156 research outputs found
Determining the influence of ship hull deformations caused by draught change on shaft alignment application using FE analysis
This paper was to address the shortcomings of current design practice to evaluate the stability of the shaft alignment for a 300,000 DWT Very Large Crude Oil Carrier. An enhanced approach using FE was applied to identify the influence of hull deformation on the alignment of the shafting system. The effectiveness of this method was demonstrated in comparison with Jack up technique. Analysis results showed that the hull deformation could be a key factor affecting the offset distortion of each bearing supporting the shaft line. Moreover, it was confirmed that the deformation pattern of cargo hold was opposite to the deformation of engine room structure when hull deformation occurred due to draught change of the case ship. As new research findings, they are believed to contribute significantly to the prevention of shaft damage associated with hull deformations, thereby improving the reliability of shaft alignment for similar types of vessels
Sicyos angulatus ameliorates atherosclerosis through downregulation of aortic inflammatory responses in apolipoprotein E-deficient mice
Sicyos angulatus (SA), a summer annual vine originating from Northeastern USA, is a widely distributed noxious invasive plant. However, the clinical application of SA has not been investigated previously. The purpose of present study was to determine the effects of SA on atherosclerosis and its underlying mechanism. Atherosclerosis was induced by feeding apolipoprotein E-deficient (apoE(-/-)) mice with an atherogenic diet for 8 weeks. SA was administered daily by oral gavage during induction of atherosclerosis. ApoE(-/-) mice treated with SA demonstrated a significant reduction in atherosclerotic plaque area in the whole aorta and aortic sinus compared with vehicle-treated mice. The plasma lipid profiles, including triglyceride, total cholesterol, high-density lipoprotein and low-density lipoprotein, were not affected by SA administration. Of note, gene expression levels of proatherogenic cytokines including tumor necrosis factor alpha (Tnf alpha) and interleukin-6 (Il-6) were significantly decreased in the aorta of SA administered apoE(-/-) mice. In lipopolysaccharide-stimulated RAW 264.7 macrophage cells, SA also inhibited the induction Tnfa, Il-6 and Il-1 beta in a dose-dependent manner. Furthermore, gene expression levels of endothelial cell adhesion molecules, including vascular cell adhesion protein 1 and intercellular adhesion molecule 1 were reduced in the aorta of apoE(-/-) mice treated with SA, which was followed by diminished aortic infiltration of monocytes/macrophages. In conclusion, to the best of our knowledge, this is the first study to demonstrate that SA is able to suppress the development of atherosclerosis by inhibiting the aortic expression of proinflammatory factors in atherogenic diet-fed apoE(-/-) mice. The present study may provide novel insights into the application of the environmentally problematic weed SA as a therapeutically effective natural product for preventing atherosclerosis.N
A Case of Intra- and Extra-Mural Hematomas During Recanalization for Chronic Total Occlusion
An intramural hematoma is an accumulation of blood between the internal and external elastic membranes within the medial space, whereas an extramural hematoma is a dilution and/or dissemination of blood throughout the adventitia. Intra- and extra-hematomas are observed by intravascular ultrasound during percutaneous coronary intervention (PCI). The patient described herein presented with angina pectoris. Her coronary angiogram showed diffuse narrowing of the mid-left anterior descending artery and total occlusion of the distal right coronary artery (RCA). Intra- and extra-mural hematomas developed during PCI of the RCA; however, the lesions were covered successfully using long drug-eluting stents
A multi-institutional study of the prevalence of BRCA1 and BRCA2 large genomic rearrangements in familial breast cancer patients
Background: Large genomic rearrangements (LGRs) in the BRCA1/2 genes are frequently observed in breast cancer patients who are negative for BRCA1/2 small mutations. Here, we examined 221 familial breast cancer patients from 37 hospitals to estimate the contribution of LGRs, in a nationwide context, to the development of breast cancer.
