Machine-learning-based classification of obstructive sleep apnea using 19-channel sleep EEG data.

OBJECTIVE: This study aimed to investigate the neurophysiological effects of obstructive sleep apnea (OSA) using multi-channel sleep electroencephalography (EEG) through machine learning methods encompassing various analysis methodologies including power spectral analysis, network analysis, and microstate analysis. METHODS: Twenty participants with apnea-hypopnea index (AHI) ≥ 15 and 18 participants with AHI <15 were recruited. Overnight polysomnography was conducted concurrently with 19-channel EEG. Preprocessed EEG data underwent computation of relative spectral power. A weighted network based on graph theory was generated; and indices of strength, path length, eigenvector centrality, and clustering coefficient were calculated. Microstate analysis was conducted to derive four topographic maps. Machine learning techniques were employed to assess EEG features capable of differentiating two groups. RESULTS: Among 71 features that showed significant differences between the two groups, seven exhibited good classification performance, achieving 88.3 % accuracy, 92 % sensitivity, and 84 % specificity. These features were power at C4 theta, P3 theta, P4 theta, and F8 gamma during NREM1 sleep and at Pz gamma during REM sleep from power spectral analysis; eigenvector centrality at F7 gamma during REM sleep from network analysis; and duration of microstate 4 during NREM2 sleep from microstate analysis. These seven EEG features were significantly correlated with polysomnographic parameters reflecting the severity of OSA. CONCLUSIONS: The application of machine learning techniques and various EEG analytical methods resulted in a model that showed good performance in classifying moderate to severe OSA and highlights the potential of EEG to serve as a biomarker of functional changes in OSA.

Changes in shoulder function and muscle strength following rehabilitation exercise program in male patients with forward shoulder posture undergoing rotator cuff repair.

BACKGROUND: Abnormal posture is known to affect the efficacy of exercise therapy for musculoskeletal diseases. However, no studies to date have examined the effect of exercise programs should take into account the posture of the upper body in patients with rotator cuff disease. This study aimed to assess how rotator cuff and corrective exercises impact shoulder function and muscle strength post-arthroscopic rotator cuff repair surgery, providing tailored rehabilitation programs for patients with forward posture. METHODS: Ninety male patients who underwent arthroscopic rotator cuff repair participated in this study. The patients were randomly divided into three groups corrective exercise group (CEG, n = 29), rotator cuff exercise group (REG, n = 27), and control group (CG, n = 28). Each group was instructed to apply different exercise programs to correct posture and enhance rotator cuff strength. All patients were checked by the American Shoulder and Elbow Surgeons (ASES) score, Constant score and muscle strength, and range of motion preoperatively and postoperatively at 6 months and 1 year. RESULTS: ASES shoulder function scores showed significant difference between the three groups (p = 0.002, F = 7.03), indicating that the corrective exercise program was more beneficial than rotator cuff exercises (p = 0.009, F = 3.78). A significant intergroup difference in mean Constant score was also noted (p = 0.025, F = 3.86), while a statistically significant interaction between time and group was observed (p = 0.032, F = 2.96). CONCLUSIONS: These results suggested that a corrective exercise program can improve shoulder muscle strength and function after rotator cuff repair in male patients with a forward shoulder posture.

Photobiomodulation regulates astrocyte activity and ameliorates scopolamine-induced cognitive behavioral decline.

Introduction: The pathophysiological mechanism of Alzheimer's disease (AD) has not been clearly identified, and effective treatment methods have not yet been established. Scopolamine causes cholinergic dysfunction in the brain, including the accumulation of amyloid-beta plaques, thereby increasing oxidative stress and neuroinflammation, mimicking AD. Glial cells such as astrocytes have recently been identified as possible biomarkers for AD. Photobiomodulation (PBM) elicits a beneficial biological response in cells and tissues. PBM effects on the central nervous system (CNS) have been widely researched, including effects on astrocyte activity. Methods: In the present study, PBM was performed using light at the near-infrared wavelength of 825 nm. The Morris water maze and Y-maze tests were employed to evaluate cognitive function decline in a scopolamine-induced memory dysfunction model and its improvement with PBM. In addition, alteration of the mitogen-activated protein kinase (MAPK) pathway and immunofluorescence expression levels of active astrocytes were observed in the hippocampus, which is one of the areas affected by AD, to evaluate the mechanism of action of PBM. Results: A reduction in the neuronal cell death in the hippocampus caused by scopolamine was observed with PBM. Moreover, alteration of a MAPK pathway-related marker and changes in glial fibrillary acidic protein (an active astrocyte marker) expression were observed in the PBM-treated group. Finally, significant correlations between functional and histological results were found, validating the results. Discussion: These findings indicate the possibility of behavioral and histological improvement due to PBM in scopolamine-induced CNS alteration, which mimics AD. This improvement could be related to neuroinflammatory modulation and altered astrocyte activity.

