Understanding patient perspectives on digital therapeutics and its platform for insomnia: insights from focused group interviews.

BACKGROUND: Digital therapeutics (DTx) is a treatment option that uses computer software to provide evidence-based interventions for medical disorders. DTx platforms are digital services that facilitate interactions among stakeholders of DTx treatment within a standardized structure. However, there is still a lack of overall awareness regarding the effectiveness and usage of DTx and DTx platforms. This study aimed to investigate insomnia patients' recognition, thoughts, feelings, and demands for conventional treatments versus DTx for insomnia. METHODS: Nine participants, aged 19-50 years, who had experience with professional medical interventions for insomnia, were recruited through purposive sampling. Two online focus group interviews, each lasting 1.5 h, were conducted. The interview questions focused on difficulties encountered during conventional treatment, inadequate recognition of DTx, and concerns and demands regarding DTx and its platform. The data were analyzed using thematic analysis. RESULTS: The participants reported subjective difficulties associated with receiving conventional treatment, including concerns about drug side effects and dependence, social stigma, and lack of perceived necessity for treatment. They expressed concerns about DTx, such as cost-effectiveness, evidence on efficacy, and concerns about breach of personal information. Additionally, their demands included convenience of use, reduction in social stigma related to the use of DTx, compatibility of DTx with other healthcare systems, and enhanced communication with healthcare providers when using DTx platforms. CONCLUSIONS: The focus group highlighted the need for increased awareness, demonstrated efficacy, cost-effectiveness, cybersecurity measures, and accessibility of insomnia DTx and its platforms. Tailored approaches considering patient characteristics are crucial for widespread adoption of insomnia DTx and its platforms.

Factors affecting the cleavage efficiency of the CRISPR-Cas9 system.

The CRISPR-Cas system stands out as a promising genome editing tool due to its cost-effectiveness and time efficiency compared to other methods. This system has tremendous potential for treating various diseases, including genetic disorders and cancer, and promotes therapeutic research for a wide range of genetic diseases. Additionally, the CRISPR-Cas system simplifies the generation of animal models, offering a more accessible alternative to traditional methods. The CRISPR-Cas9 system can be used to cleave target DNA strands that need to be corrected, causing double-strand breaks (DSBs). DNA with DSBs can then be recovered by the DNA repair pathway that the CRISPR-Cas9 system uses to edit target gene sequences. High cleavage efficiency of the CRISPR-Cas9 system is thus imperative for effective gene editing. Herein, we explore several factors affecting the cleavage efficiency of the CRISPR-Cas9 system. These factors include the GC content of the protospacer-adjacent motif (PAM) proximal and distal regions, single-guide RNA (sgRNA) properties, and chromatin state. These considerations contribute to the efficiency of genome editing.

Precise base editing without unintended indels in human cells and mouse primary myoblasts.

Base editors are powerful tools for making precise single-nucleotide changes in the genome. However, they can lead to unintended insertions and deletions at the target sites, which is a significant limitation for clinical applications. In this study, we aimed to eliminate unwanted indels at the target sites caused by various evolved base editors. Accordingly, we applied dead Cas9 instead of nickase Cas9 in the base editors to induce accurate substitutions without indels. Additionally, we tested the use of chromatin-modulating peptides in the base editors to improve nucleotide conversion efficiency. We found that using both dead Cas9 and chromatin-modulating peptides in base editing improved the nucleotide substitution efficiency without unintended indel mutations at the desired target sites in human cell lines and mouse primary myoblasts. Furthermore, the proposed scheme had fewer off-target effects than conventional base editors at the DNA level. These results indicate that the suggested approach is promising for the development of more accurate and safer base editing techniques for use in clinical applications.

Effect of a massage chair (BFM-M8040) on neck and shoulder pain in office workers: A randomized controlled clinical trial.

