Messenger RNA (mRNA) vaccines are a relatively new class of vaccines. They combine the potential of mRNA to encode for almost any protein with an excellent safety profile and a flexible production process. During the last decade, the mRNA vaccine approach has been increasingly recognized and viewed as a versatile tool for the development of new innovative therapeutics not only in infectious disease settings but also in cancer. mRNA vaccines traditionally consist of a messenger RNA synthesized by in vitro transcription using a bacteriophage RNA polymerase and a template DNA that encodes the antigen(s) of interest. Once administered and internalized by host cells, the mRNA transcripts are translated directly in the cytoplasm of the cell. The resulting antigens are presented to the immune system cells to stimulate an immune response. Dendritic cells (DCs) can be utilized as a carrier by delivering tumor-associated antigen mRNAs or total tumor RNA to their cytoplasm; then, the mRNA-loaded DCs can be delivered to the host to elicit a specific immune response. Recently, 2 mRNA vaccines were approved for the first time for human use-to prevent COVID-19 infection-bringing excitement for the future possibilities of this approach for cancer immunotherapy as well as for preventing other infectious diseases.Clostridioides difficile is a Gram-positive, spore-forming, toxin-producing anaerobe that can cause nosocomial antibiotic-associated intestinal disease. Although the production of toxin A (TcdA) and toxin B (TcdB) contribute to the main pathogenesis of C. difficile, the mechanism of TcdA and TcdB release from cell remains unclear. In this study, we identified and characterized a new cell wall hydrolase Cwl0971 (CDR20291_0971) from C. difficile R20291, which is involved in bacterial autolysis. The gene 0971 deletion mutant (R20291Δ0971) generated with CRISPR-AsCpfI exhibited significantly delayed cell autolysis and increased cell viability compared to R20291, and the purified Cwl0971 exhibited hydrolase activity for Bacillus subtilis cell wall. Meanwhile, 0971 gene deletion impaired TcdA and TcdB release due to the decreased cell autolysis in the stationary/late phase of cell growth. Moreover, sporulation of the mutant strain decreased significantly compared to the wild type strain. In vivo, the defect of Cwl0971 decreased fitness over the parent strain in a mouse infection model. Collectively, Cwl0971 is involved in cell wall lysis and cell viability, which affects toxin release, sporulation, germination, and pathogenicity of R20291, indicating that Cwl0971 could be an attractive target for C. this website difficile infection therapeutics and prophylactics.
Leading Teratology Information Systems (TIS) arose in major industrial nations and are mostly in English. The prevalence of anglophone speakers in Ukraine is among the lowest in Europe. A TIS in Ukrainian (UTIS) seeks to diminish an information gap concerning teratogens. The process and results related to UTIS are applicable to formulations of other TIS in vernacular languages.
Implementation of a free-access UTIS and analysis of utilization patterns. UTIS provides access to articles in Ukrainian (AU) which are summaries extracted from leading international TIS and other sources. AU are revised at least tri-annually.
UTIS provides access to over 1,100 AU accrued since 2016 to the present. The number AU views increased from nearly 30,000 (2016) to over 80,000 (2020); the number of visitors increased from 3,500 to 58,000 during the same periods. The highest percent of users per urban population (2.09, 1.77, and 1.72) was in Ternopil, Ivano-Frankivsk, and Kyiv (capital), respectively; the lowest was in Odesa (0.17).
UTIS reduced an information gap in Ukraine concerning teratogenic risk factors. The process can be implemented elsewhere relying on generally available local resources.
UTIS reduced an information gap in Ukraine concerning teratogenic risk factors. The process can be implemented elsewhere relying on generally available local resources.Refractory angina is considered a devastating condition with limited medical and therapeutic options. The Neovasc Reducer device, when implanted in the coronary sinus, is designed to alleviate anginal symptoms. However, the available clinical data are sparse. The US Food and Drug Administration (FDA) assembled the Circulatory Systems Devices Panel to discuss the Reducer's safety and effectiveness. Because of the coronavirus disease 2019 pandemic, this meeting was held virtually. In this manuscript, we detail the deliberation and discussion among the circulatory panel members, including their final vote.Highlights A novel heterozygous mutation in the SLC5A2 gene in a 2-year-old girl with severe asymptomatic glycosuria, mild failure to thrive, and subclinical hypoglycemia Continuous glucose monitoring identified 14% hypoglycemic excursions ( less then 70 mg/dl), reduced at 1% with 1 g/Kg uncooked cornstarch at bed-time milk and eliminated (0%) adjusting the dose at 1.5 g/Kg, as shown by Flash technology.Sotos syndrome (SS) is a genetic disorder characterized by accelerated growth in childhood, developmental deficits, and characteristic craniofacial features. While clinicians and parents have reported unusual sleep habits, only one study by Rutter and Cole in 1991 mentioned sleep complaints (Rutter and Cole, Developmental Medicine and Child Neurology, 1991, 33, 898-902). This study aimed to characterize the sleep habits of individuals with SS. We performed a cross-sectional study of individuals with a definite, probable, or possible diagnosis of Sotos syndrome. Participants were asked to complete the Children's Sleep Habits Questionnaire (CHSQ). We compared our data to historical data available from the literature. Subjects with SS showed more sleep disturbance than typically developing individuals (TD), although their sleep onset was less likely to be delayed and their sleep duration was longer. Participants with SS also showed different sleep patterns compared to children with other forms of intellectual and developmental disabilities (IDD). Individuals with SS exhibited early bed and rise times, frequently used transitional objects, displayed repetitive motion at sleep onset, and did not show a decrease in sleep duration with age. The majority of participants fell asleep at the same time each night, in their own bed, and within 20 min, and rarely showed signs of sleepwalking or night terrors. These results improve our understanding of sleep habits of individuals with SS and may be used to guide treatment and provide normalization for children with SS.this website
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