Mercury supply limits methylmercury production in paddy soils.

The neurotoxic methylmercury (MeHg) is a product of inorganic mercury (IHg) after microbial transformation. Yet it remains unclear whether microbial activity or IHg supply dominates Hg methylation in paddies, hotspots of MeHg formation. Here, we quantified the response of MeHg production to changes in microbial activity and Hg supply using 63 paddy soils under the common scenario of straw amendment, a globally prevalent agricultural practice. We demonstrate that the IHg supply is the limiting factor for Hg methylation in paddies. This is because IHg supply is generally low in soils and can largely be facilitated (by 336-747 %) by straw amendment. The generally high activities of sulfate-reducing bacteria (SRB) do not limit Hg methylation, even though SRB have been validated as the predominant microbial Hg methylators in paddies in this study. These findings caution against the mobilization of legacy Hg triggered by human activities and climate change, resulting in increased MeHg production and the subsequent flux of this potent neurotoxin to our dining tables.

Soil Geobacteraceae are the key predictors of neurotoxic methylmercury bioaccumulation in rice.

Contamination of rice by the potent neurotoxin methylmercury (MeHg) originates from microbe-mediated Hg methylation in soils. However, the high diversity of Hg methylating microorganisms in soils hinders the prediction of MeHg formation and challenges the mitigation of MeHg bioaccumulation via regulating soil microbiomes. Here we explored the roles of various cropland microbial communities in MeHg formation in the potentials leading to MeHg accumulation in rice and reveal that Geobacteraceae are the key predictors of MeHg bioaccumulation in paddy soil systems. We characterized Hg methylating microorganisms from 67 cropland ecosystems across 3,600 latitudinal kilometres. The simulations of a rice-paddy biogeochemical model show that MeHg accumulation in rice is 1.3-1.7-fold more sensitive to changes in the relative abundance of Geobacteraceae compared to Hg input, which is recognized as the primary parameter in controlling MeHg exposure. These findings open up a window to predict MeHg formation and accumulation in human food webs, enabling more efficient mitigation of risks to human health through regulations of key soil microbiomes.

Clinical and genetic factors associated with tumor response to neoadjuvant (chemo)radiotherapy, survival and recurrence risk in rectal cancer.

Rectal cancer poses challenges in preoperative treatment response, with up to 30% achieving a complete response (CR). Personalized treatment relies on accurate identification of responders at diagnosis. This study aimed to unravel CR determinants, overall survival (OS), and time to recurrence (TTR) using clinical and targeted sequencing data. Analyzing 402 patients undergoing preoperative treatment, tumor stage, size, and treatment emerged as robust response predictors. CR rates were higher in smaller, early-stage, and intensively treated tumors. Targeted sequencing analyzed 216 cases, while 120 patients provided hotspot mutation data. KRAS mutation dramatically reduced CR odds by over 50% (odds ratio [OR] = 0.3 in the targeted sequencing and OR = 0.4 hotspot cohorts, respectively). In contrast, SMAD4 and SYNE1 mutations were associated with higher CR rates (OR = 6.0 and 6.8, respectively). Favorable OS was linked to younger age, CR, and low baseline carcinoembryonic antigen levels. Notably, CR and an APC mutation increased TTR, while a BRAF mutation negatively affected TTR. Beyond tumor burden, SMAD4 and SYNE1 mutations significantly influenced CR. KRAS mutations independently correlated with radiotherapy resistance, and BRAF mutations heightened recurrence risk. Intriguingly, non-responding tumors with initially small sizes carried a higher risk of recurrence. The findings, even if limited in addition to the imperfect clinical factors, offer insights into rectal cancer treatment response, guiding personalized therapeutic strategies. By uncovering factors impacting CR, OS, and TTR, this study underscores the importance of tailored approaches for rectal cancer patients. These findings, based on extensive analysis and mutation data, pave the way for personalized interventions, optimizing outcomes in the challenges of rectal cancer preoperative treatment.

Sensitive and Specific Analyses of Colorectal Cancer Recurrence through Multiplex superRCA Mutation Detection in Blood Plasma.

