Role of biorelevant dissolution media in the selection of optimal Salt forms of oral drugs: maximizing the gastrointestinal solubility and in vitro activity of the antimicrobial molecule, clofazimine

peer-reviewedClofazimine is an antimycobacterial agent that is routinely used for the treatment of leprosy. Clofazimine has also been shown to have high clinical potential for the treatment of many Gram-positive pathogens, including those that exhibit high levels of antibiotic resistance in the medical community. The use of clofazimine against these pathogens has largely been limited by the inherently poor water solubility of the drug substance. In this work, the possibility of repurposing and reformulating clofazimine to maximize its clinical potential is investigated. To achieve this, the potential of novel salt forms of clofazimine as supersaturating drug delivery vehicles to enhance the aqueous solubility and gastrointestinal solubility of the drug substance was explored. The solution properties of seven novel salt forms, identified during an initial screening process, were examined in water and in a gastrointestinal-like media and were compared and contrasted with those of the free base, clofazimine, and the commercial formulation of the drug, Lamprene. The stability of the most promising solid forms was tested, and their bioactivity against Staphylococcus aureus was also compared with that of the clofazimine free base and Lamprene. Salts forms which showed superior stability as well as solubility and activity to the commercial drug formulation were fully characterized using a combination of spectroscopic techniques, including X-ray diffraction, solid-state NMR, and Fourier transform infrared spectroscopy

Co-reductive fabrication of carbon nanodots with high quantum yield for bioimaging of bacteria

A simple and straightforward synthetic approach for carbon nanodots (C-dots) is proposed. The strategy is based on a one-step hydrothermal chemical reduction with thiourea and urea, leading to high quantum yield C-dots. The obtained C-dots are well-dispersed with a uniform size and a graphite-like structure. A synergistic reduction mechanism was investigated using Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. The findings show that using both thiourea and urea during the one-pot synthesis enhances the luminescence of the generated C-dots. Moreover, the prepared C-dots have a high distribution of functional groups on their surface. In this work, C-dots proved to be a suitable nanomaterial for imaging of bacteria and exhibit potential for application in bioimaging thanks to their low cytotoxicity

Co-reductive fabrication of carbon nanodots with high quantum yield for bioimaging of bacteria

A simple and straightforward synthetic approach for carbon nanodots (C-dots) is proposed. The strategy is based on a one-step hydrothermal chemical reduction with thiourea and urea, leading to high quantum yield C-dots. The obtained C-dots are welldispersed with a uniform size and a graphite-like structure. A synergistic reduction mechanism was investigated using Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. The findings show that using both thiourea and urea during the one-pot synthesis enhances the luminescence of the generated C-dots. Moreover, the prepared C-dots have a high distribution of functional groups on their surface. In this work, C-dots proved to be a suitable nanomaterial for imaging of bacteria and exhibit potential for application in bioimaging thanks to their low cytotoxicity

Challenges in quantifying changes in the global water cycle

Human influences have likely already impacted the large-scale water cycle but natural variability and observational uncertainty are substantial. It is essential to maintain and improve observational capabilities to better characterize changes. Understanding observed changes to the global water cycle is key to predicting future climate changes and their impacts. While many datasets document crucial variables such as precipitation, ocean salinity, runoff, and humidity, most are uncertain for determining long-term changes. In situ networks provide long time-series over land but are sparse in many regions, particularly the tropics. Satellite and reanalysis datasets provide global coverage, but their long-term stability is lacking. However, comparisons of changes among related variables can give insights into the robustness of observed changes. For example, ocean salinity, interpreted with an understanding of ocean processes, can help cross-validate precipitation. Observational evidence for human influences on the water cycle is emerging, but uncertainties resulting from internal variability and observational errors are too large to determine whether the observed and simulated changes are consistent. Improvements to the in situ and satellite observing networks that monitor the changing water cycle are required, yet continued data coverage is threatened by funding reductions. Uncertainty both in the role of anthropogenic aerosols, and due to large climate variability presently limits confidence in attribution of observed changes

