Presoaking hamstring autograft with vancomycin does not jeopardize its biomechanical properties, including graft elongation, after cyclic loading.

PURPOSE: Presoaking the graft with vancomycin before implantation has been shown to reduce the risk of postoperative infection after anterior cruciate ligament reconstruction (ACLR). However, the effects of presoaking on the graft biomechanical properties remain unclear. This study aimed to determine whether presoaking the graft with vancomycin affects the graft biomechanical properties and length after cyclic loading. METHODS: Ten paired (20 specimens) gracilis and semitendinous tendons were harvested from fresh-frozen human cadaveric specimens. Two tendons were folded in half to make four strands, and the grafts were randomized into the vancomycin and control groups. The graft was exposed to the antibiotic solution for 15 min (5 mg/mL) and prepared by mixing 1 g of vancomycin with 200 mL of normal saline (NaCl 0.9%). The control group was soaked in normal saline for 15 min. The prepared grafts were attached to the actuator of a dynamic tensile-testing machine. All grafts were tested with 3000 cycles of cyclic loading followed by a pull-to-failure. The cyclic loading protocol consisted of position and load control blocks to simulate the graft in vivo in the postoperative phase after ACLR. RESULTS: Presoaking in vancomycin did not jeopardize the biomechanical properties of the graft. In addition, presoaking with vancomycin did not elongate the grafts. No significant differences were found in the mean Young's modulus and the mean total elongation of the graft of the specimen between the vancomycin group and the control group. CONCLUSION: Presoaking the graft with vancomycin jeopardized neither its biomechanical properties nor elongation even after cyclic loading in this in vitro study. It is suggested that vancomycin presoaking could be considered a safe and effective preventive measure for postoperative infections after ACLR. LEVEL OF EVIDENCE: Not applicable.

Radiological and Clinical Significance of Cervical Dynamic Magnetic Resonance Imaging for Cervical Spondylotic Myelopathy.

OBJECTIVE: The study compared the morphometric changes of the cervical spinal cord using dynamic magnetic resonance imaging (MRI) in patients with cervical spondylotic myelopathy (CSM) and assessed the correlation with kinematic changes, cord cross-sectional area (CSA), and high signal intensity (SI) on T2-weighted imaging (T2WI). METHODS: Patients with CSM were evaluated through dynamic MRI for sagittal and axial CSA changes of the cervical cord, cerebrospinal fluid (CSF) reserve ratio, degree of cord impingement, cord compression rate, range of motion (ROM), and severity of SI on T2WI. The degree of cord impingement was evaluated using the Muhle grading system. Clinical outcomes were assessed using Japanese Orthopaedic Association scoring and Nurick grade. RESULTS: The study included 191 patients (113 males) with a mean age of 55.34 ± 12.09 years. The lowest sagittal CSF reserve ratio and cord occupation rate were observed during extension. Cord impingement and SI change were more prevalent in extension-positioned MRI. There was no difference between ROM on dynamic radiographs and dynamic MRI. Preoperative cervical ROM was greater in patients with intensely high SI change. CONCLUSION: Dynamic MRI is useful for evaluating neck movement. Patients with high SI had greater ROM before surgery but worse outcomes after. Neck extension exacerbated cervical stenosis and cord compression compared to flexion, and cervical spinal motion contributed to the severity of CSM. Cervical spinal motion should be carefully evaluated, particularly in hyperextension, to prevent worsening of CSM.

Prognostic Impact of Reactive Oxygen Species Modulator 1 in Surgically Resected Epidermal Growth Factor Receptor-mutant Lung Adenocarcinomas.

