We have used 2D NMR spectroscopy to study the sugar conformations of oligonucleotides containing a conformationally restricted nucleotide (LNA) with a 2'-O, 4'-C-methylene bridge. We have investigated a modified 9-mer single stranded oligonucleotide as well as three 9- and 10-mer modified oligonucleotides hybridized to unmodified DNA. The single-stranded LNA contained three modifications whereas the duplexes contained one, three and four modifications, respectively. The LNA:DNA duplexes have normal Watson-Crick base-pairing with all the nucleotides in anti-conformation. By use of selective DQF-COSY spectra we determined the ratio between the N-type (C3'-endo) and S-type (C2'-endo) sugar conformations of the nucleotides. In contrast to the corresponding single-stranded DNA (ssDNA), we found that the sugar conformations of the single-stranded LNA oligonucleotide (ssLNA) cannot be described by a major S-type conformer of all the nucleotides. The nucleotides flanking an LNA nucleotide have sugar conformations with a significant population of the N-type conformer. Similarly, the sugar conformations of the nucleotides in the LNA:DNA duplexes flanking a modification were also shown to have significant contributions from the N-type conformation. In all cases, the sugar conformations of the nucleotides in the complementary DNA strand in the duplex remain in the S-type conformation. We found that the locked conformation of the LNA nucleotides both in ssLNA and in the duplexes organize the phosphate backbone in such a way as to introduce higher population of the N-type conformation. These conformational changes are associated with an improved stacking of the nucleobases. Based on the results reported herein, we propose that the exceptional stability of the LNA modified duplexes is caused by a quenching of concerted local backbone motions (preorganization) by the LNA nucleotides in ssLNA so as to decrease the entropy loss on duplex formation combined with a more efficient stacking of the nucleobases.

The aim of this study was to investigate the experiences of patients and providers regarding the use of videoconferences in older patients with depression. The qualitative study consisted of semi‐structured interviews with patients and providers and focus group interviews with providers. Themes were identified through using thematic analysis. Three main themes were as follows: 1. Technical Challenges experienced by patients and providers experiences; 2. Videoconferencing as clinical supportive technology; and 3. Therapeutic relationship across face‐to‐face and videoconferencing formats. Several subthemes describing patients’ and providers’ experiences were identified. Taken together, there was a similarity between expectations, opinions, and attitudes in relation to experiences vertically across all main themes, and horizontally between the main themes. An optimistic outlook influenced user expectations, opinions, and attitudes and acted to mitigate an negative sentiment about technical challenges. This increased the adoption of videoconferencing as a tool for clinical support and enabled the development of a therapeutic relationship using videoconferencing, especially for provider users. Both patients and providers agreed that videoconferences could not replace all face‐to‐face conversations and that videoconferences, in most cases, were best suited for shorter follow‐up consultations. Expectations, opinions, and attitudes, whether negative or positive, seemed to have significant impact on the experiences of patients and especially providers.

Patients' and providers' experiences with video consultations used in the treatment of older patients with unipolar depression: a systematic review