Mutation analysis of circulating tumor DNA (ctDNA) has applications in monitoring of colorectal cancer (CRC) patients for recurrence. Considering the low tumor fraction of ctDNA in cell-free DNA (cfDNA) isolated from blood plasma, the sensitivity of the detection method is important. Here, plasma DNA collected at diagnosis and follow-up from 25 CRC patients was analyzed using a multiplex superRCA mutation detection assay. The assay was also performed on genomic DNA (gDNA) from tumor and normal tissue from 20 of these patients. The lower limit of detection for most sequence variants was in the range of 10-5, while when analyzing cfDNA from plasma with a typical input of 33 ng, the practical detection limit was ~10-4 or 0.01% mutant allele frequency (MAF). In 17 of 19 patients with identified hotspot mutations in tumor gDNA, at least one hotspot mutation could be detected in plasma DNA at the time of diagnosis. The MAF increased at subsequent time points in four of the patients who experienced a clinical relapse. Multiplex superRCA analysis of the remaining six patients did not reveal any hotspot mutations. In conclusion, multiplex superRCA assays proved suitable for monitoring CRC patients by analyzing hotspot mutations in cfDNA, and dynamic changes in MAF were observed in patients with clinical relapse.

Contamination and Carcinogenic Risks of Lead in Lip Cosmetics in China.

There are growing concerns about elevated lead (Pb) levels in lip cosmetics, yet in China, the largest lip cosmetic market, recent Pb contamination in lip cosmetics and associated Pb exposure remain unclear. Here, we measured Pb levels of 29 popular lip cosmetics in China and conducted the bioaccessibility-corrected carcinogenic risk assessments and sensitivity analysis regarding Pb exposure for consumers using Monte Carlo simulation. The Pb concentrations of collected samples ranged from undetectable (< 0.05 µg/kg) to 0.21 mg/kg, all of which were well below the Pb concentration limit set for cosmetics in China (10 mg/kg). The 50th percentile incremental lifetime cancer risk (ILCR) of Pb in Chinese cosmetics (1.20E-07) was below the acceptable level (1E-06), indicating that the application of lip cosmetics and subsequent Pb exposure does not pose carcinogenic risks to consumers in most cases. The results of this study provide new insights into understanding the Pb risk in lip cosmetics.

A hidden demethylation pathway removes mercury from rice plants and mitigates mercury flux to food chains.

Dietary exposure to methylmercury (MeHg) causes irreversible damage to human cognition and is mitigated by photolysis and microbial demethylation of MeHg. Rice (Oryza sativa L.) has been identified as a major dietary source of MeHg. However, it remains unknown what drives the process within plants for MeHg to make its way from soils to rice and the subsequent human dietary exposure to Hg. Here we report a hidden pathway of MeHg demethylation independent of light and microorganisms in rice plants. This natural pathway is driven by reactive oxygen species generated in vivo, rapidly transforming MeHg to inorganic Hg and then eliminating Hg from plants as gaseous Hg°. MeHg concentrations in rice grains would increase by 2.4- to 4.7-fold without this pathway, which equates to intelligence quotient losses of 0.01-0.51 points per newborn in major rice-consuming countries, corresponding to annual economic losses of US$30.7-84.2 billion globally. This discovered pathway effectively removes Hg from human food webs, playing an important role in exposure mitigation and global Hg cycling.

Atypical (non-V600E) BRAF mutations in metastatic colorectal cancer in population and real-world cohorts.

