Hypercompact adenine base editors based on transposase B guided by engineered RNA.

Transposon-associated transposase B (TnpB) is deemed an ancestral protein for type V, Cas12 family members, and the closest ancestor to UnCas12f1. Previously, we reported a set of engineered guide RNAs supporting high indel efficiency for Cas12f1 in human cells. Here we suggest a new technology whereby the engineered guide RNAs also manifest high-efficiency programmable endonuclease activity for TnpB. We have termed this technology TaRGET (TnpB-augment RNA-based Genome Editing Technology). Having this feature in mind, we established TnpB-based adenine base editors (ABEs). A Tad-Tad mutant (V106W, D108Q) dimer fused to the C terminus of dTnpB (D354A) showed the highest levels of A-to-G conversion. The limited targetable sites for TaRGET-ABE were expanded with engineered variants of TnpB or optimized deaminases. Delivery of TaRGET-ABE also ensured potent A-to-G conversion rates in mammalian genomes. Collectively, the TaRGET-ABE will contribute to improving precise genome-editing tools that can be delivered by adeno-associated viruses, thereby harnessing the development of clustered regularly interspaced short palindromic repeats (CRISPR)-based gene therapy.

Analgesic effect of ultrasound-guided transversus abdominis plane block with or without rectus sheath block in laparoscopic cholecystectomy: a randomized, controlled trial.

BACKGROUND: Ultrasound-guided transversus abdominis plane (TAP) block is commonly used for pain control in laparoscopic cholecystectomy. However, significant pain persists, affecting patient recovery and sleep quality on the day of surgery. We compared the analgesic effect of ultrasound-guided TAP block with or without rectus sheath (RS) block in patients undergoing laparoscopic cholecystectomy using the visual analog scale (VAS) scores. METHODS: The study was registered before patient enrollment at the Clinical Research Information Service (registration number: KCT0006468, 19/08/2021). 88 American Society of Anesthesiologist physical status I-III patients undergoing laparoscopic cholecystectomy were divided into two groups. RS-TAP group received right lateral and right subcostal TAP block, and RS block with 0.2% ropivacaine (30 mL); Bi-TAP group received bilateral and right subcostal TAP block with same amount of ropivacaine. The primary outcome was visual analogue scale (VAS) for 48 h postoperatively. Secondary outcomes included the use of rescue analgesics, cumulative intravenous patient-controlled analgesia (IV-PCA) consumption, patient satisfaction, sleep quality, and incidence of adverse events. RESULTS: There was no significant difference in VAS score between two groups for 48 h postoperatively. We found no difference between the groups in any of the secondary outcomes: the use of rescue analgesics, consumption of IV-PCA, patient satisfaction with postoperative pain control, sleep quality, and the incidence of postoperative adverse events. CONCLUSION: Both RS-TAP and Bi-TAP blocks provided clinically acceptable pain control in patients undergoing laparoscopic cholecystectomy, although there was no significant difference between two combination blocks in postoperative analgesia or sleep quality.

Development of an Acute Pain Assessment Tool for Patients in Post-anesthesia Care Units.

BACKGROUND: Post-operative pain is a common form of acute pain. Objective pain assessment in post-anesthesia care units after surgery is useful regardless of the patient's condition. AIMS: This study aimed to develop and evaluate an acute pain assessment tool for patients in post-anesthesia care units. DESIGN: This was a cross-sectional observational study comprising two stages: scale development and psychometric evaluation. SETTINGS:  . PARTICIPANTS/SUBJECTS:  . METHODS: Scale items were developed based on a literature review and content validity by experts. The validity and interrater reliability of the pain scale were evaluated using data from 218 patients admitted to the post-anesthesia care unit at a university hospital. A receiver operating characteristic curve was used to identify the sensitivity and specificity for determining the cutoff point for acute pain. RESULTS: We developed an objective acute pain scale, called the APA5, which ranges from 0-10 and comprises behavioral (facial and verbal expressions and body movement) and physiological (changes in heart rate and blood pressure) responses. The APA5 is valid and reliable for assessing acute pain in the recovery room. Sensitivity and specificity were acceptable when the cutoff was 2 out of 10 points. CONCLUSIONS: The APA5 is an easy and simple tool for measuring pain in patients in post-anesthesia care units who have difficulties with self-reporting.

