Molecular basis of convergent evolution of ACE2 receptor utilization among HKU5 coronaviruses.

DPP4 was considered a canonical receptor for merbecoviruses until the recent discovery of African bat-borne MERS-related coronaviruses using ACE2. The extent and diversity with which merbecoviruses engage ACE2 and their receptor species tropism remain unknown. Here, we reveal that HKU5 enters host cells utilizing Pipistrellus abramus (P.abr) and several non-bat mammalian ACE2s through a binding mode distinct from that of any other known ACE2-using coronaviruses. These results show that several merbecovirus clades independently evolved ACE2 utilization, which appears to be a broadly shared property among these pathogens, through an extraordinary diversity of ACE2 recognition modes. We show that MERS-CoV and HKU5 have markedly distinct antigenicity, due to extensive genetic divergence, and identified several HKU5 inhibitors, including two clinical compounds. Our findings profoundly alter our understanding of coronavirus evolution and pave the way for developing countermeasures against viruses poised for human emergence.

All-in-one wearable drug efficacy assessment systems for bulbar muscle function using amyotrophic lateral sclerosis animal models.

Preclinical studies are crucial for developing amyotrophic lateral sclerosis drugs. Current FDA-approved drugs have been created by monitoring limb muscle function and histological analysis of amyotrophic lateral sclerosis model animals. Drug candidates for this disease have yet to be tested for bulbar-onset type due to the limitations of traditional preclinical tools: excessive animal use and discrete detection of disease progress. Here, our study introduces an all-in-one, wireless, integrated wearable system for facilitating continuous drug efficacy assessment of dysphagia-related muscles in animals during natural eating behaviors. By incorporating a kirigami-based strain-isolation mechanism, this device mounted on the skin of animals mitigates electromyography signal contamination caused by unpredictable animal movements. Our findings indicate this system, measuring the progression of motor neuron denervation, offers high precision in monitoring drug effects on dysphagia-responsible bulbar muscles. This study paves the way for more humane and efficient approaches to developing treatment solutions for degenerative neuromuscular diseases.

Insights from Li and Zn systems for advancing Mg and Ca metal batteries.

The inherent limitations of lithium (Li)-ion batteries have sparked interest in exploring alternative technologies, especially those relying on metallic anodes: monovalent Li and divalent zinc (Zn), magnesium (Mg), and calcium (Ca) metals. In particular, Mg and Ca metal batteries offer significant advantages based on the natural abundance of their raw materials and high energy-storage capabilities resulting from the bivalency of the carrier ions. Yet, these battery systems are far from commercialization, and the lack of reliable electrolytes constitutes a primary concern. The formation of ion-insulating passivation layers on these metallic anodes and their inferior desolvation kinetics have long been recognized as formidable hurdles in the way of optimizing the electrolyte composition. These impediments call for innovative strategies in electrolyte engineering and an extensive analysis of the resulting solid-electrolyte-interphase (SEI) layer. In this review, we introduce recent pioneering studies of divalent Mg and Ca metal batteries that have been concerned with these issues. This review particularly focuses on drawing an analogy with Li and Zn metal batteries in terms of the relative advancement and by benchmarking against the strategies developed for these analogous systems. The areas of interest include a fundamental understanding of the thermodynamics and evolution of the morphology of metallic anodes, a correlation between the electrolyte and SEI compositions, state-of-the-art electrolyte strategies to realize reversible (de)plating of Mg and Ca, and new perspectives on the SEI properties and their relevance to corrosion and the calendar life. We finally encourage researchers in the community to delve into these emerging areas by linking with successful stories in the analogous systems, but identifying distinct aspects of Mg and Ca batteries that still require attention.

A pan-variant miniprotein inhibitor protects against SARS-CoV-2 variants.

