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Golimumab (GLM) is the latest anti-tumor necrosis factor (TNF) that gained its marketing license. Thanks to the PURSUIT induction and maintenance trials, it was approved for the treatment of ulcerative colitis (UC) in 2013. The other anti-TNF drugs available are infliximab and adalimumab. These two drugs have validated algorithms concerning prescription and therapeutic drug monitoring (TDM) but little is known about GLM. The available data on GLM’s exposure–response relationship in UC are from the PURSUIT trials and are recently published. The data reveal all the factors that may impact the pharmacokinetic (PK) parameters: dosage, body weight (BW), concomitant drugs, the presence of anti-drug antibodies (ADAbs), sex and age. In addition, the GLM trough level at steady-state appears to be correlated with the patient’s improvement which may make it a precious indicator to predict the clinical response. There is, however, no consensus on a possible therapeutic level or cutoff associated with clinical response, remission, or any other outcome measure such as endoscopic healing in UC. This lack of a threshold value, and its validation with different assay techniques, makes it difficult to use GLM TDM in clinical practice. As with other anti-TNF agents, GLM is associated with development of ADAbs, of which the prevalence and effects are still insufficiently described. The objective of this review is to describe current data and understanding of the PK of GLM including serum concentrations of GLM and ADAbs in UC patients. Better understanding of these parameters could lead to improved patient care with GLM.

Objective Intellectual Disability (ID) represents a neuropsychiatric disorder, which its etiopathogenesis remains insufficiently understood. Mutations in the Aristaless Related Homeobox gene ( ARX ) have been identified to cause syndromic and nonsyndromic (NS-ID). The most recurrent mutation of this gene is a duplication of 24pb, c.428-451dup. Epidemiological and genetic studies about ID in the Moroccan population remain very scarce, and none study is carried out on the ARX gene. This work aimed to study c.428–451dup (24 bp) mutation in the exon 2 of the ARX gene in 118 males’ Moroccan patients with milder NS-ID to evaluate if the gene screening is a good tool for identifying NS-ID. Results Our mutational analysis did not show any dup(24pb) in our patients. This is because based on findings from previous studies that found ARX mutations in 70% of families with NS-ID, and in most cases, 1.5–6.1% of individuals with NS-ID have this duplication. Since 1/118 = 0.0084 (0.84%) is not much different from 1.5%, then it is reasonable that this could a sample size artifact. A complete screening of the entire ARX gene, including the five exons, should be fulfilled. Further investigations are required to confirm these results.

(1) Background: Congenital erythropoietic porphyria (CEP), named Günther’s disease, is a rare recessive type of porphyria, resulting from deficient uroporphyrinogen III synthase (UROS), the fourth enzyme of heme biosynthesis. The phenotype ranges from extremely severe perinatal onset, with life-threatening hemolytic anaemia, to mild or moderate cutaneous involvement in late-onset forms. This work reviewed the perinatal CEP cases recorded in France in order to analyse their various presentations and evolution. (2) Methods: Clinical and biological data were retrospectively collected through medical and published records. (3) Results: Twenty CEP cases, who presented with severe manifestations during perinatal period, were classified according to the main course of the disease: antenatal features, acute neonatal distress and postnatal diagnosis. Antenatal symptoms (seven patients) were mainly hydrops fetalis, hepatosplenomegaly, anemia, and malformations. Six of them died prematurely. Five babies showed acute neonatal distress, associated with severe anemia, thrombocytopenia, hepatosplenomegaly, liver dysfunction, and marked photosensitivity leading to diagnosis. The only two neonates who survived underwent hematopoietic stem cell transplantation (HSCT). Common features in post-natal diagnosis (eight patients) included hemolytic anemia, splenomegaly, skin sensitivity, and discoloured teeth and urine. All patients underwent HSCT, with success for six of them, but with fatal complications in two patients. The frequency of the missense variant named C73R is striking in antenatal and neonatal presentations, with 9/12 and 7/8 independent alleles, respectively. (4) Conclusions: The most recent cases in this series are remarkable, as they had a less fatal outcome than expected. Regular transfusions from the intrauterine period and early access to HSCT are the main objectives.

