Impact of trametinib on the neuropsychological profile of NF1 patients.

PURPOSE: The use of trametinib in the treatment of pediatric low-grade gliomas (PLGG) and plexiform neurofibroma (PN) is being investigated in an ongoing multicenter phase II trial (NCT03363217). Preliminary data shows potential benefits with significant response in the majority of PLGG and PN and an overall good tolerance. Moreover, possible benefits of MEK inhibitor therapy on cognitive functioning in neurofibromatosis type 1 (NF1) were recently shown which supports the need for further evaluation. METHODS: Thirty-six patients with NF1 (age range 3-19 years) enrolled in the phase II study of trametinib underwent a neurocognitive assessment at inclusion and at completion of the 72-week treatment. Age-appropriate Wechsler Intelligence Scales and the Trail Making Test (for children over 8 years old) were administered at each assessment. Paired t-tests and Reliable Change Index (RCI) analyses were performed to investigate change in neurocognitive outcomes. Regression analyses were used to investigate the contribution of age and baseline score in the prediction of change. RESULTS: Stable performance on neurocognitive tests was revealed at a group-level using paired t-tests. Clinically significant improvements were however found on specific indexes of the Wechsler intelligence scales and Trail Making Test, using RCI analyses. No significant impact of age on cognitive change was evidenced. However, lower initial cognitive performance was associated with increased odds of presenting clinically significant improvements on neurocognitive outcomes. CONCLUSION: These preliminary results show a potential positive effect of trametinib on cognition in patients with NF1. We observed significant improvements in processing speed, visuo-motor and verbal abilities. This study demonstrates the importance of including neuropsychological evaluations into clinical trial when using MEK inhibitors for patients with NF1.

Endoscopic transmural management of abdominal fluid collection following gastrointestinal, bariatric, and hepato-bilio-pancreatic surgery.

BACKGROUND: Post-operative collections are a recognized source of morbidity after abdominal surgery. Percutaneous drainage is currently considered the standard treatment but not all collections are accessible using this method. Since the adoption of EUS, endoscopic transmural drainage has become an attractive option in the management of such complications. The present study aimed to assess the efficacy, safety and modalities of endoscopic transmural drainage in the treatment of post-operative collections. METHODS: Data of all patients referred to our dedicated multidisciplinary facility from 2014 to 2017 for endoscopic drainage of symptomatic post-operative collections after failure of percutaneous drainage or when it was deemed impossible, were retrospectively analyzed. RESULTS: Thirty-two patients (17 males and 15 females) with a median age of 53 years old (range 31-74) were included. Collections resulted from pancreatic (n = 10), colorectal (n = 6), bariatric (n = 5), and other type of surgery (n = 11). Collection size was less than 5 cm in diameter in 10 (31%), between 5 and 10 cm in 17 (53%) ,and more than 10 cm in 5 (16%) patients. The median time from surgery to endoscopic drainage was 38 days (range 6-360). Eight (25%) patients underwent endoscopic guided drainage whereas 24 (75%) patients underwent EUS-guided drainage. Technical success was 100% and clinical success was achieved in 30 (93.4%) after a mean follow-up of 13.5 months (1.2-24.8). Overall complication was 12.5% including four patients who bled following trans-gastric drainage treated with conservative therapy. CONCLUSIONS: The present series suggests that endoscopic transmural drainage represents an interesting alternative in the treatment of post-operative collection when percutaneous drainage is not possible or fails.

COMP Report: CPQR technical quality control guidelines for conventional radiotherapy simulators.

The Canadian Organization of Medical Physicists (COMP), in close partnership with the Canadian Partnership for Quality Radiotherapy (CPQR) has developed a series of Technical Quality Control (TQC) guidelines for radiation treatment equipment. These guidelines outline the performance objectives that equipment should meet in order to ensure an acceptable level of radiation treatment quality. The TQC guidelines have been rigorously reviewed and field tested in a variety of Canadian radiation treatment facilities. The development process enables rapid review and update to keep the guidelines current with changes in technology (the most updated version of this guideline can be found on the CPQR website). This particular TQC details recommended quality control testing of conventional radiotherapy simulators.