The continued evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has compromised neutralizing antibody responses elicited by prior infection or vaccination and abolished the utility of most monoclonal antibody therapeutics. We previously described a computationally-designed, homotrimeric miniprotein inhibitor, designated TRI2-2, that protects mice against pre-Omicron SARS-CoV-2 variants. Here, we show that TRI2-2 exhibits pan neutralization of variants that evolved during the 4.5 years since the emergence of SARS-CoV-2 and protects mice against BQ.1.1, XBB.1.5 and BA.2.86 challenge when administered post-exposure by an intranasal route. The resistance of TRI2-2 to viral escape and its direct delivery to the upper airways rationalize a path toward clinical advancement.

Double-bar technique for the correction of asymmetric pectus excavatum.

Background: Minimally invasive repair of pectus excavatum (MIRPE) improves clinical outcomes and chest wall morphology. However, asymmetry in patients with pectus excavatum (PE) remains as an important issue, even after surgery. Here, we evaluated the benefit of double-bar technique in achieving a symmetric chest wall. Methods: This retrospective study included 79 patients with PE who underwent MIRPE between 2017 and 2021. The patients were divided into the double- or non-double-bar groups. Asymmetric degree (AD) and sternal rotation angle (SRA) were used to assess the severity of asymmetry based on computed tomography (CT) images. The primary outcome was the change in radiologic parameters. Secondary outcomes were clinical results, including hospital stay, pain scores, and complication rates. Subgroup analysis of patients with preoperative asymmetric PE was performed. Results: Patients in the double-bar group (n=23) were younger than those in the non-double-bar group (n=56). Additionally, the double-bar group exhibited lower pain scores and shorter hospital stay. Based on radiological assessments, the double-bar group demonstrated a greater decrease in AD without compromising improvement in the Haller index (HI). The benefit of the double-bar technique was more obvious among patients with asymmetry with a preoperative AD >5%, resulting in a significant reduction in AD. In this subgroup, a better correction of sternal rotation was observed. Conclusions: The double-bar technique may be a promising option for correcting asymmetry in patients with PE. Simplified AD and SRA radiologic assessments can be used to evaluate improvements in chest wall configuration.

Computationally designed mRNA-launched protein nanoparticle vaccines.

Both protein nanoparticle and mRNA vaccines were clinically de-risked during the COVID-19 pandemic1-6. These vaccine modalities have complementary strengths: antigen display on protein nanoparticles can enhance the magnitude, quality, and durability of antibody responses7-10, while mRNA vaccines can be rapidly manufactured11 and elicit antigen-specific CD4 and CD8 T cells12,13. Here we leverage a computationally designed icosahedral protein nanoparticle that was redesigned for optimal secretion from eukaryotic cells14 to develop an mRNA-launched nanoparticle vaccine for SARS-CoV-2. The nanoparticle, which displays 60 copies of a stabilized variant of the Wuhan-Hu-1 Spike receptor binding domain (RBD)15, formed monodisperse, antigenically intact assemblies upon secretion from transfected cells. An mRNA vaccine encoding the secreted RBD nanoparticle elicited 5- to 28-fold higher levels of neutralizing antibodies than an mRNA vaccine encoding membrane-anchored Spike, induced higher levels of CD8 T cells than the same immunogen when delivered as an adjuvanted protein nanoparticle, and protected mice from vaccine-matched and -mismatched SARS-CoV-2 challenge. Our data establish that delivering protein nanoparticle immunogens via mRNA vaccines can combine the benefits of each modality and, more broadly, highlight the utility of computational protein design in genetic immunization strategies.

Computed Tomography of Contemporary Occupational Lung Disease: A Pictorial Review.

Occupational lung disease remains one of the most common work-related illnesses and accounts for most deaths from occupational illness. Occupational lung diseases often have delayed manifestation over decades and nonspecific clinical presentations, making it challenging for clinicians to promptly identify the disease and implement preventive measures. Radiologists play a crucial role in identifying and diagnosing occupational lung diseases, allowing for removal of the exposure and early medical intervention. In this review, we share our clinical and radiologic approach to diagnosing occupational lung disease and its subtypes. A collection of sample cases of occupational lung diseases commonly encountered in the modern era at a large Canadian university hospital is included to facilitate understanding. This review will provide radiologists with valuable insights into recognizing and diagnosing occupational lung diseases.