INTRODUCTION: Reactive oxygen species modulator 1 (Romo1) is a novel protein that is critically involved in intracellular production of reactive oxygen species. Evidence revealed that Romo1 is related with treatment outcomes of various human malignancies including lung cancer. However, clinical implication of this protein in surgically-resected lung cancer harboring the epidermal growth factor receptor (EGFR) mutation has not been investigated. METHODS: Data were collected from the patients who underwent curative resection for EGFR-mutant lung adenocarcinoma. Romo1 protein expression level was measured in the resected tumor tissue using immunohitochemical staining and evaluated semiquantatively using histochemical score (H score). Univariate and multivariate analyses were performed to identify clinicopathological parameters that may be associated with clinical outcomes. RESULTS: A total of 98 samples were analyzed. Using the cutoff H score 150, the population was classified into low (n=73) and high (n=25) Romo1 groups. Romo1 expression was significantly higher in smokers, patients with stage III disease, and patient who experienced recurrence after surgery (all p<0.05). In the multivariate analyses, advanced stage and poorly differentiated cancer were associated with shorter disease-free survival (DFS). In addition, high Romo1 expression was independently associated with poor DFS (hazard ratio [HR] = 2.20, 95% confidence interval [CI]:1.10-5.42, p = 0.0324). CONCLUSIONS: Our data showed that Romo1 overexpression was significantly associated with early recurrence in patients with resected, EGFR-mutant lung adenocarcinoma. Although large-scaled data are needed, Romo1 may have prognostic role for this patient population.

Underlying Microstructure of the Lamina Cribrosa at the Site of Microvasculature Dropout.

Purpose: To determine the microstructure of the lamina cribrosa (LC) associated with microvasculature dropout (MvD) of the deep optic nerve head (ONH) in primary open-angle glaucoma (POAG) and to identify factors related to the presence of MvD. Methods: POAG eyes that exhibited MvD in the LC (MvD-LC) or MvD in the peripapillary choroid (MvD-PC) underwent optical coherence tomography and optical coherence tomography angiography (OCTA) to evaluate the structure and microvasculature of the deep ONH, respectively. The presence of MvD-LC or MvD-PC was determined using en face OCTA images of the deep ONH. The sectoral LC thickness (LCT) and LC curvature index (LCCI) (at MvD-LC site, when applicable), the mean LCT and LCCI of the global ONH, and other clinical characteristics were measured and compared between eyes with and without MvD-LC. Results: The study included 93 eyes with and 51 without MvD-LC. The presence of MvD-LC was associated with lower sectoral LCT (odds ratio [OR] = 0.96, P < 0.001) and mean LCT (OR = 0.97, P = 0.032), larger visual field pattern standard deviation (PSD; OR = 1.20, P = 0.038), and higher pretreatment intraocular pressure (IOP; OR = 1.22, P = 0.012). Fifteen percent of the eyes with MvD-LC (14/93) did not present MvD-PC. Those eyes had younger age (P = 0.043), thicker juxtapapillary choroid (P = 0.018), larger sectoral LCCI (P = 0.040), thicker retinal nerve fiber layer (P = 0.024), smaller PSD (P = 0.008), and higher pretreatment IOP (P = 0.006) than those with both MvD-LC and MvD-PC. Conclusions: MvD-LC was associated with a localized morphologic alteration of the LC, and eyes with MvD-LC tended to have a higher pretreatment IOP. The clinical implications of MvD-LC should differ from those of MvD-PC in eyes with POAG.

Rapid Retinal Nerve Fiber Layer Thinning in the Unaffected Contralateral Eyes of Patients with Unilateral Normal-Tension Glaucoma: A Retrospective Observational Study.

PURPOSE: To observe the rate of progressive retinal nerve fiber layer (RNFL) thinning in the unaffected eyes of patients with unilateral normal-tension glaucoma (NTG), in comparison with that of healthy subjects, and to identify the factors associated with progressive RNFL thinning. DESIGN: Retrospective, longitudinal, observational study. PARTICIPANTS: Ninety-five patients with unilateral NTG and 61 healthy controls. METHODS: This study included unilateral NTG and healthy control subjects who were followed up for longer than 4 years and in whom at least 5 reliable retinal nerve fiber layer thickness (RNFLT) measurements were performed using OCT. Factors associated with the rate of thinning of the unaffected eyes of unilateral patients with NTG were identified using regression analysis. MAIN OUTCOME MEASURES: The rate of progressive RNFL thinning and the associated factors. RESULTS: Retinal nerve fiber layer thickness decreased significantly in both the unaffected eyes of unilateral patients with NTG and the healthy eyes (both P < 0.001). The RNFL thinning was significantly faster in the unaffected eyes of unilateral patients with NTG than in the healthy eyes (P < 0.001), specifically in the temporal-inferior (TI) sector (P = 0.003). Factors associated with faster RNFL thinning in the unaffected eyes of unilateral patients with NTG were thicker baseline RNFL of the unaffected eyes (P = 0.002) and a worse visual field (VF) mean deviation (MD) in the NTG eyes (P = 0.040). In the healthy controls, the rate of RNFL thinning in the contralateral eyes was the only factor associated with faster thinning (P = 0.007). CONCLUSIONS: The unaffected eyes of unilateral patients with NTG showed faster RNFL thinning than healthy control eyes, more obviously in the TI sector, and were likely to progress faster when they had a thicker baseline RNFL, and when the NTG eyes had a worse VF MD. In unilateral patients with NTG, initiation of prophylactic treatment could be considered for the unaffected eyes when they are accompanied by a risk of developing glaucoma. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Effects of Rosa multiflora root extract on adipogenesis and lipogenesis in 3T3-L1 adipocytes and SD rat models.