COMP report: CPQR technical quality control guidelines for radiation treatment centers.

The Canadian Organization of Medical Physicists (COMP), in close partnership with the Canadian Partnership for Quality Radiotherapy (CPQR) has developed a series of Technical Quality Control (TQC) guidelines for radiation treatment equipment. These guidelines outline the performance objectives that equipment should meet in order to ensure an acceptable level of radiation treatment quality. The TQC guidelines have been rigorously reviewed and field tested in a variety of Canadian radiation treatment facilities. The development process enables rapid review and update to keep the guidelines current with changes in technology. This announcement provides an introduction to the guidelines, describing their scope and how they should be interpreted. Details of recommended tests can be found in separate, equipment specific TQC guidelines published in the JACMP (COMP Reports), or the website of the Canadian Partnership for Quality Radiotherapy (www.cpqr.ca).

Inflammation and beyond: new directions and emerging drugs for treating atherosclerosis.

INTRODUCTION: Cardiovascular (CV) atherosclerotic disease remains the leading cause of morbidity and mortality worldwide, despite the advances in contemporary therapies. Inflammation is an important process in atherosclerosis, leading to plaque rupture and acute coronary syndrome. Although statin therapy has substantially reduced CV events in primary and secondary prevention, many treated patients will have recurrent adverse CV events despite the standard of care. Thus, drug development aiming to target inflammatory pathways seems a promising avenue for novel therapies in atherosclerosis. Areas covered: Statins have been extensively studied and are the most effective lipid-lowering drugs available for CV prevention. Novel anti-inflammatory drugs are being tested in Phase II and III trials, targeting pathways like interleukin-1, leukotrienes, TNF-α, P-selectin, CCL2-CCR2 and MAP Kinase. Expert opinion: Novel anti-inflammatory therapies seem promising additions to address the residual CV risk present despite the current standard of care, but large clinical trials have not yet shown beneficial effects on clinical events. PCSK9 inhibitors have been shown to substantially reduce LDL-C, however their long-term safety and effects on CV risk are currently being investigated. Pharmacogenomics holds great potential in future lipid trials, enabling the identification of patients who will respond with greater benefits and smaller risk to therapies and to decrease failure rates in drug development, as genotype-dependent effects of the CETP inhibitor dalcetrapib were shown in the dal-OUTCOMES and dal-PLAQUE-2 trials.

Comparison of macroscopic and microscopic (stereomicroscopy and scanning electron microscopy) features of bone lesions due to hatchet hacking trauma.

This experimental study examined the lesions produced by a hatchet on human bones (tibiae). A total of 30 lesions were produced and examined macroscopically (naked eye) and by stereomicroscopy. 13 of them were also analyzed using scanning electron microscopy. The general shape of the lesion, both edges, both walls, the kerf floor and the extremities were described. The length and maximum width of the lesions were also recorded. The microscopic analysis of the lesions led to the description of a sharp-blunt mechanism. Specific criteria were identified (lateral pushing back, fragmentation of the upraising, fossa dug laterally to the edge and vertical striae) enabling the forensic expert to conclude that a hacking instrument was used. These criteria are easily identifiable using scanning electron microscopy, but can also be observed with stereomicroscopy. Overall, lateral pushing back and vertical striae visible using stereomicroscopy and scanning electron microscopy signal the use of a hacking tool.

Hierarchizing caries risk factors among first-year university students in Nice (France): a cross-sectional study.

