Review article: the effects of antitumour necrosis factor-α on bone metabolism in inflammatory bowel disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk of osteoporosis. A number of studies have emerged in recent years indicating that tumour necrosis factor (TNF) blockade appears to have a beneficial effect on bone mineral density (BMD) in IBD patients. AIMS: To provide a review of the available data regarding the effect of the currently licensed anti-TNF-α therapies on bone metabolism and BMD in IBD patients. METHODS: A Medline search was performed using the search terms \u27infliximab\u27, \u27bone metabolism\u27, \u27IBD\u27, \u27BMD\u27, \u27bone markers\u27, \u27adalimumab\u27, \u27bone disease\u27, \u27Crohn\u27s disease\u27 and \u27ulcerative colitis\u27. RESULTS: Infliximab has a beneficial effect on bone turnover markers in Crohn\u27s disease (CD) patients in the short term. The longest study to date comprising 24 CD patients showed an overall improvement in two bone formation markers - b-alkaline phosphatase (P = 0.022) and osteocalcin (P = 0.008) at 4 months post-treatment. Moreover, the largest study to date comprising 71 CD patients showed significant improvement in sCTx, a bone resorption marker (P = 0.04) at week-8 post-treatment. There is little data looking at the effect of anti-TNF-α therapy on bone metabolism in ulcerative colitis. Moreover, the long-term effects of anti-TNF-α therapy on bone structure and fracture risk in IBD patients are currently not known. The effect of cessation of anti-TNF-α therapy on bone metabolism is also unknown. CONCLUSION: Properly controlled long-term trials are needed to fully evaluate the impact of TNF blockade on bone mineral density

Global neurosurgery in the context of Global Public Health Practice - a literature review of case studies

Neurosurgical conditions are a substantial contributor to surgical burden in the world, with LMICs carrying a disproportionately large part. Policy initiatives such as the National Surgical, Obstetrics and Anesthesia Plans (NSOAPs) and CHYSPR have highlighted the need for an intersectoral approach, not just at the hospital level but on a large scale encompassing national public health strategies. This article aims to illustrate through case studies, how addressing this surgical burden is not limited to the clinical context but extends to public health strategies as well. For example, vitamin B12 and folic acid are micronutrients that, if not at adequate levels, can result in debilitating neurosurgical conditions. In Ethiopia, through coalesced efforts between neurosurgeons and policy makers, the government has made strides in implementing food fortification programs at a national level to address the neurosurgical burden. Traumatic brain injuries (TBIs) are another neurosurgical burden that unevenly affect LMICs. Countries such as Colombia and India have demonstrated the importance of legislation and enforcement, coupled with robust data collection and auditing systems and strong academic advocacy of neurosurgeons can drastically reduce TBIs. Despite the importance of public health efforts in addressing neurosurgical conditions, there is lack of neurosurgeon involvement in public health and lack of integration of neurosurgical burden in national health planning systems. It is imperative that neurosurgeons advocate for and are included in aspects of public health policy. Neurosurgery does not stop within the bounds of the hospital, and neither should the role of a neurosurgeon

Toward allele-specific targeting therapy and pharmacodynamic marker for spinocerebellar ataxia type 3

Spinocerebellar ataxia type 3 (SCA3), caused by a CAG repeat expansion in the ataxin-3 gene (ATXN3), is characterized by neuronal polyglutamine (polyQ) ATXN3 protein aggregates. Although there is no cure for SCA3, gene-silencing approaches to reduce toxic polyQ ATXN3 showed promise in preclinical models. However, a major limitation in translating putative treatments for this rare disease to the clinic is the lack of pharmacodynamic markers for use in clinical trials. Here, we developed an immunoassay that readily detects polyQ ATXN3 proteins in human biological fluids and discriminates patients with SCA3 from healthy controls and individuals with other ataxias. We show that polyQ ATXN3 serves as a marker of target engagement in human fibroblasts, which may bode well for its use in clinical trials. Last, we identified a single-nucleotide polymorphism that strongly associates with the expanded allele, thus providing an exciting drug target to abrogate detrimental events initiated by mutant ATXN3. Gene-silencing strategies for several repeat diseases are well under way, and our results are expected to improve clinical trial preparedness for SCA3 therapies

First characterization of the SPADnet sensor:a digital silicon photomultiplier for PET applications

Silicon Photomultipliers have the ability to replace photomultiplier tubes when used as light sensors in scintillation gamma-ray detectors. Their timing properties, compactness, and magnetic field compatibility make them interesting for use in Time-of-Flight Magnetic Resonance Imaging compatible Positron Emission Tomography. In this paper, we present a new fully digital Single Photon Avalanche Diode (SPAD) based detector fabricated in CMOS image sensor technology. It contains 16x8 pixels with a pitch of 610x571.2 mu m(2). The Dark Count Rate and the Photon Detection Probability of each SPAD has been measured and the homogeneity of these parameters in the entire 92000 SPAD array is shown. The sensor has been optically coupled to a single LYSO needle and a LYSO array. The scintillator crystal was irradiated with several gamma sources and the resulting images and energy spectra are presented

SPADnet: Embedded coincidence in a smart sensor network for PET applications

n this paper we illustrate the core technologies at the basis of the European SPADnet project (www.spadnet.eu), and present the corresponding first results. SPADnet is aimed at a new generation of MRI-compatible, scalable large area image sensors, based on CMOS technology, that are networked to perform gamma-ray detection and coincidence to be used primarily in (Time-of-Flight) Positron Emission Tomography (PET). The project innovates in several areas of PET systems, from optical coupling to single-photon sensor architectures, from intelligent ring networks to reconstruction algorithms. In addition, SPADnet introduced the first computational model enabling study of the full chain from gamma photons to network coincidence detection through scintillation events, optical coupling, etc