Transcatheter arterial embolization for iatrogenic bleeding after endoscopic ultrasound-guided pancreaticobiliary drainage.

PURPOSE: The purpose of this study was to report the incidence of massive bleeding after endoscopic ultrasound-guided transmural pancreaticobiliary drainage (EUS-TPBD) and the clinical outcomes in patients with this condition treated with transcatheter arterial embolization (TAE). PATIENTS AND METHODS: We performed a 9-year retrospective analysis of 797 EUS-TPBD procedures (excluding gallbladder or pseudocysts) in 729 patients. Among them, twelve (12/729, 1.65%) patients were referred for TAE to manage active bleeding adjacent to the TPBD sites. There were 8 men and 4 women with a mean age of 66.1 years±13.4 (SD) (range: 45-89 years). The clinical and procedure data of these 12 patients were reviewed. RESULTS: Thirteen TAE procedures in 12 patients were performed. The bleeding sites were the left hepatic artery (n=7), the right hepatic artery (n=3), the left gastric artery (n=1), the left accessory gastric artery (n=1) and gastroduodenal artery (n=1). TAE was performed with gelatin sponge particles (n=1), coil (n=1) and n-butyl-2 cyanoacrylate with/without coils (n=11), with technical and clinical success rates of 100% (13/13) and 85% (11/13), respectively. Re-bleeding following embolization with gelatin sponge particles occurred in one patient. Procedure-related ischemic hepatitis was observed in another patient with pancreatic cancer with portal vein involvement. CONCLUSION: On the basis of our results, TAE using n-butyl-2 cyanoacrylate seems safe and effective for the treatment of bleeding after EUS-TPBD procedures. When the portal vein is compromised, TAE of the hepatic artery can cause ischemic liver damage.

Osteoglycin, a novel coordinator of bone and glucose homeostasis.

OBJECTIVE: The skeleton, which is strongly controlled by endocrine factors, has recently been shown to also play an active endocrine role itself, specifically influencing energy metabolism. However, much less is known about this role. Therefore, we sought to identify novel endocrine factors involved in the regulation of both bone mass and whole-body glucose homeostasis. METHODS: We used transcriptomic and proteomic analysis of Y1 receptor deficient osteoblasts combined with the generation of a novel osteoglycin deficient mouse model and performed comprehensive in vivo phenotype profiling, combined with osteoglycin administration in wildtype mice and human studies. RESULTS: Here we identify a novel role for osteoglycin, a secreted proteoglycan, in coordinating bone accretion with changes in energy balance. Using an osteoglycin knockout mouse model, we show that at a whole body level, osteoglycin acts to suppress bone formation and modulate whole body energy supplies by altering glucose uptake through changes in insulin secretion and sensitivity, as well as by altering food intake through central signaling. Examining humans following gastric surgery as a model of negative energy balance, we show that osteoglycin is associated with BMI and lean mass as well as changes in weight, BMI, and glucose levels. CONCLUSIONS: Thus, we identify osteoglycin as a novel factor involved in the regulation of energy homeostasis and identify a role for it in facilitating the matching of bone acquisition to alterations in energy status.

Central RANK signalling in NPY neurons alters bone mass in male mice.

RANKL signalling known to be important for the control of bone mass, has recently also been implicated in the brain to control thermoregulation, however, it is not known which neuronal pathways are involved and whether other aspects of energy homeostasis are also affected. Here we show that selective deletion of RANK from NPY neurons down-regulated NPY mRNA expression in the hypothalamus. While comprehensive phenotyping of germline-induced NPY neuron specific RANK deficient mice revealed no significant changes in physical or metabolic parameters, adult onset deletion of RANK from NPY neurons led to a significant increase in fat mass and a decrease in whole body bone mineral content and bone mineral density. Intriguingly, when these conditional knockout mice were placed on a high fat diet, body weight and fat mass did not differ to control mice. However, they were able to significantly increase their bone mass to match their increased body weight, an ability that was lacking in control mice. Taken together, results from this study demonstrate that RANK signalling in NPY neurons is involved in modulating NPY levels and through that matching bone mass to body weight.

Comparison of High-Resolution MR Imaging and Digital Subtraction Angiography for the Characterization and Diagnosis of Intracranial Artery Disease.