Methods: Direct sequencing or mutation scanning followed by direct sequencing was performed to screen small mutations. BRCA1/2 small mutation-negative patients were screened for the presence of LGRs using a multiple ligation-dependent probe amplification (MLPA) assay.
Results: Using a combined strategy to detect the presence of small mutations and LGRs, we identified BRCA1/2 small mutations in 78 (35.3%) out of 221 familial breast cancer patients and BRCA1 LGRs in 3 (2.1%) out of 143 BRCA1/2 small mutation-negative patients: the deletion of exons 11โ13, the deletion of exons 13โ15, and whole gene deletion of exons 1-24. The novel deletion of exons 11โ13 is thought to result from a non-homologous recombination event mediated by a microhomology sequence comprised of 3 or 4 base pairs: c.3416_4357 + 1863delins187 (NG_005905.2: g.33369_44944delins187).
Conclusions: In this study, we showed that LGRs were found in 3.7% (3/81) of the patients who had mutations in BRCA1 or BRCA2, and 7.5% (3/40) of patients with mutations in BRCA1. This suggests that the contribution of LGRs to familial breast cancer in this population might be comparable to that in other ethnic populations. Given these findings, an MLPA to screen for mutations in the BRCA1 gene is recommended as an initial screening test in highly selective settings.Peer Reviewe
Efficacy and Tolerability of Aripiprazole: A 26-Week Switching Study from Oral Antipsychotics
Objective To determine if the maintenance effectiveness and tolerability of aripiprazole demonstrated in a 12-week study were maintained in an extension phase (up to 26 weeks). Methods This study was the extension of our switching study from other antipsychotics to aripiprazole in symptomatically stable patients with schizophrenia or schizoaffective disorder. All the patients were randomly assigned to the aripiprazole group or the non-aripiprazole group. The effectiveness analysis consisted of the comparison of the upper bound of the 95% confidence interval (CI) of the mean Clinical Global Impression-Improvement (CGI-I) score to 4 (no change) at the end of the study. Results At the baseline, the aripiprazole group (n=135) and the non-aripiprazole group (n=31) were comparable with respect to their mean ages, gender distribution, baseline Positive and Negative Syndrome Scale scores, and Clinical Global Impression-Severity (CGI-S) scores. The study showed that the mean CGI-I score was 2.92 (95% CI: 2.72-3.12) in the aripiprazole group and 2.81 (95% CI: 2.35-3.26) in the non-aripiprazole group at 26 weeks. In the aripiprazole group, the remission rates at 12 and 26 weeks were 74.8% and 72.6%, respectively, and 80.2% of the patients with remission at 12 weeks maintained their remission state until the end of the study. About one-fourth of the patients in the aripiprazole group reported one or more spontaneous treatment-emergent adverse events, such as insomnia, headache, and nausea. Conclusion This study suggested that most clinically stable outpatients with schizophrenia maintain their remission states after being switched to aripiprazole, without serious symptom aggravation and adverse events over a course of 26 weeks. Psychiatry Investig 2010;7:189-195This study was supported by Korea Otsuka Pharmaceuticals (KOP 010402).Kim CY, 2009, INT CLIN PSYCHOPHARM, V24, P181, DOI 10.1097/YIC.0b013e32832c25d7Kolotkin RL, 2008, EUR PSYCHIAT, V23, P561, DOI 10.1016/j.eurpsy.2008.01.1421Findling RL, 2008, AM J PSYCHIAT, V165, P1432, DOI 10.1176/appi.ajp.2008.07061035Tandon R, 2008, SCHIZOPHR RES, V100, P20, DOI 10.1016/j.schres.2007.11.033Wolf J, 2007, CURR MED RES OPIN, V23, P2313, DOI 10.1185/030079907X225448Moeller KE, 2006, J CLIN PSYCHIAT, V67, P1942Chrzanowski WK, 2006, PSYCHOPHARMACOLOGY, V189, P259, DOI 10.1007/s00213-006-0564-3Tandon R, 2006, SCHIZOPHR RES, V84, P77, DOI 10.1016/j.schres.2005.12.857Lieberman JA, 2005, NEW ENGL J MED, V353, P1209Kim CY, 2005, J CLIN PSYCHIAT, V66, P887Kasper S, 2003, INT J NEUROPSYCHOPH, V6, P325, DOI 10.1017/S1461145703003651Pigott TA, 2003, J CLIN PSYCHIAT, V64, P1048Potkin SG, 2003, ARCH GEN PSYCHIAT, V60, P681Marder SR, 2003, SCHIZOPHR RES, V61, P123, DOI 10.1016/S0920-9964(03)00050-1Kane JM, 2002, J CLIN PSYCHIAT, V63, P763WEIDEN PJ, 1995, SCHIZOPHRENIA BULL, V21, P419
