Impact of COVID-19 Infection and Its Association With Previous Vaccination in Patients With Myasthenia Gravis in Korea: A Multicenter Retrospective Study.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, patients with myasthenia gravis (MG) were more susceptible to poor outcomes owing to respiratory muscle weakness and immunotherapy. Several studies conducted in the early stages of the COVID-19 pandemic reported higher mortality in patients with MG compared to the general population. This study aimed to investigate the clinical course and prognosis of COVID-19 in patients with MG and to compare these parameters between vaccinated and unvaccinated patients in South Korea. METHODS: This multicenter, retrospective study, which was conducted at 14 tertiary hospitals in South Korea, reviewed the medical records and identified MG patients who contracted COVID-19 between February 2022 and April 2022. The demographic and clinical characteristics associated with MG and vaccination status were collected. The clinical outcomes of COVID-19 infection and MG were investigated and compared between the vaccinated and unvaccinated patients. RESULTS: Ninety-two patients with MG contracted COVID-19 during the study. Nine (9.8%) patients required hospitalization, 4 (4.3%) of whom were admitted to the intensive care unit. Seventy-five of 92 patients were vaccinated before contracting COVID-19 infection, and 17 were not. During the COVID-19 infection, 6 of 17 (35.3%) unvaccinated patients were hospitalized, whereas 3 of 75 (4.0%) vaccinated patients were hospitalized (P < 0.001). The frequencies of ICU admission and mechanical ventilation were significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.019 and P = 0.032, respectively). The rate of MG deterioration was significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.041). Logistic regression after weighting revealed that the risk of hospitalization and MG deterioration after COVID-19 infection was significantly lower in the vaccinated patients than in the unvaccinated patients. CONCLUSION: This study suggests that the clinical course and prognosis of patients with MG who contracted COVID-19 during the dominance of the omicron variant of COVID-19 may be milder than those at the early phase of the COVID-19 pandemic when vaccination was unavailable. Vaccination may reduce the morbidity of COVID-19 in patients with MG and effectively prevent MG deterioration induced by COVID-19 infection.

Cyclic stretch induced epigenetic activation of periodontal ligament cells.

Periodontal ligament (PDL) cells play a crucial role in maintaining periodontal integrity and function by providing cell sources for ligament regeneration. While biophysical stimulation is known to regulate cell behaviors and functions, its impact on epigenetics of PDL cells has not yet been elucidated. Here, we aimed to investigate the cytoskeletal changes, epigenetic modifications, and lineage commitment of PDL cells following the application of stretch stimuli to PDL. PDL cells were subjected to stretching (0.1 Hz, 10 %). Subsequently, changes in focal adhesion, tubulin, and histone modification were observed. The survival ability in inflammatory conditions was also evaluated. Furthermore, using a rat hypo-occlusion model, we verified whether these phenomena are observed in vivo. Stretched PDL cells showed maximal histone 3 acetylation (H3Ace) at 2 h, aligning perpendicularly to the stretch direction. RNA sequencing revealed stretching altered gene sets related to mechanotransduction, histone modification, reactive oxygen species (ROS) metabolism, and differentiation. We further found that anchorage, cell elongation, and actin/microtubule acetylation were highly upregulated with mechanosensitive chromatin remodelers such as H3Ace and histone H3 trimethyl lysine 9 (H3K9me3) adopting euchromatin status. Inhibitor studies showed mechanotransduction-mediated chromatin modification alters PDL cells behaviors. Stretched PDL cells displayed enhanced survival against bacterial toxin (C12-HSL) or ROS (H2O2) attack. Furthermore, cyclic stretch priming enhanced the osteoclast and osteoblast differentiation potential of PDL cells, as evidenced by upregulation of lineage-specific genes. In vivo, PDL cells from normally loaded teeth displayed an elongated morphology and higher levels of H3Ace compared to PDL cells with hypo-occlusion, where mechanical stimulus is removed. Overall, these data strongly link external physical forces to subsequent mechanotransduction and epigenetic changes, impacting gene expression and multiple cellular behaviors, providing important implications in cell biology and tissue regeneration.

