The clinical genetics of multiple endocrine neoplasia type 1 in Chinese

published_or_final_versio

High-intensity focused ultrasound for hepatocellular carcinoma: A single-center experience

Objective: This study aims to evaluate the outcome of patients with hepatocellular carcinoma (HCC) treated by high-intensity focused ultrasound (HIFU) in a single tertiary referral center. Background: HIFU is the latest developed local ablation technique for unresectable HCC. The initial experience on its efficacy is promising, but the survival benefit of patients undergoing HIFU for HCC is poorly defined. Methods: From October 2006 to December 2008, 49 patients received HIFU for unresectable HCC. Each patient underwent a single session of HIFU with a curative intent. Treatment efficacy and survival outcome were evaluated. Clinicopathologic factors affecting the primary technique effectiveness and overall survival rates were investigated by univariate analysis. Results: The median size of the treated tumors was 2.2 cm, ranging from 0.9 to 8 cm. The majority of patients had single tumors (n = 41, 83.6%). Thirty-one patients (63.2%) had artificial right pleural effusion during HIFU treatment to reduce damage to the lung and diaphragm. The hospital mortality rate was 2% (n = 1) and the complication rate was 8.1% (n = 4). The primary technique effectiveness rate was 79.5% (39 of 49 patients). It increased from 66.6% in the initial series to 89.2% in the last 28 patients. Tumor size (3.0 cm) was the significant risk factor affecting the complete ablation rate. The 1- and 3-year overall survival rates were 87.7% and 62.4%, respectively. Child-Pugh liver function grading was the significant prognostic factor influencing the overall survival rate. Conclusions: HIFU is an effective treatment modality for unresectable HCC with a high technique effectiveness rate and favorable survival outcome. © 2011 Lippincott Williams & Wilkins.postprin

Chronic kidney-disease screening service quality: questionnaire survey research evidence from Taichung city

<p>Abstract</p> <p>Background</p> <p>Chronic kidney disease (CKD) is a serious public health problem in Taiwan and the world. The most effective, affordable treatments involve early prevention/detection/intervention, requiring screening. Successfully implementing CKD programs requires good patient participation, affected by patient perceptions of screening service quality. Service quality improvements can help make such programs more successful. Thus, good tools for assessing service quality perceptions are important. Aim: to investigate using a modified SERVQUAL questionnaire in assessing patient expectations, perceptions, and loyalty towards kidney disease screening service quality.</p> <p>Method</p> <p>1595 kidney disease screening program patients in Taichung City were requested to complete and return a modified kidney disease screening SERVQUAL questionnaire. 1187 returned them. Incomplete ones (102) were culled and 1085 were chosen as effective for use. Paired t-tests, correlation tests, ANOVA, LSD test, and factor analysis identified the characteristics and factors of service quality. The paired t-test tested expectation score and perception score gaps. A structural equation modeling system examined satisfaction-based components' relationships.</p> <p>Results</p> <p>The effective response rate was 91.4%. Several methods verified validity. Cronbach's alpha on internal reliability was above 0.902. On patient satisfaction, expectation scores are high: 6.50 (0.82), but perception scores are significantly lower 6.14 (1.02). Older patients' perception scores are lower than younger patients'. Expectation and perception scores for patients with different types of jobs are significantly different. Patients higher on education have lower scores for expectation (r = -0.09) and perception (r = -0.26). Factor analysis identified three factors in the 22 item SERVQUAL form, which account for 80.8% of the total variance for the expectation scores and 86.9% of the total variance for the satisfaction scores. Expectation and perception score gaps in all 22 items are significant. The goodness-of-fit summary of the SEM results indicates that expectations and perceptions are positively correlated, perceptions and loyalty are positively correlated, but expectations and loyalty are not positively correlated.</p> <p>Conclusions</p> <p>The results of this research suggest that the SERVQUAL instrument is a useful measurement tool in assessing and monitoring service quality in kidney disease screening services, enabling the staff to identify where service improvements are needed from the patients' perspectives.</p

