Abstract: In most eukaryotes, pairing of homologous chromosomes is an essential feature of meiosis that ensures homologous recombination and segregation. However, when the pairing process begins, it is still under investigation. Contrasting data exists in Mus musculus, since both leptotene DSB-dependent and preleptotene DSB-independent mechanisms have been described. To unravel this contention, we examined homologous pairing in pre-meiotic and meiotic Mus musculus cells using a threedimensional fuorescence in situ hybridization-based protocol, which enables the analysis of the entire karyotype using DNA painting probes. Our data establishes in an unambiguously manner that 73.83% of homologous chromosomes are already paired at premeiotic stages (spermatogonia-early preleptotene spermatocytes). The percentage of paired homologous chromosomes increases to 84.60% at mid-preleptotene-zygotene stage, reaching 100% at pachytene stage. Importantly, our results demonstrate a high percentage of homologous pairing observed before the onset of meiosis; this pairing does not occur randomly, as the percentage was higher than that observed in somatic cells (19.47%) and between nonhomologous chromosomes (41.1%). Finally, we have also observed that premeiotic homologous pairing is asynchronous and independent of the chromosome size, GC content, or presence of NOR regions.

Abstract: Background: Bronchoscopy is a safe technique for diagnosing peripheral pulmonary lesions (PPLs), and virtual bronchoscopic navigation (VBN) helps guide the bronchoscope to PPLs. Objectives: We aimed to compare the diagnostic yield of VBN-guided and unguided ultrathin bronchoscopy (UTB) and explore clinical and technical factors associated with better results. We developed a diagnostic algorithm for deciding whether to use VBN to reach PPLs or choose an alternative diagnostic approach. Methods: We compared diagnostic yield between VBN-UTB (prospective cases) and unguided UTB (historical controls) and analyzed the VBN-UTB subgroup to identify clinical and technical variables that could predict the success of VBN-UTB. Results: Fifty-five cases and 110 controls were included. The overall diagnostic yield did not differ between the VBN-guided and unguided arms (47 and 40%, respectively; p = 0.354). Although the yield was slightly higher for PPLs ≤20 mm in the VBN-UTB arm, the difference was not significant (p = 0.069). No other clinical characteristics were associated with a higher yield in a subgroup analysis, but an 85% diagnostic yield was observed when segmentation was optimal and the PPL was endobronchial (vs. 30% when segmentation was suboptimal and 20% when segmentation was optimal but the PPL was extrabronchial). Conclusions: VBN-guided UTB is not superior to unguided UTB. A greater impact of VBN-guided over unguided UTB is highly dependent on both segmentation quality and an endobronchial location of the PPL. Segmentation quality should be considered before starting a procedure, when an alternative technique that may improve yield can be chosen, saving time and resources.