BRAF-V600E mutation (mt) is a strong negative prognostic and predictive biomarker in metastatic colorectal cancer (mCRC). Non-V600Emt, designated atypical BRAFmt (aBRAFmt) are rare, and little is known about their frequency, co-mutations and prognostic and predictive role. These were compared between mutational groups of mCRC patients collected from three Nordic population-based or real-world cohorts. Pathology of aBRAFmt was studied. The study included 1449 mCRC patients with 51 (3%) aBRAFmt, 182 (13%) BRAF-V600Emt, 456 (31%) RAS&BRAF wild-type (wt) and 760 (52%) RASmt tumours. aBRAFmt were seen in 2% of real-world and 4% of population-based cohorts. Twenty-six different aBRAFmt were detected, 11 (22%) class 2 (serrated adenocarcinoma in 2/9 tested), 32 (64%) class 3 (serrated in 15/25) and 4 (8%) unclassified. aBRAFmt patients were predominantly male, had more rectal primaries, less peritoneal metastases, deficient mismatch repair in one (2%), and better survival after metastasectomy (89% 5-year overall survival [OS]-rate) compared with BRAF-V600Emt. aBRAFmt and BRAF-V600Emt had poorer performance status and received fewer treatment lines than RAS&BRAFwt and RASmt. OS among aBRAFmt (median 14.4 months) was longer than for BRAF-V600Emt (11.2 months), but shorter than for RAS&BRAFwt (30.5 months) and RASmt (23.4 months). Addition of bevacizumab trended for better OS for the aBRAFmt. Nine patients with aBRAFmt received cetuximab/panitumumab without response. aBRAFmt represents a distinct subgroup differing from other RAS/BRAF groups, with serrated adenocarcinoma in only half. OS for patients with aBRAFmt tumours was slightly better than for BRAF-V600Emt, but worse than for RASmt and RAS&BRAFwt. aBRAFmt should not be a contraindication for metastasectomy.

Recurring EPHB1 mutations in human cancers alter receptor signalling and compartmentalisation of colorectal cancer cells.

BACKGROUND: Ephrin (EPH) receptors have been implicated in tumorigenesis and metastasis, but the functional understanding of mutations observed in human cancers is limited. We previously demonstrated reduced cell compartmentalisation for somatic EPHB1 mutations found in metastatic colorectal cancer cases. We therefore integrated pan-cancer and pan-EPH mutational data to prioritise recurrent EPHB1 mutations for functional studies to understand their contribution to cancer development and metastasis. METHODS: Here, 79,151 somatic mutations in 9,898 samples of 33 different tumour types were analysed with a bioinformatic pipeline to find 3D-mutated cluster pairs and hotspot mutations in EPH receptors. From these, 15 recurring EPHB1 mutations were stably expressed in colorectal cancer followed by confocal microscopy based in vitro compartmentalisation assays and phospho-proteome analysis. RESULTS: The 3D-protein structure-based bioinformatics analysis resulted in 63% EPHB1 mutants with compartmentalisation phenotypes vs 43% for hotspot mutations. Whereas the ligand-binding domain mutations C61Y, R90C, and R170W, the fibronectin domain mutation R351L, and the kinase domain mutation D762N displayed reduced to strongly compromised cell compartmentalisation, the kinase domain mutations R743W and G821R enhanced this phenotype. While mutants with reduced compartmentalisation also had reduced ligand induced receptor phosphorylation, the enhanced compartmentalisation was not linked to receptor phosphorylation level. Phosphoproteome mapping pinpointed the PI3K pathway and PIK3C2B phosphorylation in cells harbouring mutants with reduced compartmentalisation. CONCLUSIONS: This is the first integrative study of pan-cancer EPH receptor mutations followed by in vitro validation, a robust way to identify cancer-causing mutations, uncovering EPHB1 mutation phenotypes and demonstrating the utility of protein structure-based mutation analysis in characterization of novel cancer genes. Video Abstract.

Microplastics in feces and pellets from yellow-legged gull (Larus michahellis) in the Atlantic Islands National Park of Galicia (NW Spain).

The Atlantic Islands National Park (AINP) in Galicia (NW of Spain) are host to large colonies of yellow-legged gulls (Larus michahellis). Here, we aimed to provide baseline data for the presence of microplastics (MP) in feces and pellets regurgitated of these resident yellow-legged gulls within this unique ecosystem. MP particles found in the samples were of five shapes (fiber, fragment, foam, film and rubber) and the predominant color was blue. The main plastic polymers identified by Raman spectroscopy were polypropylene and cellulose. The average size of the MP particles in the regurgitations was larger than that in the feces. Considering the population of Larus michahellis in the AINP, our estimates suggested an annual deposition of approximately 32.2 million of MP particles from feces and regurgitated pellets in the area.

