Molnupiravir; an effective drug in treating COVID-19?

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Work-Related Human T-lymphotropic Virus 1 and 2 (HTLV-1/2) Infection: A Systematic Review

Human T-lymphotropic virus 1 and 2 (HTLV-1/2) belong to the delta group of retroviruses which may cause a life-long infection in humans, HTLV-1 leading to adult T-cell leukemia/lymphoma and other diseases. Different transmission modes have been described, such as breastfeeding, and, as for other blood-borne pathogens, unsafe sexual activity, intravenous drug usage, and blood transfusion and transplantation. The present systematic review was conducted to identify all peer- reviewed studies concerning the work-related infection by HTLV-1/2. A literature search was conducted from January to May 2021, according to the PRISMA methodology, selecting 29 studies: seven related to health care workers (HCWs), five to non-HCWs, and 17 to sex workers (SWs). The findings showed no clear evidence as to the possibility of HTLV-1/2 occupational transmission in HCWs, according to the limited number and quality of the papers. Moreover, non-HCWs showed a higher prevalence in jobs consistent with a lower socioeconomic status or that could represent a familial cluster, and an increased risk of zoonotic transmission from STLV-1-infected non-human primates has been observed in African hunters. Finally, a general increase of HTLV-1 infection was observed in SWs, whereas only one paper described an increased prevalence for HTLV-2, supporting the urgent need for prevention and control measures, including screening, diagnosis, and treatment of HTLV-1/2, to be offered routinely as part of a comprehensive approach to decrease the impact of sexually transmitted diseases in SWs

Hope and fear; Paxlovid for COVID-19 treatment: A Letter to the Editor

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Case Report: Mutation in AIMP2/P38, the Scaffold for the Multi-Trna Synthetase Complex, and Association With Progressive Neurodevelopmental Disorders

Background: Leukodystrophies constitute a heterogeneous group of inherited disorders primarily affecting the white matter of the central nervous system. Aminoacyl-tRNA synthetases (ARSs) catalyze the attachment of an amino acids to their cognate transfer RNAs (tRNAs). Pathogenic variants in both cytosolic and mitochondrial ARSs have been linked to a broad range of neurological disorders, including hypomyelinating leukodystrophies and pontocerebellar hypoplasias (PCH). Aminoacyl tRNA synthetase-interacting multifunctional protein 2 (AIMP2), one of the three non-catalytic components of multi ARS complex, harbors anti-proliferative activity and functions as a proapoptotic factor thus promoting cell death. We report a case of a 7-month-old infant with a complex clinical presentation, including weight loss, severe anemia, skeletal abnormalities, microcephaly and MR imaging features of leukodystrophy with a novel mutation in AIMP2. Methods: Whole-exome sequencing (WES) was performed on the proband. Parental samples were analyzed by PCR amplification and Sanger sequencing. Results: Whole-exome sequencing revealed a novel variant c.A463T in the homozygous state in exon 3 (NM_001,326,607) of AIMP2 [p.(K155X)] in the proband. Parental carrier status was confirmed by target sequencing. Conclusion: Here, we present an Iranian case with leukodystrophy with a novel AIMP2 mutation. This finding broadens the mutational and phenotypic spectra of AIMP2-related leukodystrophy and offers guidance for proper genetic counselling for pre- and post-natal screenings as well as for disease management

Systemic lupus erythematosus following SARS-CoV-2 vaccination; a review of literature

From March 2020, the coronavirus disease 2019 (COVID-19) pandemic challenged public health and healthcare systems worldwide. Viral infection is one of the environmental factors that has been associated with the development, relapse, or exacerbation of systemic lupus erythematosus (SLE). SLE patients are at an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) because of immune system dysfunction related to their disease as well as immunosuppression medications. So far, the most effective way to reduce SARS-CoV-2 infection-induced hospitalization and death is vaccination. On the other hand, SLE patients present distinct challenges related to the safety and effectiveness of SARS-CoV-2 vaccination. We have reviewed some reports on the onset or flare of SLE post-COVID-19 vaccination. Of note, the mRNA COVID-19 vaccines are associated with increased SLE disease activity, more frequently than the other types of COVID-19 vaccines

Antibacterial Activity of Ethyl Acetate and Methanol Extracts of Securigera securidaca, Withania sominefra, Rosmarinus officinalis and Aloe vera Plants against Important Human Pathogens

