A study of a decade of road traffic accidents in Benghazi-Libya: 2001 to 2010

This paper aims to observe and to study the trends of road traffic accidents (RTA's) for the past ten years in Benghazi-Libya. A retrospective analysis was done using the patient records of Al-Jalaa hospital (the main trauma center in Benghazi) from over 21,753 RTA cases. The annual data were compared to each other and changes of trends were observed. RTA's represented an increasing percentage of Al-Jalaa's case load across the years. Around 41% of these cases needed to undergo surgery. The younger age group (20-29 years of age) formed the majority of cases while there was a trend towards an increasing average age of patients involved in an accident. Male patients were found to be younger than their female counterparts. Males comprised 81.5% while females formed 18.5% of RTA patients. In terms of inpatient duration, most patients stayed in the hospital for less than 1 week. Vehicle occupants (drivers and passengers) were admitted more often than pedestrians. There was a trend across the years towards an increased involvement of vehicle occupants and decrease in the proportion of pedestrians that had to be hospitalized. Additionally, there was a decrease in the fatalities of pedestrians. Overall, most RTA patients were discharged and made to follow-up in outpatient clinics however there was a startling trend towards increased LAMA and absconded patients. There were both encouraging findings as well as points that needed further emphasis and action. Public education, life support training and diversification of transport (apart from the use of the roads) should be looked into, as possible means of improving the current situation.     

Amplification ratio control system for copy number variation genotyping

We describe a generic design for ratiometric analysis suitable for determination of copy number variation (CNV) class of a gene. Following two initial sequence-specific PCR priming cycles, both ends of both amplicons (one test and one reference) in a duplex reaction, are all primed by the same universal primer (UP). Following each amplification denaturation step, the UP target and its reverse complement (UP') in each strand form a hairpin. The bases immediately beyond the 3'-end of the UP and 5' of UP' are chosen such as not to base pair in the hairpin (otherwise priming is ablated). This hairpin creates a single constant environment for priming events and chaperones free 3'-ends of amplicon strands. The resultant 'amplification ratio control system' (ARCS) permits ratiometric representation of amplicons relative to the original template into PCR plateau phase. These advantages circumvent the need for real-time PCR for quantitation. Choice of different %(G+C) content for the target and reference amplicons allows liquid phase thermal melt discrimination and quantitation of amplicons. The design is generic, simple to set up and economical. Comparisons with real-time PCR and other techniques are made and CNV assays demonstrated for haptoglobin duplicon and 'chemokine (C-C motif) ligand 3-like 1' gene.     

AFN-1252 is a potent inhibitor of enoyl-ACP reductase from Burkholderia pseudomallei—Crystal structure,mode of action,and biological activity

Melioidosis is a tropical bacterial infection caused by Burkholderia pseudomallei (B. pseudomallei; Bpm), a Gram-negative bacterium. Current therapeutic options are largely limited to trimethoprim-sulfamethoxazole and β-lactam drugs, and the treatment duration is about 4 months. Moreover, resistance has been reported to these drugs. Hence, there is a pressing need to develop new antibiotics for Melioidosis. Inhibition of enoyl-ACP reducatase (FabI), a key enzyme in the fatty acid biosynthesis pathway has shown significant promise for antibacterial drug development. FabI has been identified as the major enoyl-ACP reductase present in B. pseudomallei. In this study, we evaluated AFN-1252, a Staphylococcus aureus FabI inhibitor currently in clinical development, for its potential to bind to BpmFabI enzyme and inhibit B. pseudomallei bacterial growth. AFN-1252 stabilized BpmFabI and inhibited the enzyme activity with an IC₅₀ of 9.6 nM. It showed good antibacterial activity against B. pseudomallei R15 strain, isolated from a melioidosis patient (MIC of 2.35 mg/L). X-ray structure of BpmFabI with AFN-1252 was determined at a resolution of 2.3 Å. Complex of BpmFabI with AFN-1252 formed a symmetrical tetrameric structure with one molecule of AFN-1252 bound to each monomeric subunit. The kinetic and thermal melting studies supported the finding that AFN-1252 can bind to BpmFabI independent of cofactor. The structural and mechanistic insights from these studies might help the rational design and development of new FabI inhibitors.