The evaluation of dual laser handheld raman spectroscopy for identifying novel psychoactive substances

Novel psychoactive substances have been increasing over the last decade with more than 450 derivatives available on the market. The issue with novel psychoactive substances is much more complicated than their effects/side effects. Hence, these substances often contain mixtures of pharmacologically active/inactive impurities which interfere with their effects. The accelerated development of these substances (at a rate above once a week) urges the need to develop rapid and mobile techniques for their characterisation. Handheld Raman spectroscopy offers the advantage of being quick, nondestructive and specific to chemical entities within the measured analyte. One issue with the Raman signatures of analytes is associated with several variables including the laser wavelength that could be shorter (such as 532 785 nm) or longer wavelength lasers (such as 833 - 1064 nm). Using a longer wavelength laser decreases the fluorescence of the sample, but decreases peak resolution and thus limits the sensitivity of detection. Uptoour knowledge the use of dual laser wavelength for identifying novel psychoactive substances has not been explored. Therefore, this work aims to evaluate the use of dual laser handheld Raman spectroscopy for identifying novel psychoactive substances

Global long terminal repeat activation participates in establishing the unique gene expression programme of classical Hodgkin lymphoma

Long terminal repeat (LTR) elements are wide-spread in the human genome and have the potential to act as promoters and enhancers. Their expression is therefore under tight epigenetic control. We previously reported in classical Hodgkin Lymphoma (cHL) that a member of the THE1B class of LTR elements acted as a promoter for the proto-oncogene and growth factor receptor gene CSF1R and that expression of this gene is required for cHL tumour survival. However, to which extent and how such elements participate in globally shaping the unique cHL gene expression programme is unknown. To address this question we mapped the genome-wide activation of THE1-LTRs in cHL cells using a targeted next generation sequencing approach (RACE-Seq). Integration of these data with global gene expression data from cHL and control B cell lines showed a unique pattern of LTR activation impacting on gene expression, including genes associated with the cHL phenotype. We also show that global LTR activation is induced by strong inflammatory stimuli. Together these results demonstrate that LTR activation provides an additional layer of gene deregulation in classical Hodgkin lymphoma and highlight the potential impact of genome-wide LTR activation in other inflammatory diseases

EFFICACY OF ARGENTUM-QUARTZ SOLUTION IN THE TREATMENT OF PERIANAL FISTULAS: A PRELIMINARY STUDY

Objective: Nowadays, an optional and effective medical surgery remains the gold standard for perianal fistulas. Hereby we reported preliminary rsults in favor of using Argentum-Quartz solution for both primary and recurrent perianal fisrtulas. Methods: Three patients with intersphimncter and extrasphinteric fistulas were enrolled. Argentum-Quartz solution was administrated twice a week for sa period of 4 weeks, followed by a pause of 8 days and then another 4 weeks of treatment, totally 16 administrations. After treatment, all patients were monitored for 4-months follow-up. Results: Complete closures of 2 extrasphinteric fistulas and a partial closure with absence of inflammation and superative phenomena in the intraspinteric fistula were both manifested. Conclusions: Selective treatment of perianal fistulas with argentum-quartz solution is safe and effective. and may represent a reliable alternative

Knowledge and perspectives of the public towards the prevalence and harm associated with counterfeit medicines in Lebanon