Strontium/Silicon/Calcium-Releasing Hierarchically Structured 3D-Printed Scaffolds Accelerate Osteochondral Defect Repair.

Articular cartilage defects are a global challenge, causing substantial disability. Repairing large defects is problematic, often exceeding cartilage's self-healing capacity and damaging bone structures. To tackle this problem, a scaffold-mediated therapeutic ion delivery system is developed. These scaffolds are constructed from poly(ε-caprolactone) and strontium (Sr)-doped bioactive nanoglasses (SrBGn), creating a unique hierarchical structure featuring macropores from 3D printing, micropores, and nanotopologies due to SrBGn integration. The SrBGn-embedded scaffolds (SrBGn-µCh) release Sr, silicon (Si), and calcium (Ca) ions, which improve chondrocyte activation, adhesion, proliferation, and maturation-related gene expression. This multiple ion delivery significantly affects metabolic activity and maturation of chondrocytes. Importantly, Sr ions may play a role in chondrocyte regulation through the Notch signaling pathway. Notably, the scaffold's structure and topological cues expedite the recruitment, adhesion, spreading, and proliferation of chondrocytes and bone marrow-derived mesenchymal stem cells. Si and Ca ions accelerate osteogenic differentiation and blood vessel formation, while Sr ions enhance the polarization of M2 macrophages. The findings show that SrBGn-µCh scaffolds accelerate osteochondral defect repair by delivering multiple ions and providing structural/topological cues, ultimately supporting host cell functions and defect healing. This scaffold holds great promise for osteochondral repair applications.

Complementary Therapeutic Effect of Fecal Microbiota Transplantation in Ulcerative Colitis after the Response to Anti-Tumor Necrosis Factor Alpha Agent Was Lost: A Case Report.

In patients with ulcerative colitis (UC), the development of an antidrug antibody (ADA) to anti-tumor necrosis factor (TNF)α agent is a crucial problem which aggravates the clinical course of the disease, being cited as one of the most common causes for discontinuing anti-TNFα treatment. This is due to ADA eventually causing secondary LOR, leading to discontinuation of anti-TNFα treatment. Recently, research on the microbiome and relationship between worsening UC and dysbiosis has been conducted. Further, investigations on the association between the microbiome and secondary LOR are increasing. Here, we present the therapeutic effect of fecal microbiota transplantation (FMT) on a 42-year-old man with secondary LOR and high ADA levels. FMT has recently been used for the treatment of, and for overcoming, drug resistance through microbiome modification. Stool samples were collected from the patient before and 4 weeks after FMT. Symptoms, including hematochezia and Mayo endoscopy sub-scores, improved after FMT, while ADA levels decreased by one-third to less than half the value (29 ng/mL) compared to before FMT (79 ng/mL). Additionally, the trough level of infliximab became measurable, which reflects the improvement in the area under the concentration (AUC). Butyricicoccus, Faecalibacterium, Bifidobacterium, Ligilactobacillus, Alistipes, and Odoribacter, which regulate immune responses and alleviate inflammation, also increased after FMT. We report a case in which microbiome modification by FMT increased the AUC of anti-TNFα in a patient who developed secondary LOR during anti-TNFα treatment, thereby improving symptoms and mucosal inflammation.

Near-strain-free anode architecture enabled by interfacial diffusion creep for initial-anode-free quasi-solid-state batteries.

Anode-free (or lithium-metal-free) batteries with garnet-type solid-state electrolytes are considered a promising path in the development of safe and high-energy-density batteries. However, their practical implementation has been hindered by the internal strain that arises from the repeated plating and stripping of lithium metal at the interlayer between the solid electrolyte and negative electrode. Herein, we utilize the titanium nitrate nanotube architecture and a silver-carbon interlayer to mitigate the anisotropic stress caused by the recurring formation of lithium deposition layers during the cycling process. The mixed ionic-electronic conducting nature of the titanium nitrate nanotubes effectively accommodates the entry of reduced Li into its free volume space via interfacial diffusion creep, achieving near-strain-free operation with nearly tenfold volume suppressing capability compared to a conventional Cu anode counterpart during the lithiation process. Notably, the fabricated Li6.4La3Zr1.7Ta0.3O12 (LLZTO)-based initial-anode-free quasi-solid-state battery full cell, coupled with an ionic liquid catholyte infused high voltage LiNi0.33Co0.33Mn0.33O2-based cathode with an areal capacity of 3.2 mA cm-2, exhibits remarkable room temperature (25 °C) cyclability of over 600 cycles at 1 mA cm-2 with an average coulombic efficiency of 99.8%.

