Dengue virus type 3 genotype III (DENV-3/III) is widely distributed in most dengue-endemic regions. It emerged in Malaysia in 2008 and autochthonously spread in the midst of endemic DENV-3/I circulation. The spread, however, was limited and the virus did not cause any major outbreak. Spatiotemporal distribution study of DENV-3 over the period between 2005 and 2011 revealed that dengue cases involving DENV-3/III occurred mostly in areas without pre-existing circulating DENV-3. Neutralisation assays performed using sera of patients with the respective infection showed that the DENV-3/III viruses can be effectively neutralised by sera of patients with DENV-3 infection (50% foci reduction neutralisation titres (FRNT50) > 1300). Sera of patients with DENV-1 infection (FRNT50 ⩾ 190), but not sera of patients with DENV-2 infection (FRNT50 ⩽ 50), were also able to neutralise the virus. These findings highlight the possibility that the pre-existing homotypic DENV-3 and the cross-reacting heterotypic DENV-1 antibody responses could play a role in mitigating a major outbreak involving DENV-3/III in the Klang Valley, Malaysia.
D-amino acid oxidase (DAO) is a flavoenzyme that metabolizes D-amino acids by oxidative deamination, producing hydrogen peroxide (H2O2) as a by-product. The generation of intracellular H2O2 may alter the redox-homeostasis mechanism of cells and increase the oxidative stress levels in tissues, associated with the pathogenesis of age-related diseases and organ decline. This study investigates the effect of DAO knockdown using clustered regularly interspaced short palindromic repeats (CRISPR) through an in silico approach on its protein-protein interactions (PPIs) and their potential roles in the process of aging. The target sequence and guide RNA of DAO were designed using the CCTop database, PPI analysis using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, Reactome biological pathway, protein docking using GalaxyTongDock database, and structure analysis. The translated target sequence of DAO lies between amino acids 43 to 50. The 10 proteins that were predicted to interact with DAO are involved in peroxisome pathways such as acyl-coenzyme A oxidase 1 (ACOX1), alanine-glyoxylate and serine-pyruvate aminotransferase (AGXT), catalase (CAT), carnitine O-acetyltransferase (CRAT), glyceronephosphate O-acyltransferase (GNPAT), hydroxyacid oxidase 1 (HAO1), hydroxyacid oxidase 2 (HAO2), trans-L-3-hydroxyproline dehydratase (L3HYPDH), polyamine oxidase (PAOX), and pipecolic acid and sarcosine oxidase (PIPOX). In summary, DAO mutation would most likely reduce activity with its interacting proteins that generate H2O2. However, DAO mutation may result in peroxisomal disorders, and thus, alternative techniques should be considered for an in vivo approach.
Necrotizing fasciitis is a limb- and life-threatening rapidly spreading infection affecting the deep fascia with secondary necrosis of the subcutaneous tissue. It requires immediate medical attention and emergency surgery to prevent morbidity and death. This study was undertaken to determine its co-morbidity and risk factors affecting the outcome of its surgical treatment. This is a retrospective review of 36 cases of necrotizing fasciitis of the lower limb treated in our center between 1998 and 2002. Only 19% of the cases were correctly diagnosed upon admission and 48.6% were initially diagnosed as 'cellulitis'. Diabetes mellitus was the most common co-morbid. Pseudomonas, Staphylococcus, Streptococcus and Enterobactericae were the common pathogens isolated. Ten patients (27.8%) had major amputation as part of radical debridement. The overall mortality rate was 36% with laboratory parameters: high serum urea and creatinine, and low haemoglobin levels were predictors for higher mortality. Poor white cell response which is common in diabetic patients and a delay in surgical debridement were. notable attributes to a higher mortality. Necrotizing fasciitis is a serious infection associated with significant morbidity and mortality. A poor white blood cell response, high serum urea and creatinine, and low haemoglobin level were the predictors for mortality. Early diagnosis and prompt treatment are of paramount importance in the treatment of this infection.