Use of cortical hemodynamic responses in digital therapeutics for upper limb rehabilitation in patients with stroke.

BACKGROUND: Stroke causes long-term disabilities, highlighting the need for innovative rehabilitation strategies for reducing residual impairments. This study explored the potential of functional near-infrared spectroscopy (fNIRS) for monitoring cortical activation during rehabilitation using digital therapeutics. METHODS: This cross-sectional study included 18 patients with chronic stroke, of whom 13 were men. The mean age of the patients was 67.0 ± 7.1 years. Motor function was evaluated through various tests, including the Fugl-Meyer assessment for upper extremity (FMA-UE), grip and pinch strength test, and box and block test. All the patients completed the digital rehabilitation program (MotoCog®, Cybermedic Co., Ltd., Republic of Korea) while being monitored using fNIRS (NIRScout®, NIRx Inc., Germany). Statistical parametric mapping (SPM) was employed to analyze the cortical activation patterns from the fNIRS data. Furthermore, the K-nearest neighbor (K-NN) algorithm was used to analyze task performance and fNIRS data to classify the severity of motor impairment. RESULTS: The participants showed diverse task performances in the digital rehabilitation program, demonstrating distinct patterns of cortical activation that correlated with different motor function levels. Significant activation was observed in the ipsilesional primary motor area (M1), primary somatosensory area (S1), and contralateral prefrontal cortex. The activation patterns varied according to the FMA-UE scores. Positive correlations were observed between the FMA-UE scores and SPM t-values in the ipsilesional M1, whereas negative correlations were observed in the ipsilesional S1, frontal lobe, and parietal lobe. The incorporation of cortical hemodynamic responses with task scores in a digital rehabilitation program substantially improves the accuracy of the K-NN algorithm in classifying upper limb functional levels in patients with stroke. The accuracy for tasks, such as the gas stove-operation task, increased from 44.4% using only task scores to 83.3% when these scores were combined with oxy-Hb t-values from the ipsilesional M1. CONCLUSIONS: The results advocated the development of tailored digital rehabilitation strategies by combining the behavioral and cerebral hemodynamic data of patients with stroke. This approach aligns with the evolving paradigm of personalized rehabilitation in stroke recovery, highlighting the need for further extensive research to optimize rehabilitation outcomes.

Investigation of the Fasciola Cinereum, Absent in BTBR mice, and Comparison with the Hippocampal Area CA2.

The arginine vasopressin 1b receptor (Avpr1b) plays an important role in social behaviors including social learning, memory, and aggression, and is known to be a specific marker for the cornu ammonis area 2 (CA2) regions of the hippocampus. The fasciola cinereum (FC) is an anatomical region in which Avpr1b expressing neurons are prominent, but the functional roles of the FC have yet to be investigated. Surprisingly, the FC is absent in the inbred BTBR T+tf/J (BTBR) mouse strain used to study core behavioral deficits of autism. Here, we characterized and compared transcriptomic expression profiles using single nucleus RNA sequencing and identified 7 different subpopulations and heterogeneity within the dorsal CA2 (dCA2) and FC. Mef2c, involved in autism spectrum disorder, is more highly expressed in the FC. Using Hiplex in situ hybridization, we examined the neuroanatomical locations of these subpopulations in the proximal and distal regions of the hippocampus. Anterograde tracing of Avpr1b neurons specific for the FC showed projections to the IG, dCA2, lacunosum molecular layer of CA1, dorsal fornix, septofibrial nuclei, and intermediate lateral septum (iLS). In contrast to the dCA2, inhibition of Avpr1b neurons in the FC by the inhibitory DREADD system during behavioral testing did not impair social memory. We performed single nucleus RNA sequencing in the dCA2 region and compared between wildtype (WT) and BTBR mice. We found that transcriptomic profiles of dCA2 neurons between BTBR and WT mice are very similar as they did not form any unique clusters; yet, we found there were differentially expressed genes between the dCA2s of BTBR and WT mice. Overall, this is a comprehensive study of the comparison of Avpr1b neuronal subpopulations between the FC and dCA2. The fact that FC is absent in BTBR mice, a mouse model for autism spectrum disorder, suggests that the FC may play a role in understanding neuropsychiatric disease.

