Molecular detection, phylogenetic analysis and genetic diversity of recently isolated foot-and-mouth disease virus serotype A African topotype, Genotype IV

Background Surveillance for circulating emerging diseases of economic importance has a major role in the rapid response to major pathogen outbreaks. Foot-and-mouth disease virus (FMDV) is one of the significant endemic viruses in Egypt. FMDV is periodically investigated for monitoring evolution and emergence of new variants. The genetic characterization of foot-and-mouth disease (FMD) virus serotype A responsible for recent outbreaks of FMD in Egypt was determined. Methods Samples were collected from different locations and virus isolation was performed using BHK-21 cells. Viral RNA was extracted and samples were screened for FMDV using real-time RT-PCR. DNA sequence analysis was performed and computational and bioinformatics analyses were used to determine the substitution rates and phylogenetic relationship. Results Sequence and phylogenetic analyses of full-length 1D region of FMDV samples collected from different governorates in 2020 showed close similarity to Egyptian FMDV strains from serotype A-African topotype-G-IV with genetic variation of 6.5%. Recently isolated FMDV strains showed high genetic variations from locally used vaccine strains in the major antigenic sites of VP1 region. Conclusions Although, efforts made by the veterinary authorities to implement an effective mass vaccination plan, the recently detected FMDV strains in this study could not be subtyped using the FMDV primers routinely used for molecular serotyping. These dissimilarities raise the alarm for reconsideration of the FMDV isolates used in vaccine manufacture. Clearly close monitoring of FMD in Egypt is urgently required to define the risks of future outbreaks and to ensure appropriate control measures against FMD major outbreaks

Overview of African horse sickness virus (AHSV) situation in Egypt from 2017 to 2022

African horse sickness (AHS) is a non-contagious arthropod-borne infectious disease of Equidae. Because of its severity and quick spread, It is cosidered as a notifiable disease. The current study intended to look into the current suitation of the vector-borne African horse sickness virus (AHSV) in Egypt, determine viral seroprevelance, and assess the associated risk factors. In this context, 2739 sera and 150 spleen samples were collected from different Egyptian governorates and tested for AHSV screening. The sera were investigated for presence of antibodies against AHSV whilst spleen samples were tested for AHSV Ag and RNA detection. The obtained results revealed that all 2739 sera samples tested negative for AHSV antibodies. Furthermore, using ELISA and conventional reverse-transcription polymerase chain reaction (RT-PCR), to identify AHSV Ag and nucleic acid, the 150 tested spleen samples gave negative results with both assays. In conclusion, the recorded results indicated the absence of antibodies, antigen, and viral nucleic acid of AHSV in all tested samples which proved that there is no circulating virus in the investigated Egyptian governorates in the period from 2017 to 2022. Evenually, the effective control programs are recommended by carrying out further epidemiological investigations to understand the current situation of arboviruses in the country

Overview of African horse sickness virus (AHSV) situation in Egypt from 2017 to 2022

African horse sickness (AHS) is a non-contagious arthropod-borne infectious disease of Equidae. Because of its severity and quick spread, It is cosidered as a notifiable disease. The current study intended to look into the current suitation of the vector-borne African horse sickness virus (AHSV) in Egypt, determine viral seroprevelance, and assess the associated risk factors. In this context, 2739 sera and 150 spleen samples were collected from different Egyptian governorates and tested for AHSV screening. The sera were investigated for presence of antibodies against AHSV whilst spleen samples were tested for AHSV Ag and RNA detection. The obtained results revealed that all 2739 sera samples tested negative for AHSV antibodies. Furthermore, using ELISA and conventional reverse-transcription polymerase chain reaction (RT-PCR), to identify AHSV Ag and nucleic acid, the 150 tested spleen samples gave negative results with both assays. In conclusion, the recorded results indicated the absence of antibodies, antigen, and viral nucleic acid of AHSV in all tested samples which proved that there is no circulating virus in the investigated Egyptian governorates in the period from 2017 to 2022. Evenually, the effective control programs are recommended by carrying out further epidemiological investigations to understand the current situation of arboviruses in the country

Triple-Negative Breast Cancer:Distinguishing between Basal and Nonbasal Subtypes

Purpose: Triple-negative (TN; estrogen receptor, progesterone receptor, and HER-2 negative) cancer and basal-like breast cancer (BLBC) are associated with poor outcome and lack the benefit of targeted therapy. It is widely perceived that BLBC and TN tumors are synonymous and BLBC can be defined using a TN definition without the need for the expression of basal markers. Experimental Design: We have used two well-defined cohorts of breast cancers with a large panel of biomarkers, BRCA1 mutation status, and follow-up data to compare the clinicopathologic and immunohistochemical features of TN tumors expressing one or more of the specific basal markers (CK5/6, CK17, CK14, and epidermal growth factor receptor; BLBC) with those TN tumors that express none of these markers (TN3BKE-). Results: Here, we show that although the morphologic features of BLBC are not significantly different from that of TN3BKE- tumors, BLBC showed distinct clinical and immunophenotypic differences. BLBC showed a statistically significant association with the expression of the hypoxia-associated factor (CA9), neuroendocrine markers, and other markers of poor prognosis such as p53. A difference in the expression of cell cycle-associated proteins and biomarkers involved in the immunologic portrait of tumors was seen. Compared with TN3BKE- tumors, BLBC was positively associated with BRCA1 mutation status and showed a unique pattern of distant metastasis, better response to chemotherapy, and shorter survival. Conclusion: TN breast cancers encompass a remarkably heterogeneous group of tumors. Expression of basal markers identifies a biologically and clinically distinct subgroup of TN tumors, justifying the use of basal markers (in TN tumors) to define BLBC

Targeting the TGFβ signalling pathway in disease

Many drugs that target transforming growth factor-β (TGFβ) signalling have disease applications. Preclinical and clinical studies indicate the utility of these agents in fibrosis and oncology, particularly in augmentation of existing cancer therapies, such as radiation and chemotherapy, as well as in tumour vaccines. There are also reports of specialized applications, such as the reduction of vascular symptoms of Marfan syndrome. Here, we consider why the TGFβ signalling pathway is a drug target, the potential clinical applications of TGFβ inhibition, the issues arising with anti-TGFβ therapy and how these might be tackled using personalized approaches to dosing, monitoring of biomarkers as well as brief and/or localized drug-dosing regimens