Hierarchically porous surface of HA-sandblasted Ti implant screw using the plasma electrolytic oxidation: Physical characterization and biological responses.

The surface topological features of bioimplants are among the key indicators for bone tissue replacement because they directly affect cell morphology, adhesion, proliferation, and differentiation. In this study, we investigated the physical, electrochemical, and biological responses of sandblasted titanium (SB-Ti) surfaces with pore geometries fabricated using a plasma electrolytic oxidation (PEO) process. The PEO treatment was conducted at an applied voltage of 280 V in a solution bath consisting of 0.15 mol L-1 calcium acetate monohydrate and 0.02 mol L-1 calcium glycerophosphate for 3 min. The surface chemistry, wettability, mechanical properties and corrosion behavior of PEO-treated sandblasted Ti implants using hydroxyapatite particles (PEO-SB-Ti) were improved with the distribution of calcium phosphorous porous oxide layers, and showed a homogeneous and hierarchically porous surface with clusters of nanopores in a bath containing calcium acetate monohydrate and calcium glycerophosphate. To demonstrate the efficacy of PEO-SB-Ti, we investigated whether the implant affects biological responses. The proposed PEO-SB-Ti were evaluated with the aim of obtaining a multifunctional bone replacement model that could efficiently induce osteogenic differentiation as well as antibacterial activities. These physical and biological responses suggest that the PEO-SB-Ti may have a great potential for use an artificial bone replacement compared to that of the controls.

Development of an Injectable Biphasic Hyaluronic Acid-Based Hydrogel With Stress Relaxation Properties for Cartilage Regeneration.

Biomimetic stress-relaxing hydrogels with reversible crosslinks attract significant attention for stem cell tissue regeneration compared with elastic hydrogels. However, stress-relaxing hyaluronic acid (HA)-based hydrogels fabricated using conventional technologies lack stability, biocompatibility, and mechanical tunability. Here, it is aimed to address these challenges by incorporating calcium or phosphate components into the HA backbone, which allows reversible crosslinking of HA with alginate to form interpenetrating networks, offering stability and mechanical tunability for mimicking cartilage. Diverse stress-relaxing hydrogels (τ1/2; SR50, 60-2000 s) are successfully prepared at ≈3 kPa stiffness with self-healing and shear-thinning abilities, favoring hydrogel injection. In vitro cell experiments with RNA sequencing analysis demonstrate that hydrogels tune chondrogenesis in a biphasic manner (hyaline or calcified) depending on the stress-relaxation properties and phosphate components. In vivo studies confirm the potential for biphasic chondrogenesis. These results indicate that the proposed stress-relaxing HA-based hydrogel with biphasic chondrogenesis (hyaline or calcified) is a promising material for cartilage regeneration.

Surface-Engineered Titanium with Nanoceria to Enhance Soft Tissue Integration Via Reactive Oxygen Species Modulation and Nanotopographical Sensing.

The design of implantable biomaterials involves precise tuning of surface features because the early cellular fate on such engineered surfaces is highly influenced by many physicochemical factors [roughness, hydrophilicity, reactive oxygen species (ROS) responsiveness, etc.]. Herein, to enhance soft tissue integration for successful implantation, Ti substrates decorated with uniform layers of nanoceria (Ce), called Ti@Ce, were optimally developed by a simple and cost-effective in situ immersion coating technique. The characterization of Ti@Ce shows a uniform Ce distribution with enhanced roughness (∼3-fold increase) and hydrophilicity (∼4-fold increase) and adopted ROS-scavenging capacity by nanoceria coating. When human gingival fibroblasts were seeded on Ti@Ce under oxidative stress conditions, Ti@Ce supported cellular adhesion, spreading, and survivability by its cellular ROS-scavenging capacity. Mechanistically, the unique nanocoating resulted in higher expression of amphiphysin (a nanotopology sensor), paxillin (a focal adhesion protein), and cell adhesive proteins (collagen-1 and fibronectin). Ti@Ce also led to global chromatin condensation by decreasing histone 3 acetylation as an early differentiation feature. Transcriptome analysis by RNA sequencing confirmed the chromatin remodeling, antiapoptosis, antioxidant, cell adhesion, and TGF-ß signaling-related gene signatures in Ti@Ce. As key fibroblast transcription (co)factors, Ti@Ce promotes serum response factor and MRTF-α nucleus localization. Considering all of this, it is proposed that the surface engineering approach using Ce could improve the biological properties of Ti implants, supporting their functioning at soft tissue interfaces and utilization as a bioactive implant for clinical conditions such as peri-implantitis.