Background:      Considering the importance of new antibiotics, the potential antibacterial activity of ethyl acetate and Methanol extracts of Securigera securidaca, Withania sominefra, Rosmarinus officinalis and Aloe vera plants against important human pathogens was studied.   Methods:   Streptococcus pneumoniae, Enterococcus faecalis, Proteus mirabilis, Staphylococcus aureus, E. coli, P. aeruginosa were the pathogenic bacteria used to determine the antibacterial effect of ethyl acetate and mathanol extracts of Securigera securidaca, Withania sominefra, Rosmarinus officinalis and Aloe vera in broth micro-dilution method. Results:      The results of studying the methanol extract of S. securidaca with the lowest inhibitory concentration of 25, showed that all used bacterial pathogens were inhibited at this concentration, while the lowest inhibitory concentration of ethyl acetate extract of Securigera securidaca was 12.5, which were P. mirabilis and S. aureus is inhibited in this concentration. The highest bactericidal concentration (MBC) of S. securidaca ethyl acetate extract was 100, and S. aureus, P. aeruginosa were inhibitory at this concentration. The lowest inhibitory concentration of methanol extract of W. sominefra was 6.25, which S. pneumoniae, P. mirabilis, S. aureus and E. coli bacteria were inhibited at this concentration, while the highest inhibitory concentration was observed against P. aeruginosa (25 ppm), The lowest inhibitory concentration of the ethyl acetate W. sominefra extract was 3.1ppm in comparison with P. mirabilis and E. coli. Conclusion:     In conclusion, it seems that S. securidaca, W. sominefra, R. officinalis and Aloe vera extracts could inhibit the growth of all of the mentioned bacteria

Targeted delivery of oral vaccine antigens to aminopeptidase N protects pigs against pathogenic E. coli challenge infection

Oral subunit vaccines are an interesting alternative strategy to traditional live-attenuated or inactivated vaccines for conferring protection against gut pathogens. Despite being safer and more cost-effective, the development of oral subunit vaccines remains challenging due to barriers imposed by the gastrointestinal tract, such as digestive enzymes, a tolerogenic immune environment and the inability of larger proteins to cross the epithelial barrier. Recent advances have focused on overcoming these barriers by using potent mucosal adjuvants or pH-responsive delivery vehicles to protect antigens from degradation and promote their release in the intestinal lumen. A promising approach to allow vaccine antigens to pass the epithelial barrier is by their targeting towards aminopeptidase N (APN; CD13), an abundant membrane protein present on small intestinal enterocytes. APN is a peptidase involved in digestion, but also a receptor for several enteric pathogens. In addition, upon antibody-mediated crosslinking, APN facilitated the transport of antibody-antigen fusion constructs across the gut epithelium. This epithelial transport resulted in antigen-specific immune responses. Here, we present evidence that oral administration of APN-specific antibody-antigen fusion constructs comprising the porcine IgA Fc-domain and the FedF tipadhesin of F18-fimbriated E. coli elicited both mucosal and systemic immune responses and provided at least partial protection to piglets against a subsequent challenge infection with an F18-fimbriated STEC strain. Altogether, these findings will contribute to the further development of new oral subunit vaccines and provide a first proof-of-concept for the protective efficacy of APN-targeted vaccine antigens

An Epitope Platform for Safe and Effective HTLV-1-Immunization: Potential Applications for mRNA and Peptide-Based Vaccines

Human T-cell lymphotropic virus type 1 (HTLV-1) infection affects millions of individuals worldwide and can lead to severe leukemia, myelopathy/tropical spastic paraparesis, and numerous other disorders. Pursuing a safe and effective immunotherapeutic approach, we compared the viral polyprotein and the human proteome with a sliding window approach in order to identify oligopeptide sequences unique to the virus. The immunological relevance of the viral unique oligopeptides was assessed by searching them in the immune epitope database (IEDB). We found that HTLV-1 has 15 peptide stretches each consisting of uniquely viral non-human pentapeptides which are ideal candidate for a safe and effective anti-HTLV-1 vaccine. Indeed, experimentally validated HTLV-1 epitopes, as retrieved from the IEDB, contain peptide sequences also present in a vast number of human proteins, thus potentially instituting the basis for cross-reactions. We found a potential for cross-reactivity between the virus and the human proteome and described an epitope platform to be used in order to avoid it, thus obtaining effective, specific, and safe immunization. Potential advantages for mRNA and peptide-based vaccine formulations are discussed