RFC2 may contribute to the pathogenicity of Williams syndrome revealed in a zebrafish model.

Williams syndrome (WS) is a rare multisystemic disorder caused by recurrent microdeletions on 7q11.23, characterized by intellectual disability, distinctive craniofacial and dental features, and cardiovascular problems. Previous studies have explored the roles of individual genes within these microdeletions in contributing to WS phenotypes. Here, we report five patients with WS with 1.4 Mb-1.5 Mb microdeletions that include RFC2, as well as one patient with a 167 kb microdeletion involving RFC2 and six patients with intragenic variants within RFC2. To investigate the potential involvement of RFC2 in WS pathogenicity, we generate a rfc2 knockout (KO) zebrafish using CRISPR-Cas9 technology. Additionally, we generate a KO zebrafish of its paralog gene, rfc5, to better understand the functions of these RFC genes in development and disease. Both rfc2 and rfc5 KO zebrafish exhibit similar phenotypes reminiscent of WS, including small head and brain, jaw and dental defects, and vascular problems. RNA-seq analysis reveals that genes associated with neural cell survival and differentiation are specifically affected in rfc2 KO zebrafish. In addition, heterozygous rfc2 KO adult zebrafish demonstrate an anxiety-like behavior with increased social cohesion. These results suggest that RFC2 may contribute to the pathogenicity of Williams syndrome, as evidenced by the zebrafish model.

Sensitivity analysis for unmeasured confounding in estimating the difference in restricted mean survival time.

The difference in restricted mean survival time has been increasingly used as an alternative measure to the hazard ratio in survival analysis. Although some statistical methods have been developed for estimating the difference in restricted mean survival time adjusted for measured confounders in observational studies, the impact of unmeasured confounding on the estimate has rarely been assessed. We develop a novel sensitivity analysis for the estimate of the difference in restricted mean survival time with respect to unmeasured confounding. After formulating the sensitivity analysis problem as an optimization problem, we explain how to obtain the sensitivity range of the difference in restricted mean survival time efficiently and assess its uncertainty using the percentile bootstrap confidence interval. Analytic results are provided for some important survival settings. Simulation studies show that the proposed methods perform well in various settings. We illustrate the proposed sensitivity analysis method by analyzing data from the German Breast Cancer Study Group study.

Development and Feasibility Assessment of Mobile Application-Based Digital Therapeutics for Postoperative Supportive Care in Gastric Cancer Patients Following Gastrectomy.

PURPOSE: This study aimed to develop and assess the feasibility and effectiveness of digital therapeutics for supportive care after gastrectomy. MATERIALS AND METHOD: The study included 39 patients with gastric cancer who underwent minimally invasive gastrectomy and were able to use a mobile application (app) on their smartphones. The developed research app automatically calculates and provides daily targets for calorie and protein intake based on the patient's body mass index (BMI). Patients recorded their daily diets, weights, and symptoms in the app and completed special questionnaires to assess the feasibility of the app in real-world clinical practice. RESULTS: At the 10-week follow-up, the mean questionnaire scores for ease of learning, usability, and effectiveness of the app (primary endpoint) were 2.32±0.41, 2.35±0.43, and 2.4±0.39 (range: 0-3), respectively. Patients were classified as underweight (<18.5, n=4), normal (18.5-24.9, n=24), or overweight (≥25.0, n=11) according to predischarge BMI. Underweight patients showed higher compliance with app usage and a higher rate of achieving the target calorie and protein intake than normal weight and overweight patients (98% vs. 77% vs. 81%, p=0.0313; 102% vs. 75% vs. 61%, P=0.0111; 106% vs. 79% vs. 64%, P=0.0429). Two patients transitioned from underweight to normal weight (50.0%), one patient (4.3%) transitioned from normal weight to underweight, and two patients (22.2%) transitioned from overweight to normal weight. CONCLUSIONS: The mobile app is feasible and useful for postoperative supportive care in terms of ease of learning, usability, and effectiveness. Digital therapeutics may be an effective way to provide supportive care for postgastrectomy patients, particularly in terms of nutrition. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04800991.

