Deletions of Chromosome 1p and 15q are Associated with Aggressiveness of Gastrointestinal Stromal Tumors

Background/PurposeSite-dependent profiles of chromosome imbalances (CIs) have been reported in gastrointestinal stromal tumors (GISTs). However, the role of specific CIs in association with metastasis is not clear.MethodsThirteen resected liver metastatic GISTs, including seven from the stomach and six from the small intestine, were analyzed using comparative genomic hybridization (CGH). The CIs associated with metastatic risk were assessed by comparing them with those identified in our previous study of 25 primary GISTs, including 14 from the stomach and 11 from the small intestine.ResultsSynchronous detection of liver metastasis was found more often in patients with intestinal than gastric GIST (5/6 vs. 2/7, p = 0.048). When compared with the primary tumors, the CI profile of liver metastases was similar in the intestinal group, but became more complex in the gastric group. Deletions of chromosomes 1p and 15q were very common (> 80%) in primary and metastatic tumors of the intestinal group, and exhibited a trend towards increase in the metastatic tumors of the gastric group. Both groups had a doubling in the frequency of 22q deletion in the liver metastases, which was not significantly different. Other CIs, including 9p deletion, increased significantly in the liver metastases of the gastric group, but not in the intestinal group.ConclusionOur results, together with clinical findings, indicated a CGH profile associated with the intrinsic aggressiveness of the GISTs. Deletion of 1p and 15q play a critical role in the acquisition of aggressiveness during early GIST development

Multiplex PCR System for Rapid Detection of Pathogens in Patients with Presumed Sepsis – A Systemic Review and Meta-Analysis

Background: Blood culture is viewed as the golden standard for the diagnosis of sepsis but suffers from low sensitivity and long turnaround time. LightCycler SeptiFast (LC-SF) is a real-time multiplex polymerase chain reaction test able to detect 25 common pathogens responsible for bloodstream infections within hours. We aim to assess the accuracy of LC-SF by systematically reviewing the published studies. Method Related literature on Medline, Embase, and Cochrane databases was searched up to October 2012 for studies utilizing LC-SF to diagnose suspected sepsis and that provided sufficient data to construct two-by-two tables. Results: A total of 34 studies enrolling 6012 patients of suspected sepsis were included. The overall sensitivity and specificity for LC-SF to detect bacteremia or fungemia was 0·75 (95% CI: 0·65–0·83) and 0·92 (95%CI:0·90–0·95), respectively. LC-SF had a high positive likelihood ratio (10·10) and a moderate negative likelihood ratio (0·27). Specifically, LC-SF had a sensitivity of 0·80 (95%CI: 0·70–0·88) and a specificity of 0·95(95%CI: 0·93–0·97) for the bacteremia outcome, and a sensitivity of 0·61 (95%CI: 0·48–0·72) and a specificity of 0·99 (95%CI: 0·99–0·99) for the fungemia outcome. High heterogeneity was found in the bacteremia outcome subgroup but not in the fungemia outcome subgroup. Conclusion: LC-SF is of high rule-in value for early detection of septic patients. In a population with low pretest probability, LC-SF test can still provide valuable information for ruling out bacteremia or fungemia

Efficacy and safety of nanohybrids comprising silver nanoparticles and silicate clay for controlling Salmonella infection

Developing effective and safe drugs is imperative for replacing antibiotics and controlling multidrug-resistant microbes. Nanoscale silicate platelet (NSP) and its nanohybrid, silver nanoparticle/NSP (AgNP/NSP), have been developed, and the nanohybrids show a strong and general antibacterial activity in vitro. Here, their efficacy for protecting Salmonella-infected chicks from fatality and septicemia was evaluated. Both orally administrated NSP and AgNP/NSP, but not AgNPs alone, effectively reduced the systemic Salmonella infection and mortality. In addition, quantitative Ag analyses demonstrated that Ag deposition from AgNP/NSP in the intestines was less than that from conventional AgNPs, indicating that the presence of NSP for immobilizing AgNPs reduced Ag accumulation in tissue and improved the safety of AgNPs. These in vivo results illustrated that both NSP and AgNP/NSP nanohybrid represent potential agents for controlling enteric bacterial infections

Non-invasive and transdermal measurement of blood uric acid level in human by electroporation and reverse iontophoresis

