The epidemiology of pneumococcal carriage and infections in Malaysia

In Malaysia, various aspects of the epidemiology of pneumococcal carriage and disease remain largely unclear due to the lack of supporting data. Although a number of relevant studies have been documented, their individual discrete findings are not sufficient to inform experts on pneumococcal epidemiology at a national level. Therefore, in this review we aim to bring together and systematically evaluate the key information regarding pneumococcal disease epidemiology in Malaysia and provide a comprehensive overview of the data. Major aspects discussed include pneumococcal carriage, disease incidence and prevalence, age factors, invasiveness of pneumococci, serotypes, molecular epidemiology and antibiotic susceptibility. Penicillin resistance is increasingly prevalent and studies suggest that the majority of pneumococcal serotypes causing pneumococcal disease in Malaysia are covered by currently available conjugate vaccines. Continued surveillance is needed to provide a better understanding of pneumococcal epidemiology in Malaysia.     

Inhibitory potential of Quercus lusitanica extract on dengue virus type 2 replication

This study reports the in vitro inhibitory potential of crude extract of Quercus lusitanica (Q. lusitanica) seeds on the replication of dengue virus type 2 (DEN-2). In vitro antiviral activity of Q. lusitanica extract, assessed in C6/36 cells (cloned cells of Aedes albopictus larvae) employing a virus inhibition assay, showed dose-dependent inhibition. The Q. lusitanica extract at its maximum non-toxic concentration of 0.25 mg/ml completely inhibited 10-1,000 TCID50 of virus, as indicated by the absence of cytopathic effect (CPE). The low dose of Q. lusitanica (0.032 mg/ml) showed 100% inhibition with 10 TCID50 of virus, but only 50% and 25% inhibition with 100 and 1,000 TCID50, respectively. The NS1 is a glycoprotein present in all flaviviruses and appears essential for virus viability. To further evaluate Q. lusitanica extract as an antiviral compound, we investigated the effect of Q. lusitanica extract on the NS1 protein expression of infected C6/36 cells through proteomics technique. The result showed downregulation of NS1 protein expression of infected C6/36 cells after treatment with this extract. In conclusion, we found that Q. lusitanica extract has a good inhibitory effect on the replication of dengue virus type 2, both in conventional cell culture and proteomics technique.     

Cartilage oligomeric matrix protein (COMP) in rheumatoid arthritis and its correlation with sonographic knee cartilage thickness and disease activity

Clinical Rheumatology - The aim of the study is to investigate the correlation of serum cartilage oligomeric matrix protein (COMP) levels with articular cartilage damage based on sonographic knee...     

Serological evidence of possible human infection with Tioman virus, a newly described paramyxovirus of bat origin

Tioman virus, a relatively new paramyxovirus, was isolated from fruit bats (Pteropus species) on Tioman Island, Malaysia, in 2001. The objective of this study was to determine the prevalence of antibodies to T. virus in island inhabitants, by use of comparative ELISA and serum neutralization assays. Of the 169 human sera analyzed, 5 (approximately 3.0%) were positive for T. virus, by comparative ELISA. Of these 5 sera, 3 (1.8% of the total) had neutralizing antibodies against T. virus, suggesting previous infection of this study population by this virus or a similar virus.     

Suppression of ERK1/2 and hypoxia pathways by four Phyllanthus species inhibits metastasis of human breast cancer cells

Chemotherapies remain far from ideal due to drug resistance; therefore, novel chemotherapeutic agents with higher effectiveness are crucial. The extracts of four Phyllanthus species, namely Phyllanthus niruri, Phyllanthus urinaria, Phyllanthus watsonii, and Phyllanthus amarus, were shown to induce apoptosis and inhibit metastasis of breast carcinoma cells (MCF-7). The main objective of this study was to determine the pathways utilized by these four Phyllanthus species to exert anti-metastatic activities. A cancer 10-pathway reporter was used to investigate the pathways affected by the four Phyllanthus species. Results indicated that these Phyllanthus species suppressed breast carcinoma metastasis and proliferation by suppressing matrix metalloprotein 2 and 9 expression via inhibition of the extracellular signal-related kinase (ERK) pathway. Additionally, inhibition of hypoxia-inducible factor 1-α in the hypoxia pathway caused reduced vascular endothelial growth factor and inducible nitric oxide synthase expression, resulting in anti-angiogenic effects and eventually anti-metastasis. Two-dimensional gel electrophoresis identified numerous proteins suppressed by these Phyllanthus species, including invasion proteins, anti-apoptotic protein, protein-synthesis proteins, angiogenic and mobility proteins, and various glycolytic enzymes. Our results indicated that ERK and hypoxia pathways are the most likely targets of the four Phyllanthus species for the inhibition of MCF-7 metastasis.     

Two decades of off-label prescribing in children: a literature review

Background

In the past two decades, many legislative and regulatory initiatives were taken globally to improve drug use in children. However, children are still found to be prescribed with off-label drugs. This study was conducted to provide an overview of the worldwide trend in off-label prescribing in children from the year 1996 to 2016.

Data sources

The articles published in PubMed, MEDLINE and Google Scholar were searched using text words: off-label, unlicensed, paediatric and children. Additional articles were identified by reviewing the bibliography of the retrieved articles. Full-text articles published in English which reported on the prevalence of off-label prescribing in children between January 1996 and December 2016 were included.

Results

A total of 101 studies met the inclusion criteria. Off-label prescribing definition included four main categories: age, indication, dose and route of administration. The three most common reference sources used in the studies were summary of product characteristics, national formularies and package inserts. Overall, the off-label prescribing rates in children ranged from 1.2 to 99.7%. The most common category of off-label prescribing in children was dose and age.

Conclusions

This review highlighted that off-label prescribing in children was found to be highly prevalent throughout the past two decades, persistently in the neonatal intensive care units. This suggests that besides legislative and regulatory initiatives, behavioural, knowledge aspects and efforts to integrate evidence into practice related to off-label prescribing also need to be evaluated and consolidated as part of the concerted efforts to narrow the gaps in prescribing for children.

     

Three-dimensional structure of flavocytochrome b2 from baker''s yeast at 3.0-A resolution.

The structure of flavocytochrome b2 from baker's yeast was solved at 3.0-A resolution by the multiple isomorphous replacement method combined with solvent leveling procedures, using data collected from an area detector. The tetramer of Mr 230,000 has 4-fold symmetry. Each subunit contains a cytochrome domain consisting of the first 100 residues, a flavin-binding domain containing the next 386 residues, and an extended C-terminal tail of 25 residues. The cytochrome domain closely resembles microsomal cytochrome b5, whereas the flavin-binding domain contains a parallel beta 8/alpha 8 barrel motif similar to glycolate oxidase and trimethylamine dehydrogenase. Two of the four cytochrome domains are disordered in the crystals. The flavin ring and heme group are separated by about 16 A between their centers, and their planes are inclined by about 17 degrees to each other.