Seismic analysis of Fujian Hakka Tulous

The overall earthquake response of Hakka Tulous, traditional earth constructions of the Fujian Province (China) and listed among the UNESCO World Heritage buildings, is investigated. Non-linear static analysis (pushover) with the equivalent frame approach is used. Although some rough approximations are assumed, this approach is well suited to model complex masonry structures, like Tulous. In fact, nonlinear analysis implemented by finite elements or by discrete elements would involve complex models hard to converge and needing long computational time. After carrying out seismic analysis of a Tulou prototype, its failure modes and overall seismic response were evaluated. The Tulou has shown to have good earthquake resistance with respect to the maximum seismic action that can be expected in the Fujian Province

Short-Burst Bipolar Coagulation for Repairing Partially Damaged Brain Arteries Preserving Their Flow : Technical Note

Peer reviewe

T-level downstaging and complete pathologic response after preoperative long-term radiochemotherapy for locally advanced rectal cancer

Advantages of neoadjuvant chemoradiotherapy for locally advanced carcinoma of the middle and the lower third of the rectum are downstaging and downsizing of the tumor. Results of pathologic results are affected by post-treatment tissue changes and may influence the choice of surgical procedure. Forthy-three consecutive patients (27 male, 16 female; mean age 64 years) were operated after receiving a long-term chemoradiotherapy during a period of 16 months. The data of initial staging procedure (high resolution magnetic resonance imaging) and results of pathological examination of the surgical specimens were analyzed. Regression of tumor was assessed by the absence of vital tumor cells and the post-treatment fibrotic tissue alterations. Regression of tumor size was seen in 42/43 patients leading to an improved T-stage in 27 patients. R0-resection was possible in all cases, although there was a perirectal tumor infiltration to less than 2 mm to circumference of the surgical specimen in 2 cases and unexpected small liver metastasis in 5 cases. Complete remission rate was 23.3% (10 cases). Detecting small amounts of vital tumor cells in altered tissue after chemoradiotherapy is a major problem of pathological examination procedure and should be taken into consideration by the surgeons. The choice of operation (resection vs. abdominoperineal extirpation vs. local excision) should be committed to the initial imaging procedure and not to any restaging procedure after neoadjuvant chemoradiotherap

FRI0376 EFFECT OF CARBAMYLATED LOW-DENSITY LIPOPROTEINS ON BONE CELLS HOMEOSTASIS

Background:Carbamylation is a post-translational modification occurring under several conditions such as uremia, smoking and chronic inflammation as in rheumatoid arthritis (RA). Low-density lipoproteins (LDL) represent a target of carbamylation. Carbamylated-LDL (cLDL) have an increased inflammatory and atherogenic potential. Growing evidence supports an influence of modified lipids on bone cells homeostasis. However, the role of cLDL on bone cells physiology is still unknown.Objectives:Considering the rate of carbamylation and the role of anti-carbamylated proteins antibodies as markers of erosive disease in RA, the purpose of this study is to investigate the effect of cLDL on bone homeostasis.Methods:In-vitrocarbamylation of LDL was performed as previously described by Ok et al. (Kidney Int. 2005). Briefly, native LDL (nLDL) were treated with potassium cyanate (KOCN) for 4 hours, followed by excessive dialysis for 36 hours to remove KOCN. Both osteoclasts (OCs) and osteoblasts (OBLs) were treated at baseline with 20 μg/ml, 100 μg/ml and 200 μg/ml of cLDL or nLDL. To induce osteoclast differentiation, CD14+ monocytes were isolated from peripheral blood of healthy donors by magnetic microbeads separation and then cultured on a 96-wells plate in DMEM media supplemented with RANKL and M-CSF. After 10 days cells were fixed, stained for tartrate-resistant acid phosphatase (TRAP), a marker of OC differentiation, and counted. OBLs were isolated from bone specimens of 3 patients who had undergone to knee or hip arthroplasty for osteoarthritis and treated for 5 days with different concentrations of cLDL and nLDL. OBLs were fixed and stained for alkaline phosphatase positive activity (ALP), a marker of osteogenic differentiation. Total RNA was extracted from cell lysates. Copies of single-stranded complementary DNA (cDNA) were synthesized and analyzed by real-time PCR to evaluate RANKL and Osteoprotegerin (OPG) mRNA expression levels.Results:In OCLs culture, cLDL significantly decreased the number of OC compared to untreated cells (200 μg/ml p=0,0015) and nLDL treated cells (200 μg/ml p= 0,011; 20 μg/ml p= 0,0014) (Fig 1). Moreover, treatment with cLDL induced an increase of not terminally differentiated OCs, reduced dimensions of OCs, less intense TRAP staining and vacuolization (Fig 2). In OBLs culture, cLDL (20, 100 μg/ml) significantly reduced the ALP activity of OBLs compared with untreated cells (p<0.05) (Fig 3). nLDL did not affect the ALP expression. Treatment with cLDL stimulated RANKL mRNA expression in osteoblasts increasing the RANKL/OPG ratio (Fig 4).Fig 1.Fig 2.Fig 3.Fig 4.Conclusion:cLDL induce a significant depression of OC and OBL differentiation. Moreover, cLDL increase RANKL expression in OBL, unbalancing bone tissue turnover towards bone resorption. Accordingly, cLDL could be implicated in the bone loss characterizing several conditions associated to an increased carbamylation, such as RADisclosure of Interests:Bruno Lucchino: None declared, Martina Leopizzi: None declared, Tania Colasanti: None declared, Valeria Di Maio: None declared, cristiano alessandri Grant/research support from: Pfizer, Guido Valesini: None declared, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi, Manuela Di Franco: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lill

