miRNA signatures associated with vulnerability to food addiction in mice and humans.

Food addiction is characterized by a loss of behavioral control over food intake and is associated with obesity and other eating disorders. The mechanisms underlying this behavioral disorder are largely unknown. We aimed to investigate the changes in miRNA expression promoted by food addiction in animals and humans and their involvement in the mechanisms underlying the behavioral hallmarks of this disorder. We found sharp similitudes between miRNA signatures in the medial prefrontal cortex (mPFC) of our animal cohort and circulating miRNA levels in our human cohort, which allowed us to identify several miRNAs of potential interest in the development of this disorder. Tough decoy (TuD) inhibition of miRNA-29c-3p in the mouse mPFC promoted persistence of the response and enhanced vulnerability to developing food addiction, whereas miRNA-665-3p inhibition promoted compulsion-like behavior and also enhanced food addiction vulnerability. In contrast, we found that miRNA-137-3p inhibition in the mPFC did not lead to the development of food addiction. Therefore, miRNA-29c-3p and miRNA-665-3p could be acting as protective factors with regard to food addiction. We believe the elucidation of these epigenetic mechanisms will lead to advances toward identifying innovative biomarkers and possible future interventions for food addiction and related disorders based on the strategies now available to modify miRNA activity and expression.

COVID-19 mRNA Vaccines Preserve Immunogenicity after Re-Freezing.

The massive COVID-19 vaccine purchases made by high-income countries have resulted in important sample losses, mainly due to the complexity of their handling. Here, we evaluated the possibility of preserving the immunogenicity of COVID-19 mRNA vaccines after re-freezing vials, following the extraction of the maximum possible number of samples, as an alternative approach to minimizing their wastage. Thus, we exposed the vaccine vials to different re-freezing conditions and evaluated mRNA integrity and the effects in mice after in vivo administration. We reveal that the mRNA integrity of Comirnaty® and Spikevax® vaccines remained unaffected after re-freezing during 1 month at -20 °C or -80 °C. The immunological responses also remained unchanged in mice after these re-freezing conditions and no apparent side effects were revealed. The preservation of mRNA integrity and immunogenicity under these handling conditions opens the possibility of re-freezing the mRNA COVID-19 vaccine vials to limit their wastage and to facilitate vaccination processes.

Reconstituted mRNA COVID-19 vaccines may maintain stability after continuous movement.

OBJECTIVES: There is an urgent need to ameliorate the possibilities of transporting reconstituted mRNA vaccines from the centralized preparation centres to the vaccination sites to improve the efficiency of the vaccination campaign against coronavirus disease 2019 (COVID-19). We have analysed the integrity of the Pfizer-BioNTech and Moderna vaccines under different movement conditions to provide information that may improve the distribution of vaccines to the target population. METHODS: Syringes of reconstituted Pfizer-BioNTech or Moderna COVID-19 vaccines were prepared in a laminar flow chamber to be subjected to a stability analysis in order to evaluate the impact of movement on mRNA integrity. RNA integrity was checked by the lack of RNA peaks under the original mRNA peak in the electropherogram resulting from potential fragments from RNA degradation. Samples were then exposed for 180 min at room temperature (21 ± 1°C, 55 ± 10% humidity) under different movement conditions. RESULTS: We report that the integrity of the mRNA in the reconstituted COVID-19 vaccines after continuous moderate movement at room temperature is maintained for at least 3 hours, with values of fluorescence units (FU) under the original mRNA peak of 0.38 ± 0.06 in the Pfizer-BioNTech vaccine and 0.96 ± 1.18 FU in the Moderna vaccine, equal to the values obtained without movement (0.36 ± 0.08 FU in the Pfizer-BioNTech and 1.12 ± 0.19 FU in the Moderna). In contrast, the integrity of these vaccines exposed to repeated Vortex shaking was significantly impaired (p < 0.001) with values under the original mRNA peak of 1.34 ± 0.31 FU for the Pfizer-BioNTech and 5.03 ± 1.16 FU for the Moderna samples. CONCLUSIONS: The stability of these reconstituted vaccines reported here may improve the efficiency of the ground transportation and distribution of the vaccines, which may lead to shorter and more homogeneous vaccinations in cities and rural areas.

Accidental Interruption of the Cold Chain for the Preservation of the Moderna COVID-19 Vaccine.

Maintenance in restricted cold temperature conditions is a mandatory requirement to preserve the stability of mRNA vaccines [...].

COVID-19 Incidence in Patients With Immunomediated Inflammatory Diseases: Influence of Immunosuppressant Treatments.

The effect of immunosuppressant treatments on the incidence of coronavirus disease (COVID-19) remains largely unknown. We studied the association between the pre-exposure to disease-modifying antirheumatic drugs (DMARDs) that decrease immunological responses and the incidence of COVID-19 to explore the possible effects of these treatments in early manifestations of the disease. For this purpose, we performed a cross-sectional study including 2,494 patients with immunomediated inflammatory diseases (IMIDs) recruited at the outpatient Rheumatology, Dermatology and Gastroenterology services of Hospital del Mar. The primary outcome was the clinical diagnosis of COVID-19 performed by a physician at the hospital or at the primary care center, from the March 1-29, 2020. Multivariable Poisson regression models were fitted to estimate COVID-19 relative risk (RR) adjusted by comorbidities. We revealed that biological (RR = 0.46, CI 95% = 0.31-0.67) and synthetic (RR = 0.62, CI 95% = 0.43-0.91) DMARDs used in IMIDs diminished the incidence of COVID-19. Striking sex differences were revealed with anti-TNFα compounds (RR = 0.50, CI 95% = 0.33-0.75) with higher effects in women (RR = 0.33, CI 95% = 0.17-0.647). Treatment with low glucocorticoid doses also revealed sex differences decreasing the incidence of COVID-19 predominantly in women (RR = 0.72, CI 95% = 0.42-1.22). Our results report a decreased incidence of COVID-19 in patients receiving specific DMARDs with different immunodepressor mechanisms with striking sex differences. These results underline the interest of repurposing specific DMARDs for the possibility of minimizing the severity of disease progression in the early stages of COVID-19.