Assessment of safety: In vitro reverse mutation and in vivo acute oral toxicity tests of three biomass products from amino acid-producing Corynebacterium glutamicum.

Microbial fermentation has emerged as a pivotal process for sustainable production of essential goods and chemicals. Corynebacterium glutamicum is a proficient platform organism that contributes significantly to amino acid production through microbial fermentation. Despite its recognized safety, challenges persist in efficiently biosynthesizing natural products compared with other organisms. This study evaluated the safety of biomass products from bioengineered C. glutamicum through two different toxicological studies: a bacterial reverse mutation test (AMES test) and an acute oral toxicity test in rats. Three types of dried fermentation biomass products, each engineered for the enhanced production of specific amino acids (L-lysine, L-threonine, and L-tryptophan), were examined. The tests were conducted in compliance with Organization for Economic Co-operation and Development guidelines and revealed no mutagenicity or acute toxicity at the tested doses. These findings suggest the safety of biomass products from bioengineered C. glutamicum as potential feed materials, although further toxicity studies are recommended for comprehensive evaluation. This study underscores the importance of stringent safety assessments for advancing biotechnological applications and provides valuable insights into the potential utilization of microbial fermentation products in various industries. Moreover, this study highlights the significance of regulatory compliance and adherence to international standards to ensure the safety and efficacy of novel biotechnological products.

Treatment of Macrolide-resistant Mycoplasma pneumoniae Pneumonia in Children: A Meta-analysis of Macrolides Versus Tetracyclines.

BACKGROUND: The global prevalence of macrolide-resistant Mycoplasma pneumoniae (MRMP) pneumonia infections, particularly in children, is on the rise. It is imperative to assess the clinical efficacies of alternative antibiotics such as tetracyclines to ensure effective treatment, mitigate antibiotic resistance, enhance clinical outcomes, and minimize the spread of resistant strains among MRMP-infected children. The objective of this study was to compare the therapeutic efficacies of macrolides and tetracyclines in treating MRMP pneumonia in children. METHODS: We systematically searched the literature to identify comparative studies that examined the clinical outcomes of macrolide and tetracycline antibiotics in children with MRMP pneumonia. We conducted a meta-analysis of the mean duration of fever, hospital stay duration, therapeutic efficacies, and time to defervescence to compare macrolides and tetracyclines. RESULTS: Eleven studies involving 1143 patients compared the clinical efficacies of macrolides and tetracyclines in children with MRMP pneumonia. The studies were conducted in China, Japan, and Korea, and the outcomes of febrile days, hospital stay duration, therapeutic efficacy, and time to defervescence were analyzed. The macrolides studied were azithromycin and clarithromycin, whereas the tetracyclines included minocycline and doxycycline. The pooled estimate of 5 studies showed that the mean duration of febrile days and hospital stay was longer in the macrolides group than tetracycline group [weighted mean difference = 1.64 days, 95% confidence interval (CI): 0.68-2.59, weighted mean difference = 1.22 days, 95% CI: 0.82-1.62, respectively]. The therapeutic efficacy was significantly lower in the macrolide group than in the tetracycline group (odds ratio: 0.33, 95% CI: 0.20-0.57). CONCLUSIONS: The clinical efficacy of tetracycline treatment was superior to that of macrolide treatment in children with MRMP pneumonia. However, further research is required to validate these findings and inform evidence-based clinical practice guidelines.

Helicobacter pylori VacA-induced mitochondrial damage in the gastric pit cells of the antrum and therapeutic rescue.