Objective The objective of the study is to characterize the pathomechanisms underlying actininopathies. Distal myopathies are a group of rare, inherited muscular disorders characterized by progressive loss of muscle fibers that begin in the distal parts of arms and legs. Recently, variants in a new disease gene, ACTN2, have been shown to cause distal myopathy. ACTN2, a gene previously only associated with cardiomyopathies, encodes alpha‐actinin‐2, a protein expressed in both cardiac and skeletal sarcomeres. The primary function of alpha‐actinin‐2 is to link actin and titin to the sarcomere Z‐disk. New ACTN2 variants are continuously discovered; however, the clinical significance of many variants remains unknown. Thus, lack of clear genotype–phenotype correlations in ACTN2‐related diseases, actininopathies, persists. Methods Functional characterization in C2C12 cell model of several ACTN2 variants is conducted, including frameshift and missense variants associated with dominant and recessive actininopathies. We assess the genotype–phenotype correlations of actininopathies using clinical data from several patients carrying these variants. Results The results show that the missense variants associated with a recessive form of actininopathy do not cause detectable alpha‐actinin‐2 aggregates in the cell model. Conversely, dominant frameshift variants causing a protein extension do form alpha‐actinin‐2 aggregates. Interpretation The results suggest that alpha‐actinin‐2 aggregation is the disease mechanism underlying some dominant actininopathies, and thus, we recommend that protein‐extending frameshift variants in ACTN2 should be classified as pathogenic. However, this mechanism is likely elicited by only a limited number of variants. Alternative functional characterization methods should be explored to further investigate other molecular mechanisms underlying actininopathies.

Abstract Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy that is deadly if not treated promptly. The treatment of choice in patients presenting with TTP is plasma exchanges. However, immunosuppressive therapy and caplacizumab have significantly improved outcomes in TTP. This microangiopathy is classically divided into 2 entities: hereditary and acquired TTP (aTTP), caused by an autoantibody against ADAMTS 13. We present a case study of a patient wth TTP occurring after a second dose of the BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine along with a review of the literature. A 55-year-old patient presented with gastrointestinal symptoms, anemia, and severe thrombocytopenia. The blood film revealed the presence of schistocytes. A diagnosis of aTTP was established because the patient had severe ADAMTS 13 deficiency and autoantibodies against ADAMTS 13 were positive. This episode occurred 10 days after the patient received the COVID-19 vaccine. The patient received plasma exchanges, prednisone, rituximab, and caplacizumab and achieved complete remission. Ten patients with aTTP induced by the COVID-19 vaccine have been reported in the literature. Most of these situations occurred after the second dose of COVID-19 vaccine, and 7 patients were noted to have received the BNT162b2 vaccine. Caplacizumab was used in 6 patients, and complete remission was achieved in 8 patients.

ObjectiveThe primary objective is to assess whether the POC assays to measure infliximab residual trough level in the serum of IBD patients were non-inferior to the ELISA techniques available on the market, and to determine which of them was the most robust. The second is to compare three different ELISA kits for monitoring anti-infliximab antibodies (ATI).MethodsThe assays were carried out on patients’ sera using four ELISA kits from four different suppliers (three with a monoclonal antibody and one polyclonal) and two rapid techniques provided by BÜHLMANN (Quantum Blue®) and R-Biopharm (Ridaquick) for monitoring infliximab levels. ATI were measured by three ELISA sets (Grifols, Theradiag, and R-Biopharm) which have different positivity limits and different units.ResultsWe measured infliximab residual level and ATI in the serum of 90 IBD patients (85 treated with infliximab and five with adalimumab). All of the infliximab assays were very well correlated when analyzed with Spearman nonparametric correlation (0.93 ≤ r ≤ 0.99), and the two POC assays were also excellently correlated (r = 0.98). The ATI monitoring kits revealed a correlation ranging from 0.73 to 0.96 when comparing positive and negative patients. When normalizing the quantitative values between the different ELISA tests (expressed arbitrarily by using multiples of the positivity limits defined by each supplier), the Spearman r coefficient ranged from 0.81 to 0.93.ConclusionThe available evidence allows us to conclude that all of the infliximab monitoring assays correlate well and may be used for IFX monitoring; albeit variations in measured IFX concentration among different assays remain present, these assays could be interchangeable. The ATI monitoring techniques are all capable of detecting ATI-positive patients, but because of the difference in the positivity limits and the measurement units, it is better to follow a patient rate with one definite kit.