BACKGROUND: The purpose of this study was to rank the risk factors for dental caries among first-year university students in Nice (France). METHODS: All first-year students are required to undergo a compulsory preventive medical examination. Among these students, volunteers were offered a dental visit. Information was collected through an interview followed by an oral examination. We assessed the volunteers' oral hygiene habits (daily toothbrushing frequency, type of toothbrush used, frequency of toothbrush replacement, place of toothpaste purchase, and flossing), daily health-related behaviors (number of main daily meals, daily sugary intakes, smoking, alcohol consumption, consumption of cannabis or other drugs), oral-health-related behaviors (self-reported oral health, dental visits during the past year, reason for the last dental consultation, and failure to seek dental care due to financial reasons), and oral health issues (dental crowding, oral hygiene, presence of caries, presence of pit and fissure sealant remnants). The dependent variable was the presence of at least one untreated carious lesion. The data were subjected to univariate analyses to select explanatory variables, and subsequently, a logistic regression was performed. RESULTS: Six hundred twenty-nine students aged 18.8±1.6 years were enrolled in this study. The sex ratio was 0.72, with a strong predominance of the female gender. Only 59.3% of the students had never experienced dental caries, while 22.4% had already undergone restorative procedures and did not have any carious lesion at the time of the examination, and 11.6% presented with carious lesions and had never been treated by a dentist. Lastly, 6.7% had carious lesions despite evidence of prior restorative procedures. The multivariate analysis revealed the following pejorative risk factors: failure to seek dental care due to financial reasons (OR:3.06, 95% CI: 1.40-6.70), poor oral hygiene revealed during the oral examination (OR:2.59, 95% CI: 1.60-4.20), and poor self-reported oral health (OR:2.43, 95% CI: 1.24-4.77). Conversely, the analysis revealed the following protective factors: preventive visits to the dentist (OR:0.63, 95% CI: 0.41-0.99), the use of an electric toothbrush (OR:0.36, 95% CI: 0.17-0.77), and sealant remnants (OR:0.22, 95% CI: 0.05-0.97). CONCLUSIONS: The highest-ranking caries risk factor for the study population was the financial barrier.

Pharmacogenomic approaches to lipid-regulating trials.

PURPOSE OF REVIEW: Randomized clinical outcome trials are costly, long, and often yield neutral or modestly positive results, and these issues have impeded cardiovascular drug development in the past decade. Despite the significant reduction of cardiovascular morbidity and mortality with statins, substantial residual risk of major cardiovascular events remains. This could be because of the difficulty of demonstrating benefits of new drugs in addition to the current standard of care in unselected populations as well as the interindividual variability in drug response. Pharmacogenomics is a promising avenue for the development of novel or failed drugs and for the repurposing of other medications. RECENT FINDINGS: Several variants were identified in genes that were associated with the effects of statins on plasma lipids. Genomic studies of mutations in genes that encode drug targets have the potential to inform on the link between drug therapy acting on those targets and clinical outcomes. Recently, ADCY9 gene variants were shown to be significantly associated with responses to dalcetrapib in terms of clinical outcomes, atherosclerosis imaging, cholesterol efflux, and inflammation, which provided support for the conduct of a new prospective clinical trial in a genetically determined population. SUMMARY: Pharmacogenomics hold great potential in future lipid trials to decrease failure rates in drug development and to identify patients who will respond with greater benefits and smaller risk.

Remote Biodegradation of Ge-Imogolite Nanotubes Controlled by the Iron Homeostasis of Pseudomonas brassicacearum.

The toxicity of high-aspect-ratio nanomaterials (HARNs) is often associated with oxidative stress. The essential nutrient Fe may also be responsible of oxidative stress through the production of reactive oxygen species. In the present study, it has been examined to what extent adding Fenton reaction promoting Fe impacted the toxicity of an alumino-germanate model HARN. Structural addition of only 0.95% wt Fe to Ge-imogolite not only alleviated the toxicity observed in the case of Fe-free nanotubes but also stimulated bacterial growth. This was attributed to the metabolization of siderophore-mobilized Fe from the nanotube structure. This was evidenced by the regulation of the homeostasis-monitoring intracellular Fe levels. This was accompanied by a biodegradation of the nanotubes approaching 40%, whereas the Fe-free nanomaterial remained nearly untouched.

Inter- and Intra-Operator Reliability of Facial and Dental Measurements Using 3D-Stereophotogrammetry.