BACKGROUND/OBJECTIVES: Obesity is a major cause of metabolic disorders; to prevent obesity, research is ongoing to develop natural and safe ingredients with few adverse effects. In this study, we determined the anti-obesity effects of Rosa multiflora root extract (KWFD-H01) in 3T3-L1 adipocytes and Sprague-Dawley (SD) rats. MATERIALS/METHODS: The anti-obesity effects of KWFD-H01in 3T3-L1 adipocytes and SD rats were examined using various assays, including Oil Red O staining, gene expression analyses, protein expression analyses, and blood biochemical analyses. RESULTS: KWFD-H01 reduced intracellular lipid accumulation and inhibited the mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ), cytidine-cytidine-adenosine-adenosine-thymidine (CCAAT)/enhancer binding proteins (C/EBPα), sterol regulatory element-binding transcription factor 1 (SREBP-1c), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) in 3T3-L1 cells. KWFD-H01 also reduced body weight, weight gain, and the levels of triglycerides, total and LDL-cholesterol, glucose, and leptin, while increasing high-density lipoprotein-cholesterol and adiponectin in SD rats. PPARγ, C/EBPα, SREBP-1c, ACC, and FAS protein expression was inhibited in the epididymal fat of SD rats. CONCLUSION: Overall, these results confirm the anti-obesity effects of KWFD-H01 in 3T3-L1 adipocytes and SD rats, indicating their potential as baseline data for developing functional health foods or pharmaceuticals to control obesity.

Investigation on the Initial Stage of the Dehydration Process in Mg(OH)2 by Density Functional Theory Calculations.

Mg(OH)2/MgO has been attracting considerable interest as a viable candidate for thermochemical heat storage materials, particularly within the temperature range of 200-400 °C. Nonetheless, the typical dehydration temperature of Mg(OH)2, which occurs within the 300-400 °C range, needs to be reduced to enhance its effectiveness in various applications for thermal energy storage. While several studies have shown that heterospecies doping can lower the dehydration temperature, the fundamental mechanism underlying this effect still remains unclear. Here, we employed density functional theory calculations to elucidate the dehydration mechanism of Mg(OH)2, with a particular focus on the initial stage of the dehydration that determines the temperature beginning the reaction. Our findings indicate that the formation of water molecules on the (001) surface is critical in the early stages of the dehydration. This discovery provides a comprehensive explanation for the role of dopants (Na, Li, or LiCl) in reducing the dehydration temperature by decreasing the formation energy of paired H and OH defects and the migration barrier of H on the surface. The present study will significantly advance the development of novel dopants for Mg(OH)2, facilitating a lower dehydration temperature and, thereby, increasing its suitability for heat storage applications.

Effect of Meniscal Tear Patterns and Preoperative Cartilage Status on Joint Space Width After Medial Opening-Wedge High Tibial Osteotomy.