[Functional dyspepsia : update 2023]. / Dyspepsie fonctionnelle : update 2023.

Functional dyspepsia is defined by epigastric pain/burning, postprandial fullness and/or early satiety that have been present for at least six months before diagnosis, including three consecutive months, without evidence of an organic cause likely to explain these symptoms. The pathogenesis is complex and incompletely understood. The initial assessment includes a thorough history, physical examination, blood work, celiac disease serology and ruling out Helicobacter pylori infection. Most patients will undergo upper gastrointestinal endoscopy and abdominal ultrasound to exclude organic differential diagnoses. The therapy is multi-facetted and includes, among others, proton pump inhibitors, Helicobacter pylori eradication, herbal agents, and neuromodulators.

La dyspepsie fonctionnelle est définie par la présence d'un ou plusieurs des symptômes suivants : douleur/brûlure épigastrique, plénitude postprandiale, satiété précoce qui doivent être présents depuis au moins six mois avant le diagnostic, dont trois mois consécutifs, sans qu'il y ait de preuve d'une cause organique. La physiopathologie est complexe et mal comprise. Le bilan initial comprend une anamnèse approfondie, un examen physique, un bilan sanguin, une sérologie de la maladie cœliaque et écarter une infection à Helicobacter pylori. Une gastroscopie et un ultrason abdominal sont indiqués chez la majorité des patients afin d'exclure les diagnostics différentiels organiques. Le traitement est multiple et comprend les inhibiteurs de la pompe à proton, l'éradication d'Helicobacter pylori, la phytothérapie et les neuromodulateurs.

Assessment of variations in air quality in cities of Ecuador in relation to the lockdown due to the COVID-19 pandemic.

This study analyzes the effect of lockdown due to COVID-19 on the spatiotemporal variability of ozone (O3), sulfur dioxide (SO2), and nitrogen dioxide (NO2) concentrations in different provinces of continental Ecuador using satellite information from Sentinel - 5P. The statistical analysis includes data from 2018 to March 2021 and was performed based on three periods defined a priori: before, during, and after lockdown due to COVID-19, focusing on the provinces with the highest concentrations of the studied gases (hotspots). The results showed a significant decrease in NO2 concentrations during the COVID-19 lockdown period in all the study areas: the Metropolitan District of Quito (DMQ) and the provinces of Guayas and Santo Domingo de los Tsáchilas. In the period after lockdown, NO2 concentrations increased by over 20% when compared to the pre-lockdown period, which may be attributable to a shift towards private transportation due to health concerns. On the other hand, SO2 concentrations during the lockdown period showed irregular, non-significant variations; however, increases were observed in the provinces of Chimborazo, Guayas, Santa Elena, and Morona Santiago, which could be partly attributed to the eruptive activity of the Sangay volcano during 2019-2020. Conversely, O3 concentrations increased by 2-3% in the study areas; this anomalous behavior could be attributed to decreased levels of NOx, which react with ozone, reducing its concentration. Finally, satellite data validation using the corresponding data from monitoring stations in the DMQ showed correlation values of 0.9 for O3 data and 0.7 for NO2 data, while no significant correlation was found for SO2.

Age-dependent memory impairment induced by co-exposure to nicotine and a synthetic cannabinoid in mice.

Co-use of marijuana and tobacco products is the second most common drug combination among adolescents. Nicotine (NIC) and cannabinoid use during adolescence induce similar detrimental changes, raising the hypothesis that simultaneous exposure could result in even more severe outcomes. Thus, we investigated whether the co-exposure to NIC and the synthetic cannabinoid WIN 55,212-2 (WIN) in adolescent mice causes behavioral outcomes different from those observed after exposure to a single drug. Male Swiss mice were exposed twice daily to NIC, WIN, or NIC + WIN during adolescence (PND28-47) or adulthood (PND70-89). Drug combination led to a greater reduction in weight gain in adolescent mice, while NIC-induced weight loss was observed in adults. During administration, NIC provoked hypothermia, and WIN produced hyperlocomotion in adolescent and adult mice. Animals exposed to NIC + WIN presented a profile of changes similar to those exposed to NIC. After drug exposure, changes in locomotion, thigmotaxis, social preference, prepulse inhibition, and working and recognition memory were evaluated. Adolescent but not adult mice exposed to NIC showed withdrawal-related hyperlocomotion unaffected by WIN co-administration. An age-specific impairment in object recognition memory was induced only by drug co-exposure during adolescence, which resolved spontaneously before reaching early adulthood. A transient decrease in hippocampal α7 nAChR subunit and CB1 receptor mRNA levels was induced by NIC exposure, which may be involved but is not enough to explain the memory impairment. Our work confirms the potential of NIC and cannabinoids association to aggravate some of the individual drug effects during critical neurodevelopmental periods.

