observed in pellets derived from adult human bone marrow stromal cells.

Suppressors of cytokine signalling (SOCS) are reduced in osteoarthritis.

Objectives: Suppressor of cytokine signalling (SOCS) proteins are inhibitors of cytokine signalling that function via the JAK/STAT pathway (Janus kinase/signal transducers and activators of transcription). Eight SOCS proteins, SOCS1-SOCS7 and CIS-1 (cytokine-inducible SH2-domain, with similar structure to the other SOCS proteins) have been identified, of which SOCS1, 2, and 3 and CIS-1 are the best characterised. A characteristic feature of osteoarthritis (OA) is increased production by articular chondrocytes of pro-inflammatory cytokines, such as interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNFα), which may be induced by mechanotransduction and contribute to cartilage destruction.

Roles of inflammatory and anabolic cytokines in cartilage metabolism: signals and multiple effectors converge upon MMP-13 regulation in osteoarthritis.

Human cartilage is a complex tissue of matrix proteins that vary in amount and orientation from superficial to deep layers and from loaded to unloaded zones. A major challenge to efforts to repair cartilage by stem cell-based and other tissue engineering strategies is the inability of the resident chondrocytes to lay down new matrix with the same structural and resilient properties that it had upon its original formation. This is particularly true of the collagen network, which is susceptible to cleavage once proteoglycans are depleted.

The epigenetic effect of glucosamine and a nuclear factor-kappa B (NF-kB) inhibitor on primary human chondrocytes--implications for osteoarthritis.

Objective: Idiopathic osteoarthritis is the most common form of osteoarthritis (OA) world-wide and remains the leading cause of disability and the associated socio-economic burden in an increasing aging population. Traditionally, OA has been viewed as a degenerative joint disease characterized by progressive destruction of the articular cartilage and changes in the subchondral bone culminating in joint failure. However, the etiology of OA is multifactorial involving genetic, mechanical and environmental factors.

Epigenetic modifiers influence lineage commitment of human bone marrow stromal cells: Differential effects of 5-aza-deoxycytidine and trichostatin A.

Clinical imperatives for new bone to replace or restore the function of traumatized or bone lost as a consequence of age or disease has led to the need for therapies or procedures to generate bone for skeletal applications. However, current in vitro methods for the differentiation of human bone marrow stromal cells (HBMSCs) do not, to date, produce homogeneous cell populations of the osteogenic or chondrogenic lineages. As epigenetic modifiers are known to influence differentiation, we investigated the effects of the DNA demethylating agent 5-aza-2'-deoxycytidine (5-aza-dC) or the histone deacetylase inhibitor trichostatin A (TSA) on osteogenic and chondrogenic differentiation.

DNA demethylation at specific CpG sites in the IL1B promoter in response to inflammatory cytokines in human articular chondrocytes.

Objective: To determine whether changes in the DNA methylation status in the promoter region of the gene encoding interleukin-1beta (IL-1beta) account for expression of IL1B messenger RNA (mRNA) after long-term treatment of human articular chondrocytes with inflammatory cytokines.

Methods: IL-1beta, tumor necrosis factor alpha (TNFalpha) plus oncostatin M (OSM), or 5-azadeoxycytidine (5-aza-dC) was added twice weekly for 4-5 weeks to primary cultures of normal human articular chondrocytes derived from the femoral head cartilage of patients with a fracture of the femoral neck. Expression of MMP13, IL1B, TNFA, and DNMT1 was determined by SYBR Green-based quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis of genomic DNA and total RNA extracted from the same sample before and after culture.

Cellular and epigenetic features of a young healthy and a young osteoarthritic cartilage compared with aged control and OA cartilage.

Osteoarthritis (OA) is generally a disease of the elderly population, but can occur in young patients in exceptional cases. This study compares the cellular and epigenetic features of primary old-age OA with those of secondary OA in a 23-year-old patient with developmental dysplasia of the hip. In addition, control cartilage from a 14-year-old was compared with that from patients with a fracture of the neck of femur (#NOF) to establish to what extent the latter is a useful control for OA.

Expression of ADAMTS-4 by chondrocytes in the surface zone of human osteoarthritic cartilage is regulated by epigenetic DNA de-methylation.

The two major aggrecanases involved in osteoarthritis (OA) are ADAMTS-4 and ADAMTS-5. Knock-out studies suggested that ADAMTS-5, but not ADAMTS-4, is the major aggrecanase in murine OA. However, studies of human articular cartilage suggest that ADAMTS-4 also contributes to aggrecan degradation in human OA.

More than just stones: a pictorial review of common and less common gallbladder pathologies.

Although stone disease is by far the most commonly encountered pathology of the gallbladder, there are several other important disease processes affecting it. These include adenomyomatosis, cholesterolosis, polyps, porcelain gallbladder, acalculous cholecystitis, xanthogranulomatous cholecystitis, emphysematous cholecystitis, gallbladder cancer, and gallbladder hemorrhage. The purpose of this article was to review the different gallbladder pathologies encountered in everyday radiological practice and to describe their features in the standard imaging modalities.

Potential directions for drug development for osteoarthritis.

Background: Osteoarthritis (OA) is a frustrating disease for both patient and physician because neither cause nor cure is known and there are currently no disease-modifying drugs.

Objective: To review current therapeutic approaches as well as new findings regarding OA pathoetiology that could form the basis of future direction for the development of drugs to prevent or slow down disease progression.

Methods: After reviewing disease progression in human OA, as demonstrated by histological analyses, the reasons for cartilage erosion are explored and possible therapeutic approaches are highlighted.

Normal bone growth requires optimal estrogen levels: negative effects of both high and low dose estrogen on the number of growth plate chondrocytes.

Endochondral bone formation at epiphyseal growth plate consists of the synchronized processes of chondrogenesis and cartilage ossification. Estrogen, the major female sex hormone, plays an important role in this process, particularly during the pubertal growth spurt. However, its effects on the growth plate are not completely understood.

Jejunal diverticulitis: an unusual cause of an intra-abdominal abscess - coronal Computed Tomography reconstruction can aid the diagnosis.

Jejunal diverticulitis is a rare condition that can present with an acute abdomen and be referred for imaging. We present the case of an elderly patient who at CT was diagnosed with an intra-abdominal abscess involving both jejunum and transverse colon. However, the underlying eitiology was not initially clear until small bowel barium follow-through.

Improved quantification of DNA methylation using methylation-sensitive restriction enzymes and real-time PCR.

Heterogeneity of cells with respect to the DNA methylation status at a specific CpG site is a problem when assessing methylation status. We have developed a simple two-step method for the quantification of the percent of cells that display methylation at a specific CpG site in the promoter of a specific gene. The first step is overnight digestion of genomic DNA (optimal conc.