BACKGROUND AND PURPOSE: High-resolution MR imaging has recently been introduced as a promising diagnostic modality in intracranial artery disease. Our aim was to compare high-resolution MR imaging with digital subtraction angiography for the characterization and diagnosis of various intracranial artery diseases. MATERIALS AND METHODS: Thirty-seven patients who had undergone both high-resolution MR imaging and DSA for intracranial artery disease were enrolled in our study (August 2011 to April 2014). The time interval between the high-resolution MR imaging and DSA was within 1 month. The degree of stenosis and the minimal luminal diameter were independently measured by 2 observers in both DSA and high-resolution MR imaging, and the results were compared. Two observers independently diagnosed intracranial artery diseases on DSA and high-resolution MR imaging. The time interval between the diagnoses on DSA and high-resolution MR imaging was 2 weeks. Interobserver diagnostic agreement for each technique and intermodality diagnostic agreement for each observer were acquired. RESULTS: High-resolution MR imaging showed moderate-to-excellent agreement (interclass correlation coefficient = 0.892-0.949; κ = 0.548-0.614) and significant correlations (R = 0.766-892) with DSA on the degree of stenosis and minimal luminal diameter. The interobserver diagnostic agreement was good for DSA (κ = 0.643) and excellent for high-resolution MR imaging (κ = 0.818). The intermodality diagnostic agreement was good (κ = 0.704) for observer 1 and moderate (κ = 0.579) for observer 2, respectively. CONCLUSIONS: High-resolution MR imaging may be an imaging method comparable with DSA for the characterization and diagnosis of various intracranial artery diseases.

Interlocking polyetheretherketone implant.

Polyetheretherketone (PEEK) is a versatile material and is used increasingly for the correction of facial deformity. We have used bespoke implants with an interlocking mechanism to add stability and to facilitate ease of insertion in areas with difficult access. The interlocking mechanism also reduces the need for fixation to segments that are difficult to access.

Global variability in withholding and withdrawal of life-sustaining treatment in the intensive care unit: a systematic review.

PURPOSE: Prior studies identified high variability in prevalence of withdrawal of life-sustaining treatment in the ICU. Variability in end-of-life decision-making has been reported at many levels: between countries, ICUs, and individual intensivists. We performed a systematic review examining regional, national, inter-hospital, and inter-physician variability in withdrawal of life-sustaining treatment in the ICU. METHODS: Using a predefined search strategy, we queried three electronic databases for peer-reviewed articles addressing withdrawal of life-sustaining treatment in adult patients in the ICU. Data were analyzed for variability in prevalence of withdrawal of life-sustaining treatment. Withholding of life-sustaining treatment was also examined where information was provided. An assessment tool was developed to quantify the risk of bias in the included articles. RESULTS: We identified 1284 studies, with 56 included after review. Most studies had unclear or high risk of bias, primarily due to unclear case definitions or potential confounding. The mean prevalence of withdrawal of life-sustaining treatment for patients who died varied from 0 to 84.1% between studies, with standard deviation of 23.7%. Sensitivity analysis of general ICU patients yielded similar results. Withholding also varied between 5.3 and 67.3% (mean 27.3, SD 18.5%). Substantial variability was found between world regions, countries, individual ICUs within a country, and individual intensivists within one ICU. CONCLUSIONS: We identified substantial variability in the withdrawal of life-sustaining treatment across world regions and countries. Similar variability existed between ICUs within countries and even between providers within the same ICU. Further study is necessary, and could lead to interventions to improve end-of-life care in the ICU.

Neuropeptide y attenuates stress-induced bone loss through suppression of noradrenaline circuits.

