New exposure technique for management of giant internal carotid artery aneurysm

We are presenting a case of giant internal carotid artery aneurysm (ICAA) managed by a new exposure technique. Following double mandibular osteotomy, the exposure of the entire aneurysm was achieved by mandible mobilization. The aneurysm repair was performed by resection and graft interposition. Mandible bone reconstruction was succeeded via mini plate osteosynthesis. No adverse events were noticed during the 24-month follow-up period. The surgical ICAA management is necessary to prevent severe complications. In cases of aneurysm extension to the skull base, double mandibular osteotomy is a safe technique that facilitates aneurysm exposure and control

Helical EndoStaples enhance endograft fixation in an experimental model using human cadaveric aortas

ObjectiveThis study evaluated the contribution of Aptus EndoStaples (Aptus Endosystems, Sunnyvale, Calif) in the proximal fixation of eight endografts used in the endovascular repair of abdominal aortic aneurysms (EVAR).MethodsNine human cadaveric aortas were exposed, left in situ, and transected to serve as fixation zones. The Zenith (Cook, Bloomington, Ind), Anaconda (Vascutek, Inchinnan, Scotland, UK), Endurant (Medtronic, Minneapolis, Minn), Excluder (W. L. Gore and Associates, Flagstaff, Ariz), Aptus (Aptus Endosystems), Aorfix (Lombard Medical, Didcot, UK), Talent (Medtronic), and AneuRx (Medtronic) stent grafts were proximally deployed and caudal displacement force (DF) was applied via a force gauge, recording the DF required to dislocate each device ≥20 mm from the infrarenal neck. Measurements were repeated after four and six EndoStaples were applied at the proximal fixation zone, as well as after a Dacron graft was sutured at the proximal neck in standard fashion. Finally, a silicone tube was used as a control fixation zone to test the DF of grafts with EndoStaples in a material that exceeded the integrity of a typical human cadaveric aorta and provided a consistent substrate to examine the differential effect of variable degrees of EndoStaple implantation using zero, two, four, and six EndoStaples.ResultsIn the cadaveric model, the mean DF required to dislocate the endografts without the application of EndoStaples was 19.73 ± 12.52 N; this increased to 49.72 ± 12.53 N (P < .0001) when four EndoStaples where applied and to 79.77 ± 28.04 N when six EndoStaples were applied (P = .003). The DF necessary to separate the conventionally hand-sutured Dacron graft from the aorta was 56 N. In the silicone tube model, the Aptus endograft without EndoStaples withstood 3.2 N of DF. The DF increased to 39 ± 3 N when two EndoStaples were added, to 71 ± 6 N when four were added, and to 98 ± 5 N when six were added. In eight of the 13 cadaver experiments conducted with four and six EndoStaples, the displacement occurred as a result of complete aortic transection proximal to the fixation site, indicating that aortic tissue integrity was the limiting factor in these experiments.ConclusionsThe fixation of eight different endografts was increased by a mean of 30 N with four Aptus EndoStaples and by a mean of 57 N with six EndoStaples in this model. Endostaples can increase endograft fixation to levels equivalent or superior to that of a hand-sewn anastomosis. The application of six EndoStaples results in aortic tissue failure above the fixation zone, demonstrating fixation strength that exceeds inherent aortic integrity in these cadavers.Clinical RelevanceThe proximal fixation of an endovascular device in the endovascular repair of abdominal aortic aneurysms (EVAR) is of crucial importance to avoid complications such as kinking, migration, and endoleak. This study represents the first attempt to quantify the effect of a new innovative device (Aptus EndoStaples) aimed to enhance endograft fixation. A cadaveric model, which resembles the forces applied onto the endovascular devices in vivo, was chosen to test the effect of the EndoStaples. The results suggest that endograft fixation is significantly better after the application of the EndoStaples, to an extent where it surpasses the inherent durability of the vessel wall

Morphological, histochemical, and interstitial pressure changes in the tibialis anterior muscle before and after aortofemoral bypass in patients with peripheral arterial occlusive disease

