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Background Mosquito-borne arboviral diseases represent a growing threat and serious worldwide concern for public health authorities. Host immunoglobulin G (IgG) responses to mosquito salivary antigens emerged as a useful additional tool to evaluate human–vector contact, which is crucial for transmission risk assessment and planning vector control interventions. We previously reported that IgG responses to the Aedes albopictus 34k2 salivary protein (al34k2) are suitable, although with some limitations, to reveal variation of human exposure to the tiger mosquito. In this study we evaluated the Ae. albopictus Ag5-3 (alAg5-3), an Antigen 5 family member specifically and abundantly expressed in the saliva of adult females. Methods IgG responses to recombinant alAg5-3, as well as to a combination of alAg5-3 and al34k2, were measured in a set of sera previously collected from healthy human blood donors before and after the summer season of exposure to mosquito bites. Surveys were conducted in two districts of Northeast Italy, Padua and Belluno, with different density and history of colonization by the tiger mosquito Ae. albopictus . Results A preliminary pilot study, performed on a small subset of individuals from Padua, indicated that alAg5-3 was more immunogenic than al34k2 and may be suitable to detect variations of exposure to Ae. albopictus . Analysis of the whole set of 523 sera showed that anti-alAg5-3 IgG levels significantly increased, in both study areas, after the summer period of high mosquito density. However, differences between the two study sites were only found when a mixture of the two antigens, alAg5-3 and al34k2, was used. Conclusions IgG responses to alAg5-3 represent a novel appropriate marker to evaluate seasonal variation of human exposure to Ae. albopictus and, because of its higher sensitivity, it appears preferable to al34k2, especially for longitudinal studies in conditions of low-to-moderate mosquito density. However, the combination of both antigens may be a better surrogate of Ae. albopictus saliva since it allows the detection of both temporal and spatial variations of exposure to Ae. albopictus bites. The high conservation of the Ag5-3 protein among Aedes species suggests it may be exploited to also reveal exposure to Aedes aegypti and perhaps to other Aedes species. Graphical Abstract

The transcription of human telomeres gives rise to a family of long noncoding RNAs, named TERRA. We previously showed that TERRA transcription is driven by CpG island promoters that are composed by stretches of three types of repeats. Using the human genome assembly that was available at that time, putative promoter sequences were localized at several subtelomeres. In this work, using the T2T-CHM13v2.0 human reference genome, we found that 39 out of 46 subtelomeres contain TERRA promoters and grouped them in classes depending on their organization. We then discovered 106 intrachromosomal TERRA-like promoters, adjacent to interstitial telomeric sequences (ITSs) or far away from them. Fortyseven of these promoters are flanked and may regulate the transcription of coding genes, ncRNAs or pseudogenes. Comparative sequence analysis showed that interstitial and subtelomeric promoters belong to a previously undescribed family of segmental duplications deriving from common ancestral sequences. RT-PCR experiments in seven cell lines demonstrated that TERRA transcripts can be synthesized from ITSs. TERRA expression was always low in primary fibroblasts and HeLa cells while highly variable in the other two telomerase positive (HT1080 and HEK293) and in the three telomerase negative ALT cell lines (GM847, U2OS and VA13). The analysis of RNA-seq data from U2OS, HeLa and HEK293 cells showed that 205 ITSs were transcribed in at least one cell lines. The fraction of transcribed ITSs and the level of their transcription increased with the length of the telomeric repeat stretch. Given the large number of transcribed ITSs, we propose that these loci contribute significantly to the production of the TERRA pool.

Background: Currently, transcatheter aortic valve implantation (TAVI) is the standard procedure recommended for patients over 75 years of age with symptomatic aortic valve stenosis. Percutaneous transfemoral (TF) access is the main route used to perform the procedure. Among periprocedural complications, access-related ones are the most frequent, potentially leading to prolonged in-hospital stays and transfusions. Methods: We performed a retrospective analysis of prospectively collected data on consecutive patients undergoing TF-TAVI with the latest generation balloon-expandable transcatheter valve between 2013 and 2022. Results: A total of 600 patients were analyzed, differentiating the population between ultrasound-guided and blind common femoral artery puncture. Valve Academic Research Consortium 3 (VARC-3)criteria were used to report at 30 days and follow-up. In our propensity-matched comparison of the two groups, we found a strong reduction in access-related complications in the echo-guided group, particularly in terms of reduction of major and minor bleedings. We also found a significant trend in reduction of local complications, such as pseudoaneurysms, hematomas, arterio-venous fistulas, dissection of the femoral or iliac arteries, and stenosis. Conclusions: Although there is a lack of consensus on the role of ultrasound-guided puncture, we found better outcomes for patients having an echo-guided puncture of the main access, particularly with regard to access-related complications, early mobilization, and early discharge home.