The aim of this study was to find out the optimum combination of electroporation (EP) and reverse iontophoresis (RI) on noninvasive and transdermal determination of blood uric acid level in humans. EP is the use of high-voltage electric pulse to create nano-channels on the stratum corneum, temporarily and reversibly. RI is the use of small current to facilitate both charged and uncharged molecule transportation across the skin. It is believed that the combination of these two techniques has additional benefits on the molecules’ extraction across the human skin. In vitro studies using porcine skin and diffusion cell have indicated that the optimum mode for transdermal uric acid extraction is the combination of RI with symmetrical biphasic direct current (current density = 0.3 mA/cm2; phase duration = 180 s) and EP with 10 pulses per second (voltage = 100 V/cm2; pulse width = 1 ms). This optimum mode was applied to six human subjects. Uric acid was successfully extracted through the subjects’ skin into the collection solution. A good correlation (r2 = 0.88) between the subject’s blood uric acid level and uric acid concentrations in collection solutions was observed. The results suggest that it may be possible to noninvasively and transdermally determine blood uric acid levels

Dual Supramolecular Nanoparticle Vectors Enable CRISPR/Cas9-Mediated Knockin of Retinoschisin 1 Gene-A Potential Nonviral Therapeutic Solution for X-Linked Juvenile Retinoschisis.

The homology-independent targeted integration (HITI) strategy enables effective CRISPR/Cas9-mediated knockin of therapeutic genes in nondividing cells in vivo, promising general therapeutic solutions for treating genetic diseases like X-linked juvenile retinoschisis. Herein, supramolecular nanoparticle (SMNP) vectors are used for codelivery of two DNA plasmids-CRISPR-Cas9 genome-editing system and a therapeutic gene, Retinoschisin 1 (RS1)-enabling clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR/Cas9) knockin of the RS1 gene with HITI. Through small-scale combinatorial screenings, two SMNP vectors, with Cas9 and single guide RNA (sgRNA)-plasmid in one and Donor-RS1 and green fluorescent protein (GFP)-plasmid in the other, with optimal delivery performances are identified. These SMNP vectors are then employed for CRISPR/Cas9 knockin of RS1/GFP genes into the mouse Rosa26 safe-harbor site in vitro and in vivo. The in vivo study involves intravitreally injecting the two SMNP vectors into the mouse eyes, followed by repeated ocular imaging by fundus camera and optical coherence tomography, and pathological and molecular analyses of the harvested retina tissues. Mice ocular organs retain their anatomical integrity, a single-copy 3.0-kb RS1/GFP gene is precisely integrated into the Rosa26 site in the retinas, and the integrated RS1/GFP gene is expressed in the retinas, demonstrating CRISPR/Cas9 knockin of RS1/GFP gene

RANKL Is a Downstream Mediator for Insulin-Induced Osteoblastic Differentiation of Vascular Smooth Muscle Cells

Several reports have shown that circulating insulin level is positively correlated with arterial calcification; however, the relationship between insulin and arterial calcification remains controversial and the mechanism involved is still unclear. We used calcifying vascular smooth muscle cells (CVSMCs), a specific subpopulation of vascular smooth muscle cells that could spontaneously express osteoblastic phenotype genes and form calcification nodules, to investigate the effect of insulin on osteoblastic differentiation of CVSMCs and the cell signals involved. Our experiments demonstrated that insulin could promote alkaline phosphatase (ALP) activity, osteocalcin expression and the formation of mineralized nodules in CVSMCs. Suppression of receptor activator of nuclear factor κB ligand (RANKL) with small interfering RNA (siRNA) abolished the insulin-induced ALP activity. Insulin induced the activation of extracellular signal-regulated kinase (ERK)1/2, mitogen-activated protein kinase (MAPK) and RAC-alpha serine/threonine-protein kinase (Akt). Furthermore, pretreatment of human osteoblasts with the ERK1/2 inhibitor PD98059, but not the phosphoinositide 3-kinase (PI3K) inhibitor, LY294002, or the Akt inhibitor, 1L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate (HIMO), abolished the insulin-induced RANKL secretion and blocked the promoting effect of insulin on ALP activities of CVSMCs. Recombinant RANKL protein recovered the ALP activities decreased by RANKL siRNA in insulin-stimulated CVSMCs. These data demonstrated that insulin could promote osteoblastic differentiation of CVSMCs by increased RANKL expression through ERK1/2 activation, but not PI3K/Akt activation

[[alternative]]Co-creating unique value with customers--a study of the artistic coffee shof