Chronic stress and depression have adverse consequences on many organ systems, including the skeleton, but the mechanisms underlying stress-induced bone loss remain unclear. Here we demonstrate that neuropeptide Y (NPY), centrally and peripherally, plays a critical role in protecting against stress-induced bone loss. Mice lacking the anxiolytic factor NPY exhibit more anxious behavior and elevated corticosterone levels. Additionally, following a 6-week restraint, or cold-stress protocol, Npy-null mice exhibit three-fold greater bone loss compared to wild-type mice, owing to suppression of osteoblast activity. This stress-protective NPY pathway acts specifically through Y2 receptors. Centrally, Y2 receptors suppress corticotropin-releasing factor expression and inhibit activation of noradrenergic neurons in the paraventricular nucleus. In the periphery, they act to control noradrenaline release from sympathetic neurons. Specific deletion of arcuate Y2 receptors recapitulates the Npy-null stress response, coincident with elevated serum noradrenaline. Importantly, specific reintroduction of NPY solely in noradrenergic neurons of otherwise Npy-null mice blocks the increase in circulating noradrenaline and the stress-induced bone loss. Thus, NPY protects against excessive stress-induced bone loss, through Y2 receptor-mediated modulation of central and peripheral noradrenergic neurons.

Effects of family caregivers on the use of formal long-term care in South Korea.

AIM: We investigated whether the presence and characteristics of a family caregiver affect the use of formal long-term care under the new Korean long-term care system. BACKGROUND: In July 2008, Korea introduced public long-term care insurance, a form of social insurance, in order to cope with the reality of the growing elderly population and the increasing demand for long-term care. METHODS: The family caregivers of 271 applicants for long-term care insurance who had a caregiver and 36 applicants without a caregiver living in one city participated in this cross-sectional study. Data were collected from November 2010 to June 2011 using self-report questionnaires. Variables included the applicant's gender; age; physical and cognitive function; type of long-term care used; presence and type of family caregivers; caregiver's gender, age, education level, marital status, and employment status; and service use covered by long-term care insurance. Logistic multiple regression was used. RESULTS: The effect of the presence and characteristics of a family caregiver on the use of a long-term care facility was significant. A nursing home was used for care more frequently when the applicant had no family caregiver. An elderly subject who had a spouse as a caregiver used home healthcare services more often than nursing home services. CONCLUSION: The decision to use formal services may depend not only on the care level required by the applicant, but also on the presence and type of caregivers. To successfully implement the new long-term care insurance system, consideration of the caregiver situation should be included in policy development.

4-O-methylhonokiol, a PPARγ agonist, inhibits prostate tumour growth: p21-mediated suppression of NF-κB activity.

BACKGROUND AND PURPOSE: The effects of 4-O-methylhonokiol (MH), a constituent of Magnolia officinalis, were investigated on human prostate cancer cells and its mechanism of action elucidated. EXPERIMENTAL APPROACH: The anti-cancer effects of MH were examined in prostate cancer and normal cells. The effects were validated in vivo using a mouse xenograft model. KEY RESULTS: MH increased the expression of PPARγ in prostate PC-3 and LNCap cells. The pull-down assay and molecular docking study indicated that MH directly binds to PPARγ. MH also increased transcriptional activity of PPARγ but decreased NF-κB activity. MH inhibited the growth of human prostate cancer cells, an effect attenuated by the PPARγ antagonist GW9662. MH induced apoptotic cell death and this was related to G(0) -G(1) phase cell cycle arrest. MH increased the expression of the cell cycle regulator p21, and apoptotic proteins, whereas it decreased phosphorylation of Rb and anti-apoptotic proteins. Transfection of PC3 cells with p21 siRNA or a p21 mutant plasmid on the cyclin D1/ cycline-dependent kinase 4 binding site abolished the effects of MH on cell growth, cell viability and related protein expression. In the animal studies, MH inhibited tumour growth, NF-κB activity and expression of anti-apoptotic proteins, whereas it increased the transcriptional activity and expression of PPARγ, and the expression of apoptotic proteins and p21 in tumour tissues. CONCLUSIONS AND IMPLICATION: MH inhibits growth of human prostate cancer cells through activation of PPARγ, suppression of NF-κB and arrest of the cell cycle. Thus, MH might be a useful tool for treatment of prostate cancer.

Isoflurane decreases death of human embryonic stem cell-derived, transcriptional marker Nkx2.5(+) cardiac progenitor cells.