SALM4 suppresses excitatory synapse development by cis-inhibiting trans-synaptic SALM3-LAR adhesion
Synaptic adhesion molecules regulate various aspects of synapse development, function and plasticity. These functions mainly involve trans-synaptic interactions and positive regulations, whereas cis-interactions and negative regulation are less understood. Here we report that SALM4, a member of the SALM/Lrfn family of synaptic adhesion molecules, suppresses excitatory synapse development through cis inhibition of SALM3, another SALM family protein with synaptogenic activity. Salm4-mutant (Salm4) mice show increased excitatory synapse numbers in the hippocampus. SALM4 cis-interacts with SALM3, inhibits trans-synaptic SALM3 interaction with presynaptic LAR family receptor tyrosine phosphatases and suppresses SALM3-dependent presynaptic differentiation. Importantly, deletion of Salm3 in Salm4 mice (Salm3, Salm4) normalizes the increased excitatory synapse number. These results suggest that SALM4 negatively regulates excitatory synapses via cis inhibition of the trans-synaptic SALM3-LAR adhesion. ยฉ The Author(s) 2016110101sciescopu
Elucidation of Akkermansia muciniphila Probiotic Traits Driven by Mucin Depletion
Akkermansia muciniphila is widely considered a next-generation beneficial microbe. This bacterium resides in the mucus layer of its host and regulates intestinal homeostasis and intestinal barrier integrity by affecting host signaling pathways. However, it remains unknown how the expression of genes encoding extracellular proteins is regulated in response to dynamic mucosal environments. In this study, we elucidated the effect of mucin on the gene expression and probiotic traits of A. muciniphila. Transcriptome analysis showed that the genes encoding most mucin-degrading enzymes were significantly upregulated in the presence of mucin. By contrast, most genes involved in glycolysis and energy metabolic pathways were upregulated under mucin-depleted conditions. Interestingly, the absence of mucin resulted in the upregulation of 79 genes encoding secreted protein candidates, including Amuc-1100 as well as members of major protein secretion systems. These transcript level changes were consistent with the fact that administration of A. muciniphila grown under mucin-depleted conditions to high-fat diet-induced diabetic mice reduced obesity and improved intestinal barrier integrity more efficiently than administration of A. muciniphila grown under mucin-containing conditions. In conclusion, mucin content in the growth medium plays a critical role in the improvement by A. muciniphila of high-fat diet-induced obesity, intestinal inflammation, and compromised intestinal barrier integrity related to a decrease in goblet cell density. Our findings suggest the depletion of animal-derived mucin in growth medium as a novel principle for the development of A. muciniphila for human therapeutics
Intravascular Ultrasound-Guided Troubleshooting in a Large Hematoma Treated With Fenestration Using a Cutting Balloon
Intramural hematoma formation is not a well-studied complication of percutaneous coronary intervention. We describe a patient with stable angina who developed an intramural hematoma during elective percutaneous coronary intervention (PCI) in the right coronary artery (RCA). Total occlusion with dense dye staining developed a long way from the distal RCA, near the posterior descending artery bifurcation site. The true lumen was compressed by the enlarged, tense, false lumen. The patient was successfully treating with intravascular ultrasound-guided fenestration using a cutting balloon, and a stent was implanted in the distal RCA
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