The Effect of Preventive Measures and Vaccination against SARS-CoV-2 on the Infection Risk, Treatment, and Hospitalization. A Cross-Sectional Study of Algeria

Coronavirus disease (COVID-19) caused by the SARS-CoV-2 virus continues to afflict many countries around the world. The resurgence of COVID-19 cases and deaths in many countries shows a complacency in adhering to preventive guidelines. Consequently, vaccination continues to be a crucial intervention to reduce the effects of this pandemic. This study investigated the impact of preventive measures and COVID-19 vaccination on the infection, medication, and hospitalization. A cross-sectional online survey was conducted between 23 December 2021 and 12 March 2022 in Algeria. To evaluate the effectiveness of strategies aimed at avoiding and minimizing SARS-CoV-2 infection and severity, a questionnaire was created and validated. Descriptive statistics and logistic regression analyses were computed to identify associations between dependent and independent variables. Variables with a p-value of < 0.05 were considered statistically significant. Our results indicated that out of 2294 answers received, only 16% of our sample was vaccinated, and more than 60% did not apply preventive guidelines. As a result, 45% were infected with SARS-CoV-2, 75% took treatment (even preventive), and 9% were hospitalized. The logistic regression showed that the impact of preventive measures on the unvaccinated is statistically not significant (OR: 0.764, 95% CI = 0. 555-1.052; p = 0.09). However, this relationship changes significantly for people who are vaccinated (OR: 0.108, 95% CI = 0.047-0.248; p < 0.0001). Our results also demonstrated that the impact of protective measures on non-vaccinated individuals is statistically significant in reducing the need to receive anti-COVID-19 treatments (OR: 0.447, 95% CI = 0.321-0.623; p < 0.0001). Furthermore, the results showed that the impact of preventive measures on the non-vaccinated population is also statistically significant in reducing the risk of hospitalization (OR: 0.211, 95% CI = 0.081-0.548; p < 0.0001). Moreover, vaccinated individuals who neglect preventive measures must take the COVID-19 medication at a rate of 3.77 times (OR: 3.77) higher than those who follow preventive measures and are vaccinated. In short, our findings demonstrate the importance of combining preventive measures and vaccination in order to fight against the pandemic. Therefore, we advise the Ministry of Health and relevant authorities to put more effort into enhancing public knowledge about the COVID-19 infection and vaccination through education and awareness initiatives. Parallel to implementing vaccination as additional preventive strategy, behavioral change initiatives must be improved to encourage adherence to COVID-19 prevention recommendations

The Important Molecular Markers on Chromosome 17 and Their Clinical Impact in Breast Cancer

Abnormalities of chromosome 17 are important molecular genetic events in human breast cancers. Several famous oncogenes (HER2, TOP2A and TAU), tumor suppressor genes (p53, BRCA1 and HIC-1) or DNA double-strand break repair gene (RDM1) are located on chromosome 17. We searched the literature on HER2, TOP2A, TAU, RDM1, p53, BRCA1 and HIC-1 on the Pubmed database. The association of genes with chromosome 17, biological functions and potential significance are reviewed. In breast cancer, the polysomy 17 (three or more) is the predominant numerical aberration. HER2 amplification is widely utilized as molecular markers for trastuzumab target treatment. Amplified TOP2A, TAU and RDM1 genes are related to a significant response to anthracycline-based chemotherapy, taxane or cisplatin, respectively. In contrast, p53, BRCA1 and HIC-1 are important tumor suppressor genes related to breast carcinogenesis. This review focused on several crucial molecular markers residing on chromosome 17. The authors consider the somatic aberrations of chromosome 17 and associated genes in breast cancer

Ubc13 dosage is critical for immunoglobulin gene conversion and gene targeting in vertebrate cells

In contrast to lower eukaryotes, most vertebrate cells are characterized by a moderate efficiency of homologous recombination (HR) and limited feasibility of targeted genetic modifications. As a notable exception, the chicken DT40 B cell line is distinguished by efficient homology-mediated repair of DNA lesions during Ig gene conversion, and also shows exceptionally high gene-targeting efficiencies. The molecular basis of these phenomena is elusive. Here we show that the activity levels of Ubc13, the E2 enzyme responsible for non-canonical K63-linked polyubiquitination, are critical for high efficiency of Ig gene conversion and gene targeting in DT40. Ubc13+/− cells show substantially lower homology-mediated repair, yet do not display changes in somatic hypermutation, overall DNA repair or cell proliferation. Our results suggest that modulation of the activity of K63-linked polyubiquitination may be used to customize HR efficiencies in vertebrate cells

