Bone is the most common site of metastasis for breast cancer, however the reasons for this remain unclear. We hypothesise that under certain conditions mammary cells possess osteomimetic capabilities that may allow them to adapt to, and flourish within, the bone microenvironment. Mammary cells are known to calcify within breast tissue and we have recently reported a novel in vitro model of mammary mineralization using murine mammary adenocarcinoma 4T1 cells. In this study, the osteomimetic properties of the mammary adenocarcinoma cell line and the conditions required to induce mineralization were characterized extensively. It was found that exogenous organic phosphate and inorganic phosphate induce mineralization in a dose dependent manner in 4T1 cells. Ascorbic acid and dexamethasone alone have no effect. 4T1 cells also show enhanced mineralization in response to bone morphogenetic protein 2 in the presence of phosphate supplemented media. The expression of several bone matrix proteins were monitored throughout the process of mineralization and increased expression of collagen type 1 and bone sialoprotein were detected, as determined by real-time RT-PCR. In addition, we have shown for the first time that 3D collagen glycosaminoglycan scaffolds, bioengineered to represent the bone microenvironment, are capable of supporting the growth and mineralization of 4T1 adenocarcinoma cells. These 3D scaffolds represent a novel model system for the study of mammary mineralization and bone metastasis. This work demonstrates that mammary cells are capable of osteomimicry, which may ultimately contribute to their ability to preferentially metastasize to, survive within and colonize the bone microenvironment.
There have been few studies of patients with renal allografts functioning for more than 20 years. We sought to identify clinical factors associated with ultra longterm (>20 year) renal allograft survival and to describe the clinical features of these patients. Comorbidities included skin cancer (36.1%), coronary heart disease (17.3%) and other malignancies (14.5%). This study identifies factors associated with long-term allograft survival and a high rate of morbidity and early mortality in long-term transplant recipients.
We report a female child from an Irish Traveller family presenting with severe intellectual disability, dysmorphic features, renal anomalies, dental caries and cyclical vomiting. Current health issues include global developmental delay, mild concentric left ventricular hypertrophy, dental malocclusion and caries and a single duplex left kidney. The proband and her mother also have multiple epiphyseal dysplasia. Whole-exome sequencing was performed to identify the underlying genetic cause. DNA from the proband was enriched with the Agilent Sure Select v5 Exon array and sequenced on an Illumina HiSeq. Rare homozygous variants were prioritized. Whole-exome sequencing identified three linked homozygous missense variants in THOC6 (c.298T>A, p.Trp100Arg; c.700G>C, p.Val234Leu; c.824G>A, p.Gly275Asp) as the likely cause of this child's intellectual disability syndrome, resulting in a molecular diagnosis of Beaulieu-Boycott-Innes syndrome (BBIS). This is the first report of BBIS in Europe. BBIS has been reported previously in two Hutterite families and one Saudi family. A review of all patients to date shows a relatively homogenous phenotype. Core clinical features include low birth weight with subsequent growth failure, short stature, intellectual disability with language delay, characteristic facies, renal anomalies and dental malocclusion with caries. Some patients also have cardiac defects. All patients show characteristic dysmorphic facial features including a tall forehead with high anterior hairline and deep-set eyes with upslanting palpebral fissures. The coexistence of intellectual disability together with these characteristic facies should provide a diagnostic clue for BBIS during patient evaluation.
Background: Microvascular reconstruction is the optimal method of reconstructing the mandible but this is not always a viable option. When such a situation pertains, an alternative can be the use of autologous rib grafting; however in recent years, this technique has seen substantial decline to almost non-existent for reconstruction of the mandible. This article revisits autologous rib grafting through a case series and outlines the technique and advantages it provides especially when operating in rudimentary conditions Methods: A total of 14 patients were presented to four surgical missions in Africa with extensive growth of the mandible from ameloblastomas. Mandibular resection was carried out and the area was reconstructed with autologous rib grafting. Appropriate post-operative care was provided until discharge. Results: The cohort of 14 patients included five males and nine females with an average age of 31 years. The main complication encountered was infection seen in four patients at the grafted site and one patient at the donor site. All areas were managed with local measures of wound toilet and oral antibiotics. In only one case was the rib graft affected by infection; however, this did not impact on the final functional or aesthetic outcome for the patient. Conclusion: This article is a reminder that reconstruction by autologous rib grafts remains a viable option and the technique should not be lost to posterity but should remain part of a head and neck surgeon's armamentarium.
Compliance of achievement of SpO 2 targets in preterm infants is low, especially in maintaining the SpO 2 below the upper limits of the target range and avoidance of hyperoxemia. 1 Closed-loop automated oxygen control (CLAC) systems may provide a solution as their use in preterm infants has been associated with fewer desaturations, 2 increased percentage of the time spent within the target oxygen saturation range and fewer manual adjustments to the inspired oxygen concentration. 3,4 In the interim analysis of a randomised crossover trial of CLAC, we demonstrated that automated oxygen control had similar benefits in ventilated infants born at or above 34 weeks gestation. 5 In the interim analysis, most of our patients had a low oxygen requirement, we continued recruitment to the target sample
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