Autophagy and Exosomes in the Aged Retinal Pigment Epithelium: Possible Relevance to Drusen Formation and Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a major cause of loss of central vision in the elderly. The formation of drusen, an extracellular, amorphous deposit of material on Bruch's membrane in the macula of the retina, occurs early in the course of the disease. Although some of the molecular components of drusen are known, there is no understanding of the cell biology that leads to the formation of drusen. We have previously demonstrated increased mitochondrial DNA (mtDNA) damage and decreased DNA repair enzyme capabilities in the rodent RPE/choroid with age. In this study, we found that drusen in AMD donor eyes contain markers for autophagy and exosomes. Furthermore, these markers are also found in the region of Bruch's membrane in old mice. By in vitro modeling increased mtDNA damage induced by rotenone, an inhibitor of mitochondrial complex I, in the RPE, we found that the phagocytic activity was not altered but that there were: 1) increased autophagic markers, 2) decreased lysosomal activity, 3) increased exocytotic activity and 4) release of chemoattractants. Exosomes released by the stressed RPE are coated with complement and can bind complement factor H, mutations of which are associated with AMD. We speculate that increased autophagy and the release of intracellular proteins via exosomes by the aged RPE may contribute to the formation of drusen. Molecular and cellular changes in the old RPE may underlie susceptibility to genetic mutations that are found in AMD patients and may be associated with the pathogenesis of AMD in the elderly

Metabolic syndrome is associated with change in subclinical arterial stiffness - A community-based Taichung Community Health Study

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to evaluate the effect of MetS on arterial stiffness in a longitudinal study.</p> <p>Methods</p> <p>Brachial-ankle pulse wave velocity (baPWV), a measurement interpreted as arterial stiffness, was measured in 1518 community-dwelling persons at baseline and re-examined within a mean follow-up period of 3 years. Multivariate linear regression with generalized estimating equations (GEE) were used to examine the longitudinal relationship between MetS and its individual components and baPWV, while multivariate logistic regression with GEE was used to examine the longitudinal relationship between MetS and its individual components and the high risk group with arterial stiffness.</p> <p>Results</p> <p>Subjects with MetS showed significantly greater baPWV at the end point than those without MetS, after adjusting for age, gender, education, hypertension medication and mean arterial pressure (MAP). MetS was associated with the top quartile of baPWV (the high-risk group of arterial stiffness, adjusted odds ratio [95% confidence interval] 1.52 [1.21-1.90]), and a significant linear trend of risk for the number of components of MetS was found (p for trend < 0.05). In further considering the individual MetS component, elevated blood pressure and fasting glucose significantly predicted a high risk of arterial stiffness (adjusted OR [95% CI] 3.72 [2.81-4.93] and 1.35 [1.08-1.68], respectively).</p> <p>Conclusions</p> <p>MetS affects the subject's progression to arterial stiffness. Arterial stiffness increased as the number of MetS components increased. Management of MetS is important for preventing the progression to advanced arterial stiffness.</p

Restricted Genetic Diversity of HIV-1 Subtype C Envelope Glycoprotein from Perinatally Infected Zambian Infants

Background: Mother-to-child transmission of HIV-1 remains a significant problem in the resource-constrained settings where anti-retroviral therapy is still not widely available. Understanding the earliest events during HIV-1 transmission and characterizing the newly transmitted or founder virus is central to intervention efforts. In this study, we analyzed the viral env quasispecies of six mother-infant transmission pairs (MIPs) and characterized the genetic features of envelope glycoprotein that could influence HIV-1 subtype C perinatal transmission. Methodology and Findings: The V1-V5 region of env was amplified from 6 MIPs baseline samples and 334 DNA sequences in total were analyzed. A comparison of the viral population derived from the mother and infant revealed a severe genetic bottleneck occurring during perinatal transmission, which was characterized by low sequence diversity in the infant. Phylogenetic analysis indicates that most likely in all our infant subjects a single founder virus was responsible for establishing infection. Furthermore, the newly transmitted viruses from the infant had significantly fewer potential N-linked glycosylation sites in Env V1-V5 region and showed a propensity to encode shorter variable loops compared to the nontransmitted viruses. In addition, a similar intensity of selection was seen between mothers and infants with a higher rate of synonymous (dS) compared to nonsynonymous (dN) substitutions evident (dN/dS\u3c1). Conclusions: Our results indicate that a strong genetic bottleneck occurs during perinatal transmission of HIV-1 subtype C. This is evident through population diversity and phylogenetic patterns where a single viral variant appears to be responsible for infection in the infants. As a result the newly transmitted viruses are less diverse and harbored significantly less glycosylated envelope. This suggests that viruses with the restricted glycosylation in envelope glycoprotein appeared to be preferentially transmitted during HIV-1 subtype C perinatal transmission. In addition, our findings also indicated that purifying selection appears to predominate in shaping the early intrahost evolution of HIV-1 subtype C envelope sequences

A multidisciplinary systematic review of the use of diagrams as a means of collecting data from research subjects: application, benefits and recommendations