Investigating miR-6880-5p in extracellular vesicle from plasma as a prognostic biomarker in endocrine therapy-treated castration-resistant prostate cancer.

BACKGROUND: Advancements in the diagnosis, treatment, and surveillance of castration-resistant prostate cancer (CRPC) have progressed considerably, but a new biomarker that combines existing clinical and pathological data could be useful for a more precise diagnosis and prognosis. Some investigations have found that extracellular vesicle (EV)-derived miRNAs play crucial roles in various types of malignant tumors. The objective of this study was to explore EV miRNA and identify its biologic function as a biomarker for the diagnosis and prognosis of CRPC. METHODS: Plasma samples were collected from five healthy donors (Control, CT) and 17 CRPC patients, categorizing into two groups based on their endocrine treatment response: partial response (PR; n = 10) and progressive disease (PD; n = 7). Candidate extracellular vesicle (EV) miRNAs were identified using miRNA microarray and RT-qPCR. The biological functions of the selected miRNAs were evaluated using the MTT assay, wound healing assay, trans-well assay, and RNA sequencing in CRPC cells after transient miRNA expression. RESULTS: Microarray analysis revealed a significant downregulation of EV-miR-6880-5p in the PD samples compared to both CT and PR samples (p < 0.01). The expression of EV-miR-6880-5p in CRPC patients was decreased compared with that CT group (p = 0.0336) using RT-qPCR. In the PR group, EV-miR-6880-5p was increased at follow-up compared with the baseline (p = 0.2803), while in the PD group, it decreased at follow-up compared with the baseline samples (p = 0.4356). Furthermore, overexpression of miR-6880-5p hampered cell proliferation, migration, and invasion, downregulated pathways associated with tumor progression, and simultaneously upregulated pathways associated with cell growth and apoptosis in CRPC cells. CONCLUSIONS: EV-miR-6880-5p shows promise as a prognostic biomarker in patients with CRPC. Further, prospective validations are necessary to evaluate the potential of these candidate miRNAs.

Spike deep mutational scanning helps predict success of SARS-CoV-2 clades.

SARS-CoV-2 variants acquire mutations in the spike protein that promote immune evasion1 and affect other properties that contribute to viral fitness, such as ACE2 receptor binding and cell entry2,3. Knowledge of how mutations affect these spike phenotypes can provide insight into the current and potential future evolution of the virus. Here we use pseudovirus deep mutational scanning4 to measure how more than 9,000 mutations across the full XBB.1.5 and BA.2 spikes affect ACE2 binding, cell entry or escape from human sera. We find that mutations outside the receptor-binding domain (RBD) have meaningfully affected ACE2 binding during SARS-CoV-2 evolution. We also measure how mutations to the XBB.1.5 spike affect neutralization by serum from individuals who recently had SARS-CoV-2 infections. The strongest serum escape mutations are in the RBD at sites 357, 420, 440, 456 and 473; however, the antigenic effects of these mutations vary across individuals. We also identify strong escape mutations outside the RBD; however, many of them decrease ACE2 binding, suggesting they act by modulating RBD conformation. Notably, the growth rates of human SARS-CoV-2 clades can be explained in substantial part by the measured effects of mutations on spike phenotypes, suggesting our data could enable better prediction of viral evolution.

TIPRL Regulates Stemness and Survival in Lung Cancer Stem Cells through CaMKK2-CaMK4-CREB Feedback Loop Activation.