Exploring host cell specificity, pathogenicity, and molecular mechanisms of the vacuolating cytotoxin A (VacA), secreted by Helicobacter pylori (Hp) is crucial for developing novel treatment strategies. VacA affects subcellular events, particularly mitochondria, at a cell-type-specific level. However, the lack of reliable models that mimic VacA-induced subcellular damages and enable novel drug screening linked to the human stomach clinically limits our understanding of the mitochondrial networks in vivo. Here, human antrum gastric organoids (hAGOs) and tissue samples from Hp-infected patients were used to show the toxic effects of VacA-induced mitochondrial damage mainly in mucus-producing gastric pit cells by employing transcriptional, translational, and functional analyses. In VacA-intoxicated or Hp-infected hAGOs, robust mitochondrial fragmentation in gastric pit cells reduced ATP production during respiration, and loss of mucosal barrier integrity was first demonstrated experimentally. Using hAGOs, clinically relevant small molecules were screened for efficacy, and MLN8054, an Aurora kinase A inhibitor, reversed VacA-induced mitochondrial damage and loss of gastric epithelium integrity. MLN8054 was effective in VacA-treated and Hp-infected hAGOs and mice, highlighting hAGOs as a promising drug-screening model. These findings suggest that mitochondrial quality control may serve as a promising therapeutic target for Hp VacA-mediated toxicity and disease progression.

Conventional machine learning-based prediction models did not outperform the International IgA Nephropathy Prediction Tool.

Background: Immunoglobulin A nephropathy (IgAN) is a major cause of end-stage kidney disease (ESKD). The International IgA Nephropathy Prediction Tool (IIgAN-PT) predicts IgAN prognosis, but improvement in the prediction performance using machine learning (ML)-based methods is needed. Methods: We analyzed 4,425 biopsy-confirmed patients with IgAN and ≥6 months of follow-up from nine tertiary university hospitals in Korea. The study population was divided into development and validation cohorts. Using the collected 87 clinicodemographic and pathological variables, ML-based prediction models for ESKD or estimated glomerular filtration rate were constructed: 1) the conventional CatBoost model, 2) the optimized CatBoost model with Cox proportional hazards, 3) the deep Cox proportional hazards model, and 4) the deep Cox mixture model. The area under the curve (AUC) and calibration plots were used to investigate the discriminative and calibration performance of the models, which were then compared with those of the IIgAN-PT full model. Results: The full model showed excellent performance (AUC [95% confidence interval] for 5-year outcome, 0.896 [0.8530.940]), with acceptable calibration results. The ML-based models showed good performance in predicting adverse kidney outcomes and revealed acceptable discrimination performance in the external validation (AUC [95% confidence interval] for the 5-year outcome: 1) 0.829 [0.791-0.866]; 2) 0.847 [0.804-0.890]; 3) 0.823 [0.784-0.862]; and 4) 0.832 [0.794-0.870]), although they underestimated the external validation cohort risks. With the validation data, the overall performance of the IIgAN-PT was non-inferior to that of the ML-based model. Conclusions: Our ML-based models showed good performance in predicting adverse kidney outcomes in patients with IgAN but they did not outperform the IIgAN-PT.

Efficacy of Nd:YAG Laser and Intralesional Triamcinolone Injection Combination Therapy in the Postoperative Management of Keloids.

BACKGROUND: Keloids, characterized by protruding scars that extend beyond the original skin damage site, cause significant emotional stress and reduced quality of life. Their exact pathogenesis remains unclear, with various hypotheses including growth factor imbalances and extracellular matrix changes. No single treatment is universally accepted, but multiple modalities like triamcinolone acetonide injection (TAC), laser therapies, and surgery are commonly used. METHODS: This retrospective study involved East Asian patients who underwent keloid scar excision between March 2019 and June 2022. Patients were divided into two groups: one receiving only TAC injections and the other a combination of TAC and Nd:YAG laser therapy. The efficacy of treatments was evaluated using the modified Vancouver Scar Scale (mVSS) and the Patient and Observer Scar Assessment Scale (POSAS), with follow-ups at six and twelve months after operation. RESULTS: The study involved 111 patients. Both treatment groups showed significant improvements in mVSS and POSAS scores, but the combination therapy group demonstrated a statistically significant improvement in POSAS scores and lower recurrence rates at 12 months compared to the TAC-only group. However, there was no significant difference in patient satisfaction between the groups. CONCLUSION: Dual therapy involving TAC injection and Nd:YAG laser treatment was more effective than TAC injection alone for managing keloid scars after surgery. This combination therapy showed better outcomes in preventing keloid recurrence and improving scar status at 12 months after operation, along with significant improvements in patient-reported outcomes. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Overlapping and Distinct Physical and Biological Phenotypes Related to Pure Frailty and Frail Obesity.

