Selective amyloid-β lowering agents

The amyloid-β peptide (Aβ), implicated in the pathogenesis of Alzheimer's disease (AD), is produced through sequential proteolysis of the Aβ precursor protein (APP) by β- and γ-secretases. Thus, blocking either of these two proteases, directly or indirectly, is potentially worthwhile toward developing AD therapeutics. β-Secretase is a membrane-tethered pepsin-like aspartyl protease suitable for structure-based design, whereas γ-secretase is an unusual, heterotetrameric membrane-embedded aspartyl protease. While γ-secretase inhibitors entered clinical trials first due to their superior pharmacological properties (for example, brain penetration) over β-secretase inhibitors, it has since become clear that γ-secretase inhibitors can cause mechanism-based toxicities owing to interference with the proteolysis of another γ-secretase substrate, the Notch receptor. Strategies for targeting Aβ production at the γ-secretase level without blocking Notch signalling will be discussed. Other strategies utilizing cell-based screening have led to the identification of novel Aβ lowering agents that likewise leave Notch proteolysis intact. The mechanism by which these agents lower Aβ is unknown, but these compounds may ultimately reveal new targets for AD therapeutics

Chromosomal-level assembly of the Asian Seabass genome using long sequence reads and multi-layered scaffolding

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics

Massive variceal bleeding secondary to splenic vein thrombosis successfully treated with splenic artery embolization: a case report

<p>Abstract</p> <p>Introduction</p> <p>Splenic vein thrombosis results in localized portal hypertension called sinistral portal hypertension, which may also lead to massive upper gastrointestinal bleeding. Symptomatic sinistral portal hypertension is usually best treated by splenectomy, but interventional radiological techniques are safe and effective alternatives in the management of a massive hemorrhage, particularly in cases that have a high surgical risk.</p> <p>Case presentation</p> <p>We describe a 23-year-old Greek man with acute massive gastric variceal bleeding caused by splenic vein thrombosis due to a missing von Leiden factor, which was successfully managed with splenic arterial embolization.</p> <p>Conclusions</p> <p>Interventional radiological techniques are attractive alternatives for patients with a high surgical risk or in cases when the immediate surgical excision of the spleen is technically difficult. Additionally, surgery is not always successful because of the presence of numerous portal collaterals and adhesion. Splenic artery embolization is now emerging as a safe and effective alternative to surgery in the management of massive hemorrhage from gastric varices due to splenic vein thrombosis, which often occurs in patients with hypercoagulability.</p

Fluorescence in-situ hybridisation on biopsies from clam ileocystoplasties and on a clam cancer

The incidence of carcinoma following an enterocystoplasty increases with time and is a major concern after such procedures. The aim of this study was to investigate genetic instability (in the form of numerical chromosomal aberrations) at the enterovesical anastomosis in patients who had undergone a clam ileocystoplasty using fluorescent in-situ hybridisation (FISH). Fluorescent in-situ hybridisation was performed on touch preparation samples prepared from fresh endoscopic biopsies obtained from the enterovesical anastomosis and native bladder remnant (control specimens) of 15 patients who had undergone a clam ileocystoplasty. Fluorescent in-situ hybridisation was also performed on one squamous cell cancer specimen. Significant aneusomic changes were found at the enterovesical anastomosis in all 15 patients. Alterations in chromosome 18 copy number were the most frequent abnormal finding (trisomy 18, n=8; monosomy 18, n=7). Nine patients were monosomic for chromosome 9. Isolated monosomy 8 and trisomy 8 were each found in one patient. The control specimens were all normal. An unusually high incidence of polysomic cells was found in the clam tumour specimen, reflecting the aggressive nature of this cancer. Chromosomal numerical abnormalities occur at the enterovesical anastomosis following a clam ileocystoplasty and chromosome 18 appears to be a particularly good marker of genetic instability. The results of this study indicate that morphologically normal tissue obtained from the enterovesical anastomosis displays evidence of chromosomal instability that may predispose to tumour formation. However, further prospective, blinded, longitudinal studies are required to establish whether predetermined FISH signal patterns in enterocystoplasty cells in urine or obtained by biopsy predict the presence or absence of tumour

Predicting the demand of physician workforce: an international model based on "crowd behaviors"