Bronchial Washing Using a Thin Versus a Thick Bronchoscope to Diagnose Pulmonary Tuberculosis: A Randomized Trial.

BACKGROUND: This study was performed to evaluate the efficacy of using a thin bronchoscope for the diagnosis of pulmonary tuberculosis (PTB). METHODS: Between March 2019 and November 2021, we prospectively enrolled participants with suspected PTB whose sputum acid-fast bacilli (AFB) smear and tuberculosis (TB) polymerase chain reaction (PCR) tests were negative or who could not produce self-expectorated sputum. Participants were randomized to a control group (bronchial washing [BW] using a 5.9-mm conventional bronchoscope guided by chest computed tomography) or an investigational group (BW using a 4.0-mm thin bronchoscope under virtual bronchoscopic navigation guidance). The primary outcome was detection of TB in BW fluid, defined as a positive result in the Xpert MTB/RIF assay. The secondary outcomes included AFB smear and Mycobacterium tuberculosis culture positivity, time to treatment initiation, and bronchoscopy-related complications. RESULTS: In total, 85 participants were included in the final analysis (43 in the control group and 42 in the investigational group). Twenty-three and 29, respectively, were finally diagnosed with PTB. The TB detection rate in BW fluid was higher in the investigational group (72.4% vs 43.5%, P = .035). Mycobacterium tuberculosis culture positivity was also higher in the investigational group (79.3% vs 52.2%, P = .038). No participants required premature bronchoscopy termination because of complications. Of the participants with PTB, the time to treatment initiation was shorter in the investigational group (median, 2.0 days vs 4.0 days, P = .001). CONCLUSIONS: BW using a thin bronchoscope increases the TB detection rate in patients with PTB compared to conventional bronchoscopy. Clinical Trials Registration.ȃNCT03802812.

Curcumin inhibits human cancer cell growth and migration through downregulation of SVCT2.

Curcumin is a natural polyphenol that is extracted from the rhizomes of the turmeric plant (Curcuma longa), a member of the ginger family. It has been used for centuries in traditional Indian and Chinese medicine for its medicinal properties, including anti-inflammatory, antioxidant and antitumor effects. SVCT2 (Solute Carrier Family 23 Member 2, also known as SLC23A2) is a protein that plays a role in the transport of Vitamin C (Ascorbic Acid) into cells. SVCT2 plays an important role in tumor progression and metastasis, however, the molecular mechanisms of curcumin on SVCT2 have not been studied to date. Curcumin treatment inhibited proliferation and migration of cancer cells in a dose dependent manner. We found that curcumin reduced the expression of SVCT2 in cancer cells with a wild type p53, but not in those with a mutant type of p53. SVCT2 downregulation also reduced the MMP2 activity. Taken together, our results indicate that curcumin inhibited human cancer cell growth and migration by regulating SVCT2 through a downregulating p53. These findings provide new insights into the molecular mechanisms of curcumin's anticancer effects and potential therapeutic strategies for the treatment of metastatic migration.

A text-mining study on emotional cognition, understanding, and preventative behaviors during the COVID-19 pandemic.

BACKGROUND: This study aimed to look at emotions perceived about the attributes, prevention, diagnosis, and treatment of infectious diseases related to coronavirus disease (COVID-19) that were widespread across the world and identify their relevance to knowledge about infectious diseases and preventative behaviors. METHODS: Texts to measure emotional cognition were selected through a pre-test, and 282 people were chosen as participants based on the survey conducted for 20 days from August 19 to August 29, 2020, created with Google Forms. IBM SPSS Statistics 25.0 was used for the primary analysis, and the SNA package in R (version 4.0.2) was utilized to conduct the network analysis. RESULTS: It was found that universal negative emotions such as feeling "anxious" (65.5%), "afraid" (46.1%), and "scared" (32.7%) commonly appeared among most people. Also, they were found to be feeling both positive ("caring" [42.3%] and "strict" [28.2%]) and negative ("frustrating" [39.1%] and "isolated" [31.0%]) emotions about efforts to prevent and curb the spread of COVID-19. In terms of emotional cognition for the diagnosis and treatment of such diseases, "reliable" (43.3%) took the biggest ratio among the replies. The level of understanding about infectious diseases showed differences in emotional cognition, thereby affecting people's emotions. However, no differences were found in the practice of preventative behaviors. CONCLUSIONS: Emotions associated with cognition in the context of pandemic infectious diseases have been found to be mixed. Furthermore, it can be seen that feelings vary depending on the degree of understanding of the infectious disease.