BACKGROUND:  Pure frailty and obese frailty are common types of frailty syndrome. However, the overlapping and distinct characteristics between pure frailty and obese frailty remain unclear. This study aims to reveal the overlapping/distinct physical and biological phenotypes of pure frailty and obese frailty, providing theoretical support for their prevention, diagnosis, and treatment.  Method: Mice were fed either a normal or high-fat diet and assessed at 20 months of age. They were assigned to one of four groups: control, obesity, pure frailty, and obese frailty. Grip strength, walking speed, physical activity, endurance, and body weight were measured to determine pure frailty and obese frailty. Physical and biological phenotypes were assessed.

Deciphering mouse brain spatial diversity via glyco-lipidomic mapping.

Gangliosides in the brain play a crucial role in modulating the integrity of vertebrate central nervous system in a region-specific manner. However, to date, a comprehensive structural elucidation of complex intact ganglioside isomers has not been achieved, resulting in the elusiveness into related molecular mechanism. Here, we present a glycolipidomic approach for isomer-specific and brain region-specific profiling of the mouse brain. Considerable region-specificity and commonality in specific group of regions are highlighted. Notably, we observe a similarity in the abundance of major isomers, GD1a and GD1b, within certain regions, which provides significant biological implications with interpretation through the lens of a theoretical retrosynthetic state-transition network. Furthermore, A glycocentric-omics approaches using gangliosides and N-glycans reveal a remarkable convergence in spatial dynamics, providing valuable insight into molecular interaction network. Collectively, this study uncovers the spatial dynamics of intact glyco-conjugates in the brain, which are relevant to regional function and accelerates the discovery of potential therapeutic targets for brain diseases.

Novel therapeutic strategy for intractable keloids: Suppression of intracellular mechanotransduction and actin polymerisation via Rho-kinase pathway inhibition.

BACKGROUND: Keloid is a dermal fibrotic disorder characterised by excessive extracellular matrix production by fibroblasts. Despite the significance of mechanostimulation in fibrotic diseases, its association with keloid pathophysiology or treatment remains unexplored. OBJECTIVE: We investigated the role of mechanical force in keloid formation and elucidated the significance of Rho-associated coiled-coil-containing kinase 1 (ROCK1) as a mechanoresponsive target for keloid treatment. METHODS: Patient-derived keloid fibroblasts (KFs) were subjected to cyclic stretching ranging from 0 to 20% elongation using a cell-stretching system. We observed the inhibitory effects of the ROCK1 inhibitor Y27632 on KFs and keloid formation. Validation was performed using keloid xenograft severe combined immune-deficient (SCID) mouse model. RESULTS: ROCK1 was overexpressed in KFs isolated from patients. Cyclic stretching induced fibroblast proliferation and actin polymerisation by activating Rho/ROCK1 signalling. Treatment with Y27632 downregulated fibrotic markers, reduced the migration capacity of KFs, and induced extensive actin cytoskeleton remodelling. In keloid xenograft SCID mouse model, Y27632 effectively suppressed keloid formation, mitigating inflammation and fibrosis. CONCLUSIONS: The ROCK1 inhibitor Y27632 is a promising molecule for keloid treatment, exerting its effects through actin cytoskeleton remodelling and nuclear inhibition of fibrotic markers in keloid pathogenesis.

3D spheroids versus 2D-cultured human adipose stem cells to generate smooth muscle cells in an internal anal sphincter-targeting cryoinjured mouse model.

