The long QT syndromes: genetic basis and clinical implications

AbstractIt is becoming clear that mutations in the KVLQT1, human “ether-a-go-go” related gene, cardiac voltage-dependent sodium channel gene, minK and MiRP1 genes, respectively, are responsible for the LQT1, LQT2, LQT3, LQT5 and LQT6 variants of the Romano-Ward syndrome, characterized by autosomal dominant transmission and no deafness. The much rarer Jervell-Lange-Nielsen syndrome (with marked QT prolongation and sensorineural deafness) arises when a child inherits mutant KVLQT1 or minK alleles from both parents. In addition, some families are not linked to the known genetic loci. Cardiac voltage-dependent sodium channel gene encodes the cardiac sodium channel, and long QT syndrome (LQTS) mutations prolong action potentials by increasing inward plateau sodium current. The other mutations cause a decrease in net repolarizing current by reducing potassium currents through “dominant negative” or “loss of function” mechanisms. Polymorphic ventricular tachycardia (torsade de pointes) is thought to be initiated by early after- depolarizations in the Purkinje system and maintained by reentry in the myocardium. Clinical presentations vary with the specific gene affected and the specific mutation. Nevertheless, patients with identical mutations can also present differently, and some patients with LQTS mutations may have no manifest baseline phenotype. The question of whether the latter situation is one of high risk for administration of QT prolonging drugs or during myocardial ischemia is under active investigation. More generally, the identification of LQTS genes has provided tremendous new insights for our understanding of normal cardiac electrophysiology and its perturbation in a wide range of conditions associated with sudden death. It seems likely that the approach of applying information from the genetics of uncommon congenital syndromes to the study of common acquired diseases will be an increasingly important one in the next millennium

Development of a DSS to Estimate the Sales for the Retailing Industry in Taiwan

An algorithm is constructed in this study to estimate the market sizes of daily commodity in Taiwan based on the sampled sales information provided by retailer chains. Though retailer chains provide sampled sales information from only small portions of their retailing stores, they expect to receive more valuable processed information from that. As result of this research, a DSS is proposed to compute value-added information from this joint sales information database, namely the estimation information. Through certain public accessible data such number of stores by each chain and retailers’ financial reports, the sampled sales information can be transferred to the market size information of each item in Taiwan. Two similar algorithms are constructed for convenient stores and supermarkets/hypermarkets separately. A simple integration method is used to combine these results. Finally, a DSS is built based on these estimation algorithms and is implemented successfull

BEHAVIOR OF REGULAR TRIANGULAR JOINTS UNDER CYCLIC SHEARING

ABSTRACT Synthetic regular triangular joints made of gypsum plaster were cyclicly sheared to measure asperity degradation and mathematical behavior of regular triangular joints. Laboratory cyclic shear tests were conducted for three joint types under three different normal stresses. Asperity degradation and shear strength of joints were found to be a function of joint roughness, normal stress, shearing displacement and number of loading cycles. Based on the experimental results, mathematical models were developed for evaluation of shear strength in cyclic loading conditions. Comparison of the test results with that of the proposed model, it was found a good agreement was observed

Molecular characterization of two hantavirus strains from different rattus species in Singapore