Trophic transfer of silver nanoparticles shifts metabolism in snails and reduces food safety.

Food security and sustainable development of agriculture has been a key challenge for decades. To support this, nanotechnology in the agricultural sectors increases productivity and food security, while leaving complex environmental negative impacts including pollution of the human food chains by nanoparticles. Here we model the effects of silver nanoparticles (Ag-NPs) in a food chain consisting of soil-grown lettuce Lactuca sativa and snail Achatina fulica. Soil-grown lettuce were exposed to sulfurized Ag-NPs via root or metallic Ag-NPs via leaves before fed to snails. We discover an important biomagnification of silver in snails sourced from plant root uptake, with trophic transfer factors of 2.0-5.9 in soft tissues. NPs shifts from original size (55-68 nm) toward much smaller size (17-26 nm) in snails. Trophic transfer of Ag-NPs reprograms the global metabolic profile by down-regulating or up-regulating metabolites for up to 0.25- or 4.20- fold, respectively, relative to the control. These metabolites control osmoregulation, phospholipid, energy, and amino acid metabolism in snails, reflecting molecular pathways of biomagnification and pontential adverse biological effects on lower trophic levels. Consumption of these Ag-NP contaminated snails causes non-carcinogenic effects on human health. Global public health risks decrease by 72% under foliar Ag-NP application in agriculture or through a reduction in the consumption of snails sourced from root application. The latter strategy is at the expense of domestic economic losses in food security of $177.3 and $58.3 million annually for countries such as Nigeria and Cameroon. Foliar Ag-NP application in nano-agriculture has lower hazard quotient risks on public health than root application to ensure global food safety, as brought forward by the United Nations Sustainable Development Goals.

Eosinophilic Esophagitis beyond Eosinophils - an Emerging Phenomenon Overlapping with Eosinophilic Esophagitis: Collegium Internationale Allergologicum (CIA) Update 2023.

Having long been considered the mainstay in eosinophilic esophagitis (EoE) diagnosis and pathogenesis, the role of eosinophils has been questioned and might be less important than previously thought. It is well known now that EoE is a Th2-mediated disease with many more disease features than eosinophilic infiltration. With more knowledge on EoE, less pronounced phenotypes or nuances of the disease have become apparent. In fact, EoE might be only the tip of the iceberg (and the most extreme phenotype) with several variant forms, at least three, lying on a disease spectrum. Although a common (food induced) pathogenesis has yet to be confirmed, gastroenterologists and allergologists should be aware of these new phenomena in order to further characterize these patients. In the following review, we discuss the pathogenesis of EoE, particularly those mechanisms beyond eosinophilic infiltration of the esophageal mucosa, non-eosinophilic inflammatory cell populations, the new disease entity EoE-like disease, variant forms of EoE, and the recently coined term mast cell esophagitis.

Eccentric exercise is more effective than other exercises in the treatment of mid-portion Achilles tendinopathy: systematic review and meta-analysis.

