👤 Samuel Abecassis

We aimed to assess differences in (1) first-pass intubation success, (2) frequency of a hypoxic event, and (3) time from decision to intubate to successful intubation among direct laryngoscopy (DL) versus video laryngoscopy (VL) intubations in emergency department (ED) patients with traumatic injuries. This retrospective cohort study was performed at a Level I trauma center ED where trauma activations are video recorded. All patients requiring a Level I trauma activation and intubation from 2016 through 2019 were included. Multivariable logistic regression was used to assess the association between initial method of intubation and first-pass success. Differences in frequency of a hypoxic event and time to successful intubation were assessed using bivariate tests. Of 164 patients, 68 (41.5%) were initially intubated via DL and 96 (58.5%) were initially intubated via VL. First-pass success for DL and VL were 63.2% and 79.2%, respectively. In multivariable regression analysis, VL was associated with higher odds of first-pass intubation success compared with DL (odds ratio: 2.28; 95% confidence interval: 1.04, 4.98), independent of mechanism of injury, presence of airway hemorrhage or obstruction, and experience of intubator. Frequency of a hypoxic event during intubation was not significantly different (13.2% for DL and 7.3% VL; Video laryngoscopy, compared with direct laryngoscopy, was associated with higher odds of first-pass intubation success among a sample of ED trauma patients. Frequency of a hypoxic event during intubation and time to successful intubation was not significantly different between the 2 intubation methods. Show less

The unwinding of nucleic acid secondary structures within cells is crucial to maintain genomic integrity and prevent abortive transcription and translation initiation. DHX36, also known as RHAU or G4R1, is a DEAH-box ATP-dependent helicase highly specific for DNA and RNA G-quadruplexes (G4s). A fundamental mechanistic understanding of the interaction between helicases and their G4 substrates is important to elucidate G4 biology and pave the way toward G4-targeted therapies. Here we analyze how the thermodynamic stability of G4 substrates affects binding and unwinding by DHX36. We modulated the stability of the G4 substrates by varying the sequence and the number of G-tetrads and by using small, G4-stabilizing molecules. We found an inverse correlation between the thermodynamic stability of the G4 substrates and rates of unwinding by DHX36. In stark contrast, the ATPase activity of the helicase was largely independent of substrate stability pointing toward a decoupling mechanism akin to what has been observed for many double-stranded DEAD-box RNA helicases. Our study provides the first evidence that DHX36 uses a local, non-processive mechanism to unwind G4 substrates, reminiscent of that of eukaryotic initiation factor 4A (eIF4A) on double-stranded substrates. Show less

Propensity for subsequent distant metastasis in head and neck squamous-cell carcinoma (HNSCC) was analysed using 186 primary tumours from patients initially treated by surgery that developed (M) or did not develop (NM) metastases as the first recurrent event. Transcriptome (Affymetrix HGU133_Plus2, QRT-PCR) and array-comparative genomic hybridization data were collected. Non-supervised hierarchical clustering based on Affymetrix data distinguished tumours differing in pathological differentiation, and identified associated functional changes. Propensity for metastasis was not associated with these subgroups. Using QRT-PCR data we identified a four-gene model (PSMD10, HSD17B12, FLOT2 and KRT17) that predicts M/NM status with 77% success in a separate 79-sample validation group of HNSCC samples. This prediction is independent of clinical criteria (age, lymph node status, stage, differentiation and localization). The most significantly altered transcripts in M versus NM were significantly associated to metastasis-related functions, including adhesion, mobility and cell survival. Several genomic modifications were significantly associated with M/NM status (most notably gains at 4q11-22 and Xq12-28; losses at 11q14-24 and 17q11 losses) and partly linked to transcription modifications. This work yields a basis for the development of prognostic molecular signatures, markers and therapeutic targets for HNSCC metastasis. Show less