A Role for PCNA Ubiquitination in Immunoglobulin Hypermutation

Proliferating cell nuclear antigen (PCNA) is a DNA polymerase cofactor and regulator of replication-linked functions. Upon DNA damage, yeast and vertebrate PCNA is modified at the conserved lysine K164 by ubiquitin, which mediates error-prone replication across lesions via translesion polymerases. We investigated the role of PCNA ubiquitination in variants of the DT40 B cell line that are mutant in K164 of PCNA or in Rad18, which is involved in PCNA ubiquitination. Remarkably, the PCNA(K164R) mutation not only renders cells sensitive to DNA-damaging agents, but also strongly reduces activation induced deaminase-dependent single-nucleotide substitutions in the immunoglobulin light-chain locus. This is the first evidence, to our knowledge, that vertebrates exploit the PCNA-ubiquitin pathway for immunoglobulin hypermutation, most likely through the recruitment of error-prone DNA polymerases

Subcellular distribution of human RDM1 protein isoforms and their nucleolar accumulation in response to heat shock and proteotoxic stress

The RDM1 gene encodes a RNA recognition motif (RRM)-containing protein involved in the cellular response to the anti-cancer drug cisplatin in vertebrates. We previously reported a cDNA encoding the full-length human RDM1 protein. Here, we describe the identification of 11 human cDNAs encoding RDM1 protein isoforms. This repertoire is generated by alternative pre-mRNA splicing and differential usage of two translational start sites, resulting in proteins with long or short N-terminus and a great diversity in the exonic composition of their C-terminus. By using tagged proteins and fluorescent microscopy, we examined the subcellular distribution of full-length RDM1 (renamed RDM1α), and other RDM1 isoforms. We show that RDM1α undergoes subcellular redistribution and nucleolar accumulation in response to proteotoxic stress and mild heat shock. In unstressed cells, the long N-terminal isoforms displayed distinct subcellular distribution patterns, ranging from a predominantly cytoplasmic to almost exclusive nuclear localization, suggesting functional differences among the RDM1 proteins. However, all isoforms underwent stress-induced nucleolar accumulation. We identified nuclear and nucleolar localization determinants as well as domains conferring cytoplasmic retention to the RDM1 proteins. Finally, RDM1 null chicken DT40 cells displayed an increased sensitivity to heat shock, compared to wild-type (wt) cells, suggesting a function for RDM1 in the heat-shock response

A Novel Small Acid Soluble Protein Variant Is Important for Spore Resistance of Most Clostridium perfringens Food Poisoning Isolates

Clostridium perfringens is a major cause of food poisoning (FP) in developed countries. C. perfringens isolates usually induce the gastrointestinal symptoms of this FP by producing an enterotoxin that is encoded by a chromosomal (cpe) gene. Those typical FP strains also produce spores that are extremely resistant to food preservation approaches such as heating and chemical preservatives. This resistance favors their survival and subsequent germination in improperly cooked, prepared, or stored foods. The current study identified a novel α/β-type small acid soluble protein, now named Ssp4, and showed that sporulating cultures of FP isolates producing resistant spores consistently express a variant Ssp4 with an Asp substitution at residue 36. In contrast, Gly was detected at Ssp4 residue 36 in C. perfringens strains producing sensitive spores. Studies with isogenic mutants and complementing strains demonstrated the importance of the Asp 36 Ssp4 variant for the exceptional heat and sodium nitrite resistance of spores made by most FP strains carrying a chromosomal cpe gene. Electrophoretic mobility shift assays and DNA binding studies showed that Ssp4 variants with an Asp at residue 36 bind more efficiently and tightly to DNA than do Ssp4 variants with Gly at residue 36. Besides suggesting one possible mechanistic explanation for the highly resistant spore phenotype of most FP strains carrying a chromosomal cpe gene, these findings may facilitate eventual development of targeted strategies to increase killing of the resistant spores in foods. They also provide the first indication that SASP variants can be important contributors to intra-species (and perhaps inter-species) variations in bacterial spore resistance phenotypes. Finally, Ssp4 may contribute to spore resistance properties throughout the genus Clostridium since ssp4 genes also exist in the genomes of other clostridial species

The importance of selecting Bayesian nonparametric survival models: application to the estimation of unemployment durations

International audienceThe Kaplan-Meier and Fleming-Harrington estimator in the frequentist approach are functional methods. We compare in this article the different Bayesian structures of the Kaplan-Meier and Fleming-Harrington estimators through the information deviance criterion in a real example describes the duration of unemployment of 1064 individuals in an employment agency. employment at the local employment agency in Ain El Benian. This study clearly shows the importance of bayesian model selection in duration models

The importance of selecting Bayesian nonparametric survival models: application to the estimation of unemployment durations

The Kaplan-Meier and Fleming-Harrington estimator in the frequentist approach are functional methods. We compare in this article the different Bayesian structures of the Kaplan-Meier and Fleming-Harrington estimators through the information deviance criterion in a real example describes the duration of unemployment of 1064 individuals in an employment agency. employment at the local employment agency in Ain El Benian. This study clearly shows the importance of bayesian model selection in duration models