The Knowledge about the use of counterfeit medicines in Lebanon is still very limited. Thus, the objective of this study was to evaluate the degree of awareness of counterfeit medicines among the Lebanese population and the harm associated with their consumption. A cross-sectional study based on a questionnaire survey has been applied where a semi-structured survey questionnaire was distributed, between June 2017 and May 2018, among 750 participants from 98 Lebanese areas to assess their awareness regarding counterfeit medicines. Seven hundred and four participants completed the questionnaire. 55.4% purchased medicines regularly. The main sources of medicines were pharmacies (52.6%), government clinics (16.3%) and private clinics (8.7%). The most common purchased medicines were lifesaving ones (80%). In the majority of cases (71.9%), participants could not identify the manufacturer country. Overall, 46.2% of the participants were aware of counterfeit medicines. 5.4% of the participants experienced self-reporting adverse effects, among which 89.5% of cases were reported to pharmacists or other authorities. Despite the risk, 4.7% of participants were willing to buy a potential counterfeit medicine. In fact, 56. 4% of the participants associated low harm level with the use of counterfeit medicines. Despite their awareness of counterfeit drugs-associated risks, the majority of participants tend to buy them again. Informative public health campaign and health professionals training, to prevent counterfeit medicines-associated harms, should be implemented

Authentication of Antibiotics Using Portable Near-Infrared Spectroscopy and Multivariate Data Analysis

Counterfeit medicines represent a global public health threat warranting the development of accurate, rapid, and nondestructive methods for their identification. Portable near-infrared (NIR) spectroscopy offers this advantage. This work sheds light on the potential of combining NIR spectroscopy with principal component analysis (PCA) and soft independent modelling of class analogy (SIMCA) for authenticating branded and generic antibiotics. A total of 23 antibiotics were measured “nondestructively” using a portable NIR spectrometer. The antibiotics corresponded to six different active pharmaceutical ingredients being: amoxicillin trihydrate and clavulanic acid, azithromycin dihydrate, ciprofloxacin hydrochloride, doxycycline hydrochloride, and ofloxacin. NIR spectra were exported into Matlab R2018b where data analysis was applied. The results showed that the NIR spectra of the medicines showed characteristic features that corresponded to the main excipient(s). When combined with PCA, NIR spectroscopy could distinguish between branded and generic medicines and could classify medicines according to their manufacturing sources. The PCA scores showed the distinct clusters corresponding to each group of antibiotics, whereas the loadings indicated which spectral features were significant. SIMCA provided more accurate classification over PCA for all antibiotics except ciprofloxacin which products shared many overlapping excipients. In summary, the findings of the study demonstrated the feasibility of portable NIR as an initial method for screening antibiotics

A FOXO1-induced oncogenic network defines the AML1-ETO preleukemic program

Key Points Increased FOXO1 is oncogenic in human CD34+ cells and promotes preleukemia transition. FOXO1 is required by AE preleukemia cells for the activation of a stem cell molecular program.</jats:p

Heat Treated NiP–SiC Composite Coatings: Elaboration and Tribocorrosion Behaviour in NaCl Solution

Tribocorrosion behaviour of heat-treated NiP and NiP–SiC composite coatings was investigated in a 0.6 M NaCl solution. The tribocorrosion tests were performed in a linear sliding tribometer with an electrochemical cell interface. It was analyzed the influence of SiC particles dispersion in the NiP matrix on current density developed, on coefficient of friction and on wear volume loss. The results showed that NiP–SiC composite coatings had a lower wear volume loss compared to NiP coatings. However, the incorporation of SiC particles into the metallic matrix affects the current density developed by the system during the tribocorrosion test. It was verified that not only the volume of co-deposited particles (SiC vol.%) but also the number of SiC particles per coating area unit (and consequently the SiC particles size) have made influence on the tribocorrosion behaviour of NiP–SiC composite coatings

Depletion of RUNX1/ETO in t(8;21) AML cells leads to genome-wide changes in chromatin structure and transcription factor binding