Vinpocetine, a phosphodiesterase 1 inhibitor, mitigates atopic dermatitis-like skin inflammation.

Atopic dermatitis (AD) is the most common inflammatory pruritic skin disease worldwide, characterized by the infiltration of multiple pathogenic T lymphocytes and histological symptoms such as epidermal and dermal thickening. This study aims to investigate the effect of vinpocetine (Vinp; a phosphodiesterase 1 inhibitor) on a 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD-like model. DNCB (1%) was administered on day 1 in the AD model. Subsequently, from day 14 onward, mice in each group (Vinp-treated groups: 1 mg/kg and 2 mg/kg and dexamethasone- treated group: 2 mg/kg) were administered 100 µl of a specific drug daily, whereas 0.2% DNCB was administered every other day for 30 min over 14 days. The Vinp-treated groups showed improved Eczema Area and Severity Index scores and trans-epidermal water loss, indicating the efficacy of Vinp in improving AD and enhancing skin barrier function. Histological analysis further confirmed the reduction in hyperplasia of the epidermis and the infiltration of inflammatory cells, including macrophages, eosinophils, and mast cells, with Vinp treatment. Moreover, Vinp reduced serum concentrations of IgE, interleukin (IL)-6, IL-13, and monocyte chemotactic protein-1. The mRNA levels of IL-1ß, IL-6, Thymic stromal lymphopoietin, and transforming growth factor-beta (TGF-ß) were reduced by Vinp treatment. Reduction of TGF-ß protein by Vinp in skin tissue was also observed. Collectively, our results underscore the effectiveness of Vinp in mitigating DNCB-induced AD by modulating the expression of various biomarkers. Consequently, Vinp is a promising therapeutic candidate for treating AD.

Background Breast Parenchymal Signal During Menstrual Cycle on Diffusion-Weighted MRI: A Prospective Study in Healthy Premenopausal Women.

OBJECTIVE: To prospectively investigate the influence of the menstrual cycle on the background parenchymal signal (BPS) and apparent diffusion coefficient (ADC) of the breast on diffusion-weighted MRI (DW-MRI) in healthy premenopausal women. MATERIALS AND METHODS: Seven healthy premenopausal women (median age, 37 years; range, 33-49 years) with regular menstrual cycles participated in this study. DW-MRI was performed during each of the four phases of the menstrual cycle (four examinations in total). Three radiologists independently assessed the BPS visual grade on images with b-values of 800 sec/mm² (b800), 1200 sec/mm² (b1200), and a synthetic 1500 sec/mm² (sb1500). Additionally, one radiologist conducted a quantitative analysis to measure the BPS volume (%) and ADC values of the BPS (ADCBPS) and fibroglandular tissue (ADCFGT). Changes in the visual grade, BPS volume (%), ADCBPS, and ADCFGT during the menstrual cycle were descriptively analyzed. RESULTS: The visual grade of BPS in seven women varied from mild to marked on b800 and from minimal to moderate on b1200 and sb1500. As the b-value increased, the visual grade of BPS decreased. On b800 and sb1500, two of the seven volunteers showed the highest visual grade in the early follicular phase (EFP). On b1200, three of the seven volunteers showed the highest visual grades in EFP. The BPS volume (%) on b800 and b1200 showed the highest value in three of the six volunteers with dense breasts in EFP. Three of the seven volunteers showed the lowest ADCBPS in the EFP. Four of the seven volunteers showed the highest ADCBPS in the early luteal phase (ELP) and the lowest ADCFGT in the late follicular phase (LFP). CONCLUSION: Most volunteers did not exhibit specific BPS patterns during their menstrual cycles. However, the highest BPS and lowest ADCBPS were more frequently observed in EFP than in the other menstrual cycle phases, whereas the highest ADCBPS was more common in ELP. The lowest ADCFGT was more frequent in LFP.