OBJECTIVES: The goal of this study was to assess the reproducibility of an innovative method for facial analysis with three-dimensional-stereophotogrammetry (3D-spg). METHODS: Twelve subjects with no obvious malocclusion participated in this study. For each of them, four photographs were acquired using the LifeViz(TM) , an absolute calibration 3D-spg system. The facial reconstructions were analyzed with the DermaPix(TM) image management software. Two different operators recorded distances between landmarks and each operator repeated the measurements after one week. The intra- and inter-examiner reproducibilities were assessed using the Intraclass Correlation Coefficient (ICC). RESULTS: This study showed reproducible intra and inter-examiners results for facial measurements (ICC comprised between 0.732 and 0.976) except for measurements that involve the inner part of the dental corridor (ICC comprised between 0.598 and 0.914). CONCLUSION: The measurements recorded by 3D-LifeViz(TM) system are accurate and reliable for research and clinical use. Moreover, it is simple and inexpensive compared with other 3D methods (laser scanner, 3D Computed Tomography, and 3D Cone Beam CT). CLINICAL SIGNIFICANCE: The inter- and intra-operator reliability of the LifeViz(TM) 3D-spg method was demonstrated. The LifeViz(TM) 3D-spg method might be a useful method to accomplish indirect 3D measurements that are relevant to dental and facial diagnosis. (J Esthet Restor Dent, 2016).

Validating Intravascular Imaging with Serial Optical Coherence Tomography and Confocal Fluorescence Microscopy.

Atherosclerotic cardiovascular diseases are characterized by the formation of a plaque in the arterial wall. Intravascular ultrasound (IVUS) provides high-resolution images allowing delineation of atherosclerotic plaques. When combined with near infrared fluorescence (NIRF), the plaque can also be studied at a molecular level with a large variety of biomarkers. In this work, we present a system enabling automated volumetric histology imaging of excised aortas that can spatially correlate results with combined IVUS/NIRF imaging of lipid-rich atheroma in cholesterol-fed rabbits. Pullbacks in the rabbit aortas were performed with a dual modality IVUS/NIRF catheter developed by our group. Ex vivo three-dimensional (3D) histology was performed combining optical coherence tomography (OCT) and confocal fluorescence microscopy, providing high-resolution anatomical and molecular information, respectively, to validate in vivo findings. The microscope was combined with a serial slicer allowing for the imaging of the whole vessel automatically. Colocalization of in vivo and ex vivo results is demonstrated. Slices can then be recovered to be tested in conventional histology.

Transformation of pristine and citrate-functionalized CeO2 nanoparticles in a laboratory-scale activated sludge reactor.

Engineered nanomaterials (ENMs) are used to enhance the properties of many manufactured products and technologies. Increased use of ENMs will inevitably lead to their release into the environment. An important route of exposure is through the waste stream, where ENMs will enter wastewater treatment plants (WWTPs), undergo transformations, and be discharged with treated effluent or biosolids. To better understand the fate of a common ENM in WWTPs, experiments with laboratory-scale activated sludge reactors and pristine and citrate-functionalized CeO2 nanoparticles (NPs) were conducted. Greater than 90% of the CeO2 introduced was observed to associate with biosolids. This association was accompanied by reduction of the Ce(IV) NPs to Ce(III). After 5 weeks in the reactor, 44 ± 4% reduction was observed for the pristine NPs and 31 ± 3% for the citrate-functionalized NPs, illustrating surface functionality dependence. Thermodynamic arguments suggest that the likely Ce(III) phase generated would be Ce2S3. This study indicates that the majority of CeO2 NPs (>90% by mass) entering WWTPs will be associated with the solid phase, and a significant portion will be present as Ce(III). At maximum, 10% of the CeO2 will remain in the effluent and be discharged as a Ce(IV) phase, governed by cerianite (CeO2).

Portrait of Montréal healthcare workers infected with SARS-CoV-2 during the first wave of the pandemic: a cross-sectional study.