Mechanophysical and Anti-Adhesive Properties of a Nanoclay-Containing PMMA Denture Resin.

Poly(methyl methacrylate) (PMMA) is commonly used for dental dentures, but it has the drawback of promoting oral health risks due to oral bacterial adhesion. Recently, various nanoparticles have been incorporated into PMMA to tackle these issues. This study aims to investigate the mechanophysical and antimicrobial adhesive properties of a denture resin by incorporating of nanoclay into PMMA. Specimens were prepared by adding 0, 1, 2, and 4 wt % surface-modified nanoclay (Sigma) to self-polymerizing PMMA denture resin. These specimens were then evaluated using FTIR, TGA/DTG, and FE-SEM with EDS. Various mechanical and surface physical properties, including nanoindentation, were measured and compared with those of pure PMMA. Antiadhesion experiments were conducted by applying a Candida albicans (ATCC 11006) suspension to the surface of the specimens. The antiadhesion activity of C. albicans was confirmed through a yeast-wall component (mannan) and mRNA-seq analysis. The bulk mechanical properties of nanoclay-PMMA composites were decreased compared to those of pure PMMA, while the flexural strength and modulus met the ISO 20795-1 requirement. However, there were no significant differences in the nanoindentation hardness and elastic modulus. The surface energy revealed a significant decrease at 4 wt % nanoclay-PMMA. The antiadhesion effect of Candida albicans was evident along with nanoclay content in the nanocomposites and confirmed by the reduced attachment of mannan on nanoclay-PMMA composites. mRNA-seq analysis supported overall transcriptome changes in altering attachment and metabolism behaviors on the surface. The nanoclay-PMMA materials showed a lower surface energy as the content increased, leading to an antiadhesion effect against Candida albicans. These findings indicate that incorporating nanoclay into PMMA surfaces could be a valuable strategy for preventing the fungal biofilm formation of denture base materials.

Targeting Nuclear Mechanics Mitigates the Fibroblast Invasiveness in Pathological Dermal Scars Induced by Matrix Stiffening.

Pathological dermal scars such as keloids present significant clinical challenges lacking effective treatment options. Given the distinctive feature of highly stiffened scar tissues, deciphering how matrix mechanics regulate pathological progression can inform new therapeutic strategies. Here, it is shown that pathological dermal scar keloid fibroblasts display unique metamorphoses to stiffened matrix. Compared to normal fibroblasts, keloid fibroblasts show high sensitivity to stiffness rather than biochemical stimulation, activating cytoskeletal-to-nuclear mechanosensing molecules. Notably, keloid fibroblasts on stiff matrices exhibit nuclear softening, concomitant with reduced lamin A/C expression, and disrupted anchoring of lamina-associated chromatin. This nuclear softening, combined with weak adhesion and high contractility, facilitates the invasive migration of keloid fibroblasts through confining matrices. Inhibiting lamin A/C-driven nuclear softening, via lamin A/C overexpression or actin disruption, mitigates such invasiveness of keloid fibroblasts. These findings highlight the significance of the nuclear mechanics of keloid fibroblasts in scar pathogenesis and propose lamin A/C as a potential therapeutic target for managing pathological scars.

Nanozyme-Engineered Hydrogels for Anti-Inflammation and Skin Regeneration.