BACKGROUND: Medial opening-wedge high tibial osteotomy (MOWHTO) is performed to treat young adults with medial compartment knee osteoarthritis associated with varus deformity. However, factors influencing joint space width (JSW) vary according to the type of medial meniscal tear and have not yet been completely elucidated. PURPOSE: To examine changes in JSW according to the type of medial meniscal tear after MOWHTO and analyze the influencing factors. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This study was conducted on 134 patients who underwent MOWHTO for medial osteoarthritis and were followed up for >2 years. The patients were classified into 3 groups based on medial meniscal status: intact, nonroot tear, and root tear. The authors then measured the JSW preoperatively and at 3 months, 6 months, 1 year, and >2 years postoperatively; analyzed whether the change in JSW varied according to meniscal status; and determined the association of these changes with the preoperative cartilage grade of the medial femoral condyle (MFC) and medial tibial plateau (MTP). International Knee Documentation Committee (IKDC) scores were used to evaluate clinical function. RESULTS: Of the 134 patients, the medial meniscus was intact in 29 patients, a nonroot tear was observed in 58 patients, and a root tear was observed in 47 patients. Postoperatively, JSW increased for all groups, but the timing of the increase varied between the groups (P < .001). JSW increased the most 6 months postoperatively in the intact group and 3 months postoperatively in the nonroot tear and root tear groups (P < .001). Additionally, the increase in JSW was the greatest in the root tear group. Preoperatively, MFC and MTP cartilage status differed among the groups; MTP status did not affect the JSW, but MFC status did (P < .001). The IKDC score increased from the preoperative to postoperative time point in all groups, but there was no significant difference between groups. CONCLUSION: The authors observed that the amount and timing of increase in JSW were dependent on the pattern of medial meniscal tear observed when MOWHTO was performed. In addition, the cartilage grade of MFC before surgery was associated with changes in JSW. The IKDC score was not significantly different between groups. However, a longer follow-up period is needed to analyze the correlation with the meniscal tear pattern and JSW.

Body mass index and meniscal tears: Evidence from meta-analysis of observational studies and Mendelian randomization.

Obesity is a potential risk factor for meniscal tear (MT). We utilized meta-analysis of observational studies and Mendelian randomization (MR) analyses to elucidate the association between body mass index (BMI) and MT. In meta-analysis, a search was performed on June 27, 2022, using PubMed and Embase databases. Odds ratios and 95% confidence intervals were extracted from included studies. In MR analyses, the research utilized summary-level data on BMI and MT obtained from Genetic Investigation of Anthropometric Traits and the FinnGen Consortium, respectively. In meta-analysis, four studies comprising 826,383 participants were included. The pooled odds ratio of MT in the high BMI group was 1.32 (95% confidence interval, 0.83-2.09), compared with the nonhigh BMI group. The pooled odds ratio in the under 30 group was 1.76 (95% confidence interval, 0.61-5.03). In MR analyses, one standard deviation increase in genetically predicted BMI was associated with meniscus derangement as a chronic subtype of MT (odds ratio, 1.36; 95% confidential interval, 1.17-1.59). We found that a high BMI was not associated with an increased likelihood of MT based on meta-analysis of observational studies; however, by complementing MR analyses, we elucidated the causality of BMI increase on meniscus derangement as a chronic subtype of MT.

Optimized trans-cranial direct current stimulation for prolonged consciousness disorder in a patient with titanium mesh cranioplasty.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been used for the restoration of awareness in patients with a minimal consciousness state (MCS). Most brains of patients in MCS may structurally and electrophysiologically differ from un-damaged brains. Moreover, tDCS is currently contraindicated for patients with craniotomy or skull with metallic implants. CASE PRESENTATION: We present a case with prolonged MCS over 1 year, who had severe brain damage, ventriculoperitoneal shunt, and cranioplasty with a titanium mesh, which was treated with tDCS which optimized with the simulation of the electric field based on the patient's brain MRI. The patient was resulting in emergence from MCS. Six months later, she ate meals orally and started walking with assistance. DISCUSSION AND PERSPECTIVE: This personalized simulation based on MRI would make the treatment available even to patients with severe brain structural changes and metallic instrumentation.

Enrichment and MALDI-TOF MS Analysis of Phosphoinositides in Brain Tissue.

Triazolium cyclodextrin click cluster (+CCC) is an ideal scaffold to specifically bind phosphoinositides (PIPs) via multivalent electrostatic interaction. A new enrichment material, triazolium cyclodextrin click cluster-magnetic agarose bead conjugate (+CCC-MAB), was synthesized and applied to the PIP enrichment of brain tissue. The enriched sample was analyzed using MALDI-TOF MS in negative ion mode without any derivatization. The PIP extract of brain tissue is known to contain abundant lipid interferences. By employing magnetic pull-down separation using +CCC-MAB, we effectively removed the weak-binding interferences in the PIP extract, thereby improving the signal-to-noise ratio (S/N) of the PIPs. Our +CCC-MAB-based PIP enrichment enabled us to analyze 16 PIP species in brain tissue. Six species with high S/N were assigned by MS/MS, while the remaining 10 species with low S/N were characterized by an empirical selection guide based on the biological relevance of PIPs. We conclude that +CCC-MAB-based PIP enrichment is a promising MALDI sample preparation method for specific PIP analysis in brain tissue.