Unmet informatics needs of nurses regarding the use of personal smartphones in the workplace.

AIMS: This study aimed to investigate the differences in practices, policies, and perceptions of nurses regarding work-related utilization of smartphones in acute-care settings. BACKGROUND: Mobile devices utilizing emerging technology are widely used in acute-care settings; however, concerns such as potential distraction, improper use, and negative impact on the nursing image in clinical practice remain valid. METHODS: Nurse managers (n = 8) and nurses (n = 181) were enrolled from eight academic tertiary hospitals that have comprehensive electronic medical record systems and mobile versions. Between October 2018 and February 2019, participants completed a questionnaire designed to explore their use of smartphones. The reporting guide for self-administered surveys of clinicians was applied. RESULTS: Approximately 80% of nurses carried personal smartphones while working, with 70% using their devices for work. The prevalence of work-related smartphone use ranged from 3% to 43% by functionality, which was lower than that estimated by managers. Frequent uses included taking pictures/videos and internet browsing. Nurses were more positive than managers about the benefits of smartphone use and less burdened by related concerns. Novice and junior nurses were more optimistic than senior nurses. Only one hospital had a policy on nurses' use of personal devices at work. CONCLUSION: Two unmet needs in the current clinical information system were identified: information supporting task-related knowledge at the bedside and security of data capture and communication. IMPLICATION FOR NURSING POLICY: The unintended perception gaps between nurses and managers regarding work-related smartphone use can be closed by nursing leadership. Unmet nursing informatics, particularly for information-seeking purposes, can be addressed in the context of quality assurance. Nurse leaders can advocate secure and proper use of smartphones in clinical practice.

Depression and stress in Korean parents: A cohort study.

AIM: This study identified the level of depression and stress in couples experiencing pregnancy and childbirth. BACKGROUND: Married couples who experience pregnancy and delivery, deal with psychological changes during the parenthood transition. If they do not adapt well, they experience negative emotions that negatively affect them and their child. Therefore, the incidence and changing patterns of depression among couples need to be explored. METHODS: Using a prospective cohort study design, the researchers collected the couples' depression and stress levels 6 times. This study included 219 prenatal pregnant women, 181 spouses during pregnancy in the prenatal period, 178 postpartum mothers, and 125 spouses after childbirth. The levels of depression and stress were investigated using the Edinburgh Postnatal Depression Scale and Perceived Stress Scale. RESULTS: The incidence rate of prenatal depression was 10.5- 21.5% in pregnant women and 10.5-12.7% in their spouses. After childbirth, the incidence rate of depression was 21.3- 32.0% in postpartum women and 6.4-10.4% in their spouses. The levels of depression and stress varied from the prenatal to the postpartum period, showing different patterns between women and their spouses. Significantly, the emotional patterns in the couples were different as far as parity was concerned. CONCLUSIONS: The levels of depression and stress in couples continuously changed during the prenatal and postpartum periods and the patterns differed as well. Even couples who experience a healthy pregnancy and childbirth experience negative emotional changes. Therefore, timely nursing management will alleviate stress and depression not first-time by first-time parents.

Comparison of PECS II and erector spinae plane block for postoperative analgesia following modified radical mastectomy: Bayesian network meta-analysis using a control group.