Inflammatory skin disorders can cause chronic scarring and functional impairments, posing a significant burden on patients and the healthcare system. Conventional therapies, such as corticosteroids and nonsteroidal anti-inflammatory drugs, are limited in efficacy and associated with adverse effects. Recently, nanozyme (NZ)-based hydrogels have shown great promise in addressing these challenges. NZ-based hydrogels possess unique therapeutic abilities by combining the therapeutic benefits of redox nanomaterials with enzymatic activity and the water-retaining capacity of hydrogels. The multifaceted therapeutic effects of these hydrogels include scavenging reactive oxygen species and other inflammatory mediators modulating immune responses toward a pro-regenerative environment and enhancing regenerative potential by triggering cell migration and differentiation. This review highlights the current state of the art in NZ-engineered hydrogels (NZ@hydrogels) for anti-inflammatory and skin regeneration applications. It also discusses the underlying chemo-mechano-biological mechanisms behind their effectiveness. Additionally, the challenges and future directions in this ground, particularly their clinical translation, are addressed. The insights provided in this review can aid in the design and engineering of novel NZ-based hydrogels, offering new possibilities for targeted and personalized skin-care therapies.

Association of Range of Motion Deficit and Recurrence of Pain After Treatment of Adhesive Capsulitis.

INTRODUCTION: We evaluated the factors influencing the duration of significant pain reduction after conservative management for adhesive capsulitis (AC). METHODS: Follow-up for 6-8 months was performed with 141 patients with AC who experienced significant pain reduction after treatment. Clinical and demographic factors, numeric rating scale (NRS) scores, and shoulder range of motion (ROM) were collected and assessed pretreatment (T0), at 5 weeks post-treatment (T1), and at 6-8 months post-treatment (T2). Patients were divided into successful (n = 96) and unsuccessful (n = 45) NRS groups according to the degree of pain reduction at T2. We assessed post-treatment NRS and ROM improvement scores within each group and compared these parameters between the two groups. RESULTS: Significant NRS and ROM improvements were achieved in all patients who participated in our study. The unsuccessful NRS group demonstrated a lack of significant improvement in abduction at T1 and T2. All T1 and shoulder ROM measurements among the unsuccessful NRS group were significantly smaller than those among the successful NRS group. CONCLUSIONS: Failure to achieve a significant improvement in abduction angle after conservative management of AC was significantly associated with pain recurrence.

Effect of altered gene expression in lipid metabolism on cognitive improvement in patients with Alzheimer's dementia following fecal microbiota transplantation: a preliminary study.

Background: The brain-gut axis has emerged as a potential target in neurodegenerative diseases, including dementia, as individuals with dementia exhibit distinct gut microbiota compositions. Fecal microbiota transplantation (FMT), the transfer of fecal solution from a healthy donor to a patient, has shown promise in restoring homeostasis and cognitive enhancement. Objective: This study aimed to explore the effects of FMT on specific cognitive performance measures in Alzheimer's dementia (AD) patients and investigate the relationship between cognition and the gut microbiota by evaluating changes in gene expression following FMT. Methods: Five AD patients underwent FMT, and their cognitive function [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB)] was assessed before and after FMT. The patients' fecal samples were analyzed with 16S rRNA to compare the composition of their gut microbiota. We also assessed modifications in the serum mRNA expression of patients' genes related to lipid metabolism using serum RNA sequencing and quantitative real-time polymerase chain reaction. Results: Significant improvements in cognitive function, as measured by the MMSE (pre- and post-FMT was 13.00 and 18.00) and MoCA were seen. The MoCA scores at 3 months post-FMT (21.0) were the highest (12.0). The CDR-SOB scores at pre- and post-FMT were 10.00 and 5.50, respectively. Analysis of the gut microbiome composition revealed changes via 16S rRNA sequencing with an increase in Bacteroidaceae and a decrease in Enterococcaceae. Gene expression analysis identified alterations in lipid metabolism-related genes after FMT. Conclusion: These findings suggest a link between alterations in the gut microbiome, gene expression related to lipid metabolism, and cognitive function. The study highlights the importance of gut microbiota in cognitive function and provides insights into potential biomarkers for cognitive decline progression. FMT could complement existing therapies and show potential as a therapeutic intervention to mitigate cognitive decline in AD.