BACKGROUND: The efficacy of cell implantation via 3D-spheroids to treat basal tone in fecal incontinence remains unclear. To address this, in this study, we aimed to identify cell differentiation and assess the development of a contractile phenotype corresponding to smooth muscle cells (SMCs) following implantation of 3D-spheroid and 2D-cultured human adipose stem cells (hASCs) in an in vivo internal anal sphincter (IAS)-targeted mouse model. METHODS: We developed an IAS-targeted in vivo model via rapid freezing (at - 196 °C) of the dorsal layers of the region of interest (ROI) of the IAS ring posterior quarter, between the submucosal and muscular layers, following submucosal dissection (n = 60 rats). After implantation of tetramethylindocarbocyanine perchlorate (Dil)-stained 3D and 2D-cells into randomly allocated cryoinjured rats, the entire sphincter ring or only the cryoinjured ROI was harvested. Expression of SMC markers, RhoA/ROCKII and its downstream molecules, and fibrosis markers was analyzed. Dil, α-smooth muscle actin (α-SMA), and RhoA signals were used for cell tracking. RESULTS: In vitro, 3D-spheroids exhibited higher levels of SMC markers and RhoA/ROCKII-downstream molecules than 2D-hASCs. The IAS-targeted cryoinjured model exhibited substantial loss of SMC layers of the squamous epithelium lining of the anal canal, as well as reduced expression of SMC markers and RhoA-related downstream molecules. In vivo, 3D-spheroid implantation induced SMC markers and contractile molecules weakly at 1 week. At 2 weeks, the mRNA expression of aSma, Sm22a, Smoothelin, RhoA, Mypt1, Mlc20, Cpi17, and Pp1cd increased, whereas that of fibrosis markers reduced significantly in the 3D-spheroid implanted group compared to those in the sham, non-implanted, and 2D-hASC implanted groups. Protein levels of RhoA, p-MYPT1, and p-MLC20 were higher in the 3D-spheroid-implanted group than in the other groups. At 2 weeks, in the implanted groups, the cryoinjured tissues (which exhibited Dil, α-SMA, and RhoA signals) were restored, while they remained defective in the sham and non-implanted groups. CONCLUSIONS: These findings demonstrate that, compared to 2D-cultured hASCs, 3D-spheroids more effectively induce a contractile phenotype that is initially weak but subsequently improves, inducing expression of RhoA/ROCKII-downstream molecules and SMC differentiation associated with IAS basal tone.

Laparoscopic Pylorus Preserving Gastrectomy vs Distal Gastrectomy for Early Gastric Cancer; A Multicenter Randomized Controlled Trial (KLASS-04).

OBJECTIVE: To evaluate the long-term outcomes of laparoscopic pylorus preserving gastrectomy (LPPG) with laparoscopic distal gastrectomy (LDG) for early gastric cancer (EGC). SUMMARY BACKGROUND DATA: PPG is considered as a function preserving surgery for EGC. However, there has been no multicenter randomized controlled trial comparing PPG with DG until now. METHODS: A multicenter randomized controlled trial (KLASS-04) with 256 patients with cT1N0M0 gastric cancer located in the mid portion of the stomach was conducted. The primary endpoint was the incidence of dumping syndrome at postoperative 1 year. Secondary endpoints included survival and recurrence, gallstone formation, nutritional parameters, gastroscopic findings, and quality of life (QOL) for 3 years. RESULTS: In the intention-to-treat analyses, there was no difference in the incidence of dumping syndrome at one year postoperatively (13.2% in LPPG vs. 15.8% in LDG, P=0.622). Gallstone formation after surgery was significantly lower in LPPG than in LDG (2.33% vs. 8.66%, P=0.026). Hemoglobin (+0.01 vs. -0.76 gm/dL, P<0.001) and serum protein (-0.15 vs. -0.35 gm/dL, P=0.002) were significantly preserved after LPPG. However, reflux esophagitis (17.8% vs. 6.3%, P=0.005) and grade IV delayed gastric emptying (16.3% vs. 3.9%, P=0.001) were more common in LPPG. Changes in body weight and postoperative QOL were not significantly different between groups. Three-year overall survival and disease-free survival were not different (1 case of recurrence of in each group, P=0.98). CONCLUSIONS: LPPG can be used as an alternative surgical option for cT1N0M0 gastric cancer in the mid portion of the stomach.