PPIB/Cyclophilin B expression associates with tumor progression and unfavorable survival in patients with pulmonary adenocarcinoma.

Cyclophilin B (CypB), encoded by peptidylprolyl isomerase B (PPIB), is involved in cellular transcriptional regulation, immune responses, chemotaxis, and proliferation. Recent studies have shown that PPIB/CypB is associated with tumor progression and chemoresistance in various cancers. However, the clinicopathologic significance and mechanism of action of PPIB/CypB in non-small cell lung cancer (NSCLC) remain unclear. In this study, we used RNA in situ hybridization to examine PPIB expression in 431 NSCLC tissue microarrays consisting of 295 adenocarcinomas (ADCs) and 136 squamous cell carcinomas (SCCs). Additionally, Ki-67 expression was evaluated using immunohistochemistry. The role of PPIB/CypB was assessed in five human NSCLC cell lines. There was a significant correlation between PPIB/CypB expression and Ki-67 expression in ADC (Spearman correlation r=0.374, P<0.001) and a weak correlation in SCC (r=0.229, P=0.007). In ADCs, high PPIB expression (PPIBhigh) was associated with lymph node metastasis (P=0.023), advanced disease stage (P=0.014), disease recurrence (P=0.013), and patient mortality (P=0.015). Meanwhile, high Ki-67 expression (Ki-67high) was correlated with male sex, smoking history, high pT stage, lymph node metastasis, advanced stage, disease recurrence, and patient mortality in ADC (all P<0.001). However, there was no association between either marker or clinicopathological factors, except for old age and PPIBhigh (P=0.038) in SCC. Survival analyses revealed that the combined expression of PPIBhigh/Ki-67high was an independent prognosis factor for poor disease-free survival (HR 1.424, 95% CI 1.177-1.723, P<0.001) and overall survival (HR 1.266, 95% CI 1.036-1.548, P=0.021) in ADC, but not in SCC. Furthermore, PPIB/CypB promoted the proliferation, colony formation, and migration of NSCLC cells. We also observed the oncogenic properties of PPIB/CypB expression in human bronchial epithelial cells. In conclusion, PPIB/CypB contributes to tumor growth in NSCLC, and elevated PPIB/Ki-67 levels are linked to unfavorable survival, especially in ADC.

Benefits of Robot-Assisted Upper-Limb Rehabilitation from the Subacute Stage after a Stroke of Varying Severity: A Multicenter Randomized Controlled Trial.

BACKGROUND: The aim of this study was to compare the clinical effectiveness of robot-assisted therapy with that of conventional occupational therapy according to the onset and severity of stroke. METHODS: In this multicenter randomized controlled trial, stroke patients were randomized (1:1) to receive robot-assisted therapy or conventional occupational therapy. The robot-assisted training group received 30 min of robot-assisted therapy twice and 30 min of conventional occupational therapy daily, while the conventional therapy group received 90 min of occupational therapy. Therapy was conducted 5 days/week for 4 weeks. The primary outcome was the Wolf Motor Function Test (WMFT) score after 4 and 8 weeks of therapy. RESULTS: Overall, 113 and 115 patients received robot-assisted and conventional therapy, respectively. The WMFT score after robot-assisted therapy was not significantly better than that after conventional therapy, but there were significant improvements in the Motricity Index (trunk) and the Fugl-Meyer Assessment. After robot-assisted therapy, wrist strength significantly improved in the subacute or moderate-severity group of stroke patients. CONCLUSIONS: Robot-assisted therapy improved the upper-limb functions and activities of daily living (ADL) performance as much as conventional occupational therapy. In particular, it showed signs of more therapeutic effectiveness in the subacute stage or moderate-severity group.

Effect of YC-1102 on the Improvement of Obesity in High-Fat Diet-Induced Obese Mice.

