ABSTRACT
In the COVID-19 pandemic era, safety concerns have been raised regarding the risk of severe infection following administration of ocrelizumab (OCR), a B-cell-depleting therapy. We enrolled all relapsing remitting multiple sclerosis (RRMS) patients who received maintenance doses of OCR from January 2020 to June 2021. Data were extracted in December 2021. Standard interval dosing (SID) was defined as a regular maintenance interval of OCR infusion every 6 months, whereas extended interval dosing (EID) was defined as an OCR infusion delay of at least 4 weeks. Three infusions were considered in defining SID vs. EID (infusions A, B, and C). Infusion A was the last infusion before January 2020. The primary study outcome was a comparison of disease activity during the A-C interval, which was defined as either clinical (new relapses) or radiological (new lesions on T1-gadolinium or T2-weighted magnetic resonance imaging (MRI) sequences). Second, we aimed to assess confirmed disability progression (CDP). A total cohort of 278 patients (174 on SID and 104 on EID) was enrolled. Patients who received OCR on EID had a longer disease duration and a higher rate of vaccination against severe acute respiratory syndrome-coronavirus 2 (p < 0.05). EID was associated with an increased risk of MRI activity during the A-C interval (OR 5.373, 95% CI 1.203-24.001, p = 0.028). Being on SID or EID did not influence CDP (V-Cramer 0.47, p = 0.342). EID seemed to be associated with a higher risk of MRI activity in our cohort. EID needs to be carefully considered for OCR-treated patients.
Subject(s)
COVID-19 , Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Humans , Gadolinium/therapeutic use , Immunologic Factors/adverse effects , Multiple Sclerosis/drug therapy , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Pandemics , RecurrenceABSTRACT
BACKGROUND: Vitamin D deficiency has been correlated with Multiple Sclerosis (MS) risk and disease activity. There is some controversy as to whether vitamin D could have an impact on depressive symptoms in people with MS (pwMS). The aim of this scoping review was to evaluate the association between vitamin D status and depressive symptoms in pwMS. METHODS: We searched databases to include studies published up to March 2021 to provide an overview of the available evidence on the correlation between vitamin D status and depressive symptoms in pwMS. The eligibility criteria were as follows: studies evaluating the use of vitamin D measurement on depressive symptoms in patients suffering from MS, including randomized and non-randomized studies; studies written in English; and studies exploring an adult population over the age of 18. RESULTS: Eleven studies met our inclusion criteria: two of them were abstracts only; the majority were cross-sectional studies; two were prospective longitudinal studies; one was a retrospective cohort study; and one was a randomized placebo-controlled trial (RCT). Of the eleven studies selected, seven showed a potential correlation between low vitamin D levels and depressive symptoms. CONCLUSION: Future RCT studies should include patients with greater severity of depressive symptoms and should consider confounding factors such as sun exposure and seasonal variation of vitamin D.
Subject(s)
Multiple Sclerosis , Vitamin D Deficiency , Adult , Depression/epidemiology , Humans , Middle Aged , Multiple Sclerosis/epidemiology , Randomized Controlled Trials as Topic , Vitamin D , Vitamin D Deficiency/epidemiology , VitaminsABSTRACT
Expression of the T cell receptor (TCR) genes is not restricted to T lymphocytes. Human prostate and breast express a truncated TCR gamma transcript. In the mouse, TCR alpha (TCRA) and beta partial transcripts are expressed by mesenchymal cells and TCRA transcripts by epithelial cells of the kidney. We show now that TCRA constant region expression is common in normal and neoplastic human cells of mesenchymal and neuroectodermal origin. TCR transcripts are derived from an unrearranged TCRA locus. Moreover, rhabdomyosarcoma cells highly expressed a specific J49-C splicing product deriving from the assembly of J49 segment and constant region. TCRA ectopic transcripts/proteins negatively regulate rhabdomyosarcoma cell growth as suggested by TCRA gene expression downmodulation effects using a specific duplex small interfering RNA.
Subject(s)
Gene Expression Profiling , Receptors, Antigen, T-Cell, alpha-beta/genetics , Base Sequence , Blotting, Northern , Bone Marrow Cells/metabolism , Bone Neoplasms/genetics , Bone Neoplasms/pathology , Cell Line , Cell Line, Tumor , Fibroblasts/metabolism , Gene Expression Regulation, Neoplastic , Gene Rearrangement , HT29 Cells , Humans , Jurkat Cells , Molecular Sequence Data , Osteosarcoma/genetics , Osteosarcoma/pathology , RNA Interference , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Rhabdomyosarcoma/genetics , Rhabdomyosarcoma/pathology , Sarcoma, Ewing/genetics , Sarcoma, Ewing/pathology , TransfectionABSTRACT
Fire blight, a devastating bacterial disease in pome fruits, causes severe economic losses worldwide. Hitherto, an effective control could only be achieved by using antibiotics, but this implies potential risks for human health, livestock and environment. A new approach allows transient inhibition of a step in the flavonoid pathway, thereby inducing the formation of a novel antimicrobial 3-deoxyflavonoid controlling fire blight in apple and pear leaves. This compound is closely related to natural phytoalexins in sorghum. The approach does not only provide a safe method to control fire blight: Resistance against different pathogens is also induced in other crop plants.