Background: With the increasing work-related musculoskeletal disorders, neck and shoulder pain among office workers has also increased. That said, this randomized controlled trial aimed to seek the potential effects of a massage chair (BFR-M8040) on neck and shoulder pain among office workers. Methods: This was conducted at the Wonkwang University Gwangju Medical Center from April 2022 to December 2022. Sixty adult participants were randomly allocated. The mean age of male participants was 39.63 ± 8.09 years while female participants was 43.52 ± 8.27; women participated the most (86.67%). The control group received basic physical treatments, including a 10-min heat treatment for deep regions and a 10-min hot pack for the areas on the neck and shoulder of the complained discomfort. The experimental group received the same treatment as the control group and added 20 min of the electric massage chair's PEMF Neck Mode (XD module 3) (BFR-M8040, Bodyfriend Co., Ltd.). The participants received treatments twice per week. The primary outcome was measured using the numerical rating scale and the Korean version of the neck disability index. And the secondary outcome was measured using pressure pain threshold, range of motion, the Korean occupational stress scale, the Korean version of the Euro-quality of life-5 dimension, and safety evaluation. Results: Fifty-eight participants completed a 6-week follow-up and analyzed (29 in the control group and 29 in the experimental group). There was a significant decrease in the experiment group in both scales for primary outcome measures. For secondary outcome measures, statistically significant increases were observed in pressure pain threshold. The experimental group only showed a slight increase in the quality-of-life measures. There were no reported adverse events. Conclusion: The benefit of using a massage chair (BFR-M8040) was verified to alleviate neck and shoulder pain among office workers; future studies could involve participants from other countries for further investigation.

Role of the Circadian Clock and Effect of Time-Restricted Feeding in Adenine-Induced Chronic Kidney Disease.

Most physiological functions exhibit circadian rhythmicity that is partly regulated by the molecular circadian clock. Herein, we investigated the relationship between the circadian clock and chronic kidney disease (CKD). The role of the clock gene in adenine-induced CKD and the mechanisms of interaction were investigated in mice in which Bmal1, the master regulator of the clock gene, was knocked out, and Bmal1 knockout (KO) tubule cells. We also determined whether the renoprotective effect of time-restricted feeding (TRF), a dietary strategy to enhance circadian rhythm, is clock gene-dependent. The mice with CKD showed altered expression of the core clock genes with a loss of diurnal variations in renal functions and key tubular transporter gene expression. Bmal1 KO mice developed more severe fibrosis, and transcriptome profiling followed by gene ontology analysis suggested that genes associated with the cell cycle, inflammation, and fatty acid oxidation pathways were significantly affected in the mutant mice. Tubule-specific deletion of BMAL1 in HK-2 cells by CRISPR/Cas9 led to upregulation of p21 and tumor necrosis α and exacerbated epithelial-mesenchymal transition-related gene expression upon transforming growth factor ß stimulation. Finally, TRF in the mice with CKD partially restored the disrupted oscillation of the kidney clock genes, accompanied by improved cell cycle arrest and inflammation, leading to decreased fibrosis. However, the renoprotective effect of TRF was abolished in Bmal1 KO mice, suggesting that TRF is partially dependent on the clock gene. Our data demonstrate that the molecular clock system plays an important role in CKD via cell cycle regulation and inflammation. Understanding the role of the circadian clock in kidney diseases can be a new research field for developing novel therapeutic targets.

Button battery injury: An update.

BACKGROUND: Paediatric button battery injuries present a challenge in the general practice setting. Although some children present with history or parental suspicion of button battery ingestion (BBI) or insertion, unwitnessed cases may present with non-specific symptoms that can mimic many respiratory and gastrointestinal pathologies. OBJECTIVE: The aim of this article is to increase awareness of the fast onset of life-threatening tissue injury from BBI and the importance of timely referral as well as provide an update on current management, including first aid management in the general practice setting. DISCUSSION: BBI is a medical emergency. The button battery requires urgent removal as it can cause caustic burn injury to its surrounding tissues in as little as 15 minutes. Limited awareness of the time-critical nature of this presentation has been reported in multiple triage settings. Studies have shown a role for consumption of honey or sucralfate in delaying tissue injury while awaiting surgical removal.

Management of oesophageal impaction of button batteries in Queensland.

