No abstract

Fluoropyrimidines such as 5-fluorouracil (5-FU) form the foundation of a wide variety of chemotherapy regimens. 5-FU is in fact the third most commonly used chemotherapeutic agent in the treatment of solid malignancies across the world. As with all chemotherapy, balancing the potential benefits of therapy against the risks of drug-related toxicity is crucial when clinicians and patients make shared decisions about treatment. 5-FU is the second most common chemotherapeutic drug associated with cardiotoxicity after anthracyclines, which can manifest as chest pain, acute coronary syndrome/myocardial infarction or death. Nevertheless a widespread appreciation of 5-FU-related cardiotoxicity and its implications is lacking amongst clinicians. In this review, we outline the incidence, possible risk factors, and likely pathophysiological mechanisms that may account for 5-FU-related cardiotoxicity and also highlight potential management strategies for this poorly understood clinical entity.

This paper presents the characterization of the microbial community responsible for the in-situ bioremediation of hexachlorocyclohexane (HCH). Microbial community structure and function was analyzed using 16S rRNA amplicon and shotgun metagenomic sequencing methods for three sets of soil samples. The three samples were collected from a HCH-dumpsite (450 mg HCH/g soil) and comprised of a HCH/soil ratio of 0.45, 0.0007, and 0.00003, respectively. Certain bacterial; (Chromohalobacter, Marinimicrobium, Idiomarina, Salinosphaera, Halomonas, Sphingopyxis, Novosphingobium, Sphingomonas and Pseudomonas), archaeal; (Halobacterium, Haloarcula and Halorhabdus) and fungal (Fusarium) genera were found to be more abundant in the soil sample from the HCH-dumpsite. Consistent with the phylogenetic shift, the dumpsite also exhibited a relatively higher abundance of genes coding for chemotaxis/motility, chloroaromatic and HCH degradation (lin genes). Reassembly of a draft pangenome of Chromohalobacter salaxigenes sp. (∼8X coverage) and 3 plasmids (pISP3, pISP4 and pLB1; 13X coverage) containing lin genes/clusters also provides an evidence for the horizontal transfer of HCH catabolism genes.

The contamination levels in ground and river water suggest significant run-off from the dumped HCH wastes and contamination of drinking water resources. The extent of dumping urgently needs to be assessed regarding the risks to human and ecosystem health. A plan for securing the waste isomers needs to be developed and implemented together with a plan for their final elimination. As part of the assessment, any polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDF) generated during HCH recycling operations need to be monitored.