In 1998, an outbreak of acute encephalitis with high mortality rates among pig handlers in Malaysia led to the discovery of a novel paramyxovirus named Nipah virus. A multidisciplinary investigation that included epidemiology, microbiology, molecular biology, and pathology was pivotal in the discovery of this new human infection. Clinical and autopsy findings were derived from a series of 32 fatal human cases of Nipah virus infection. Diagnosis was established in all cases by a combination of immunohistochemistry (IHC) and serology. Routine histological stains, IHC, and electron microscopy were used to examine autopsy tissues. The main histopathological findings included a systemic vasculitis with extensive thrombosis and parenchymal necrosis, particularly in the central nervous system. Endothelial cell damage, necrosis, and syncytial giant cell formation were seen in affected vessels. Characteristic viral inclusions were seen by light and electron microscopy. IHC analysis showed widespread presence of Nipah virus antigens in endothelial and smooth muscle cells of blood vessels. Abundant viral antigens were also seen in various parenchymal cells, particularly in neurons. Infection of endothelial cells and neurons as well as vasculitis and thrombosis seem to be critical to the pathogenesis of this new human disease.
Recent studies indicate that the prevalence of gastroesophageal reflux disease in Asia is either increasing or better recognized. There is a paucity of reliable data on the prevalence of reflux disease in the various races in general and in Malaysia, in particular. The prevalence of erosive esophagitis and Barrett's esophagus in a multiethnic Malaysian population was studied, as well as the relationship of various factors associated with reflux disease. Chinese, Malay, and Indian patients undergoing gastroscopy in a tertiary referral center were assessed for the presence of esophagitis, hiatus hernia, and Barrett's esophagus. Patient demographics and risk factors associated with gastroesophageal reflux disease were also documented. The prevalence of endoscopically documented esophagitis among 1985 patients was 6.1%, the majority of which were mild, Grade I or II (88%). There was a preponderance of Indians with esophagitis, as well as males (P < 0.05) and those with the presence of a hiatus hernia (P < 0.01). Long-segment Barrett's esophagus was found in 1.6% of patients, and short-segment Barrett's in 4.6%. Indians had the highest prevalence of Barrett's esophagus compared with Chinese (P < 0.05) or Malays (P < 0.01). Hiatus hernia and erosive esophagitis were both positively associated with Barrett's metaplasia (P < 0.01). A significant proportion of Malaysian patients undergoing endoscopy has mild reflux esophagitis and Barrett's esophagus. Indian ethnicity and the presence of a hiatus hernia were significantly associated with endoscopic esophagitis and Barrett's metaplasia. These observed racial differences warrant further study.
Epitheliotropic intestinal T-cell lymphoma (EITL, also known as type II enteropathy-associated T-cell lymphoma) is an aggressive intestinal disease with poor prognosis and its molecular alterations have not been comprehensively characterized. We aimed to identify actionable easy-to-screen alterations that would allow better diagnostics and/or treatment of this deadly disease. By performing whole-exome sequencing of four EITL tumor-normal pairs, followed by amplicon deep sequencing of 42 tumor samples, frequent alterations of the JAK-STAT and G-protein-coupled receptor (GPCR) signaling pathways were discovered in a large portion of samples. Specifically, STAT5B was mutated in a remarkable 63% of cases, JAK3 in 35% and GNAI2 in 24%, with the majority occurring at known activating hotspots in key functional domains. Moreover, STAT5B locus carried copy-neutral loss of heterozygosity resulting in the duplication of the mutant copy, suggesting the importance of mutant STAT5B dosage for the development of EITL. Dysregulation of the JAK-STAT and GPCR pathways was also supported by gene expression profiling and further verified in patient tumor samples. In vitro overexpression of GNAI2 mutants led to the upregulation of pERK1/2, a member of MEK-ERK pathway. Notably, inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available.
Intensive research and discussion activities on the Information system success have been found to take place since the past two decades. As systems and technologies are being improved and developed, discussions on their effectiveness and evaluation on their success have been continuously debated by researchers, scholars and practitioners. Besides the major concern on IS effectiveness, factors influencing IS effectiveness are also important. Hence, this study was conducted to investigate the influence of technological factors on Delone and McLean's IS success dimension. Using a survey method, data were gathered from 201 users from four electronic government agencies in Malaysia. The technological factors were represented by IS competency, IS facilities, IS integration, IS structure and user support. The IS success dimensions used in the study were systems quality, information quality, perceived usefulness, and user satisfaction. The findings indicate that all the technological factors are significantly correlated with the four IS success dimensions. The study concludes that the technological factors investigated were very important in ensuring the successful utilization and implementation of information systems in the electronic government agencies.
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