Sequencing of monkeypox virus from infected patients reveals viral genomes with APOBEC3-like editing, gene inactivation, and bacterial agents of skin superinfection.

A large outbreak of Monkeypox virus (MPXV) infections has arisen in May 2022 in nonendemic countries. Here, we performed DNA metagenomics using next-generation sequencing with Illumina or Nanopore technologies for clinical samples from MPXV-infected patients diagnosed between June and July 2022. Classification of the MPXV genomes and determination of their mutational patterns were performed using Nextclade. Twenty-five samples from 25 patients were studied. A MPXV genome was obtained for 18 patients, essentially from skin lesions and rectal swabbing. All 18 genomes were classified in clade IIb, lineage B.1, and we identified four B.1 sublineages (B.1.1, B.1.10, B.1.12, B.1.14). We detected a high number of mutations (range, 64-73) relatively to a 2018 Nigerian genome (genome GenBank Accession no. NC_063383.1), which were harbored by a large part of a set of 3184 MPXV genomes of lineage B.1 recovered from GenBank and Nextstrain; and we detected 35 mutations relatively to genome ON563414.3 (a B.1 lineage reference genome). Nonsynonymous mutations occurred in genes encoding central proteins, among which transcription factors and core and envelope proteins, and included two mutations that would truncate a RNA polymerase subunit and a phospholipase d-like protein, suggesting an alternative start codon and gene inactivation, respectively. A large majority (94%) of nucleotide substitutions were G > A or C > U, suggesting the action of human APOBEC3 enzymes. Finally, >1000 reads were identified as from Staphylococcus aureus and Streptococcus pyogenes for 3 and 6 samples, respectively. These findings warrant a close genomic monitoring of MPXV to get a better picture of the genetic micro-evolution and mutational patterns of this virus, and a close clinical monitoring of skin bacterial superinfection in monkeypox patients.

Adult ADHD Diagnosis, Symptoms of Impulsivity, and Emotional Dysregulation in a Clinical Sample of Outpatients Consulting for a Behavioral Addiction.

OBJECTIVE: This study aimed to investigate ADHD in adult outpatients seeking treatment for a behavioral addiction and to identify the specificity of psychopathological features if the behavioral addiction cooccurs with adult ADHD. METHOD: Sixty-five outpatients consulting for a behavioral addiction were assessed for ADHD (DIVA-5), addictive disorder (alcohol, tobacco, cannabis, gambling, gaming, food, and sex), impulsivity (UPPS-P), and emotion dysregulation (DERS-36). RESULTS: In our sample of outpatients seeking treatment for a behavioral addiction, adult ADHD was independently associated with higher compulsive sexual behavior disorder severity, "sensation seeking," "positive urgency," difficulties in "goal-directed behavior," "impulse control," and use of "emotion regulation strategies" in the context of intense emotions. A 29% of the sample was diagnosed for adult ADHD. CONCLUSION: The association of adult ADHD with specific dimensions of impulsivity and emotion dysregulation, pave the way for future clinical and research perspectives.

Thrombosis and antiphospholipid antibody syndrome during acute Q fever: A cross-sectional study.

Q fever is a neglected and potentially fatal disease. During acute Q fever, antiphospholipid antibodies are very prevalent and have been associated with fever, thrombocytopenia, acquired heart valve disease, and progression to chronic endocarditis. However, thrombosis, the main clinical criterion of the 2006 updated classification of the antiphospholipid syndrome, has not been assessed in this context. To test whether thrombosis is associated with antiphospholipid antibodies and whether the criteria for antiphospholipid syndrome can be met in patients with acute Q fever, we conducted a cross-sectional study at the French National Referral Center for Q fever.Patients included were diagnosed with acute Q fever in our Center between January 2007 and December 2015. Each patient's history and clinical characteristics were recorded with a standardized questionnaire. Predictive factors associated with thrombosis were assessed using a rare events logistic regression model. IgG anticardiolipin antibodies (IgG aCL) assessed by an enzyme-linked immunosorbent assay were tested on the Q fever diagnostic serum. A dose-dependent relationship between IgG aCL levels and thrombosis was tested using a receiver operating characteristic (ROC) analysis.Of the 664 patients identified for inclusion in the study, 313 (47.1%) had positive IgG aCL and 13 (1.9%) were diagnosed with thrombosis. Three patients fulfilled the antiphospholipid syndrome criteria. After multiple adjustments, only positive IgG aCL (relative risk, 14.46 [1.85-113.14], P = .011) were independently associated with thrombosis. ROC analysis identified a dose-dependent relationship between IgG aCL levels and occurrence of thrombosis (area under curve, 0.83, 95%CI [0.73-0.93], P < .001).During acute Q fever, antiphospholipid antibodies are associated with thrombosis, thrombocytopenia, and acquired valvular heart disease. Antiphospholipid antibodies should be systematically assessed in acute Q fever patients. Hydroxychloroquine, which has been previously shown to antagonize IgG aCL pathogenic properties, should be tested in acute Q fever patients with anticardiolipin antibodies to prevent antiphospholipid-associated complications.Key Point: In addition to fever, thrombocytopenia and acquired valvular heart disease, antiphospholipid antibodies are associated with thrombosis during acute Q fever.

In vitro stability study of methotrexate in blood and plasma samples for routine monitoring.

A study was conducted to assess the stability of methotrexate (MTX) in pooled plasma and whole blood samples during an 11-day period. The concentrations were determined by liquid chromatography with UV detection over time, in the dark or in light, at different temperatures (4 degrees C or room temperature), and for a low and a high concentration level (0.6 and 2.5 microg/mL, 1.32 and 5.5 micromol/L, respectively). The accuracy, linearity, and variability of the method were assessed. This work demonstrates that blood samples are stable for 2 days at room temperature and for 6 days at 4 degrees C. Furthermore, there is no significant loss (<17%) in plasma at any of the investigated temperatures for at least 6 days. This study shows that whole blood samples can be stored for 3 days before centrifugation and that plasma samples can be reanalyzed after 6 days without any loss.