Peripheral Rho-associated protein kinase activation mediates acupuncture analgesia.

Background: Acupuncture has been proven effective for various types of pain, and peripheral molecular signals around acupuncture-treated areas have been suggested to contribute to the analgesic effects of acupuncture. However, the underlying mechanism from these peripheral molecular signals to central ones remains unclear. The purpose of this study was to investigate whether peripheral Rho-associated protein kinase (ROCK) activation induced by acupuncture treatment mediates acupuncture analgesia, and also to investigate the relationship between ROCK activation and extracellular signal-regulated kinase (ERK), which has previously been proven to mediate acupuncture analgesia and other related molecular changes during acupuncture. Methods: Acupuncture was treated at the bilateral GB34 acupoints of C57BL/6 mice, after which changes in ROCK activation and the location of its expression in the skin were analyzed. To verify the role of ROCK in acupuncture analgesia, we administrated ROCK inhibitor Y-27632 (0.3 µg/ul) into the skin before acupuncture treatment with formalin and complete Freund adjuvant (CFA) induced pain models, then the nociceptive responses were analyzed. Results: Acupuncture treatment produced ROCK2 activation in the skin after 30 and 60 min, and the histological analyses revealed that ROCK2 was activated in the fibroblast of the dermis. The acupuncture-induced ROCK2 expression was significantly attenuated by the ERK inhibitor, whereas phospho-ERK expression was not inhibited by ROCK inhibitor. In both the formalin- and CFA-induced mouse pain models, acupuncture analgesia was blocked by ROCK inhibitor administration. Conclusion: Acupuncture treatment-induced ROCK2 expression is a downstream effector of phospho-ERK in the skin and plays a crucial role in acupuncture analgesia.

Treatment of a lip defect in a patient with choreaacanthocytosis using a combination of surgical and adjuvant onabotulinumtoxinA therapy: a case report.

Chorea-acanthocytosis (ChAc) is an extremely rare neurodegenerative disorder characterized by movement disorders and acanthocytosis. Orofacial dyskinesia is a distinct symptom of this disorder that can lead to lip injuries and feeding difficulties. This paper reports the first case of a patient with ChAc presenting with a lip defect, who was managed with surgical and adjuvant onabotulinumtoxinA (BTX-A) therapy. A 43-year-old woman diagnosed with ChAc was referred to our clinic because of a 5× 5 mm lip defect resulting from orofacial dyskinesia. Wedge resection of the scar tissue was carried out, followed by reconstruction by suturing. Postoperatively, BTX-A injections were administered to ameliorate dyskinesia. Thirty units of BTX-A were injected into each masseter muscle, and 40 units were injected into the orbicularis oris muscle. At 1, 2, and 4 weeks after the injections, assessments were performed using the Abnormal Involuntary Movement Scale, and the patient's impression of change was assessed using the Global Rating of Change Scale. Subsequent adjuvant BTX-A treatment yielded subjective and objective improvements in orofacial dyskinesia. In conclusion, lip reconstruction and adjuvant BTX-A injections were effective in treating lip defects associated with orofacial dyskinesia in patients with ChAc, which highlights the need for a multimodal treatment approach.

Iron-Chelating Hydroxyketone Ligands Promote Degradation of Fe(III)-Tannic Acid Nanofilms.

Polyphenols form nanofilms with transition metal ions by coordination-driven assembly. The as-formed metal-polyphenol nanofilms can degrade in the presence of chelating ligands that exhibit high stability constant with the nanofilm-forming metal ions. We have demonstrated the degradation of Fe(III)-tannic acid nanofilms with hydroxyketone ligands, such as maltol, kojic acid, and deferiprone, which exhibit high availability and excellent cytocompatibility. The concentration screening experiments have been performed with different ligand concentrations ranging from 1 mM to 25 mM. It is important to note that only deferiprone degrades Fe(III)-TA nanofilms even at 1 mM, and it retains the degradation activity at pH 7.4. The characteristic degradation activity of hydroxyketone ligands to Fe(III)-TA nanofilms may depend upon their pKa value and stability constant. The degradation studies herein are attractive for the development of biomedical applications utilizing metal-polyphenol nanofilms as a sacrificial template.