OBJECTIVES: During the first wave of COVID-19 in Québec, healthcare workers (HCWs) represented 25% of the cases in Montréal. A study was conducted to describe SARS-CoV-2-infected HCWs in Montréal, and certain workplace and household characteristics. Secondary objectives included estimating the associations between having had access to personal protective equipment (PPE) and training, and following self-isolation recommendations, and certain sociodemographic and workplace characteristics. METHODS: A cross-sectional study was conducted, based on a stratified random sample, among Montréal HCWs who tested positive for SARS-CoV-2 between March and July 2020. A total of 370 participants answered a telephone-administered questionnaire. Descriptive statistics were conducted, followed by log binomial regressions to estimate the associations. RESULTS: Study participants were mostly female (74%), born outside of Canada (65%), and identified as Black, Indigenous, and People of Colour (BIPOC; 63%). In terms of healthcare positions, most were orderlies (40%) or registered nurses (20%). Half (52%) of the participants reported having had insufficient access to PPE and 30% reported having received no training related to SARS-CoV-2 infection prevention, with large proportions being BIPOC women. Working evening or night shifts decreased chances of having had sufficient access to PPE (OR 0.50; 0.30-0.83). CONCLUSION: This study describes the profile of the HCWs who were infected during the first wave of the pandemic in Montréal. Recommendations include collecting comprehensive sociodemographic data on SARS-CoV-2 infections and ensuring equitable access to infection prevention and control training and PPE during health crises, particularly those at highest risk of exposure.

RéSUMé: OBJECTIFS: Lors de la première vague de la COVID-19 au Québec, les travailleurs de la santé (TS) représentaient 25 % des cas à Montréal. Une étude a été menée pour décrire les TS infectés par le SRAS-CoV-2 à Montréal, ainsi que certaines caractéristiques liées au travail et au ménage. Les objectifs secondaires visaient à estimer les associations entre le fait d'avoir eu accès à un équipement de protection individuelle (EPI) et à une formation, ainsi que la capacité de suivre les recommandations d'auto-isolement et différentes caractéristiques sociodémographiques et du lieu de travail. MéTHODOLOGIE: Une étude transversale a été menée, sur la base d'un échantillon aléatoire stratifié, parmi les TS de Montréal qui ont été testés positifs pour le SRAS-CoV-2 entre mars et juillet 2020. Un total de 370 participants a répondu à un questionnaire administré par téléphone. Des statistiques descriptives ont été réalisées, suivies de régressions log binomiales pour estimer les associations. RéSULTATS: Les participants étaient en majorité des femmes (74 %), nés à l'extérieur du Canada (65 %) et s'identifiaient comme des personnes Noires, des Autochtones et des personnes de couleur (BIPOC; 63 %). En termes d'emploi dans le système de santé, 40 % étaient des préposés aux bénéficiaires et 20 % des infirmières cliniciennes. La moitié (52 %) des participants ont déclaré ne pas avoir eu un accès suffisant à l'EPI et 30 % ont déclaré n'avoir reçu aucune formation liée à la prévention des infections SRAS-CoV-2, une grande partie d'entre eux étant des femmes BIPOC. Le fait de travailler le soir ou la nuit diminuait les chances d'avoir un accès suffisant aux EPI (OR 0,50; 0,30­0,83). CONCLUSION: Cette étude décrit le profil des travailleurs de santé qui ont été infectés lors de la première vague de la pandémie à Montréal. Les recommandations comprennent la collecte de données sociodémographiques complètes et de s'assurer de fournir de l'EPI et des formations en prévention et contrôle des infections pendant les crises sanitaires, en particulier pour les personnes les plus à risque d'exposition.

Prioritizing Solutions and Improving Resources among Young Pediatric Brain Tumor Survivors: Results of an Online Survey.