The present work aimed to characterize leaves, stems, and flowers of Carissa macrocarpa (Eckl.) A.DC., by performing an analysis of the phenolic compounds by HPLC-DAD/ESI-MS, correlating them with bioactive properties, such as antioxidant, anti-inflammatory, cytotoxic, and antimicrobial activities. Thirty polyphenols were identified in the hydroethanolic extract, including phenolic acids, flavan-3-ols, and flavonol glycosides derivatives (which presented the highest number of identified compounds). However, flavan-3-ols showed the highest concentration in stems (mainly owing to the presence of dimers, trimmers, and tetramers of type B (epi)catechin). Leaves were distinguished by their high antioxidant and anti-inflammatory activities, as well as their bactericidal effect against E. coli, while stems presented a higher cytotoxic activity and bactericidal effect against Gram-positive bacteria. Moreover, a high correlation between the studied bioactivities and the presence of phenolic compounds was also verified. The obtained results bring added value to the studied plant species.

Background Research misconduct in the academic community remains poorly understood among post-graduate dental students (PGDSs) in North Africa. Data on the knowledge of research misconduct (KoRM) level in this population is lacking. This brief report assessed KoRM of Tunisian PGDSs’. Methods A cross-sectional study was conducted at the Faculty of Dental Medicine of Monastir, involving 147 PGDSs registered in 2022. Students were recruited via email invitations and convenience sampling at a medical congress. A French survey ( i.e. ; Laval University quiz) with 11 questions on KoRM, offering three-choice answers (yes/no/maybe) was administered. Each correct answer received one point, and a total score below six indicated a low-level of KoRM. Results The mean±SD KoRM score of the 106 students who accepted to participate in the study was 4.4±1.8, indicating a low-level of KoRM. The majority of PGDSs (85.85%) demonstrated a low-level of KoRM. A comparison between subjective and objective assessments of KoRM levels revealed that a significant percentage of PGDSs underestimated their knowledge (62.26% vs. 85.85%, respectively). Conclusion North-African PGDSs have a low-level of KoRM. This emphasizes the need for further efforts to enhance awareness and promote better KoRM in this population.

Background Plagiarism remains poorly understood among post-graduate dental students (PGDSs) in North Africa. Data on the level of understanding of plagiarism (UP) in this population is lacking. This study assessed UP of Tunisian PGDSs'. Methods A cross-sectional pilot study was conducted at the Faculty of Dental Medicine of Monastir, involving 147 PGDSs registered in 2022. Students were recruited via email invitations and convenience sampling at a medical congress. A French survey with 11 questions on UP, offering three-choice answers (yes/no/maybe) was administered. Each correct answer received one point, and a total UP score below six indicated a low-level of UP. Results The mean±SD UP score of the 106 students who accepted to participate in the study was 4.7±2.2, indicating a low-level of UP. The majority of PGDSs (81.13%) demonstrated a low-level of UP. A comparison between subjective and objective assessments of UP revealed that a significant percentage of PGDSs underestimated their understanding (81.13% vs. 62.26%, respectively). The two groups of PGDSs with low (n=86) and acceptable/excellent (n=20) UP showed comparable characteristics in terms of age, sex, discipline, post-graduate-level, experience-level, graduation-status, and survey-response modality. Conclusion This study highlights a lack of awareness of UP among North African PGDSs, emphasizing the need for further efforts to enhance awareness and promote better UP in this population.

Background Misconduct in the academic community remains poorly understood among post-graduate dental students (PGDSs) in North Africa. Data on the knowledge of misconduct (KoM) level in this population is lacking. This study assessed KoM of Tunisian PGDSs'. Methods A cross-sectional study was conducted at the Faculty of Dental Medicine of Monastir, involving 147 PGDSs registered in 2022. Students were recruited via email invitations and convenience sampling at a medical congress. A French survey with 11 questions on KoM, offering three-choice answers (yes/no/maybe) was administered. Each correct answer received one point, and a total score below six indicated a low-level of KoM. Results The mean±SD KoM score of the 106 students who accepted to participate in the study was 4.4±1.8, indicating a low-level of KoM. The majority of PGDSs (85.85%) demonstrated a low-level of KoM. A comparison between subjective and objective assessments of KoM levels revealed that a significant percentage of PGDSs underestimated their knowledge (62.26% vs. 85.85%, respectively). The two groups of PGDSs with low (n=91) and acceptable or excellent (n=15) KoM levels showed comparable characteristics in terms of age, sex, discipline, post-graduate-level, experience-level, graduation-status, and survey-response modality. Conclusion This study identified a low-level of KoM among North-African PGDSs. This emphasizes the need for further efforts to enhance awareness and promote better KoM in this population.