The present study compared the effects of pectoral nerve block II (PECS II) and erector spinae plane (ESP) block for postoperative analgesia in patients who underwent modified radical mastectomy by performing a network meta-analysis (NMA) using indirect comparison with systemic analgesia. Studies comparing the analgesic effects of PECS II and ESP block were searched on MEDLINE, PubMed, EMBASE and the Cochrane Library. The primary outcome of this study was cumulative opioid consumption for 24 h postoperatively. Pain score during this period was also assessed. NMA was performed to compare the postoperative analgesic effects of plane blocks and systemic analgesia. A search of databases identified 17 studies, with a total of 1069 patients, comparing the analgesic efficacies of PECS II block, ESP block, and systemic analgesia. Compared with systemic analgesia, mean difference of opioid consumption was - 10 mg (95% credible interval [CrI] - 15.0 to - 5.6 mg) with PECS II block and - 5.7 mg (95% CrI - 11.0 to - 0.7 mg) with ESP block. Relative to systemic analgesia, PECS II block showed lower pain scores over the first postoperative 24 h, whereas ESP block did not. PECS II block showed the highest surface under the cumulative ranking curves for both opioid consumption and pain score. Both PECS II and ESP blocks were shown to be more effective than systemic analgesia regarding postoperative analgesia following modified radical mastectomy, and between the two blocks, PECS II appeared to have favorable analgesic effects compared to ESP block.

Inclusion complexes of cysteinyl ß-cyclodextrin with baicalein restore collagen synthesis in fibroblast cells following ultraviolet exposure.

Baicalein, a bioactive flavonoid, has poor water solubility, thereby limiting its use in a wide range of biological applications. In the present study, we used inclusion complexes of cysteinyl ß-cyclodextrin (ß-CD) with baicalein to enhance the stability and solubility of baicalein in aqueous solution. We examined the effects of inclusion complexes of cysteinyl ß-CD on collagen synthesis following ultraviolet (UV) irradiation, as well as the mechanisms underlying its effects. Our findings demonstrated that baicalein significantly restored collagen synthesis in the UV-exposed human fibroblast Hs68 cells. In addition, synthetic cysteine functionalized ß-CDs were found to promote baicalein-induced collagen synthesis. Inclusion complexes of cysteinyl ß-CDs with baicalein significantly upregulated the protein expression of type I collagen and activated the transcription of type I, II, and III collagen. Inclusion complexes of cysteinyl ß-CDs with baicalein also downregulated matrix metalloproteinase -1 and -3, and α-smooth muscle actin expression. In addition, inclusion complexes of cysteinyl ß-CDs with baicalein attenuated the expression of caveolin-1, but this treatment enhanced the UV-induced phosphorylation of Smad in the transforming growth factor-ß pathway. These results suggested that the newly synthesized derivative of CD can be used as a complexing agent to enhance the bioavailability of flavonoids such as baicalein, especially in restoring collagen synthesis.

Bronchoscopic management of solitary bronchial myelolipoma: a case report.

BACKGROUND: Myelolipoma is a rare benign tumor composed of mature adipose and hematopoietic tissues. Most myelolipomas are found in the adrenal glands, whereas intrathoracic myelolipoma is extremely rare. In particular, bronchial myelolipoma without the involvement of lung parenchyma has never been reported. CASE PRESENTATION: A previously healthy 38-year-old male developed dyspnea and a productive cough. Computed tomography revealed an endobronchial mass at the right bronchus intermedius and subsequent atelectasis of the right middle and lower lobes. Flexible bronchoscopy found a total obstruction of the right bronchus intermedius due to an endobronchial tumor. Using a rigid bronchoscope, the endobronchial tumor was resected and the base of the tumor was additionally ablated with a diode laser to prevent recurrence. The removed endobronchial tumor was a 13 mm × 20 mm-sized oval-shaped mass and was pathologically diagnosed as bronchial myelolipoma. Chest radiographs, obtained on the day following the procedure, showed an improvement of atelectasis, and accompanying symptoms were immediately improved. Follow-up bronchoscopy performed after 12 months evidenced no recurrence of the bronchial myelolipoma. CONCLUSIONS: We used bronchoscopic intervention in patients with solitary bronchial myelolipoma and there was no evidence of recurrence.

Effect of 24-Hour Bed Rest versus Early Ambulation on Headache after Spinal Anesthesia: Systematic Review and Meta-analysis.

