A cohort study reveals different dynamics of SARS-CoV-2-specific antibody formation after Comirnaty and Vaxzevria vaccination.

The Coronavirus (COVID-19) Disease Pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has affected millions of people worldwide, prompting a collective effort from the global scientific community to develop a vaccine against it. This study purports to investigate the influence of factors such as sex, age, type of vaccination (Comirnaty, BNT162b2, Pfizer Inc. or Vaxzevria, ChAdOx1-S, Oxford/AstraZeneca), and time since vaccine administration on the process of antibody production. Both of them are based on the introduction of SARS-CoV-2 spike protein (S protein) to the body using different mechanisms (mRNA and recombinant adenovirus, respectively). S protein is responsible for host cell attachment and penetration via its receptor-binding domain (RBD domain). The level of anti-RBD IgG antibodies was tested with an ELISA-based immunodiagnostic assay in serum samples from a total of 1395 patients at 3 time points: before vaccination, after the first dose, and after the second dose. Our novel statistical model, the Generalized Additive Model, revealed variability in antibody production dynamics for both vaccines. Interestingly, no discernible variation in antibody levels between men and women was found. A nonlinear relationship between age and antibody production was observed, characterized by decreased antibody levels for people up to 30 and over 60 years of age, with a lack of correlation in the middle age range. Collectively, our findings further the understanding of the mechanism driving vaccine-induced immunity. Additionally, we propose the Generalized Additive Model as a standardized way of presenting data in similar research.

Ultrasound-Guided Infraclavicular Axillary Vein Versus Internal Jugular Vein Cannulation in Critically Ill Mechanically Ventilated Patients: A Randomized Trial.

OBJECTIVES: This clinical trial aimed to compare the ultrasound-guided in-plane infraclavicular cannulation of the axillary vein (AXV) and the ultrasound-guided out-of-plane cannulation of the internal jugular vein (IJV). DESIGN: A prospective, single-blinded, open label, parallel-group, randomized trial. SETTING: Two university-affiliated ICUs in Poland (Opole and Lublin). PATIENTS: Mechanically ventilated intensive care patients with clinical indications for central venous line placement. INTERVENTIONS: Patients were randomly assigned into two groups: the IJV group ( n = 304) and AXV group ( n = 306). The primary outcome was to compare the IJV group and AXV group through the venipuncture and catheterization success rates. Secondary outcomes were catheter tip malposition and early mechanical complication rates. All catheterizations were performed by advanced residents and consultants in anesthesiology and intensive care. MEASUREMENTS AND MAIN RESULTS: The IJV puncture rate was 100%, and the AXV was 99.7% (chi-square, p = 0.19). The catheterization success rate in the IJV group was 98.7% and 96.7% in the AXV group (chi-square, p = 0.11). The catheter tip malposition rate was 9.9% in the IJV group and 10.1% in the AXV group (chi-square, p = 0.67). The early mechanical complication rate in the IJV group was 3% (common carotid artery puncture-4 cases, perivascular hematoma-2 cases, vertebral artery puncture-1 case, pneumothorax-1 case) and 2.6% in the AXV group (axillary artery puncture-4 cases, perivascular hematoma-4 cases) (chi-square, p = 0.79). CONCLUSIONS: No difference was found between the real-time ultrasound-guided out-of-plane cannulation of the IJV and the infraclavicular real-time ultrasound-guided in-plane cannulation of the AXV. Both techniques are equally efficient and safe in mechanically ventilated critically ill patients.

Sustainable recovery of MBNL activity in autoregulatory feedback loop in myotonic dystrophy.

Muscleblind-like proteins (MBNLs) are RNA-binding proteins essential for the developmental regulation of various processes including alternative splicing. Their activity is misregulated in myotonic dystrophy type 1 (DM1), an incurable genetic, neuro-muscular disorder caused by uncontrolled expansion of CTG repeats. Mutant RNAs containing hundreds or thousands of repeats efficiently sequester MBNL proteins. As a consequence, global alternative splicing abnormalities are induced. Importantly, the size of expansion differs significantly not only between patients but also between different parts of the same muscle as a consequence of somatic expansion. One of the potential therapeutic strategies in DM is overexpression of MBNLs. However, gene therapy tools might induce excessive activity of MBNLs, what in turn might change the metabolism of many RNAs. To overcome these limitations, we designed an autoregulated MBNL1 overexpression system. The genetic construct contains an MBNL1-coding sequence separated by the fragment of ATP2A1 pre-mRNA with an MBNL-sensitive alternative exon containing stop codon in the reading frame of MBNL1. Inclusion of this exon leads to the arrangement of an inactive form of the protein, but exclusion gives rise to fully active MBNL1. This approach enables the autoregulation of the amount of overexpressed MBNL1 with high dynamic range which ensures a homogeneous level of this protein in cells treated with the genetic construct. We demonstrated beneficial effects of an autoregulated construct on alternative splicing patterns in DM1 models and cells derived from patients with DM1.