BACKGROUND: Cardiac progenitor cells (CPCs) derived from human embryonic stem cells (hESCs) can multiply and generate cardiomyocytes, offering their tremendous potential for cardiac regenerative therapy. However, poor survival under stressful conditions is a major hurdle in the regeneration. We investigated whether isoflurane-induced preconditioning can increase hESC-derived CPC survival under oxidative stress. METHODS: Undifferentiated hESCs were cultured in suspension with 20% FBS (fetal bovine serum) and 20 ng/ml of BMP-4 (bone morphogenetic protein-4) to form embryoid bodies and grown onto Matrigel-coated plates for 2-3 weeks. To characterise the differentiated CPCs, immunostaining for Nkx2.5 (nonspecific transcriptional marker) and Isl-1 was performed. hESC-derived CPCs were exposed to oxidative stress induced by H(2) O(2) and FeSO(4) . For anaesthetic preconditioning, CPCs were exposed to isoflurane (0.25, 0.5, 1.0 mM). CPC survival was determined by trypan blue exclusion. A mitoK(ATP) channels inhibitor, 5-hydroxydecanoic acid (200 µM) and an opener, diazoxide (100 µM), were used to investigate the involvement of mitoK(ATP) channels. RESULTS: hESC-derived CPCs stained with Nkx2.5 were 95 ± 3% of total cell number. Isoflurane (0.5 and 1.0 mM)-preconditioned CPCs showed a significantly lower death rate compared with control (0.5 mM: 30.6 ± 10.7% and 1.0 mM: 28.5 ± 6.2% vs. control: 43.2 ± 9.9%). Inhibition of mitoK(ATP) channels with 5-HD completely abolished the protective effects of isoflurane. Diazoxide significantly decreased CPC death (29.5 ± 12.4%). However, when diazoxide was applied to CPC preconditioned with isoflurane, CPC death did not decrease further (28.7 ± 10.9%). CONCLUSION: Isoflurane increased hESC-derived Nkx2.5(+) CPC survival under oxidative stress, and mitoK(ATP) channels may be involved in the protective effect.

Additive actions of the cannabinoid and neuropeptide Y systems on adiposity and lipid oxidation.

AIMS: Energy homeostasis is regulated by a complex interaction of molecules and pathways, and new antiobesity treatments are likely to require multiple pharmacological targeting of anorexigenic or orexigenic pathways to achieve effective loss of excess body weight and adiposity. Cannabinoids, acting via the cannabinoid-1 (CB1) receptor, and neuropeptide Y (NPY) are important modulators of feeding behaviour, energy metabolism and body composition. We investigated the interaction of CB1 and NPY in the regulation of energy homeostasis, hypothesizing that dual blockade of CB1 and NPY signalling will induce greater weight and/or fat loss than that induced by single blockade of either system alone. METHODS: We studied the effects of the CB1 antagonist Rimonabant on food intake, body weight, body composition, energy metabolism and bone physiology in wild-type (WT) and NPY knockout (NPY(-/-)) mice. Rimonabant was administered orally at 10 mg/kg body weight twice per day for 3 weeks. Oral Rimonabant was delivered voluntarily to mice via a novel method enabling studies to be carried out in the absence of gavage-induced stress. RESULTS: Mice with dual blockade of CB1 and NPY signalling (Rimonabant-treated NPY(-/-) mice) exhibited greater reductions in body weight and adiposity than mice with single blockade of either system alone (Rimonabant-treated WT or vehicle-treated NPY(-/-) mice). These changes occurred without loss of lean tissue mass or bone mass. Furthermore, Rimonabant-treated NPY(-/-) mice showed a lower respiratory exchange ratio than that seen in Rimonabant-treated WT or vehicle-treated NPY(-/-) mice, suggesting that this additive effect of dual blockade of CB1 and NPY involves promotion of lipid oxidation. On the other hand, energy expenditure and physical activity were comparable amongst all treatment groups. Interestingly, Rimonabant similarly and transiently reduced spontaneous and fasting-induced food intake in WT and NPY(-/-) mice in the first hour after administration only, suggesting independent regulation of feeding by CB1 and NPY signalling. In contrast, Rimonabant increased serum corticosterone levels in WT mice, but this effect was not seen in NPY(-/-) mice, indicating that NPY signalling may be required for effects of CB1 on the hypothalamo-pituitary-adrenal axis. CONCLUSIONS: Dual blockade of CB1 and NPY signalling leads to additive reductions in body weight and adiposity without concomitant loss of lean body mass or bone mass. An additive increase in lipid oxidation in dual CB1 and NPY blockade may contribute to the effect on adiposity. These findings open new avenues for more effective treatment of obesity via dual pharmacological manipulations of the CB1 and NPY systems.