OBJECTIVES: We performed a systematic review of the evidence for the effectiveness of bed rest after dural puncture to update current evidence on the topic. DESIGN: The design was a systematic review and meta-analysis. DATA SOURCES: We searched 10 electronic databases in English (Medline, CINAHL, EMBASE, and the Cochrane Controlled Trial Register) and Korean (KISS, KMBASE, NDSL, and RISS) using the terms "post-dural puncture headache," "spinal anesthesia," "epidural anesthesia," and "bed rest" to identify reports discussing the effectiveness of bed rest in preventing post-dural puncture headache (PDPH) after spinal anesthesia from 1980 to 2014. Review/Analysis Methods: Original studies such as randomized and nonrandomized controlled trials, where participants were allocated to an intervention or control group, were included. A total of eight studies that met the inclusion criteria were independently reviewed and encoded by two review authors. To ensure the quality of the eight studies, levels of risk of bias were assessed by two different researchers. The main outcome was the prevalence of PDPH. RESULTS: The included studies indicated that PDPH prevalence did not differ between the group assigned to 24 hours of bed rest and the group assigned to early ambulation. In subgroup analysis, the effect size of clinical factors (severity of headache, day of onset, and needle gauge) and the study characteristics (language and sample size) did not differ between groups. CONCLUSION: This meta-analysis of studies suggested that long-term bed rest after spinal anesthesia may not be effective in preventing PDPH.

Inhibition of UV-induced matrix metabolism by a myristoyl tetrapeptide.

Regulation of extracellular matrix (ECM) composition is important in tissue homeostasis and function. We screened small peptides for their ability to inhibit ultraviolet (UV)-induced cell metabolism in epidermal fibroblasts. We found that UV irradiation increased matrix metalloproteinase (MMP) expression and inflammatory gene expression in human Hs68 fibroblast cells. We also demonstrated that a myristoyl tetrapeptide with the amino acid sequence Gly-Leu-Phe-Trp (mGLFW) suppressed the UV-induced expression of MMPs and inflammatory genes. Moreover, mGLFW stimulated the expression of ECM proteins in Hs68 fibroblasts. In order to provide the mechanism of action for mGLFW, we investigated UV-induced signaling changes in the presence of mGLFW using a cDNA microarray. UV exposure increased the expression of MMP genes, such as MMP1, MMP3, and MMP14, and inflammation-related genes, including interleukin 1 receptor and peroxisome proliferator-activated receptor gamma (PPARγ). Treatment with mGLFW abrogated the UV-induced expression of MMP-related genes and inflammatory genes. In addition, mGLFW increased the expression of collagen genes, including COL1A1, COL1A2, and COL5A1. We examined whether the activation of AP-1, a UV-activated transcription factor, is suppressed by mGLFW. The results demonstrated that AP-1 expression increased upon UV exposure and that this expression was inhibited by mGLFW. In conclusion, our results demonstrate that mGLFW reversed the effects of UV exposure by enhancing the expression of collagen proteins and suppressing the expression of MMPs, which degrade the ECM.

Use of fluorescence signals generated by elastic scattering under monochromatic incident light for determining the scattering efficiencies of various plasmonic nanoparticles.

We present a route that estimates the scattering/absorption characteristics of plasmonic nanoparticles by using fluorescence and UV-visible spectroscopy. Because elastic scattering of nanoparticles caused by a monochromatic incident light is reflected in fluorescence emission spectra when recording at the excitation wavelength, the scattering intensities at the excitation wavelength during fluorescence emission scans are used to compare the scattering characteristics of various plasmonic nanoparticles under conditions where the extinction values of all of the nanoparticles are kept constant at this wavelength. For the two excitation wavelengths (519 and 560 nm) we investigated, the scattering intensities of spherical gold nanoparticles increase with increasing size (15, 33, 51, 73, and 103 nm in diameter). These results are correlated with the nanoparticles' scattering efficiencies (the ratios of scattering to the extinction cross-sections), which are theoretically calculated in the literature using Mie theory. Then, linear calibration equations at each wavelength are derived to estimate the scattering efficiencies of two Au nanorods, Au nanocages, and spherical Ag nanoparticles (15, 25, 37, and 62 nm). The values are very comparable with literature values. For various purposes such as biomedicine and optoelectronics, the present method could be beneficial to those who wish to easily compare and determine the scattering characteristics of various plasmonic nanoparticles at a certain wavelength by using commercially-available spectroscopic techniques.