Frequent recurrence and metastasis caused by cancer stem cells (CSCs) are major challenges in lung cancer treatment. Therefore, identifying and characterizing specific CSC targets are crucial for the success of prospective targeted therapies. In this study, it is found that upregulated TOR Signaling Pathway Regulator-Like (TIPRL) in lung CSCs causes sustained activation of the calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) signaling pathway by binding to CaMKK2, thereby maintaining stemness and survival. CaMKK2-mediated activation of CaM kinase 4 (CaMK4) leads to phosphorylation of cAMP response element-binding protein (CREB) at Ser129 and Ser133, which is necessary for its maximum activation and the downstream constitutive expression of its target genes (Bcl2 and HMG20A). TIPRL depletion sensitizes lung CSCs to afatinib-induced cell death and reduces distal metastasis of lung cancer in vivo. It is determined that CREB activates the transcription of TIPRL in lung CSCs. The positive feedback loop consisting of CREB and TIPRL induces the sustained activation of the CaMKK2-CaMK4-CREB axis as a driving force and upregulates the expression of stemness- and survival-related genes, promoting tumorigenesis in patients with lung cancer. Thus, TIPRL and the CaMKK2 signaling axis may be promising targets for overcoming drug resistance and reducing metastasis in lung cancer.

Flexible Thermoelectric Wearable Architecture for Wireless Continuous Physiological Monitoring.

Continuous monitoring of physiological signals from the human body is critical in health monitoring, disease diagnosis, and therapeutics. Despite the needs, the existing wearable medical devices rely on either bulky wired systems or battery-powered devices needing frequent recharging. Here, we introduce a wearable, self-powered, thermoelectric flexible system architecture for wireless portable monitoring of physiological signals without recharging batteries. This system harvests an exceptionally high open circuit voltage of 175-180 mV from the human body, powering the wireless wearable bioelectronics to detect electrophysiological signals on the skin continuously. The thermoelectric system shows long-term stability in performance for 7 days with stable power management. Integrating screen printing, laser micromachining, and soft packaging technologies enables a multilayered, soft, wearable device to be mounted on any body part. The demonstration of the self-sustainable wearable system for detecting electromyograms and electrocardiograms captures the potential of the platform technology to offer various opportunities for continuous monitoring of biosignals, remote health monitoring, and automated disease diagnosis.

Coercive Control in 2SLGBTQQIA+ Relationships: A Scoping Review.

Existing measures and theories of intimate partner coercive control largely evaluate men's coercion of women. The extent of knowledge pertaining to intimate relationships among other genders and sexual identities is unclear. Guided by a theoretical framework of intersectionality, we examined and synthesized original studies on coercive control by (perpetration) or against (victimization) Two Spirit, lesbian, gay, bisexual, trans, queer, questioning, intersex, and asexual individuals within intimate partner relationships. We searched eight academic databases for records from 2014 through 2022 and hand-searched review articles' reference lists, supplemented with gray literature and website searches. Using duplicate screening, we identified 1,774 unique documents; 526 met preliminary eligibility criteria and 277 were retained for data extraction in duplicate. Coercive control was more common among minority individuals and was related to mental health challenges. Few studies reported on gender- or sexual-identity specific forms of coercive control, and an intersectional focus was uncommon. This review revealed a lack of agreed definition of coercive control or accepted standard of measurement, and a gap in research with individuals who identify as gender diverse, gender fluid or intersex, or those identifying their sexuality as asexual, pansexual, or sexually diverse.

Evaluation of Shear Bond Strengths of 3D Printed Materials for Permanent Restorations with Different Surface Treatments.

The development of high-filled 3D printing resin necessitates a bonding protocol for dental indirect restorations to achieve optimal bond strength after cementation. This study evaluates shear bond strengths of high-filler 3D printed materials for permanent restorations with various surface treatments. Rodin Sculpture 1.0 (50% lithium disilicate fillers) and 2.0 Ceramic Nanohybrid (>60% zirconia and lithium disilicate fillers) were tested, with Aelite All-Purpose Body composite resin as control. Samples were prepared, post-cured, and sandblasted with alumina (25 µm). Surface roughness was analyzed using an optical profilometer. Two bonding protocols were compared. First, groups were treated with lithium disilicate silane (Porcelain Primer) or zirconia primer (Z-Prime Plus) or left untreated without a bonding agent. Beam-shaped resin cement (DuoLink Universal) specimens were bonded and stored in a 37 °C water bath. Second, additional sets of materials were coated with a bonding agent (All-Bond Universal), either followed by silane application or left untreated. These sets were then similarly stored alongside resin cement specimens. Shear bond tests were performed after 24 h. SEM images were taken after debonding. One-Way ANOVA and post hoc Duncan were performed for the statistical analysis. Rodin 1.0 exhibited increased adhesive failure with silane or zirconia primer coating, but significantly improved bond strengths with bonding agent application. Rodin 2.0 showed consistent bond strengths regardless of bonding agent application, but cohesive failure rates increased with bonding agent and filler coating. In all groups, except for Rodin 1.0 without bonding agent, silane coating increased cohesive failure rate. In conclusion, optimal shear bond strength for high-filler 3D printing materials can be achieved with silane coating and bonding agent application.