Pediatric Brain Tumor Survivors (PBTS) often experience social, academic and employment difficulties during aftercare. Despite their needs, they often do not use the services available to them. Following a previous qualitative study, we formulated solutions to help support PBTS return to daily activities after treatment completion. The present study aims to confirm and prioritize these solutions with a larger sample. We used a mixed-methods survey with 68 participants (43 survivors, 25 parents, PBTS' age: 15-39 years). Firstly, we collected information about health condition, and school/work experience in aftercare. Then, we asked participants to prioritize the previously identified solutions using Likert scales and open-ended questions. We used descriptive and inferential statistics to analyze data, and qualitative information to support participants' responses. Participants prioritized the need for evaluation, counseling, and follow-up by health professionals to better understand their post-treatment needs, obtain help to access adapted services, and receive information about resources at school/work. Responses to open-ended questions highlighted major challenges regarding the implementation of professionals' recommendations at school/work and the need for timely interventions. These results will help refine solutions for PBTS and provide key elements for future implementation. Translating these priorities into action will need further work involving professionals and decision makers.

Performance Characteristics of Mass Spectrometry-Based Analytical Procedures for Quantitation of Nitrosamines in Pharmaceuticals: Insights from an Inter-laboratory Study.

With the discovery of carcinogenic nitrosamine impurities in pharmaceuticals in 2018 and subsequent regulatory requirements for risk assessment for nitrosamine formation during pharmaceutical manufacturing processes, storage or from contaminated supply chains, effective testing of nitrosamines has become essential to ensure the quality of drug substances and products. Mass spectrometry has been widely applied to detect and quantify trace amounts of nitrosamines in pharmaceuticals. As part of an effort by regulatory authorities to assess the measurement variation in the determination of nitrosamines, an inter-laboratory study was performed by the laboratories from six regulatory agencies with each of the participants using their own analytical procedures to determine the amounts of nitrosamines in a set of identical samples. The results demonstrated that accurate and precise quantitation of trace level nitrosamines can be achieved across multiple analytical procedures and provided insight into the performance characteristics of mass spectrometry-based analytical procedures in terms of accuracy, repeatability and reproducibility.

Biofilm and Orthodontic Materials: literature reviews and Scanning Electron Microscopy (SEM) images gallery / Relations entre biofilm et matériels orthodontiques : revues de la littérature et galerie d'images en microscopie électronique à balayage (MEB)

Introduction: Plaque control remains a concern in oral health but also in orthodontics. Objective: The aim of this paper was to investigate the dental plaque adhesion to different orthodontic appliances. Materials and Methods: Four literature reviews were initiated to clarify the accumulation of dental plaque to different orthodontic appliances, namely the type of brackets (conventional versus self-ligating, metal versus clear), the type of ligatures (metal versus elastomeric) in addition to the type of archwires. Moreover, a gallery of Scanning Electron Microscopy (SEM) images was made on different orthodontic appliances before and/or after time in the oral cavity. Results: Considering the strong methodological heterogeneity of the included studies, there is no consensus on which type of bracket should be preferred for the prevention of plaque retention. Metal ligatures would be less prone to plaque accumulation compared to elastomeric ligatures, which are themselves color-dependent. The type of archwire was not investigated in this topic. SEM images highlighted the presence of anfractuosities on the surface of new orthodontic archwires as well as the presence of biofilm at different degrees of maturation on the appliances after time in the oral cavity. Conclusion: Although it is not possible to establish a consensus on which orthodontic appliances should be preferred to decrease plaque retention, different stages of biofilm evolution are observable on their surface and therefore potentially associated with a proportional virulence.