BACKGROUND: Morphological and electrophysiological studies of ischemic muscles in peripheral arterial disease disclosed evidence of denervation and fibre atrophy. The purpose of the present study is to describe morphological changes in ischemic muscles before and after reperfusion surgery in patients with peripheral occlusive arterial disease, and to provide an insight into the effect of reperfusion on the histochemistry of the reperfused muscle. METHODS: Muscle biopsies were obtained from the tibialis anterior of 9 patients with chronic peripheral arterial occlusive disease of the lower extremities, before and after aortofemoral bypass, in order to evaluate the extent and type of muscle fibre changes during ischemia and after revascularization. Fibre type content and muscle fibre areas were quantified using standard histological and histochemical methods and morphometric analysis. Each patient underwent concentric needle electromyography, nerve conduction velocity studies, and interstitial pressure measurements. RESULTS: Preoperatively all patients showed muscle fibre atrophy of both types, type II fibre area being more affected. The mean fibre cross sectional area of type I was 3,745 μm(2) and of type II 4,654 μm(2) . Fibre-type grouping, great variation in fibre size and angular fibres were indicative of chronic dennervation-reinnervation, in the absence of any clinical evidence of a neuropathic process. Seven days after the reperfusion the areas of both fibre types were even more reduced, being 3,086 μm(2) for type I and 4,009 μm(2) for type II, the proportion of type I fibres, and the interstitial pressure of tibialis anterior were increased. CONCLUSIONS: The findings suggest that chronic ischemia of the leg muscles causes compensatory histochemical changes in muscle fibres resulting from muscle hypoxia, and chronic dennervation-reinnervation changes, resulting possibly from ischemic neuropathy. Reperfusion seems to bring the oxidative capacity of the previously ischemic muscle closer to normal

Disease-specific pluripotent stem cells

Induced pluripotent stem (iPS) cells are generated by epigenetic reprogramming of somatic cells through the exogenous expression of transcription factors. Recently, the generation of iPS cells from patients with a variety of genetic diseases was found to likely have a major impact on regenerative medicine, because these cells self-renew indefinitely in culture while retaining the capacity to differentiate into any cell type in the body, thereby enabling disease investigation and drug development. This review focuses on the current state of iPS cell technology and discusses the potential applications of these cells for disease modeling; drug discovery; and eventually, cell replacement therapy

East Bay Coalition for the Homeless: Branding Study and Marketing Strategy

There are a number of potential positioning strategies. The two which make the most sense for the EBCH are to “position the EBCH away from others in the category” and to “position the EBCH as unique.” These strategies have the advantage of setting the EBCH apart from the other organizations that address homelessness. Occupying its own “position” in the minds of potential and current donors is not only an effective communications/marketing strategy but also a less costly one because it avoids head-to-head competition and comparisons

Progress in Understanding and Treating SCN2A-Mediated Disorders

Advances in gene discovery for neurodevelopmental disorders have identified SCN2A dysfunction as a leading cause of infantile seizures, autism spectrum disorder, and intellectual disability. SCN2A encodes the neuronal sodium channel NaV1.2. Functional assays demonstrate strong correlation between genotype and phenotype. This insight can help guide therapeutic decisions and raises the possibility that ligands that selectively enhance or diminish channel function may improve symptoms. The well-defined function of sodium channels makes SCN2A an important test case for investigating the neurobiology of neurodevelopmental disorders more generally. Here, we discuss the progress made, through the concerted efforts of a diverse group of academic and industry scientists as well as policy advocates, in understanding and treating SCN2A-related disorders

Somatic coding mutations in human induced pluripotent stem cells

Defined transcription factors can induce epigenetic reprogramming of adult mammalian cells into induced pluripotent stem cells. Although DNA factors are integrated during some reprogramming methods, it is unknown whether the genome remains unchanged at the single nucleotide level. Here we show that 22 human induced pluripotent stem (hiPS) cell lines reprogrammed using five different methods each contained an average of five protein-coding point mutations in the regions sampled (an estimated six protein-coding point mutations per exome). The majority of these mutations were non-synonymous, nonsense or splice variants, and were enriched in genes mutated or having causative effects in cancers. At least half of these reprogramming-associated mutations pre-existed in fibroblast progenitors at low frequencies, whereas the rest occurred during or after reprogramming. Thus, hiPS cells acquire genetic modifications in addition to epigenetic modifications. Extensive genetic screening should become a standard procedure to ensure hiPS cell safety before clinical use

