Effects of virtual reality on anxiety and pain in adult patients undergoing wound-closure procedures: A pilot randomized controlled trial.

Background: In emergency departments, suturing is a typical procedure for closing lacerated wounds but is invasive and often causes anxiety and pain. Virtual reality (VR) intervention has been reported as a relaxing measure. Objective: The study aims to examine the effects of VR intervention on anxiety, pain, physiological parameters, local anesthesia requirements and satisfaction in Chinese adult patients undergoing wound closure in emergency departments in Hong Kong. Methods: Adult patients who had lacerated wounds and were undergoing wound closure by suturing can communicate in Chinese and were hemodynamically stable were invited for this trial. Eighty patients were randomly assigned to the VR group, which received VR intervention and standard care, or to the control group, which received standard care only. The primary outcome was anxiety, and the secondary outcomes included pain, blood pressure, pulse rate, satisfactory with pain management, service satisfactory, and extra local analgesia requirement. Outcomes were conducted at baseline, during the procedure and 5 min after the procedure. Results: The VR group had a significantly greater reduction in anxiety (p < 0.001), pain (p < 0.001), systolic blood pressure (p < 0.001), diastolic blood pressure (p < 0.001), pulse rate (p = 0.003) and requested less amount of additional local anesthesia (p = 0.025). The satisfactory level with pain management (p = 0.019) and service (p = 0.002) were significantly higher in participants who received VR intervention. In addition, most participants preferred to have VR in the future, and no major adverse events associated with the use of VR were reported. Conclusion: This pilot study provides insight into the use of VR and the direction of future studies. It may effectively improve psychological and physiological outcomes in adult patients during wound-closure procedures in emergency departments.

Roles for the Synechococcus elongatus RNA-Binding Protein Rbp2 in Regulating the Circadian Clock.

The cyanobacterial circadian oscillator, consisting of KaiA, KaiB, and KaiC proteins, drives global rhythms of gene expression and compaction of the chromosome and regulates the timing of cell division and natural transformation. While the KaiABC posttranslational oscillator can be reconstituted in vitro, the Kai-based oscillator is subject to several layers of regulation in vivo. Specifically, the oscillator proteins undergo changes in their subcellular localization patterns, where KaiA and KaiC are diffuse throughout the cell during the day and localized as a focus at or near the pole of the cell at night. Here, we report that the CI domain of KaiC, when in a hexameric state, is sufficient to target KaiC to the pole. Moreover, increased ATPase activity of KaiC correlates with enhanced polar localization. We identified proteins associated with KaiC in either a localized or diffuse state. We found that loss of Rbp2, found to be associated with localized KaiC, results in decreased incidence of KaiC localization and long-period circadian phenotypes. Rbp2 is an RNA-binding protein, and it appears that RNA-binding activity of Rbp2 is required to execute clock functions. These findings uncover previously unrecognized roles for Rbp2 in regulating the circadian clock and suggest that the proper localization of KaiC is required for a fully functional clock in vivo.

In vivo inhibition of nuclear ACE2 translocation protects against SARS-CoV-2 replication and lung damage through epigenetic imprinting.

In vitro, ACE2 translocates to the nucleus to induce SARS-CoV-2 replication. Here, using digital spatial profiling of lung tissues from SARS-CoV-2-infected golden Syrian hamsters, we show that a specific and selective peptide inhibitor of nuclear ACE2 (NACE2i) inhibits viral replication two days after SARS-CoV-2 infection. Moreover, the peptide also prevents inflammation and macrophage infiltration, and increases NK cell infiltration in bronchioles. NACE2i treatment increases the levels of the active histone mark, H3K27ac, restores host translation in infected hamster bronchiolar cells, and leads to an enrichment in methylated ACE2 in hamster bronchioles and lung macrophages, a signature associated with virus protection. In addition, ACE2 methylation is increased in myeloid cells from vaccinated patients and associated with reduced SARS-CoV-2 spike protein expression in monocytes from individuals who have recovered from infection. This protective epigenetic scarring of ACE2 is associated with a reduced latent viral reservoir in monocytes/macrophages and enhanced immune protection against SARS-CoV-2. Nuclear ACE2 may represent a therapeutic target independent of the variant and strain of viruses that use the ACE2 receptor for host cell entry.

Using item response theory to develop and refine patient-reported outcome measures.

There is a long tradition of incorporating patient-reported outcomes (PROs) into nursing research and practice. Classical Test Theory (CTT) has been the traditional approach used to develop and refine PROs. Item response theory (IRT) offers promise for addressing measurement problems that have been difficult to solve using CTT. This paper presents foundational concepts in IRT to illustrate how it can be used to improve the development and refinement of PRO measures, with emphasis on interpreting key IRT parameters.

Landscape of Epidermal Growth Factor Receptor Heterodimers in Brain Metastases.

HER2+ breast cancer patients have an elevated risk of developing brain metastases (BM), despite adjuvant HER2-targeted therapy. The mechanisms underpinning this reduced intracranial efficacy are unclear. We optimised the in situ proximity ligation assay (PLA) for detection of the high-affinity neuregulin-1 receptor, HER2-HER3 (a key target of pertuzumab), in archival tissue samples and developed a pipeline for high throughput extraction of PLA data from fluorescent microscope image files. Applying this to a large BM sample cohort (n = 159) showed that BM from breast, ovarian, lung and kidney cancers have higher HER2-HER3 levels than other primary tumour types (melanoma, colorectal and prostate cancers). HER2 status, and tumour cell membrane expression of pHER2(Y1221/1222) and pHER3(Y1222) were positively, but not exclusively, associated with HER2-HER3 frequency. In an independent cohort (n = 78), BM had significantly higher HER2-HER3 levels than matching primary tumours (p = 0.0002). For patients who had two craniotomy procedures, HER2-HER3 dimer levels were lower in the consecutive lesion (n = 7; p = 0.006). We also investigated the effects of trastuzumab and pertuzumab on five different heterodimers in vitro: HER2-EGFR, HER2-HER4, HER2-HER3, HER3-HER4, HER3-EGFR. Treatment significantly altered the absolute frequencies of individual complexes in SKBr3 and/or MDA-MB-361 cells, but in the presence of neuregulin-1, the overall distribution was not markedly altered, with HER2-HER3 and HER2-HER4 remaining predominant. Together, these findings suggest that markers of HER2 and HER3 expression are not always indicative of dimerization, and that pertuzumab may be less effective at reducing HER2-HER3 dimerization in the context of excess neuregulin.