Achilles tendinopathy (AT) is one of the most frequent overuse injuries in the ankle. The evidence base for its conservative management AT continues to evolve, but there is still a gap in the evidence for the efficacy of any modality of treatment in high-quality studies. This systematic review and meta-analysis investigated the efficacy of EE in improving pain and function in adult patients with mid-portion Achilles tendinopathy compared to other forms of exercise. A search was performed in PubMed, BIREME, SportDiscus, Cinahl, Web of Science and PEDro, in November 2022. The methodological quality was evaluated using the Risk of Bias 2 tool (RoB2) of the Cochrane collaboration, and the meta-analysis was performed using the Review Manager 5.1 program. 2024 articles were identified and eight fulfilled the inclusion criteria. RoB2 presented a final score with 62.5% of the studies presented "some concerns", and 37.5% (five and three articles, respectively) presenting "high risk" of bias. EE was effective for the managment of AT. The only variable for which a meta-analysis was possible was pain (five articles), analysed with the visual analogue scale/numerical visual scale. The mean difference (MD) in treatment effect using EE was - 1.21 (- 2.72 to - 0.30) with a 95% of confidence interval (CI), thus identifying a significant positive effect for the improvement of pain in patients with AT in whom EE was used. EE is effective in the management of AT. The meta-analysis shows the need for appropriately powered randomized controlled trials with better design, the use of standard outcome measures and well-planned protocols for conservative management of AT.Level of evidence: Level 1.Registration: CRD42018118016.

Promoção de saúde e qualidade de vida dos universitários em tempos de pandemia: a experiência de um curso de extensão

Objetivos: Este artigo apresenta o relato da experiência do curso/workshop RENASCERES®: saúde e qualidade de vida dos universitários em tempos de pandemia", realizado em uma universidade federal no Estado de Minas Gerais (MG), que teve o objetivo de criar espaço de diálogo, acolhimento, escuta e de construção de alternativas mediante demandas discentes, decorrentes do período de pandemia de COVID-19. Objetivou também fomentar propostas para a ampliação das condições de saúde e da qualidade de vida dos universitários e de suas famílias. Métodos: O curso foi estruturado em cinco encontros virtuais, com formato de workshop, fundamentados na metodologia dialógica e no método de Círculo de Cultura, articulando o conteúdo teórico aliado às atividades práticas e ao cotidiano dos participantes. Resultados: Participaram do curso 77 pessoas, incluindo universitários de diferentes cursos de graduação e profissionais. As reflexões sobre saúde e qualidade de vida e o atual contexto de pandemia, bem como as atividades práticas, geraram espaço de acolhimento, escuta-ativa, cuidado, acesso e troca de informações/novos conhecimentos. Conclusões: O curso/workshop possibilitou o reconhecimento da necessidade de investimentos em Promoção de saúde e qualidade de vida pelos participantes. Constatou-se, nesta atividade, a essencialidade do Método RENASCERES® como alternativa para dar suporte aos participantes nos cuidados em saúde, mudanças em suas rotinas e pilar para que as pessoas possam alcançar estilos de vida saudáveis.Palavras-chave: Educação para a saúde; Promoção da saúde; Qualidade de vida; Covid-19; Saúde Coletiva; Comunicação em saúde.

[Differential diagnosis and investigation of chronic diarrhea]. / Diagnostic différentiel et investigation de la diarrhée chronique.

Chronic diarrhea is defined by a decrease in stool consistency and a bowel frequency of more than 3 times per day, lasting for at least 4 weeks. Multiple underlying causes may be responsible for chronic diarrhea. There are four main pathomechanisms for chronic diarrhea: osmotic diarrhea, secretory diarrhea, infectious diarrhea and bowel dysmotility. Overlaps between these mechanisms may exist. A stool collection over a 72-hour period frequently allows to classify diarrhea into one of these four entities. Such classification finally helps for the identification of underlying cause(s), thereby allowing rational diagnostic measures. It also limits the costs of diagnostic workup. This article aims to present the main causes of chronic diarrhea, the diagnostic steps to perform and to provide a guideline for clinicians in daily practice.