Neurotrophic requirements of human motor neurons defined using amplified and purified stem-cell derived cultures

Neurotrophic requirements of human motor neurons defined using amplified and purified stem-cell derived culturesHuman motor neurons derived from embryonic and induced pluripotent stem cells (hESCs and hiPSCs) are a potentially important tool for studying motor neuron survival and pathological cell death. However, their basic survival requirements remain poorly characterized. Here, we sought to optimize a robust survival assay and characterize their response to different neurotrophic factors. First, to increase motor neuron yield, we screened a small-molecule collection and found that the Rho-associated kinase (ROCK) inhibitor Y-27632 enhances motor neuron progenitor proliferation up to 4-fold in hESC and hiPSC cultures. Next, we FACS-purified motor neurons expressing the Hb9::GFP reporter from Y-27632-amplified embryoid bodies and cultured them in the presence of mitotic inhibitors to eliminate dividing progenitors. Survival of these purified motor neurons in the absence of any other cell type was strongly dependent on neurotrophic support. GDNF, BDNF and CNTF all showed potent survival effects (EC(50) 1-2 pM). The number of surviving motor neurons was further enhanced in the presence of forskolin and IBMX, agents that increase endogenous cAMP levels. As a demonstration of the ability of the assay to detect novel neurotrophic agents, Y-27632 itself was found to support human motor neuron survival. Thus, purified human stem cell-derived motor neurons show survival requirements similar to those of primary rodent motor neurons and can be used for rigorous cell-based screening.This work was funded by Project A.L.S., P2ALS and NYSTEM grant number CO24415. The work of N.J.L. was supported by the Portuguese Foundation for Science and Technology SFRH/BD/33421/2008 and the Luso-American Development Foundation. B.J.-K. was supported by the National Institute of Neurological Disorders and Stroke (NINDS). L.R. was supported by the Swedish Brain Foundation/Hjarnfonden. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Role of Ucp1 enhancer methylation and chromatin remodelling in the control of Ucp1 expression in murine adipose tissue

Aims/hypothesis Increasing the expression of the brown adipose tissue-specific gene uncoupling protein-1 (Ucp1) is a potential target for treating obesity. We investigated the role of DNA methylation and histone modification in Ucp1 expression in adipose cell lines and ex vivo murine adipose tissues. Methods Methylation state of the Ucp1 enhancer was studied using bisulphite mapping in murine adipose cell lines, and tissue taken from cold-stressed mice, coupled with functional assays of the effects of methylation and demethylation of the Ucp1 promoter on gene expression and nuclear protein binding. Results We show that demethylation of the Ucp1 promoter by 5-aza-deoxycytidine increases Ucp1 expression while methylation of Ucp1 promoter–reporter constructs decreases expression. Brown adipose tissue-specific Ucp1 expression is associated with decreased CpG dinucleotide methylation of the Ucp1 enhancer. The lowest CpG dinucleotide methylation state was found in two cyclic AMP response elements (CRE3, CRE2) in the Ucp1 promoter and methylation of the CpG in CRE2, but not CRE3 decreased nuclear protein binding. Chromatin immunoprecipitation assays revealed the presence of the silencing DiMethH3K9 modification on the Ucp1 enhancer in white adipose tissue and the appearance of the active TriMethH3K4 mark at the Ucp1 promoter in brown adipose tissue in response to a cold environment. Conclusions/interpretation The results demonstrate that CpG dinucleotide methylation of the Ucp1 enhancer exhibits tissue-specific patterns in murine tissue and cell lines and suggest that adipose tissue-specific Ucp1 expression involves demethylation of CpG dinucleotides found in regulatory CREs in the Ucp1 enhancer, as well as modification of histone tails