<p>Abstract</p> <p>Background</p> <p>Hantaviruses cause human disease in endemic regions around the world. Outbreaks of hantaviral diseases have been associated with changes in rodent population density and adaptation to human settlements leading to their proliferation in close proximity to human dwellings. In a parallel study initiated to determine the prevalence of pathogens in Singapore's wild rodent population, 1206 rodents were trapped and screened. The findings established a hantavirus seroprevalence of 34%. This paper describes the molecular characterization of hantaviruses from <it>Rattus norvegicus </it>and <it>Rattus tanezumi</it>, the predominant rodents caught in urban Singapore.</p> <p>Methodology</p> <p>Pan-hanta RT-PCR performed on samples of <it>Rattus norvegicus </it>and <it>Rattus tanezumi </it>indicated that 27 (2.24%) of the animals were positive. sequence analysis of the S and M segments established that two different hantavirus strains circulate in the rodent population of Singapore. Notably, the hantavirus strains found in <it>Rattus norvegicus </it>clusters with other Asian Seoul virus sequences, while the virus strains found in <it>Rattus tanezumi </it>had the highest sequence similarity to the Serang virus from <it>Rattus tanezumi </it>in Indonesia, followed by Cambodian hantavirus isolates and the Thailand virus isolated from <it>Bandicota indica</it>.</p> <p>Conclusions</p> <p>Sequence analysis of the S and M segments of hantavirus strains found in <it>Rattus norvegicus </it>(Seoul virus strain Singapore) and <it>Rattus tanezumi </it>(Serang virus strain Jurong TJK/06) revealed that two genetically different hantavirus strains were found in rodents of Singapore. Evidently, together with Serang, Cambodian and Thailand virus the Jurong virus forms a distinct phylogroup. Interestingly, these highly similar virus strains have been identified in different rodent hosts. Further studies are underway to analyze the public health significance of finding hantavirus strains in Singapore rodents.</p

Novel hybrid vesicles co-assembled from a cationic lipid and PAAc-g-mPEG with pH-triggered transmembrane channels for controlled drug release

This work presents an important example of novel hybrid vesicles with pH-triggered transmembrane channels prepared by co-assembly of poly(acrylic acid)-g-poly(monomethoxy ethylene glycol) (PAAc-g-mPEG) with a cationic lipid, didodecyldimethylammonium bromide (DDAB), via electrostatic interaction for effective doxorubicin (DOX) release

Delayed Suspicion, Treatment and Isolation of Tuberculosis Patients in Pulmonology/Infectious Diseases and Non-Pulmonology/Infectious Diseases Wards

Background/PurposeDelayed diagnosis and isolation increases the risk of nosocomial transmission of tuberculosis (TB). To assess the risk of delayed management of TB, we analyzed the risk factors of prolonged delay in isolation of smear-positive TB patients in pulmonology/infectious diseases and other wards in a tertiary teaching hospital.MethodsWe enrolled smear-positive TB patients aged > 16 years with delayed respiratory isolation following hospitalization. Medical records were reviewed retrospectively. Time intervals between admission, order of sputum acid-fast staining, initiation of anti-tuberculous treatment and isolation were compared between pulmonology/infectious diseases wards (PIWs) and other wards. Risk factors were analyzed in patients with prolonged isolation delay of > 7 days in individual groups.ResultsIsolation was delayed in 191 (73.7%) of 259 hospitalized smear-positive TB patients. Median suspicion, treatment and isolation delays were 0, 3 and 4 days in PIWs and 1, 5 and 7 days in other wards. For patients admitted to non-PIWs, atypical chest radiographs, symptoms without dyspnea or not being admitted from the emergency department (ED) were risk factors for prolonged isolation delay exceeding 7 days. The only risk factor for delayed isolation in patients admitted to PIWs was age ≥ 70 years.ConclusionDelays in suspicion, treatment and isolation of TB patients were longer in non-PIWs. Clinicians should be alert to those admitted to non-PIWs with atypical chest radiographs, atypical symptoms, or not admitted from the ED

Stroke Prevention in Atrial Fibrillation:A Scientific Statement of JACC: Asia (Part 2)

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with substantial increases in the risk for stroke and systemic thromboembolism. With the successful introduction of the first non-vitamin K antagonistdirect oral anticoagulant agent (NOAC) in 2009, the role of vitamin K antagonists has been replaced in most clinical settings except in a few conditions for which NOACs are contraindicated. Data for the use of NOACs in different clinical scenarios have been accumulating in the past decade, and a more sophisticated strategy for patients with AF is now warranted. JACC: Asia recently appointed a working group to summarize the most updated information regarding stroke prevention in AF. The aim of this statement is to provide possible treatment options in daily practice. Local availability, cost, and patient comorbidities should also be considered. Final decisions may still need to be individualized and based on clinicians’ discretion. This is part 2 of the statement