[[abstract]]　　隨著台灣經濟成長、消費及生活型態改變，使得國人愈來愈重視飲食文化及生活品質，原於歐美盛行的咖啡風已吹進台灣，喝咖啡不再只是單純的咖啡品嚐，同時亦代表著一種社交行為。尤其，藝文咖啡館經常給予顧客「點一杯咖啡就坐上一整天」的寬容與禮遇，而成為文人墨客高談闊論或激發靈感的重要空間，也因而造就一種與消費者共生共享的獨特空間(例如台北市的明星咖啡館)。因此，本研究依循Prahalad & Ramaswamy (2004)所提出與消費者共創價值的四大基石：溝通(dialogue)、取用(access)、風險評估(risk assessment)、透明(transparency)為主軸，將鎖定其藝文咖啡館進行深度探討,除立意抽樣出18位消費者（包含愛好藝文咖啡館之文人作家與一般消費者），並對其藝文咖啡館經營者進行一對一深度訪談，同時結合研究者本身之參與觀察，試圖從業者與消費者之觀點來探究藝文咖啡館如何與消費者產生互動繼而共創價值，使其營造出獨特之文化特質與消費體驗,期使從研究結果提供業者之經營方針與建議.　　　本研究結果發現：　　1.藝文咖啡館有別於時下連鎖體制下的咖啡館，前者著重在空間情境之感官訴求，後者以標準化、客制化與便利性為主。　　2.進入體驗創新的年代，企業經營走向也朝之顧客導向為主，藝文咖館的業者以其人文、美學為主題來部署經驗舞台並有效的進行市場區隔，有意識的引導消費者在經驗空間裡互動。　　3.藝文咖啡館經營模式，經營出小眾市場的文化主題性，其經營者自身除必備的專業素養外，在與其顧客互動頻繁之際，更要不斷的積極進取。茲因，經營者本身的總總涵養亦牽扯出主流客人對其咖啡館的忠誠度。[[abstract]]　　Taiwan’s growing economy, increasing expenses and societal changes caused a shift towards a ‘diet culture’ that propagates a higher quality of life. Taiwanese people, having adjusted their money spending habits are placing more emphasis on proper diet and an increased quality of life. Imports such as coffee, brought to Taiwan via international trade, have helped to further bring dialogue in public relations. One such relation exists in literary art cafés and coffee shops which engender a courteous and generous reception that allows qualitative discourse between the enterprise and the customer. In such an environment a customer does not feel obliged to make multiple purchases if they are to continue enjoying their visit. Instead customers are allowed to take comfort and inspiration from shop owners’ amiability while enjoying the facility and beverage, having paid for merely one cup. Consequently, these types of cafes serve as gathering spots for social elites such as businesspeople, politicians, lawyers, entertainers and artists; furthermore, they serve as the auspicious workrooms for scholars, journalists, and writers, where the aforementioned may contemplate and draw on their inspirations.The Artistic Cafe has been explored in this research that is based on Prahalad’s and Ramaswamy’s four principles of dialogue, access, risk assessment and transparency. A random sample of eighteen coffee shops has been examined. One-on-one interviews were conducted with shop owners,shop managers, and customers, including writers and artists in order to present the values and prospects from the side of both the consumers and producers.　　　It is our core objective to propose a feasible way for consumers to interact with managers and to provide more-valuable strategies for managers. Our conclusion is as follows:　　1.The Artistic Coffee Shops differ from ordinary ones by their uniqueness in décor, coziness of atmosphere, tranquility in surrounding, appropriateness for social rendezvous, and in the distinction of coffee brands. The latter, regular coffee shops are prone to serving coffee for the convenience of the public only.　　2.We are entering the new era in which enterprises are guided by consumers. The management of the Artistic Coffee Shops is based on humanity and aesthetics in order to set up the stages for experience in segregated markets to effectively and deliberately encourage consumers in the co-operation scheme.　　3.The marketing for the Artistic Coffee Shops is targeting the upper class customers in our society. Gradually, it forms the characteristic of a smaller market culture. That is, we promote customer-owner interaction as the ultimate goal, where we highly value the consumers’ feedback regarding companies’ decision making. Since constant contact with customers is vital for shop managers, it is imperative that shop managers should have not only adequate professional skills, but the articulate social skills to communicate with customers efficiently and intriguingly. Certainly to achieve this, the managers must be kept constantly informed and strike for excellence to enrich themselves with knowledge from various fields incessantly. In being able to do so, we will have our customers pay back their patronages and obligations in return