Effectiveness of different treatment regimens on patients with COVID-19, hospitalized in Sanandaj hospitals: a retrospective cohort study.

OBJECTIVES: Different drugs have different effects on the prognosis of patients with COVID-19. This study aimed to evaluate the effect of different drug regimens on patients with COVID-19, hospitalized in Sanandaj city. METHODS: In this retrospective cohort study, 660 patients with COVID-19, hospitalized in the Tohid, Kowsar and Besat hospitals located Sanandaj (Kurdistan Province, Iran) were studied from February 2020 to February 2021 with clinical symptoms and positive test results. RESULTS: The results of multivariate regression analysis showed the days of hospitalization for patients who had received the drug regimen 2 (Interferons (ReciGen/Ziphron) or Interferon Vectra (lopinavir/ritonavir)) was 1.92 times higher than those who had received the drug regimen 1 (hydroxychloroquine group or a combination of chloroquine and azithromycin) while a significant association was observed (OR = 1.92, 95% CI: 1.16-3.16, P = 0.011). Also, the hospitalization in ICU was longer in patients treated by the drug regimen 2 (Interferons (ReciGen/Ziphron) or Interferon Vectra (lopinavir/ritonavir)) (OR = 4.63, 95% CI: 1.80-11.82, P = 0.001), however, drug regimens did not show a significant effect on mortality and use of ventilator in patients (P > 0.05). CONCLUSION: The study results showed the drug regimens 2 and 5 increased the days of hospitalization and hospitalization in ICU, respectively, while the other drug regimens had no significant effect on mortality and use a ventilator in the studied patients and none of the drug regimens had an effect on reducing mortality compared to other ones.

Haematopoietic stem cell gene therapy with IL-1Ra rescues cognitive loss in mucopolysaccharidosis IIIA.

Mucopolysaccharidosis IIIA is a neuronopathic lysosomal storage disease, characterised by heparan sulphate and other substrates accumulating in the brain. Patients develop behavioural disturbances and cognitive decline, a possible consequence of neuroinflammation and abnormal substrate accumulation. Interleukin (IL)-1ß and interleukin-1 receptor antagonist (IL-1Ra) expression were significantly increased in both murine models and human MPSIII patients. We identified pathogenic mechanisms of inflammasome activation, including that disease-specific 2-O-sulphated heparan sulphate was essential for priming an IL-1ß response via the Toll-like receptor 4 complex. However, mucopolysaccharidosis IIIA primary and secondary storage substrates, such as amyloid beta, were both required to activate the NLRP3 inflammasome and initiate IL-1ß secretion. IL-1 blockade in mucopolysaccharidosis IIIA mice using IL-1 receptor type 1 knockout or haematopoietic stem cell gene therapy over-expressing IL-1Ra reduced gliosis and completely prevented behavioural phenotypes. In conclusion, we demonstrate that IL-1 drives neuroinflammation, behavioural abnormality and cognitive decline in mucopolysaccharidosis IIIA, highlighting haematopoietic stem cell gene therapy treatment with IL-1Ra as a potential neuronopathic lysosomal disease treatment.

Mesalazine induced myopericarditis in a patient with ulcerative colitis.

A 25-year-old male with a background of ulcerative colitis presented with a two-week history of central chest pain. His ECG on presentation showed global T wave inversion with a peak troponin I of 165 ng/ml. Clinical diagnosis of myopericarditis/myocarditis was made. Echocardiography and cardiac MR confirmed the diagnosis. On detailed assessment of his medication history, mesalazine was suspected as an aetiological factor, with discontinuation resulting in an improvement in symptoms, inflammatory markers and cardiac enzymes. This is a unique case of mesalazine induced myopericarditis on a background of inflammatory bowel disease.

Enhanced imaging of lipid rich nanoparticles embedded in methylcellulose films for transmission electron microscopy using mixtures of heavy metals.

Synthetic and naturally occurring lipid-rich nanoparticles are of wide ranging importance in biomedicine. They include liposomes, bicelles, nanodiscs, exosomes and virus particles. The quantitative study of these particles requires methods for high-resolution visualization of the whole population. One powerful imaging method is cryo-EM of vitrified samples, but this is technically demanding, requires specialized equipment, provides low contrast and does not reveal all particles present in a population. Another approach is classical negative stain-EM, which is more accessible but is difficult to standardize for larger lipidic structures, which are prone to artifacts of structure collapse and contrast variability. A third method uses embedment in methylcellulose films containing uranyl acetate as a contrasting agent. Methylcellulose embedment has been widely used for contrasting and supporting cryosections but only sporadically for visualizing lipid rich vesicular structures such as endosomes and exosomes. Here we present a simple methylcellulose-based method for routine and comprehensive visualization of synthetic lipid rich nanoparticles preparations, such as liposomes, bicelles and nanodiscs. It combines a novel double-staining mixture of uranyl acetate (UA) and tungsten-based electron stains (namely phosphotungstic acid (PTA) or sodium silicotungstate (STA)) with methylcellulose embedment. While the methylcellulose supports the delicate lipid structures during drying, the addition of PTA or STA to UA provides significant enhancement in lipid structure display and contrast as compared to UA alone. This double staining method should aid routine structural evaluation and quantification of lipid rich nanoparticles structures.

Nanoparticle suspensions enclosed in methylcellulose: a new approach for quantifying nanoparticles in transmission electron microscopy.

Nanoparticles are of increasing importance in biomedicine but quantification is problematic because current methods depend on indirect measurements at low resolution. Here we describe a new high-resolution method for measuring and quantifying nanoparticles in suspension. It involves premixing nanoparticles in a hydrophilic support medium (methylcellulose) before introducing heavy metal stains for visualization in small air-dried droplets by transmission electron microscopy (TEM). The use of methylcellulose avoids artifacts of conventional negative stain-TEM by (1) restricting interactions between the nanoparticles, (2) inhibiting binding to the specimen support films and (3) reducing compression after drying. Methylcellulose embedment provides effective electron imaging of liposomes, nanodiscs and viruses as well as comprehensive visualization of nanoparticle populations in droplets of known size. These qualities facilitate unbiased sampling, rapid size measurement and estimation of nanoparticle numbers by means of ratio counting using a colloidal gold calibrant. Specimen preparation and quantification take minutes and require a few microliters of sample using only basic laboratory equipment and a standard TEM.