Effect of lyophilized gelatin-norbornene cryogel size on calvarial bone regeneration.

Molding processes with molds containing topographical structures have been used for fabrication of hydrogel and cryogel particles. However, they can involve difficulties in separation of fabricated particles with complex shape from the molds or repeated fabrication of the particles although the overall processes do not require much skill and equipment. In this study, molds with etched superhydrophobic patterns have been developed by etching polytetrafluoroethylene (PTFE) blocks in user-defined designs with a femtosecond (FS) laser-based etching system. Lyophilized cryogel particles with various designs and sizes were fabricated by molding precursors with these PTFE molds. Additionally, the clean and easy separation of particles from the molds allowed repeated fabrication of the particles. For an application, relatively 'big' gelatin-norbornene (GelNB) cryogel particles prepared via molding with polydimethylsiloxane (PDMS) molds, swelling in phosphate buffered saline (PBS) and slicing height in half and 'small' GelNB cryogel particles fabricated with the PTFE molds were fabricated. Then, they were used to study scaffold size effect on calvarial bone regeneration. The molds generated with the FS laser-based etching system can be useful for various applications that require the mass production of cryogel particles in various geometries.

Role of Probiotics in Preventing Carbapenem-Resistant Enterobacteriaceae Colonization in the Intensive Care Unit: Risk Factors and Microbiome Analysis Study.

Older patients with multiple comorbidities often necessitate prolonged hospital stays and antibiotic treatment in the intensive care unit (ICU), leading to a rise in multidrug-resistant organisms like carbapenem-resistant Enterobacteriaceae (CRE). This study examined risk factors for carbapenem-resistant Enterobacteriaceae colonization in the ICU and assessed probiotics' preventive role. In this single-center, retrospective study, 9099 ICU patients were tested for stool CRE culture from March 2017 to April 2022. We excluded 136 patients with CRE colonization within one week post-admission and 26 who received probiotics before CRE colonization. Ultimately, 8937 CRE-negative patients were selected. Logistic analysis identified CRE colonization risk factors and evaluated probiotics' influence, including Saccharomyces boulardii or Lactobacillus rhamnosus, used by 474 patients (5.3%) in the ICU. Compared with data on initial admission, 157 patients (1.7%) had newly discovered CRE colonization before discharge. In a multivariate analysis, coronavirus disease 2019, the ICU, tube feeding, antibiotics such as aminoglycoside, extended-spectrum penicillin, stool vancomycin-resistance enterococci colonization, and chronic kidney disease were significantly associated with de novo CRE infection. However, probiotic use was negatively correlated with CRE infection. Managing risk factors and administering probiotics in the ICU may help prevent CRE colonization; large randomized prospective studies are needed.

Treatment outcome and prognostic factors in relapsed pediatric acute myeloid leukemia.

Background: Despite improved outcomes for pediatric patients with acute myeloid leukemia (AML), the prognosis for relapse remains poor. This study aimed to examine the clinical factors associated with prognosis in relapsed pediatric AML. Methods: We conducted a chart review of pediatric patients with AML who experienced their first relapse and received treatment at our institution between 2008 and 2019. Risk stratification at diagnosis was performed according to the definition suggested by the ongoing AML 2012 study in Korea, and the clinical factors associated with prognosis were analyzed. Results: A total of 27 pediatric patients with relapsed AML were identified. The 5-year overall survival (OS) and event-free survival (EFS) rates were 32.9% and 32.9%, respectively. A duration ≥12 months from diagnosis to relapse had a favorable impact on survival outcomes (5-yr OS, 64.0% vs. 15.7%; P=0.007). Patients who achieved complete remission (CR) after 1 course of chemotherapy following relapse (N=15) had a 5-year OS rate of 59.3%, while none of the other patients survived (P＜0.0001). Additionally, the 5-year OS differed significantly based on the risk group at initial diagnosis (62.3% [favorable and intermediate prognosis groups, N=11] vs. 13.3% [poor prognosis group, N=15]; P=0.014). Conclusion: Patients with a longer duration of CR before relapse, who achieved CR following 1 course of reinduction chemotherapy, and were in the favorable or intermediate prognosis group at diagnosis demonstrated better outcomes. These findings emphasize the importance of tailoring treatment strategies based on the expected prognosis at relapse in pediatric patients with AML.