BACKGROUND: Oesophageal button battery impaction (OBBI) is a medical emergency requiring timely removal due to rapid oesophageal tissue injury. The aim of this study was to characterize circumstances of OBBI and identify potential barriers to timely removal of button batteries (BB) in the paediatric population. METHODS: This is a retrospective review of OBBI cases between January 2018 to June 2019. Medical records were used to obtain patient demographics, battery size and type, battery source, location of initial presentation and outcomes. Time to obtaining x-ray, transfer to tertiary centre and to removal of button battery were recorded. RESULTS: Eight cases of OBBI were recorded during the 18 months study timeframe. Six patients were male and two were female, aged 0.97 to 2.8 years. Six were from an English-speaking background and two were from families of non-English speaking background. Battery removal occurred at Queensland Children's Hospital (QCH) in seven of eight cases. Time from ingestion to initial presentation to hospital ranged from 39 min to 123 h with a mean time of 2 h and 13 min. Overall, the total time from ingestion of BB to removal ranged from 2 h 54 min to 126 h 51 min. CONCLUSION: Despite being recognized as a time critical emergency, diagnostic, geographic and logistic challenges in Queensland make optimal care a challenge. Primary prevention strategies coupled with an expanded network for safe battery removal, and novel management strategies such as honey and acetic acid could improve care and reduce morbidity.

Subcellular progression of mesenchymal transition identified by two discrete synchronous cell lines derived from the same glioblastoma.

Glioblastomas (GBM) exhibit intratumoral heterogeneity of various oncogenic evolutional processes. We have successfully isolated and established two distinct cancer cell lines with different morphological and biological characteristics that were derived from the same tissue sample of a GBM. When we compared their genomic and transcriptomic characteristics, each cell line harbored distinct mutation clusters while sharing core driver mutations. Transcriptomic analysis revealed that one cell line was undergoing a mesenchymal transition process, unlike the other cell line. Furthermore, we could identify four tumor samples containing our cell line-like clusters from the publicly available single-cell RNA-seq data, and in a set of paired longitudinal GBM samples, we could confirm three pairs where the recurrent sample was enriched in the genes specific to our cell line undergoing mesenchymal transition. The present study provides direct evidence and a valuable source for investigating the ongoing process of subcellular mesenchymal transition in GBM, which has prognostic and therapeutic implications.

Targeted mutagenesis in mouse cells and embryos using an enhanced prime editor.

Prime editors, novel genome-editing tools consisting of a CRISPR-Cas9 nickase and an engineered reverse transcriptase, can induce targeted mutagenesis. Nevertheless, much effort is required to optimize and improve the efficiency of prime-editing. Herein, we introduce two strategies to improve the editing efficiency using proximal dead sgRNA and chromatin-modulating peptides. We used enhanced prime-editing to generate Igf2 mutant mice with editing frequencies of up to 47% and observed germline transmission, no off-target effects, and a dwarf phenotype. This improved prime-editing method can be efficiently applied to cell research and to generate mouse models.

Effectiveness and safety of fluoroscopy-guided acupuncture for subacromial impingement syndrome: A randomized, patient-assessor blind, parallel clinical trial.

BACKGROUND: Subacromial impingement syndrome (SIS) is one of the most common causes of shoulder pain, and acupuncture treatment is widely used as treatment. However, no studies have examined image-guided acupuncture for SIS. This study evaluated the effectiveness and safety of low-dose X-ray guided acupuncture (LA) in patients with SIS. METHODS: A total of 54 patients with SIS were randomly allocated to the LA group and the conventional acupuncture (CA) group. Two acupuncture treatment sessions were conducted for a week, and follow up was conducted after three weeks. The primary outcome was pain intensity measured by the visual analogue scale (VAS) during the Neer and Hawkins test. The incidence rate of shoulder impingement sign, the modified Constant-Murley score (CMS) and the Shoulder Pain and Disability Index (SPADI) were assessed as other outcomes. All indicators were assessed at baseline and after one week and three weeks. For safety evaluation, adverse events were monitored in both groups. RESULTS: The change in pain during the Neer test after one week from baseline was more significant in the LA group than in the CA group (p=0.008). However, the Hawkins test did not show a difference between the two groups. The incidence rate of shoulder impingement sign and the changes in CMS and SPADI were not significantly different between the two groups at one week, but after three weeks, SPADI was more significantly improved in the LA group (p=0.024). No adverse events were related to this trial. CONCLUSION: LA was more effective than CA in relieving pain and improving function in terms of VAS and SPADI. TRIAL REGISTRATION: This study was registered on 23 March 2018 at the Clinical Research Information Service: KCT0002751.