Introduction: Le contrôle de la plaque dentaire reste une préoccupation en santé bucco-dentaire mais aussi en orthodontie. Objectif: Le but de cet article était d'investiguer l'adhésion de la plaque dentaire sur différents dispositifs orthodontiques. Matériels et méthodes: Quatre revues de la littérature ont été réalisées afin d'étudier l'adhésion de la plaque dentaire sur différents dispositifs orthodontiques, à savoir le type d'attaches (conventionnelles versus autoligaturantes ; métalliques versus céramiques), le type de ligatures (métalliques versus élastomériques) et, enfin, le type d'arcs. Une galerie d'images obtenues par microscopie électronique à balayage (MEB) a également été réalisée sur différents dispositifs orthodontiques avant et/ou après vie en bouche. Résultats: Tenant compte de la forte hétérogénéité méthodologique des études incluses, privilégier un type d'attaches dans la prévention de la rétention de la plaque dentaire ne fait pas l'objet d'un consensus. Les ligatures métalliques seraient moins sujettes à l'accumulation de la plaque dentaire par rapport aux ligatures élastomériques, elle-même dépendantes de leur couleur. Le type d'arcs n'a pas fait l'objet d'investigations sur cette thématique. Les images MEB mettaient en lumière la présence d'anfractuosités à la surface des arcs orthodontiques neufs, ainsi que la présence d'un biofilm à différents degrés de maturation sur les dispositifs après vie en bouche. Conclusion: Bien qu'il ne soit pas possible d'établir un consensus sur les dispositifs orthodontiques à privilégier pour diminuer la rétention de la plaque dentaire, différents stades d'évolution du biofilm sont observables à leur surface et donc potentiellement associés à une virulence proportionnelle.

FAN stimulates TNF(alpha)-induced gene expression, leukocyte recruitment, and humoral response.

Factor associated with neutral sphingomyelinase activation (FAN) is an adaptor protein that constitutively binds to TNF-R1. Microarray analysis was performed in fibroblasts derived from wild-type or FAN knockout mouse embryos to evaluate the role of FAN in TNF-induced gene expression. Approximately 70% of TNF-induced genes exhibited lower expression levels in FAN-deficient than in wild-type fibroblasts. Of particular interest, TNF-induced expression of cytokines/chemokines, such as IL-6 and CXCL-2, was impaired in FAN-deficient cells. This was confirmed by real time RT-PCR and ELISA. Upon i.p. TNF or thioglycollate injection, neutrophil recruitment into the peritoneal cavity was reduced by more than 50% in FAN-deficient mice. Nevertheless, FAN-deficient animals did not exhibit an increased susceptibility to different microorganisms including bacteria and parasites, indicating that FAN is not essential for pathogen clearance. Specific Ab response to BSA was substantially impaired in FAN-deficient mice and this was associated with a reduced content of leukocytes in the spleen of BSA-challenged FAN-deficient mice as compared with their wild-type counterparts. Altogether, our results indicate the involvement of FAN in TNF-induced gene expression and leukocyte recruitment, contributing to the establishment of the specific immune response.

The occurrence of non-anatomical therapeutic chemical-international nonproprietary name molecules in suspected illegal or illegally traded health products in Europe: A retrospective and prospective study.

The General European Official Medicines Control Laboratory (OMCL) Network (GEON), co-ordinated by the European Directorate for the Quality of Medicines & HealthCare (EDQM), regularly organises market surveillance studies on specific categories of suspected illegal or illegally traded products. These studies are generally based on a combination of retrospective and prospective data collection over a defined period of time. This paper reports the results of the most recent study in this context with the focus on health products containing non-Anatomical Therapeutic Chemical-International Nonproprietary Name (ATC-INN) molecules. In total 1104 cases were reported by 16 countries for the period between January 2017 and the end of September 2019. The vast majority of these samples (83%) were collected from the illegal market, while only 3% originated from a legal source. For the rest of the samples, categorisation was not possible. Moreover, 69% of all the reported samples were presented as medicines, including sexual performance enhancers, sports performance enhancers, physical performance enhancers and cognitive enhancers or nootropic molecules that act on the central nervous system (CNS). Although the popularity of anabolics, PDE-5 inhibitors and CNS drugs in illegal products has already been reported, the study showed some new trends and challenges. Indeed, 11% of the samples contained molecules of biological origin, that is, research peptides, representing the second most reported category in this study. Furthermore, the study also clearly shows the increasing popularity of Selective Androgen Receptor Modulators and nootropics, two categories that need attention and should be further monitored.