Research Training and Scholarly Activity during General Pediatric Residency in Canada.

OBJECTIVE: To describe the characteristics of research training and scholarly activity during pediatrics residency in Canada and identify facilitators and barriers to resident scholarly activity. STUDY DESIGN: We conducted a mixed-methods, cross-sectional survey of pediatrics residents in Canada from April to June 2023. Trainees and medical education experts developed the 55-item survey, pilot tested, and distributed electronically to residents in all 17 Canadian residency programs. Responses were complemented with program-level data from pediatrics residency program directors. RESULTS: Of 644 Canadian pediatrics residents, 230 (36%) responded. Resident respondents conducted various types of scholarly projects, including retrospective clinical study (22%), qualitative research (15%), quality improvement (13%), and medical education research (12%). Discordance between the field of career interests and primary scholarly projects was common. Among respondents, 20% had abstracts accepted at national or international conferences, and 12% had manuscripts submitted to peer-reviewed journals. Resident respondents' self-perceived progress in their scholarly projects were discrepant from their actual progress. Key themes related to barriers and facilitators to scholarly activity included protected time for research, mentorship, and research skills training. CONCLUSIONS: The research training and scholarly activity of pediatrics residents in Canada is variable. Establishing national standards, implementing progress monitoring mechanisms with tailored support, and offering flexible protected research time are important next steps.

Cholesterol profiling reveals 7ß-hydroxycholesterol as a pathologically relevant peripheral biomarker of Alzheimer's disease.

AIM: Cholesterol homeostasis is associated with Alzheimer's disease (AD). Despite the multitude of cholesterol metabolites, little is known about which metabolites are directly involved in AD pathogenesis and can serve as its potential biomarkers. METHODS: To identify "hit" metabolites, steroid profiling was conducted in mice with different age, diet, and genotype and also in humans with normal cognition, mild cognitive impairment, and AD using gas chromatography-mass spectrometry. Then, using one of the "hit" molecules (7ß-hydroxycholesterol; OHC), molecular and histopathological experiment and behavioral testing were conducted in normal mice following its intracranial stereotaxic injection to see whether this molecule drives AD pathogenesis and causes cognitive impairment. RESULTS: The serum levels of several metabolites, including 7ß-OHC, were increased by aging in the 3xTg-AD unlike normal mice. Consistently, the levels of 7ß-OHC were increased in the hairs of patients with AD and were correlated with clinical severity. We found that 7ß-OHC directly affects AD-related pathophysiology; intrahippocampal injection of 7ß-OHC induced astrocyte and microglial cell activation, increased the levels of pro-inflammatory cytokines (TNF-alpha, IL-1ß, IL-6), and enhanced amyloidogenic pathway. Mice treated with 7ß-OHC also exhibited deficits in memory and frontal/executive functions assessed by object recognition and 5-choice serial reaction time task, respectively. CONCLUSIONS: Our results suggest that 7ß-OHC could serve as a convenient, peripheral biomarker of AD. As directly involved in AD pathogenesis, 7ß-OHC assay may help actualize personalized medicine in a way to identify an at-risk subgroup as a candidate population for statin-based AD treatment.

How does the consecutive use of intraoral scanners affect musculoskeletal health? A preliminary clinical study.

