The role of a Medical Science Liaison (MSL) is of growing importance to pharmaceutical, biotechnology, diagnostic and medical device companies. Through scientific engagement MSLs add value to clinical practice, ultimately benefiting patients. The MSL role is dynamic and encompasses in-depth product and disease knowledge together with the ability to communicate relevant, unbiased scientific information concisely and timely. Tasks are focused on contributing towards the advancement of medical knowledge, scientific data generation and dissemination. Professional relationships are developed, fostering collaboration between external experts and typically the medical affairs departments of pharmaceutical companies through a credible liaison. Through such relationships, critical insights are shared that shape the development pipeline, promote successful clinical translation and guide the market deployment strategy of therapeutic interventions through-out their life cycle. Despite the rising number of MSLs in the field and the implicit medical value of the role, there remains a lack of understanding for what the roles of a MSL entails. In Africa, where exponential growth of the pharmaceutical industry is expected, the number of MSLs will increase rapidly. Given the complexities of the African continent, the MSLs in this burgeoning environment will face various challenges including remote locations, time-constraints, regulatory and bureaucratic hurdles and importantly physician misperception of the MSL role that collectively may thwart the goal of meaningful scientific engagement; but these challenges can be surmounted through astute proactive planning and utilization of opportunities including digital communication strategies.

The occurrence of selected brominated flame retardants, including nine polybrominated diphenyl ether (PBDE) congeners, hexabromocyclododecane (HBCDD) and tetrabromobisphenol A (TBBPA) in leachate samples from eight landfill sites in South Africa, were investigated. In addition, the possible influences of dissolved organic carbon on their levels were also evaluated. Filtered leachate samples were subjected to solid-phase extraction to isolate the various target compounds. PBDEs with six bromine substituents and above, as well as α-HBCDD, β-HBCDD and TBBPA, were generally found below the detection limit. However, the mean value of the total lower PBDE congeners ranged between 0.04 and 0.48 μg L, and the concentrations of γ-HBCDD ranged from not detectable (ND) to 0.05 μg L. No significant correlation was observed between the target compounds and dissolved organic carbon, although weak to moderate correlations were mostly observed for the lower PBDEs.

The bromodomain (BRD) and extra-terminal domain (BET) protein family bind to acetylated histones on lysine residues and act as epigenetic readers. Recently, the role of this protein family in bone loss has been gaining attention. Earlier studies have reported that benzotriazepine (Bzt) derivatives could be effective inhibitors of BET proteins. In this study, using in silico tools we designed three Bzt analogs (W49, W51, and W52). By docking, molecular simulations, and chemiluminescent Alpha Screen binding assay, we show that the studied analogs were selective at inhibiting BRD4 when compared to BRD2. Furthermore, we tested the effectiveness of these analogs on osteoclast formation and function. Among the examined analogs, Bzt-W49 and Bzt-W52 were found to be the most potent inhibitors of osteoclastogenesis without cytotoxicity in murine RAW264.7 osteoclast progenitors. Both the compounds also inhibited osteoclast formation without affecting cell viability in human CD14+ monocytes. Moreover, owing to attenuated osteoclastogenesis, actin ring formation and bone resorptive function of osteoclasts were severely perturbed. In conclusion, these results suggest that the novel BRD4-selective Bzt analogs designed in this study could be explored further for developing therapeutics against bone loss diseases characterized by excessive osteoclast activity.

The antiquity of the use of hunting poisons has received much attention in recent years. In this paper we present the results of a pilot study designed to detect the presence of organic compounds, typically of less than 1200 Da, from poisonous plants that may have been used as hunting poisons in the past. We used ultra-performance liquid chromatography connected to a Synapt G2 high-resolution MS-QTOF mass spectrometer (UPLC-QTOF-MS) to provisionally identify plant-based toxins present in (1) extracts of fresh plant material, (2) a blind control recipe consisting of three plant ingredients and (3) a Hei||om arrow poison of unknown ingredients. Although not all expected toxic compounds were identified, those that were identified compared favourably with those reported in the literature and confirmed through databases, specifically the Dictionary of Natural Products and ChemSpider. MS/MS fragmentation patterns and accurate mass were used for tentative identification of compounds because archaeological residues usually contain insufficient material for unambiguous identification using nuclear magnetic resonance. We highlight the potential of this method for accurately identifying plant-based toxins present on archaeological artefacts and unique (albeit non-toxic) chemical markers that may allow one to infer the presence of toxic plant ingredients in arrow poisons. Any chemical study of archaeological material should consider the unique environmental degradative factors and be sensitive to the oxidative by-products of toxic compounds.

Contemporary chemotherapy is limited by disseminated, resistant cancer. Targeting, nanoparticulate drug delivery systems that encapsulate synergistic drug combinations are a rational means to increase the therapeutic index of chemotherapeutics. A lipopolymeric micelle co-encapsulating an in vitro optimized, synergistic fixed-ratio combination of paclitaxel (PTX) and clofazimine (B663) has been developed called Riminocelles™. The present pre-clinical study investigated the acute toxicity, systemic exposure, repeat dose toxicity and efficacy of Riminocelles in parallel to Taxol® at an equivalent PTX dose of 10 mg/kg. Daily and weekly dosing schedules were evaluated against Pgp expressing, human colon adenocarcinoma (HCT-15) xenografts implanted subcutaneously in athymic mice. Riminocelles produced statistically significant (p<0.05) tumor growth delays of 3.2 and 2.7 days for the respective schedules in contrast to Taxol delaying growth by 0.5 and 0.6 days. Using the control tumor doubling time of 4.2 days, tumor-cell-kill values of 0.23 for Riminocelles and 0.04 for Taxol following daily schedules were calculated. A significant weight loss of 5.7% after 14 days (p<0.05) relative to the control group (n=8) was observed for the daily Taxol group whereas Riminocelles did not incur significant weight loss neither were blood markers of toxicity elevated after acute administration (n=3). The safety and efficacy of Riminocelles is statistically superior to Taxol. However, passive tumor targeting was not achieved and the tumor burden progressed quickly. Prior to further animal studies, the in vivo thermodynamic instability of the simple lipopolymeric micellular delivery system requires improvement so as to maintain and selectively deliver the fixed-ratio drug combination.3