Obesity is one of the major risk factors for metabolic diseases worldwide. This study examined the effects of YC-1102, an extract derived from the roots of Rosa multiflora, on 3T3-L1 preadipocytes and high-fat diet (HFD)-induced obese mice. In vivo experiments involved the oral administration of YC-1102 (100, 150, and 200 mg/kg body weight) daily to mice for eight weeks. YC-1102 was found to downregulate the expressions of PPARγ and C/EBPα during adipogenesis, inhibiting adipocyte differentiation and upregulating the expression of PGC-1α for energy metabolism to enhance mitochondrial biogenesis and fatty acid oxidation. It has been shown that daily administration of YC-1102 to mice receiving a HFD prevented an increase in body weight and the accumulation of body fat. YC-1102 administration also reduced TG, TC, and LDL cholesterol levels, as well as glucose and leptin levels, and increased adiponectin levels, thus effectively inhibiting the metabolism of lipids. YC-1102-treated mice showed significant reductions in the mRNA expression of PPARγ and C/EBPα. The levels of PGC-1α involved in energy metabolism increased significantly in the YC-1102-treated mice when compared to the HFD-treated mice. According to the findings of this study, YC-1102 has a dual mechanism that reduces transcription factors that promote the differentiation of adipocytes and increases transcription factors that promote energy consumption.

Effects of Deep Optic Nerve Head Structures on Bruch's Membrane Opening- Minimum Rim Width and Peripapillary Retinal Nerve Fiber Layer.

PURPOSE: To explore the effects of deep optic nerve head (ONH) structures on Bruch's membrane opening (BMO)-minimum rim width (MRW) and peripapillary retinal nerve fiber layer thickness (pRNFLT) in healthy eyes. DESIGN: Prospective cross-sectional study. METHODS: Two hundred five healthy eyes of 141 subjects (mean ± standard deviation of age and axial length (AXL): 46.9 ± 10.0 years and 24.79 ± 1.15 mm) were enrolled. Best fit multivariable linear mixed models identified factors associated with BMO-MRW and pRNFLT. Explanatory variables included age, gender, AXL, BMO and anterior scleral canal opening (ASCO) area and ovality, magnitude of BMO and ASCO shift, peripapillary choroidal thickness, lamina cribrosa (LC) parameters, prelaminar thickness, and peripapillary scleral (PPS) angle. RESULTS: Thinner BMO-MRW was associated with older age, smaller ASCO/BMO offset magnitude, larger BMO area, thinner prelaminar thickness, deeper LC, and thinner pRNFLT (P = .011, <.001, .004, <.001, <.001, <.001 respectively). Thinner pRNFLT was associated with shorter AXL, smaller ASCO area, a more posteriorly bowed PPS, shallower LC and thinner BMO-MRW. (P = .030, .002, .035, .012, <.001 respectively) CONCLUSIONS: BMO-MRW and pRNFLT were influenced by several deep ONH structures such as BMO and ASCO position shift, BMO or ASCO area, prelaminar thickness, PPS bowing and LC depth in addition to patient characteristics such as age and AXL. The degree and/or direction of associations varied between deep ONH structures and BMO-MRW or pRNFLT. Despite both BMO-MRW and pRNFLT being surrogate parameters for RGC loss, a complex relationship with ONH deep-layer morphology was indicated.

Electric field simulation and appropriate electrode positioning for optimized transcranial direct current stimulation of stroke patients: an in Silico model.

Transcranial Direct Current Stimulation (tDCS) has benefits for motor rehabilitation in stroke patients, but its clinical application is limited due to inter-individual heterogeneous effects. Recently, optimized tDCS that considers individual brain structure has been proposed, but the utility thereof has not been studied in detail. We explored whether optimized tDCS provides unique electrode positions for each patient and creates a higher target electric field than the conventional approach. A comparative within-subject simulation study was conducted using data collected for a randomized controlled study evaluating the effect of optimized tDCS on upper extremity function in stroke patients. Using Neurophet tES LAB 3.0 software, individual brain models were created based on magnetic resonance images and tDCS simulations were performed for each of the conventional and optimized configurations. A comparison of electrode positions between conventional tDCS and optimized tDCS was quantified by calculation of Euclidean distances. A total of 21 stroke patients were studied. Optimized tDCS produced a higher electric field in the hand motor region than conventional tDCS, with an average improvement of 20% and a maximum of 52%. The electrode montage for optimized tDCS was unique to each patient and exhibited various configurations that differed from electrode placement of conventional tDCS. Optimized tDCS afforded a higher electric field in the target of a stroke patient compared to conventional tDCS, which was made possible by appropriately positioning the electrodes. Our findings may encourage further trials on optimized tDCS for motor rehabilitation after stroke.

