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Introduction: Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor prescribed as part of first-line highly active antiretroviral therapy in South Africa. Despite administration of fixed doses of EFV, inter-individual variability in EFV plasma concentrations has been reported. Poor treatment outcomes such as the development of adverse drug reactions or treatment failure have been linked to EFV concentrations outside the therapeutic range (1 - 4 µg/mL). The drug metabolising enzyme (DME), CYP2B6, is primarily responsible for EFV metabolism with minor contributions by CYP2A6, CYP3A4, CYP3A5, UGT2B7 and CYP1A2. Genes coding for DMEs have been shown to be regulated by microRNAs through targeting the 3'-untranslated region. Genetic variation in the 3'-UTR, in addition to genetic variation in the coding regions, could potentially be used to explain a larger proportion of the inter-individual variability observed in drug response. Methods: SNPs in CYP1A2, CYP2B6, UGT2B7 and NR1I2 (PXR) were selected for genotyping among 222 Bantu-speaking South African HIV-infected patients receiving EFV-containing HAART. This study is a continuation of earlier pharmacogenetics studies emphasizing specifically the role of genetic variation in the 3'-UTR of genes which products are either pharmacokinetic or pharmacodynamic targets of EFV.Results: In addition to CYP2B6 c.516G>T and c.983T>C SNPs, the CYP2B6 c.1355A>G SNP was identified as pharmacogenetics determinant of EFV concentration among CYP2B6 intermediate and extensive metabolisers (carriers of either c.516G/G+c.983T/T or c.516G/G+c.983T/C or c.516G/T+c.983T/T genotypes). NR1I2 c.522C>T and NR1I3 c.239-1089T>C SNPs were predictors of EFV concentration among CYP2B6 poor metabolisers (carriers of either c.516T/T or c.983C/C or both c.516G/T and c.983T/C genotypes).Conclusion: Genotyping results provide support for comprehensive studies of genetic variation in the 3'-UTR of genes coding for DMEs and their inclusion in predictive pharmacogenomics models to get a clearer picture on correlates of drug response.

Light enhanced calcification (LEC) is a well documented phenomenon in reef-building corals. The main mechanism proposed for LEC is that photosynthetic CO2 uptake by the algal symbionts elevates the pH and thus enhances calcification. We evaluated the role of light and of photosynthesis on calcification by assessing the response of the corals Porites lutea and Acropora variabilis to different components of the light spectrum. Calcification and photosynthesis of both species decreased under lagoon blue, green and red light (peaks at 500, 550 and 600nm respectively). However, blue light (peak at 455nm) enhanced calcification rates of P. lutea and A. variabilis (up to 4.1 and 10.5 fold of dark values, respectively) reaching levels comparable to those measured under full spectrum illumination. However, contrary to our expectations, photosynthetic oxygen production was considerably reduced under blue light, to the extent that it remained below the compensation point even under illumination as high as 400µmol photons m-2 s-1. It is the first time that a direct effect of light not mediated by the photosynthetic process has been demonstrated to trigger LEC in corals. We propose that blue light signaling, and animal receptors thereof may be involved in the enhancement of calcification by hermatypic corals.

Objective: The emergence of extended-spectrum β-lactamase (ESBL)-producing bacteria is now a critical concern. The ESBL-producing Klebsiella pneumonia constitutes one of the most common multidrug-resistant groups of gram-negative bacteria involved in nosocomial infections worldwide. In this study we report on the molecular characterization through whole genome sequencing of an ESBL-producing K. pneumoniae strain, LAU-KP1, isolated from a stool sample from a patient admitted for a gastrointestinal procedure/surgery at the Lebanese Amrican University Medical Center-Rizk Hospital (LAUMCRH) in Lebanon. Methods: Illumina paired-end libraries were prepared and sequenced, which resulted in 4,220,969 high-quality reads. All sequence processing and assembly were performed using the A5 assembly pipeline. Results: The initial assembly produced 86 contigs, for which no scaffolding was obtained. The final collection of contigs was submitted to GenBank. The final draft genome sequence consists of a combined 5,632,663 bases with 57% G+C content. Automated annotation was performed using the RAST annotation server. Sequencing analysis revealed that the isolate harbored different β-lactamase genes, including blaoxa-1, blaCTX-M-15, blaSHV-11, and blaTEM-1b. The isolate was also characterized by the concomitant presence of other resistance determinants most notably acc(6’)-lb-cr and qnrb1. The entire plasmid content was also investigated and revealed homology with 4 major plasmids pKPN-IT, pBS512_2, pRSF1010_SL1344 and pKPN3. Conclusions: The potential role of K. pneumonia as a reservoir for ESBL genes and other resistance determinants is along with the presence of key factors that favor the spread of antimicrobial resistance a clear cause of concern and the problem that Carbapenem-non-susceptible ESBL isolates are posing in hospitals should be reconsidered through systematic exploration and molecular characterization.

Sports concussions are an increasingly recognized common type of mild traumatic brain injury (TBI) that affect athletes of all ages. The need for an increased involvement of trained physicians in the diagnosis and treatment of concussion has become more obvious as the pathophysiology and long-term sequelae of sports concussion are better understood. To date, there has been great variability in the athletic community about the recognition of symptoms, diagnosis, management, and physician role in concussion care. An awareness assessment survey administered to 96 high school coaches in a large metropolitan city demonstrated that 37.5% of responders refer their concussed players to an emergency department after the incident, only 39.5% of responders have a physician available to evaluate their players after a concussion, 71.6% of those who had a physician available sent their players to a sports medicine physician, and none of the responders had their player’s concussion evaluated by a neurologist. Interestingly, 71.8% of responders stated that their players returned to the team with return to play guidelines from their physician. This survey has highlighted two important areas where the medical community can better serve the athletic community. Because a concussion is a sport-inflicted injury to the nervous system, it is optimally evaluated and managed by a clinician with relevant training in both clinical neuroscience and sports medicine. Furthermore, all physicians who see patients suffering concussion should be educated in the current recommendations from the Consensus Statement on Concussion and provide return to play instructions that outline a graduated return to play, allowing the athlete to return to the field safely.