L-DOPA preloading increases the uptake of borophenylalanine in C6 glioma rat model: a new strategy to improve BNCT efficacy.

Purpose: Boron neutron capture therapy (BNCT) is a radiotherapeutic modality based on 10B(n,a)7Li reaction, for the treatment of malignant gliomas. One of the main limitations for BNCT effectiveness is the insufficient intake of 10B nuclei in the tumor cells. This work was aimed at investigating the use of L-DOPA as a putative enhancer for 10B-drug 4-dihydroxy-borylphenylalanine (BPA) uptake in the C6-glioma model. The investigation was first per- formed in vitro and then extended to the animal model. Methods and Materials: BPA accumulation in C6-glioma cells was assessed using radiowave dielectric spectros- copy, with and without L-DOPA preloading. Two L-DOPA incubation times (2 and 4 hours) were investigated, and the corresponding effects on BPA accumulation were quantified. C6-glioma cells were also implanted in the brain of 32 rats, and tumor growth was monitored by magnetic resonance imaging. Rats were assigned to two experimental branches: (1) BPA administration; (2) BPA administration after pretreatment with L-DOPA. All an- imals were sacrificed, and assessments of BPA concentrations in tumor tissue, normal brain, and blood samples were performed using high-performance liquid chromatography. Results: L-DOPA preloading induced a massive increase of BPA concentration in C6-glioma cells only after a 4-hour incubation. In the animal model, L-DOPA pretreatment produced a significantly higher accumulation of BPA in tumor tissue but not in normal brain and blood samples. Conclusions: This study suggests the potential use of L-DOPA as enhancer for BPA accumulation in malig- nant gliomas eligible for BNCT. L-DOPA preloading effect is discussed in terms of membrane transport mechanisms

Hippocampal neuroinflammation, functional connectivity, and depressive symptoms in multiple sclerosis

Depression, a condition commonly comorbid with multiple sclerosis (MS), is associated more generally with elevated inflammatory markers and hippocampal pathology. We hypothesized that neuroinflammation in the hippocampus is responsible for depression associated with MS. We characterized the relationship between depressive symptoms and hippocampal microglial activation in patients with MS using the 18-kDa translocator protein radioligand [18F]PBR111. To evaluate pathophysiologic mechanisms, we explored the relationships between hippocampal neuroinflammation, depressive symptoms, and hippocampal functional connectivities defined by resting-state functional magnetic resonance imaging. Methods The Beck Depression Inventory (BDI) was administered to 11 patients with MS and 22 healthy control subjects before scanning with positron emission tomography and functional magnetic resonance imaging. We tested for higher [18F]PBR111 uptake in the hippocampus of patients with MS relative to healthy control subjects and examined the correlations between [18F]PBR111 uptake, BDI scores, and hippocampal functional connectivities in the patients with MS. Results Patients with MS had an increased hippocampal [18F]PBR111 distribution volume ratio relative to healthy control subjects (p = .024), and the hippocampal distribution volume ratio was strongly correlated with the BDI score in patients with MS (r = .86, p = .006). Hippocampal functional connectivities to the subgenual cingulate and prefrontal and parietal regions correlated with BDI scores and [18F]PBR111 distribution volume ratio. Conclusions Our results provide evidence that hippocampal microglial activation in MS impairs the brain functional connectivities in regions contributing to maintenance of a normal affective state. Our results suggest a rationale for the responsiveness of depression in some patients with MS to effective control of brain neuroinflammation. Our findings also lend support to further investigation of the role of inflammatory processes in the pathogenesis of depression more generally

Management of infants with brief resolved unexplained events (Brue) and apparent life-threatening events (alte): A rand/ucla appropriateness approach

Unexpected events of breath, tone, and skin color change in infants are a cause of consider-able distress to the caregiver and there is still debate on their appropriate management. The aim of this study is to survey the trend in prevention, decision-making, and management of brief resolved unexplained events (BRUE)/apparent life-threatening events (ALTE) and to develop a shared proto-col among hospitals and primary care pediatricians regarding hospital admission criteria, work-up and post-discharge monitoring of patients with BRUE/ALTE. For the study purpose, a panel of 54 experts was selected to achieve consensus using the RAND/UCLA appropriateness method. Twelve scenarios were developed: one addressed to primary prevention of ALTE and BRUE, and 11 focused on hospital management of BRUE and ALTE. For each scenario, participants were asked to rank each option from ‘1’ (extremely inappropriate) to ‘9’ (extremely appropriate). Results derived from panel meeting and discussion showed several points of agreement but also disagreement with different opinion emerged and the need of focused education on some areas. However, by combining previous recommendations with expert opinion, the application of the RAND/UCLA appropriateness permit-ted us to drive pediatricians to reasoned and informed decisions in term of evaluation, treatment and follow-up of infants with BRUE/ALTE, reducing inappropriate exams and hospitalisation and highlighting priorities for educational interventions