Validation of a Lysis Buffer Containing 4 M Guanidinium Thiocyanate (GITC)/ Triton X-100 for Extraction of SARS-CoV-2 RNA for COVID-19 Testing: Comparison of Formulated Lysis Buffers Containing 4 to 6 M GITC, Roche External Lysis Buffer and Qiagen RTL Lysis Buffer

The COVID-19 pandemic has resulted in increased need for diagnostic testing using reverse transcriptase real-time PCR (RT-PCR). An exponential increase in demand has resulted in a shortage of numerous reagents in particular those associated with the lysis buffer required to extract the viral RNA. Herein, we describe a rapid collective effort by hospital laboratory scientists, academic researchers and the biopharma industry to generate a validated lysis buffer. We have formulated a 4M Guanidinium thiocyanate (GITC)/ Triton X-100 Lysis buffer which provides comparable results with the recommended reagents. This buffer will ease the burden on hospital labs in their heroic efforts diagnose a large population of patients

Direct microscopic examination of imprints in patients undergoing cardiac valve replacement

BACKGROUND: Bacteriological analysis of cardiac valves might be indicated in patients with suspected endocarditis. METHODS: We report here a prospective study on fifty-three consecutive patients whose native valves were sent to the bacteriological and pathological laboratories, to investigate the performance of direct microscopic examination of imprints and valve culture. RESULTS: On the basis of a histopathological gold standard to classify the inflammatory valve process, the sensitivity, the specificity, the positive and the negative predictive values of direct microscopic examination of imprints and valve culture were 21%, 100%, 100%, 60%, and 21%, 72%, 38%, 52% respectively. This weak threshold of the direct microscopic examination of imprints could be due to antimicrobial therapy prescribed before cardiac surgery and the fact that the patients came from a tertiary hospital receiving patients with a prolonged history of endocarditis. CONCLUSION: Clinical context and histopathology are indispensable when analyzing the imprints and valve culture

Decadal changes of the Western Arabian sea ecosystem

Historical data from oceanographic expeditions and remotely sensed data on outgoing longwave radiation, temperature, wind speed and ocean color in the western Arabian Sea (1950–2010) were used to investigate decadal trends in the physical and biochemical properties of the upper 300 m. 72 % of the 29,043 vertical profiles retrieved originated from USA and UK expeditions. Increasing outgoing longwave radiation, surface air temperatures and sea surface temperature were identified on decadal timescales. These were well correlated with decreasing wind speeds associated with a reduced Siberian High atmospheric anomaly. Shoaling of the oxycline and nitracline was observed as well as acidification of the upper 300 m. These physical and chemical changes were accompanied by declining chlorophyll-a concentrations, vertical macrofaunal habitat compression, declining sardine landings and an increase of fish kill incidents along the Omani coast

Rex Shunt Preoperative Imaging: Diagnostic Capability of Imaging Modalities

The purpose of this study was to evaluate the diagnostic capability of imaging modalities used for preoperative mesenteric-left portal bypass (“Rex shunt”) planning. Twenty patients with extrahepatic portal vein thrombosis underwent 57 preoperative planning abdominal imaging studies. Two readers retrospectively reviewed these studies for an ability to confidently determine left portal vein (PV) patency, superior mesenteric vein (SMV) patency, and intrahepatic left and right PV contiguity. In this study, computed tomographic arterial portography allowed for confident characterization of left PV patency, SMV patency and left and right PV continuity in 100% of the examinations. Single phase contrast-enhanced CT, multi-phase contrast-enhanced CT, multiphase contrast-enhanced MRI, and transarterial portography answered all key diagnostic questions in 33%, 30%, 0% and 8% of the examinations, respectively. In conclusion, of the variety of imaging modalities that have been employed for Rex shunt preoperative planning, computed tomographic arterial portography most reliably allows for assessment of left PV patency, SMV patency, and left and right PV contiguity in a single study