BACKGROUND: In research, diagrams are most commonly used in the analysis of data and visual presentation of results. However there has been a substantial growth in the use of diagrams in earlier stages of the research process to collect data. Despite this growth, guidance on this technique is often isolated within disciplines. METHODS: A multidisciplinary systematic review was performed, which included 13 traditional healthcare and non-health-focused indexes, non-indexed searches and contacting experts in the field. English-language articles that used diagrams as a data collection tool and reflected on the process were included in the review, with no restriction on publication date. RESULTS: The search identified 2690 documents, of which 80 were included in the final analysis. The choice to use diagrams for data collection is often determined by requirements of the research topic, such as the need to understand research subjects' knowledge or cognitive structure, to overcome cultural and linguistic differences, or to understand highly complex subject matter. How diagrams were used for data collection varied by the degrees of instruction for, and freedom in, diagram creation, the number of diagrams created or edited and the use of diagrams in conjunction with other data collection methods. Depending on how data collection is structured, a variety of options for qualitative and quantitative analysis are available to the researcher. The review identified a number of benefits to using diagrams in data collection, including the ease with which the method can be adapted to complement other data collection methods and its ability to focus discussion. However it is clear that the benefits and challenges of diagramming depend on the nature of its application and the type of diagrams used. DISCUSSION/CONCLUSION: The results of this multidisciplinary systematic review examine the application of diagrams in data collection and the methods for analyzing the unique datasets elicited. Three recommendations are presented. Firstly, the diagrammatic approach should be chosen based on the type of data needed. Secondly, appropriate instructions will depend on the approach chosen. And thirdly, the final results should present examples of original or recreated diagrams. This review also highlighted the need for a standardized terminology of the method and a supporting theoretical framework

Linking Proteomic and Transcriptional Data through the Interactome and Epigenome Reveals a Map of Oncogene-induced Signaling

Cellular signal transduction generally involves cascades of post-translational protein modifications that rapidly catalyze changes in protein-DNA interactions and gene expression. High-throughput measurements are improving our ability to study each of these stages individually, but do not capture the connections between them. Here we present an approach for building a network of physical links among these data that can be used to prioritize targets for pharmacological intervention. Our method recovers the critical missing links between proteomic and transcriptional data by relating changes in chromatin accessibility to changes in expression and then uses these links to connect proteomic and transcriptome data. We applied our approach to integrate epigenomic, phosphoproteomic and transcriptome changes induced by the variant III mutation of the epidermal growth factor receptor (EGFRvIII) in a cell line model of glioblastoma multiforme (GBM). To test the relevance of the network, we used small molecules to target highly connected nodes implicated by the network model that were not detected by the experimental data in isolation and we found that a large fraction of these agents alter cell viability. Among these are two compounds, ICG-001, targeting CREB binding protein (CREBBP), and PKF118–310, targeting β-catenin (CTNNB1), which have not been tested previously for effectiveness against GBM. At the level of transcriptional regulation, we used chromatin immunoprecipitation sequencing (ChIP-Seq) to experimentally determine the genome-wide binding locations of p300, a transcriptional co-regulator highly connected in the network. Analysis of p300 target genes suggested its role in tumorigenesis. We propose that this general method, in which experimental measurements are used as constraints for building regulatory networks from the interactome while taking into account noise and missing data, should be applicable to a wide range of high-throughput datasets.National Science Foundation (U.S.) (DB1-0821391)National Institutes of Health (U.S.) (Grant U54-CA112967)National Institutes of Health (U.S.) (Grant R01-GM089903)National Institutes of Health (U.S.) (P30-ES002109

On the Origin of the Functional Architecture of the Cortex

The basic structure of receptive fields and functional maps in primary visual cortex is established without exposure to normal sensory experience and before the onset of the critical period. How the brain wires these circuits in the early stages of development remains unknown. Possible explanations include activity-dependent mechanisms driven by spontaneous activity in the retina and thalamus, and molecular guidance orchestrating thalamo-cortical connections on a fine spatial scale. Here I propose an alternative hypothesis: the blueprint for receptive fields, feature maps, and their inter-relationships may reside in the layout of the retinal ganglion cell mosaics along with a simple statistical connectivity scheme dictating the wiring between thalamus and cortex. The model is shown to account for a number of experimental findings, including the relationship between retinotopy, orientation maps, spatial frequency maps and cytochrome oxidase patches. The theory's simplicity, explanatory and predictive power makes it a serious candidate for the origin of the functional architecture of primary visual cortex