ORIGIN: Metal Creation and Evolution from the Cosmic Dawn

ORIGIN is a proposal for the M3 mission call of ESA aimed at the study of metal creation from the epoch of cosmic dawn. Using high-spectral resolution in the soft X-ray band, ORIGIN will be able to identify the physical conditions of all abundant elements between C and Ni to red-shifts of z=10, and beyond. The mission will answer questions such as: When were the first metals created? How does the cosmic metal content evolve? Where do most of the metals reside in the Universe? What is the role of metals in structure formation and evolution? To reach out to the early Universe ORIGIN will use Gamma-Ray Bursts (GRBs) to study their local environments in their host galaxies. This requires the capability to slew the satellite in less than a minute to the GRB location. By studying the chemical composition and properties of clusters of galaxies we can extend the range of exploration to lower redshifts (z approx. 0.2). For this task we need a high-resolution spectral imaging instrument with a large field of view. Using the same instrument, we can also study the so far only partially detected baryons in the Warm-Hot Intergalactic Medium (WHIM). The less dense part of the WHIM will be studied using absorption lines at low redshift in the spectra for GRBs. The ORIGIN mission includes a Transient Event Detector (coded mask with a sensitivity of 0.4 photon/sq cm/s in 10 s in the 5-150 keV band) to identify and localize 2000 GRBs over a five year mission, of which approx.65 GRBs have a redshift >7. The Cryogenic Imaging Spectrometer, with a spectral resolution of 2.5 eV, a field of view of 30 arcmin and large effective area below 1 keV has the sensitivity to study clusters up to a significant fraction of the virial radius and to map the denser parts of the WHIM (factor 30 higher than achievable with current instruments). The payload is complemented by a Burst InfraRed Telescope to enable onboard red-shift determination of GRBs (hence securing proper follow up of high-z bursts) and also probes the mildly ionized state of the gas. Fast repointing is achieved by a dedicated Controlled Momentum Gyro and a low background is achieved by the selected low Earth orbit

Suppression of grasshopper sound production by nitric oxide-releasing neurons of the central complex

The central complex of acridid grasshoppers integrates sensory information pertinent to reproduction-related acoustic communication. Activation of nitric oxide (NO)/cyclic GMP-signaling by injection of NO donors into the central complex of restrained Chorthippus biguttulus females suppresses muscarine-stimulated sound production. In contrast, sound production is released by aminoguanidine (AG)-mediated inhibition of nitric oxide synthase (NOS) in the central body, suggesting a basal release of NO that suppresses singing in this situation. Using anti-citrulline immunocytochemistry to detect recent NO production, subtypes of columnar neurons with somata located in the pars intercerebralis and tangential neurons with somata in the ventro-median protocerebrum were distinctly labeled. Their arborizations in the central body upper division overlap with expression patterns for NOS and with the site of injection where NO donors suppress sound production. Systemic application of AG increases the responsiveness of unrestrained females to male calling songs. Identical treatment with the NOS inhibitor that increased male song-stimulated sound production in females induced a marked reduction of citrulline accumulation in central complex columnar and tangential neurons. We conclude that behavioral situations that are unfavorable for sound production (like being restrained) activate NOS-expressing central body neurons to release NO and elevate the behavioral threshold for sound production in female grasshoppers

Pain Behavior Changes Following Disc Puncture Relate to Nucleus Pulposus Rather than to the Disc Injury Per Se: An Experimental Study in Rats

It has previously been demonstrated that disc puncture in the rat induced changes in grooming and wet dog shakes, two behavioral changes that may be linked to discomfort and neuropathic pain. In this study the aim was to separate the effects of disc injury and the epidural presence of nucleus pulposus. Following anesthesia, the L4-5 disc was exposed using a dorsal approach. Ten rats received a superficial disc injury without nucleus pulposus leakage and ten rats received nucleus pulposus from a donor rat without disc injury. In ten animals the L4-5 disc was punctured using a ventral approach, with 10 corresponding controls. Spontaneous behavior was assessed after surgery. The data was matched to historical control of dorsal sham surgery and disc puncture. The study showed that the effects of nucleus pulposus were more pronounced than the effects induced by the disc injury. Ventral disc puncture did not induce any behavioral changes different from sham exposure. In conclusion, the data from the study indicate that behavioral changes induced by disc puncture are more likely to relate to the epidural presence of nucleus pulposus than the disc injury per se