Effects of ultraviolet weathering aging on the color stability and biocompatibility of various computer-aided design and computer-aided manufacturing glass-ceramic materials.

OBJECTIVES: This study assessed the changes in color stability and biocompatibility of computer-aided design and computer-aided manufacturing (CAD-CAM) glass-ceramics after ultraviolet weathering (UW) aging. METHODS: A total of 300 plate-shaped specimens (12.0 × 14.0 × 1.5 mm3) were prepared using a leucite-reinforced glass-ceramic (IPS Empress CAD; E), a lithium disilicate (IPS e.max CAD; M), and two zirconia-reinforced lithium silicate (Celtra Duo; C, Vita Suprinity; V) glass-ceramics. Specimens were divided into three groups (n = 25, each), subjected to water storage at 37 °C for 24 h (control group), or UW aging at 150 kJ/m2 (first-aged group) or 300 kJ/m2 (second-aged group). The color stability, mechanical and surface properties, and biocompatibility of the CAD-CAM glass-ceramics were investigated experimentally, followed by statistical analysis. RESULTS: The brightness and redness or greenness were reduced in all groups after aging. After the first aging, V exhibited the largest color change and E exhibited the smallest color change. After the second aging, E exhibited the highest nanoindentation hardness and Young's modulus. The surface roughness was the highest for V after the first aging. Furthermore, the hydrophilicity of the materials increased after aging process. The cell proliferation/viability of human gingival fibroblasts was the highest in E before and after aging. Almost all cells survived for all groups based on a live/dead assay. CONCLUSIONS: Leucite-reinforced glass-ceramic exhibit the highest color stability and biocompatibility after aging. The color stability and biocompatibility of CAD-CAM glass-ceramics depend on the aging process and material type. CLINICAL SIGNIFICANCE: Various CAD-CAM glass-ceramics exhibit adequate color stability after UW aging. The leucite-reinforced glass-ceramics exhibit the highest color stability, cell proliferation, and viability after aging. The color stability, mechanical and surface properties, and biocompatibility of the glass-ceramics depend on the aging process and material type.

Clinical Effectiveness of Artificial Disc Replacement in Comparison With Anterior Cervical Discectomy and Fusion in the Patients With Cervical Myelopathy: Systematic Review and Meta-analysis.

OBJECTIVE: Cervical myelopathy (CM) describes the compressive cervical spinal cord state, often accompanied by serious clinical condition, by herniated disc or hypertrophied spurs or ligament. Anterior cervical discectomy and fusion (ACDF) has been frequently employed as conventional surgical solution for this CM despite its inherent biomechanical handicap. Alternatively, an artificial disc replacement (ADR) preserves cervical motion while still decompressing the spinal canal and neural foramen. This analysis elaborated to clarify the potential benefits of ADR application to CM over ACDF from the conglomerated results of the past references. METHODS: A literature search was performed using MEDLINE, Embase, Cochrane review, and KMbase databases from the studies published until March 2023. Six studies (3 randomized controlled study [RCTs] and 3 non-RCTs) were included in a qualitative and quantitative synthesis. Data were extracted and analyzed using a random effects model to obtain effect size and its statistical significance. Quality assessment and evidence level were established in accordance with the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. RESULTS: Among 6 studies, 2 studies showed that ADR group achieved significantly better clinical improvement than the ACDF group, while the rest 4 studies revealed no significant difference. A meta-analysis showed better clinical outcomes with or without statistical significance. The level of evidence was low because of inconsistency and imprecision. CONCLUSION: ADR was superior or at least, not inferior to ACDF in terms of functional recovery. However, its application to the CM patients is merely empowered with weak strength due to low level of evidence.

Clinical Effectiveness of Posterior Annular Targeted Ablative Decompression as an Alleviative Intervention for Lumbosacral Discogenic Pain: Systematic Review and Meta-analysis.