La diarrhée chronique est définie par une diminution de la consistance des selles (défaites à liquides) et par une émission de selles supérieure à 3 ×/jour pendant plus de 4 semaines. Les raisons peuvent être multiples. Quatre pathomécanismes peuvent être à l'origine de la diarrhée chronique : osmotique, sécrétoire, inflammatoire et motrice. Des chevauchements entre ces mécanismes peuvent exister. La récolte de selles pendant 72 heures permet, dans la majorité des cas, de clarifier la physiopathologie des diarrhées et donc d'identifier la cause sous-­jacente permettant d'effectuer des mesures diagnostiques rationnelles et de limiter les coûts. Cet article a pour objectif de présenter les principales causes de diarrhée chronique, d'énumérer les étapes diagnostiques à réaliser et de donner une ligne directrice aux cliniciens dans la pratique quotidienne.

[Metabolism and therapeutic monitoring of azathioprine in gastroenterology and hepatology]. / Métabolisme et suivi thérapeutique de l'azathioprine en gastroentérologie et hépatologie.

Azathioprine keeps an important place in the treatment of inflammatory bowel disease and autoimmune hepatitis. This molecule has a narrow therapeutic margin, associated with a risk of toxicity, particularly hematological and hepatic. Its complex metabolism is subject to genetic polymorphisms that are reflected in the inter-individual variability observed in the response to treatment and its tolerance profile. Hence, its use requires a good knowledge of this molecule. Treatment is initiated after a preliminary workup, followed by a progressive titration of the dosage while closely monitoring possible toxicities. Monitoring of blood levels of metabolites (including active ones) helps guide personalized dose adjustment.

L'azathioprine garde actuellement une place importante dans le traitement des maladies inflammatoires chroniques de l'intestin et de l'hépatite autoimmune. Il s'agit d'une molécule à marge thérapeutique étroite, associée à un risque de toxicité, notamment hématologique et hépatique. Son métabolisme complexe est influencé par des polymorphismes génétiques qui sont reflétés dans la variabilité interindividuelle observée dans la réponse au traitement et le profil de tolérance. Son utilisation nécessite donc une bonne connaissance de cette molécule. L'instauration du traitement se fait après un bilan préalable, puis une titration progressive des posologies, tout en surveillant étroitement les éventuelles toxicités. Le monitoring des concentrations sanguines des métabolites (notamment actifs) permet de guider l'adaptation personnalisée des posologies.

Automated Android Malware Detection Using User Feedback.

The widespread usage of mobile devices and their seamless adaptation to each user's needs through useful applications (apps) makes them a prime target for malware developers. Malware is software built to harm the user, e.g., to access sensitive user data, such as banking details, or to hold data hostage and block user access. These apps are distributed in marketplaces that host millions and therefore have their forms of automated malware detection in place to deter malware developers and keep their app store (and reputation) trustworthy. Nevertheless, a non-negligible number of apps can bypass these detectors and remain available in the marketplace for any user to download and install on their device. Current malware detection strategies rely on using static or dynamic app extracted features (or a combination of both) to scale the detection and cover the growing number of apps submitted to the marketplace. In this paper, the main focus is on the apps that bypass the malware detectors and stay in the marketplace long enough to receive user feedback. This paper uses real-world data provided by an app store. The quantitative ratings and potential alert flags assigned to the apps by the users were used as features to train machine learning classifiers that successfully classify malware that evaded previous detection attempts. These results present reasonable accuracy and thus work to help to maintain a user-safe environment.

Maxillary Sinus Elevation Using the Bone Ring Technique with Immediate Implantation: A Case Report.

Compared to other areas of the oral cavity, an edentulous posterior maxilla poses a unique challenge for implant placement. The most important aspect to consider is the maxillary sinus. This paper describes a case in which the bone ring technique was used to raise the floor of the maxillary sinus, followed by immediate implantation. A 37-year-old woman presented with a ridge defect in the left maxilla and the absence of teeth 26 and 27 (FDI tooth-numbering system) on the same side. The treatment plan involved the extraction of tooth 25, periodontal regeneration on the distal face of tooth 24, and concomitant raising of the maxillary sinus (using the bone ring technique) with simultaneous implantation. The bone ring technique promotes bone augmentation, raises the maxillary sinus, and reduces the surgical time, surgical costs, and length of the rehabilitation period. In the case presented herein, bone tissue stability around the implants, ridge maintenance, and gingival margin stability were found at the 1-year follow-up after rehabilitation.