BACKGROUND: Minimizing muscle strain and reducing the risk of musculoskeletal disorders associated with intraoral scanner (IOS) usage require ergonomic awareness, device selection, and workplace adjustments in dental practice. This preliminary clinical study aimed to simulate intraoral scanning tasks using wired and wireless IOSs and assess muscle activation and fatigue for both types. MATERIALS AND METHODS: Fourteen participants performed intraoral scanning tasks using wired and wireless IOSs (i700; MEDIT), with weights of 280 g and 328 g, respectively. The same computer system and software conditions were maintained for both groups (N = 14 per IOS group). Electrodes were placed on arm, neck, and shoulder muscles, and maximal voluntary contraction (MVC) was measured. Surface electromyography (EMG) was performed during the simulation, and EMG values were normalized using MVC. The root mean square EMG (%MVC) and muscle fatigue (%) values were calculated. Statistical comparisons were performed using the Mann-Whitney U and Friedman tests, with the Bonferroni adjustment for multiple comparisons (α = 0.05). RESULTS: Arm (flexor digitorum superficialis) and neck muscles (left sternocleidomastoid and left splenius capitis) showed significantly higher EMG values with wireless IOS (P < 0.05). The neck (left sternocleidomastoid and right levator scapulae) and shoulder muscles (right trapezius descendens) demonstrated significantly higher muscle fatigue with wireless IOS (P < 0.05). CONCLUSIONS: The consecutive use of heavier wireless IOS may increase the risk of muscle activation and fatigue in certain muscles, which may have clinical implications for dentists in terms of ergonomics and musculoskeletal health.

A broadly generalizable stabilization strategy for sarbecovirus fusion machinery vaccines.

Evolution of SARS-CoV-2 alters the antigenicity of the immunodominant spike (S) receptor-binding domain and N-terminal domain, undermining the efficacy of vaccines and antibody therapies. To overcome this challenge, we set out to develop a vaccine focusing antibody responses on the highly conserved but metastable S2 subunit, which folds as a spring-loaded fusion machinery. We describe a strategy for prefusion-stabilization and high yield recombinant production of SARS-CoV-2 S2 trimers with native structure and antigenicity. We demonstrate that our design strategy is broadly generalizable to sarbecoviruses, as exemplified with the SARS-CoV-1 (clade 1a) and PRD-0038 (clade 3) S2 subunits. Immunization of mice with a prefusion-stabilized SARS-CoV-2 S2 trimer elicits broadly reactive sarbecovirus antibodies and neutralizing antibody titers of comparable magnitude against Wuhan-Hu-1 and the immune evasive XBB.1.5 variant. Vaccinated mice were protected from weight loss and disease upon challenge with XBB.1.5, providing proof-of-principle for fusion machinery sarbecovirus vaccines.

G Protein-Coupled Estrogen Receptor-Mediated Anti-Inflammatory and Mucosal Healing Activity of a Trimethylpyridinol Analogue in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is characterized by abnormal immune responses, including elevated proinflammatory cytokines, such as tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6) in the gastrointestinal (GI) tract. This study presents the synthesis and anti-inflammatory evaluation of 2,4,5-trimethylpyridin-3-ol analogues, which exhibit dual inhibition of TNFα- and IL-6-induced inflammation. Analysis using in silico methods, including 3D shape-based target identification, modeling, and docking, identified G protein-coupled estrogen receptor 1 (GPER) as the molecular target for the most effective analogue, 6-26, which exhibits remarkable efficacy in ameliorating inflammation and restoring colonic mucosal integrity. This was further validated by surface plasmon resonance (SPR) assay results, which showed direct binding to GPER, and by the results showing that GPER knockdown abolished the inhibitory effects of 6-26 on TNFα and IL-6 actions. Notably, 6-26 displayed no cytotoxicity, unlike G1 and G15, a well-known GPER agonist and an antagonist, respectively, which induced necroptosis independently of GPER. These findings suggest that the GPER-selective compound 6-26 holds promise as a therapeutic candidate for IBD.

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.