Effects of cloned-cattle meat on reproductive physiology in rats.

The influence of the cloned-cattle meat diets upon reproduction in mammals was rarely studied. This study was performed to analyze the effects of the diets containing cloned-cattle (Korean native beef, Hanwoo) meat on the reproductive physiology in rats. The male and female rats were fed with the diets containing 5% or 10% of normal- (N-5 or N-10) or cloned- (C-5 or C-10) cattle meat during test periods. The rats fed with commercial pellets were used as control. Lower food consumption in normal- and cloned-cattle meat diet groups is detected in both male and female rats compared with that of control (P < 0.05, 0.01 and 0.001). No signs of cloned-cattle meat diets on male reproductive parameters are found in all groups, except for lower sperm deformity in C-5 group (P < 0.05) and higher testosterone concentration in C-10 group (P < 0.05), respectively. There are no significant test substance-related differences of Caesarean section and delivery in dams and external examination and physiological development test in neonate compared with control and normal meat groups. Based on these results, it can be postulated that there are no obvious negative effects on the reproductive physiology in rats fed with cloned-cattle meat diets compared to their comparators.

Peripheral neuropeptide Y Y1 receptors regulate lipid oxidation and fat accretion.

OBJECTIVE: Neuropeptide Y and its Y receptors are important players in the regulation of energy homeostasis. However, while their functions in feeding regulation are well recognized, functions in other critical aspects of energy homeostasis are largely unknown. To investigate the function of Y1 receptors in the regulation of energy homeostasis, we examined energy expenditure, physical activity, body composition, oxidative fuel selection and mitochondrial oxidative capacity in germline Y1(-/-) mice as well as in a conditional Y1-receptor-knockdown model in which Y1 receptors were knocked down in peripheral tissues of adult mice. RESULTS: Germline Y1(-/-) mice of both genders not only exhibit a decreased respiratory exchange ratio, indicative of increased lipid oxidation, but interestingly also develop late-onset obesity. However, the increased lipid oxidation is a primary effect of Y1 deletion rather than secondary to increased adiposity, as young Y1(-/-) mice are lean and show the same effect. The mechanism behind this is likely because of increased liver and muscle protein levels of carnitine palmitoyltransferase-1 (CPT-1) and maximal activity of key enzymes involved in beta-oxidation; beta-hydroxyacyl CoA dehydrogenase (betaHAD) and medium-chain acyl-CoA dehydrogenase (MCAD), leading to increased mitochondrial capacity for fatty acid transport and oxidation. These effects are controlled by peripheral Y1-receptor signalling, as adult-onset conditional Y1 knockdown in peripheral tissues also leads to increased lipid oxidation, liver CPT-1 levels and betaHAD activity. Importantly, these mice are resistant to diet-induced obesity. CONCLUSIONS: This work shows the primary function of peripheral Y1 receptors in the regulation of oxidative fuel selection and adiposity, opening up new avenues for anti-obesity treatments by targeting energy utilization in peripheral tissues rather than suppressing appetite by central effects.

An unusual fracture of the mandible 20 months after a split sagittal osteotomy.

An unusual fracture of the mandible is reported that occurred 20 months after a bilateral split sagittal osteotomy.

Dietetic guidelines on food and nutrition in the secondary prevention of cardiovascular disease - evidence from systematic reviews of randomized controlled trials (second update, January 2006).

AIM: To update dietetic guidelines based on systematic review evidence on dietary advice to prevent further events in people with existing cardiovascular disease (CVD) (secondary prevention). METHODS: The Cochrane Library, MEDLINE and EMBASE were comprehensively searched to January 2005 for systematic reviews on aspects of diet and heart health. Reviews were included if they searched systematically for randomized controlled trials relating to diet and secondary prevention of CVD. Each review was critically appraised by at least two members of the UK Heart Health and Thoracic Dietitians Group. The quality and results of each review were discussed and summarized at a group meeting. RESULTS: Evidence-based strategies that reduce cardiovascular events in those with CVD include reduction in saturated fat and substitution with unsaturated fats. Individuals who have suffered a myocardial infarction may also benefit from adopting a Mediterranean type diet and increasing intake of omega 3 fats, but it is not clear whether they are beneficial for all patients with CVD. There is no systematic review evidence to support the use of antioxidant vitamins supplements, low glycaemic index diets, or homocysteine lowering therapies in this group. CONCLUSION: There remains good evidence that reducing saturated fat reduces morbidity in patients with CVD. This advice is consistent for most manifestations of CVD, with the addition of Mediterranean dietary advice and increased omega 3 fats for those who have had a myocardial infarction.