Predisposal of Interferon Regulatory Factor 1 Deficiency to Accumulate DNA Damage and Promote Osteoarthritis Development in Cartilage.

OBJECTIVE: Interferon regulatory factor 1 (IRF1) is a transcriptional regulator conventionally associated with immunomodulation. Recent molecular analyses mapping DNA binding sites of IRF1 have suggested its potential function in DNA repair. However, the physiologic significance of this noncanonical function remains unexplored. Here, we investigated the role of IRF1 in osteoarthritis (OA), a condition marked by senescence and chronic joint inflammation. METHODS: OA progression was examined in wild-type and Irf1-/- mice using histologic assessments and microcomputed tomography analysis of whole-joint OA manifestations and behavioral assessments of joint pain. An integrated analysis of assay for transposase-accessible chromatin with sequencing and whole transcriptome data was conducted for the functional assessment of IRF1 in chondrocytes. The role of IRF1 in DNA repair and senescence was investigated by assaying γ-H2AX foci and senescence-associated beta-galactosidase activity. RESULTS: Our genome-wide investigation of IRF1 footprinting in chondrocytes revealed its primary occupancies in the promoters of DNA repair genes without noticeable footprint patterns in those of interferon-responsive genes. Chondrocytes lacking IRF1 accumulated irreversible DNA damage under oxidative stress, facilitating their entry into cellular senescence. IRF1 was down-regulated in the cartilage of human and mouse OA. Although IRF1 overexpression did not elicit an inflammatory response in joints or affect OA development, genetic deletion of Irf1 caused enhanced chondrocyte senescence and exacerbated post-traumatic OA in mice. CONCLUSION: IRF1 offers DNA damage surveillance in chondrocytes, protecting them from oxidative stress associated with OA risk factors. Our study provides a crucial and cautionary perspective that compromising IRF1 activity renders chondrocytes vulnerable to cellular senescence and promotes OA development.

Influence of choroidal microvasculature dropout on progressive retinal nerve fibre layer thinning in primary open-angle glaucoma: comparison of parapapillary ß-zones and γ-zones.

BACKGROUND/AIMS: To compare the influence of choroidal microvasculature dropout (cMvD) on progressive retinal nerve fibre layer (RNFL) thinning in glaucomatous eyes with parapapillary ß-zones and γ-zones. METHODS: 294 eyes with primary open-angle glaucoma (POAG) and parapapillary atrophy (PPA) underwent optical coherence tomography (OCT) to determine the type of PPA and OCT angiography scanning of the optic nerve head to determine the presence of cMvD. Eyes were classified based on the type of PPA (ß-zones and γ-zones), and their clinical characteristics were compared. Factors associated with the rate of rapid progressive RNFL thinning were determined in each group, including the presence of cMvD as an independent variable. RESULTS: Of the 294 eyes, 186 and 108 were classified as having ß-zones and γ-zones, respectively. The rate of RNFL thinning was slower (p<0.001), axial length was longer (p<0.001) and presence of cMvD was less frequent (57.4% vs 73.1%, p=0.006) in eyes with γ-zone than those with ß-zone. Multivariate analyses showed that greater lamina cribrosa curvature (p=0.047) and the presence of cMvD (p=0.010) were associated with a faster rate of RNFL thinning in eyes with ß-zone, whereas larger intraocular pressure fluctuation (p<0.001), shorter axial length (p=0.042) and greater baseline RNFL thickness (p<0.001) were associated with a faster rate of RNFL thinning in eyes with γ-zone. CONCLUSIONS: The presence of cMvD was significantly associated with a faster rate of RNFL thinning in POAG eyes with ß-zone, but not γ-zone. The pathogenic consequences of cMvD in POAG eyes may depend on accompanying peripapillary structures.