Proteomic profiling of lymphedema development in mouse model.

The lymphatic vascular system plays an important role in tissue fluid homeostasis. Lymphedema is a chronic, progressive, and incurable condition that leads to lymphatic fluid retention; it may be primary (heritable) or secondary (acquired) in nature. Although there is a growing understanding of lymphedema, methods for the prevention and treatment of lymphedema are still limited. In this study, we investigated differential protein expressions in sham-operated and lymphedema-operated mice for 3 days, using two-dimensional gel electrophoresis (2-DE) and mass spectrometry analysis. Male improved methodology for culturing noninbred (ICR) mice developed lymphedema in the right hindlimb. Twenty functional proteins were found to be differentially expressed between lymphedema induced-right leg tissue and normal left leg tissue. Out of these proteins, the protein levels of apolipoprotein A-1 preprotein, alpha-actinin-3, mCG21744, parkinson disease, serum amyloid P-component precursor, annexin A8, mKIAA0098 protein, and fibrinogen beta chain precursor were differentially upregulated in the lymphedema mice compared with the sham-operated group. Western blotting analysis was used to validate the proteomics results. Our results showing differential up-regulation of serum amyloid P-component precursor, parkinson disease, and apolipoprotein A-1 preprotein in lymphedema model over sham-operated model suggest important insights into pathophysiological target for lymphedema. Copyright © 2016 John Wiley & Sons, Ltd.

Cyclic Glucans Enhance Solubility of Bioavailable Flavonoids.

Diverse flavonoids are abundant in dietary food constituents and possess useful biological activities. However, some flavonoids have limited bioavailability due to their low solubility in water. As an important approach to enhance aqueous solubility, inclusion of hydrophobic guest molecules in hydrophilic hosts such as cyclic glucans has been used. This review summarizes applications of ß-cyclodextrin, synthetic ß-cyclodextrin derivatives, and newly synthesized derivatives of cyclosophoraoses as complexing agents to enhance the bioavailability of flavonoids such as baicalein, kaempferol, and naphthoflavones.

Characterization and Enhanced Antioxidant Activity of the Cysteinyl ß-Cyclodextrin-Baicalein Inclusion Complex.

Baicalein is a type of flavonoid isolated from the roots of a medicinal plant, Scutellaria baicalensis. Although it has attracted considerable attention due to its antiviral, anti-tumor, and anti-inflammatory activities, its limited aqueous solubility inhibits the clinical application of this flavonoid. The present study aimed to prepare and characterize a host-guest complex in an effort to improve the solubility and antioxidant activity of baicalein. The host molecule is a macrocyclic ß-cyclodextrin (ß-CD) functionalized with cysteine for a synergetic effect. The structure of the synthesized cysteinyl ß-CD was analyzed using nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry. The inclusion complex with baicalein was studied by UV-vis, NMR spectroscopy, scanning electron microscopy, and X-ray powder diffractometry. The formed cysteinyl ß-CD/baicalein inclusion complex efficiently improved the solubility and antioxidant ability of baicalein. Therefore, we suggest that the present cysteinyl ß-CD is a potential host molecule for inclusion complexation and for bioavailability augmentation.

Immediate effects of the trunk stabilizing exercise on static balance parameters in double-leg and one-leg stances.

[Purpose] The purpose of this study was to evaluate the immediate effect of stabilizing exercise using the PNF technique on standing balance in one-leg and double-leg stances. [Subjects and Methods] The present study recruited 34 healthy participants from a local university. The Participants performed four balance tests (double-leg stance with and without vision, one-leg stance with and without vision), before and after exercise. The exercise consisted of exercises performed using PNF techniques (stabilizing reversal and rhythmic stabilization), which were applied to facilitate trunk musculature. To examine balance ability, total displacement of the center of pressure was measured during balance tests. [Results] The total anterior-posterior center of pressure displacement was significantly reduced after applying rhythmic stabilization compared before exercise regardless of the balance test conditions. [Conclusion] The present results suggest that trunk stability exercise using rhythmic stabilization could effectively enhance balance ability under one-leg and double-leg conditions.