BACKGROUND: Various percutaneous intradiscal procedures have been implemented to manage lumbosacral discogenic pain. But most of these procedures simply end up manipulating the central nucleus pulposus or the inner annulus, instead of accessing the posterior outer annulus where the actual, major pain generators exist. Thus, more localized percutaneous techniques, specifically derived to address the pathologic tissues creeped between the torn, posterior annulus and hyperplastic sinuvertebral nerve, have been devised. However, the clinical effectiveness of these "more" accurate procedures is still skeptical. OBJECTIVES: This study has investigated whether the posterior annular targeted decompression was a useful method to treat lumbosacral discogenic pain in terms of pain control or functional improvement. STUDY DESIGN: A systematic review and meta-analysis. SETTING: Primary clinic and tertiary referral center. PATIENTS: Published past references that have dealt with the issue of clinical effectiveness after the posterior annular targeted decompression as a treatment of discogenic pain in terms of pain control and functional improvement. METHODS: A literature search was performed using MEDLINE, EMBASE, Cochrane Review, and KoreaMed databases from the studies published until December 2022. After reviewing titles, abstracts, and full texts of 65 studies during the initial database search, 12 studies were included in a qualitative synthesis, and 9 trials from 8 studies were in quantitative meta-analysis. Data, including pain and functional scores, were extracted and were analyzed using a random effects model to obtain statistical significance of mean difference. Quality assessment and evidence level were established in accordance with the Grading of Recommendations Assessment, Development and Evaluation methodology. RESULTS: Finally, 12 single-arm studies without the control group were included. All studies showed significant pain reduction and functional improvement from a 1-month to 1-year follow-up period. A meta-analysis showed significant reduction in pain scores at 1 month, 3 months, 6 months, and 1 year and functional scores at 1 month, 6 months, and 1 year. The level of evidence was very low because of the nonrandomized study design and inconsistency and imprecision across studies. LIMITATIONS: Only single-arm studies comparing clinical results before and after treatment without the control group were analyzed. The statistical and clinical heterogeneity, due to different aspect of techniques across the studies and a relatively small number of patients, reduced the evidence level. CONCLUSIONS: Comprehensive reviews of selected articles revealed posterior annular targeted decompression could be recommended as treatment option in the patients with discogenic pain who have failed in attaining clinical improvement after the conservative managements under weak evidential strength support. KEY WORDS: Discogenic pain, minimal invasive technique, percutaneous targeted disc decompression, systematic review, meta-analysis.

Cyclic Stretch Promotes Cellular Reprogramming Process through Cytoskeletal-Nuclear Mechano-Coupling and Epigenetic Modification.

Advancing the technologies for cellular reprogramming with high efficiency has significant impact on regenerative therapy, disease modeling, and drug discovery. Biophysical cues can tune the cell fate, yet the precise role of external physical forces during reprogramming remains elusive. Here the authors show that temporal cyclic-stretching of fibroblasts significantly enhances the efficiency of induced pluripotent stem cell (iPSC) production. Generated iPSCs are proven to express pluripotency markers and exhibit in vivo functionality. Bulk RNA-sequencing reveales that cyclic-stretching enhances biological characteristics required for pluripotency acquisition, including increased cell division and mesenchymal-epithelial transition. Of note, cyclic-stretching activates key mechanosensitive molecules (integrins, perinuclear actins, nesprin-2, and YAP), across the cytoskeletal-to-nuclear space. Furthermore, stretch-mediated cytoskeletal-nuclear mechano-coupling leads to altered epigenetic modifications, mainly downregulation in H3K9 methylation, and its global gene occupancy change, as revealed by genome-wide ChIP-sequencing and pharmacological inhibition tests. Single cell RNA-sequencing further identifies subcluster of mechano-responsive iPSCs and key epigenetic modifier in stretched cells. Collectively, cyclic-stretching activates iPSC reprogramming through mechanotransduction process and epigenetic changes accompanied by altered occupancy of mechanosensitive genes. This study highlights the strong link between external physical forces with subsequent mechanotransduction process and the epigenetic changes with expression of related genes in cellular reprogramming, holding substantial implications in the field of cell biology, tissue engineering, and regenerative medicine.