<p>Abstract</p> <p>Background</p> <p>Appropriateness of physician workforce greatly influences the quality of healthcare. When facing the crisis of physician shortages, the correction of manpower always takes an extended time period, and both the public and health personnel suffer. To calculate an appropriate number of Physician Density (PD) for a specific country, this study was designed to create a PD prediction model, based on health-related data from many countries.</p> <p>Methods</p> <p>Twelve factors that could possibly impact physicians' demand were chosen, and data of these factors from 130 countries (by reviewing 195) were extracted. Multiple stepwise-linear regression was used to derive the PD prediction model, and a split-sample cross-validation procedure was performed to evaluate the generalizability of the results.</p> <p>Results</p> <p>Using data from 130 countries, with the consideration of the correlation between variables, and preventing multi-collinearity, seven out of the 12 predictor variables were selected for entry into the stepwise regression procedure. The final model was: PD = (5.014 - 0.128 × proportion under age 15 years + 0.034 × life expectancy)², with R²of 80.4%. Using the prediction equation, 70 countries had PDs with "negative discrepancy", while 58 had PDs with "positive discrepancy".</p> <p>Conclusion</p> <p>This study provided a regression-based PD model to calculate a "norm" number of PD for a specific country. A large PD discrepancy in a country indicates the needs to examine physician's workloads and their well-being, the effectiveness/efficiency of medical care, the promotion of population health and the team resource management.</p

The growth in newspaper coverage of tobacco control in China, 2000-2010

<p>Abstract</p> <p>Background</p> <p>Media coverage of tobacco-related issues can potentially shape individual beliefs, attitudes and behaviors about tobacco use. This study aims to describe news coverage of tobacco control related issues in Chinese newspapers from 2000 to 2010.</p> <p>Methods</p> <p>All 1149 articles related to tobacco control were extracted from the Database of Chinese Important Newspapers and content analyzed for the period Jan 1, 2000 to Dec 31, 2010. The changing pattern of tobacco control topic, article type, viewpoint, and article origin, and their relationship were analysed.</p> <p>Results</p> <p>News coverage of tobacco control related issues increased significantly (<it>p </it>< 0.01) from 2000 to 2010, with news coverage being relatively intensive in May and June (<it>p </it>< 0.01), around World No Tobacco Day. 24.9% (n = 286) of all articles focused on secondhand smoke, 25.3% (n = 291) warned about the dangers of active smoking, and 10.0% (n = 115) focused on prevention and cessation programs and campaigns. Tobacco control topics varied significantly between national vs city/regional newspapers (<it>χ</it>²= 24.09, <it>p </it>= 0.002) and article types (<it>χ</it>²= 193.35, <it>p </it>< 0.001). Articles in national newspapers had more coverage of the dangers of tobacco and on enforcing bans on tobacco-advertising. News stories centered around monitoring tobacco use and smoke free activity, while editorials focused on enforcing bans on tobacco-advertising, youth access and programs and campaigns. Letters to editors focused on the dangers of smoking, raising tax, and smoking cessation. More articles (50.4%) took an anti-tobacco position (compared with 10.5% which were pro-smoking), with the amount of negative coverage growing significantly across the decade. National articles tended to lean toward anti-tobacco, however, local articles tended mix of pro-tobacco and neutral/balance positions. Editorials seemed to be more anti-tobacco oriented, but letters to the editor tended to show a mix of anti-tobacco and pro-tobacco positions.</p> <p>Conclusion</p> <p>Chinese newspapers are giving increasing attention to tobacco control, but coverage remains lower than in the USA and Australia. Health workers need to give higher priority to efforts to increase news coverage beyond the present concentration around World No Tobacco Day and to develop strategies for making tobacco control issues more newsworthy to both national and local news outlets.</p

A First Generation Microsatellite- and SNP-Based Linkage Map of Jatropha

Jatropha curcas is a potential plant species for biodiesel production. However, its seed yield is too low for profitable production of biodiesel. To improve the productivity, genetic improvement through breeding is essential. A linkage map is an important component in molecular breeding. We established a first-generation linkage map using a mapping panel containing two backcross populations with 93 progeny. We mapped 506 markers (216 microsatellites and 290 SNPs from ESTs) onto 11 linkage groups. The total length of the map was 1440.9 cM with an average marker space of 2.8 cM. Blasting of 222 Jatropha ESTs containing polymorphic SSR or SNP markers against EST-databases revealed that 91.0%, 86.5% and 79.2% of Jatropha ESTs were homologous to counterparts in castor bean, poplar and Arabidopsis respectively. Mapping 192 orthologous markers to the assembled whole genome sequence of Arabidopsis thaliana identified 38 syntenic blocks and revealed that small linkage blocks were well conserved, but often shuffled. The first generation linkage map and the data of comparative mapping could lay a solid foundation for QTL mapping of agronomic traits, marker-assisted breeding and cloning genes responsible for phenotypic variation