The t(8;21) translocation fuses the DNA-binding domain of the hematopoietic master regulator RUNX1 to the ETO protein. The resultant RUNX1/ETO fusion protein is a leukemia-initiating transcription factor that interferes with RUNX1 function. The result of this interference is a block in differentiation and, finally, the development of acute myeloid leukemia (AML). To obtain insights into RUNX1/ETO-dependant alterations of the epigenetic landscape, we measured genome-wide RUNX1- and RUNX1/ETO-bound regions in t(8;21) cells and assessed to what extent the effects of RUNX1/ETO on the epigenome depend on its continued expression in established leukemic cells. To this end, we determined dynamic alterations of histone acetylation, RNA Polymerase II binding and RUNX1 occupancy in the presence or absence of RUNX1/ETO using a knockdown approach. Combined global assessments of chromatin accessibility and kinetic gene expression data show that RUNX1/ETO controls the expression of important regulators of hematopoietic differentiation and self-renewal. We show that selective removal of RUNX1/ETO leads to a widespread reversal of epigenetic reprogramming and a genome-wide redistribution of RUNX1 binding, resulting in the inhibition of leukemic proliferation and self-renewal, and the induction of differentiation. This demonstrates that RUNX1/ETO represents a pivotal therapeutic target in AML

Evaluating the detection of cocaine and its impurities concealed inside fruit- and vegetable- food products using handheld spatially offset Raman spectroscopy

This study investigated the use of handheld spatially offset Raman spectroscopy for the identification of drugs concealed within fruit and vegetable food products, which is a common method of drug trafficking in busy environments such as airports. Handheld Raman spectroscopy is advantageous due to its mobility, speed, and chemical specificity for drug analysis. In this study, spatially offset Raman spectra of six substances were collected and included cocaine and its impurities. Raman spectra were collected for drugs on their own and for drugs concealed in transparent bags and in various food products such as green pepper, pomegranate, potato, and zucchini. The collected spectra were analyzed using different algorithms. The results showed successful identification of drugs in three out of the four tested food products, except for pomegranate, which had a thick rind and spongy tissue that hindered detection. An instrumental hit quality index algorithm provided instant identification with matches above 80% in the three identified products. Correlation in wavelength space yielded high correlation coefficient values between substances in food substrates and reference substances, although there were a few false negatives due to noisy spectra. Principal component analysis successfully differentiated between drugs in different food products. In summary, the study demonstrated the potential of handheld spatially offset Raman spectroscopy for identifying drugs concealed within food products. Future work aims to expand the technique to a wider range of substances and food products and develop a quantitative approach to predict substances’ concentrations. Overall, this research contributes to the field of forensic applications and offers insights into the detection of illicit drugs in challenging scenarios

French national cohort of first use of dalbavancin: a high proportion of off-label use

Dalbavancin is a glycopeptide antibiotic with a long half-life, recently marketed in Europe for skin and soft tissue infections (SSTI), but real-life use is not well-known. We aimed to describe all first prescriptions in France over an 18-month period. We performed a retrospective study on all adult patients who received at least one dose of dalbavancin from July 1, 2017 to September 31, 2018. Data were collected thanks to a standard questionnaire. Failure was defined as: persistent or reappearance of signs of infection; and/or switch to suppressive antibiotic treatment; and/or death from infection. We included 75 patients from 29 French hospitals. Main indications were bone and joint infections (BJIs) (64.0%), endocarditis (25.3%), and SSTIs (17.3%). Main bacteria involved were: Staphylococcus aureus (51.4%), including methicillin-resistant S. aureus (MRSA) (19.4%); and coagulase-negative staphylococci (CNS) (44.4%). Median MICs for staphylococci to vancomycin and dalbavancin ranged from 0.875 mg/L to 2.0 mg/L, and 0.040 mg/L to 0.064 mg/L, respectively. Dalbavancin was used after a mean of 2.3 ± 1.2 lines of antimicrobial treatment. Main treatment regimens for dalbavancin were a weekly 2-dose regimen (1500mg each) in 38 (53.2%) cases, and a single-dose regimen (1500mg) in 13 (18.3%) cases. Overall, at the patients\u27 last visit, clinical cure was observed in 54/72 patients, while failure was found in 14/72 patients. First uses of dalbavancin in France were mostly off-label. Most of them were due to BJIs, and often as rescue therapy for severe infections. Even in off-label situations, dalbavancin seems safe and effective