Isolation of a novel mycovirus OMIV in Pleurotus ostreatus and its detection using a triple antibody sandwich-ELISA.

A novel mycovirus was isolated from a diseased mushroom, Pleurotus ostreatus, using a purification procedure involving polyethylene glycol (PEG)-NaCl precipitation, differential centrifugation, and equilibrium centrifugation in a CsCl gradient. The virion was a 43 nm isometric virus encapsulating double-stranded RNA (dsRNA) genome of 2.1, 2.0, 1.9, and 1.7 kbp with a coat protein (CP) of 58 kDa. The new mycovirus was named Oyster Mushroom Isometric Virus (OMIV). A triple antibody sandwich-ELISA (TAS-ELISA) system was constructed to detect OMIV in the mushroom using an anti-OMIV mouse monoclonal antibody and an anti-OMIV rabbit polyclonal serum. The TAS-ELISA system was sensitive enough to allow detection of OMIV in the mushroom with the naked eye. It detected successfully virus particles from 0.6 mg of diseased tissue as well as 0.4 microg/ml purified virus preparation.

Secretin-stimulated MRCP.

Secretin-stimulated magnetic resonance cholangiopancreatography not only facilitate the depiction of anatomic variations or morphologic changes of the pancreatic duct in the normal and diseased pancreas but also help assessing functional abnormalities of the exocrine pancreas. In this article, we illustrate findings of normal pancreas and various pancreatic diseases on magnetic resonance cholangiopancreatography after secretin stimulation.

Simultaneous Bilateral Carotid Stenting under the Circumstance of Neuroprotection Device. A Retrospective Analysis.

SUMMARY: In this study, in order to evaluate the feasibility and outcomes of simultaneous bilateral carotid artery stenting (CAS) with the use of neuroprotection in symptomatic patients, we conducted a retrospective analysis of 27 patients (19 men, eight women; median age, 69.2 years), all of whom had been scheduled to undergo bilateral CAS in a single setting. All patients presented with severe atherosclerotic bilateral carotid stenosis (> 50% for symptomatic side, > 80% for asymptomatic side), exhibiting symptoms of either a cerebrovascular accident or of a transient ischemic attack on at least one side. 48 arteries were treated with self-expandable stents. Neuroprotection devices were utilized for bilateral CAS in 11 patients, and in 16 unilateral CAS patients. We did not perform the second procedure in six patients, in cases in which a patient exhibited (a) hemodynamic instability, (b) a new neurological impairment, or (c) restlessness after a prolonged time for the first CAS. The second procedure was postponed in a staged manner. We achieved a mean residual stenosis of 8.1 +/- 5.0 % in the treated lesions. The mean procedural time for bilateral CAS was three hours and 18 minutes. 17 patients (63%) developed transient bradycardia during the balloon dilatation of one or both of the relevant arteries. Three patients (11%) exhibited persistent bradycardia and hypotension, which required the administration of intravenous vasopressors for several days (2~7 days). None of the patients ultimately required pacemakers, or any further therapy. Two of the patients (7%) developed transient ischemic attack during the periprocedural period, but recovered completely. One patient developed a new minor stroke after the first procedure, and the second procedure was delayed in a staged manner.We observed no periprocedural deaths, major strokes, or myocardial infarctions, nor did we detect any cases of hyperperfusion syndrome within 30 days. In summary, simultaneous bilateral CAS with neuroprotection can be performed in a single setting without increased concerns with regard to hyperperfusion syndrome, hemodynamic instability, thrombo-embolism, or procedure time, when the first CAS has been safely completed with no evidence of complications in a wellmanaged procedure time.