Aplp1 interacts with Lag3 to facilitate transmission of pathologic α-synuclein.

Pathologic α-synuclein (α-syn) spreads from cell-to-cell, in part, through binding to the lymphocyte-activation gene 3 (Lag3). Here we report that amyloid ß precursor-like protein 1 (Aplp1) interacts with Lag3 that facilitates the binding, internalization, transmission, and toxicity of pathologic α-syn. Deletion of both Aplp1 and Lag3 eliminates the loss of dopaminergic neurons and the accompanying behavioral deficits induced by α-syn preformed fibrils (PFF). Anti-Lag3 prevents the internalization of α-syn PFF by disrupting the interaction of Aplp1 and Lag3, and blocks the neurodegeneration induced by α-syn PFF in vivo. The identification of Aplp1 and the interplay with Lag3 for α-syn PFF induced pathology deepens our insight about molecular mechanisms of cell-to-cell transmission of pathologic α-syn and provides additional targets for therapeutic strategies aimed at preventing neurodegeneration in Parkinson's disease and related α-synucleinopathies.

Improvement of volatile aromatic compound levels and sensory quality of distilled soju derived from Saccharomyces cerevisiae and Wickerhamomyces anomalus co-fermentation.

Distilled soju, a Korean traditional alcoholic beverage, is produced by fermenting rice with a variety of microorganisms including molds, yeasts, and lactic acid-producing bacteria, followed by distillation. Our study sought to improve the quality of distilled soju through co-fermentation with Saccharomyces cerevisiae and Wickerhamomyces anomalus, known for producing volatile aromatic compounds during the early stages of fermentation. Analysis of volatile aromatic compounds in co-fermented distilled soju revealed a substantial increase in compounds with boiling points below 200 °C. Among them, ethyl hexanoate, isobutanol, and isoamyl alcohol were identified as the major volatile aromatic compounds based on Log2 fold change analyses of the volatile aromatic compound pattern. In sensory evaluation, co-fermented distilled soju received higher scores in terms of odor and overall preference. Therefore, incorporating W. anomalus may improve the quality of distilled soju.

Establishment of a patient-specific avatar organoid model derived from EUS-guided fine-needle biopsy for timely clinical application in pancreatic ductal adenocarcinoma (with video).

BACKGROUND AND AIMS: Pancreatic ductal adenocarcinoma (PDAC) has the worst survival rate among tumors. At the time of diagnosis, more than 80% of PDACs are considered to be surgically unresectable, and there is an unmet need for treatment options in these inoperable PDACs. This study aimed to establish a patient-derived organoid (PDO) platform from EUS-guided fine-needle biopsy (EUS-FNB) collected at diagnosis and to determine its clinical applicability for the timely treatment of unresectable PDAC. METHODS: Patients with suspected PDAC were prospectively enrolled at the Samsung Medical Center from 2015 to 2019. PDAC tissues were acquired by means of EUS-FNB to establish PDAC PDOs, which were comprehensively analyzed for histology, genomic sequencing, and high-throughput screening (HTS) drug sensitivity test. RESULTS: PDAC PDOs were established with a success rate of 83.2% (94/113). It took approximately 3 weeks from acquiring minimal EUS-FNB specimens to generating sufficient PDAC PDOs for the simultaneous HTS drug sensitivity test and genomic sequencing. The high concordance between PDAC tissues and matched PDOs was confirmed, and whole-exome sequencing revealed the increased detection of genetic alterations in PDOs compared with EUS-FNB tissues. The HTS drug sensitivity test showed clinical correlation between the ex vivo PDO response and the actual chemotherapeutic response of the study patients in the real world (13 out of 15 cases). In addition, whole-transcriptome sequencing identified candidate genes associated with nab-paclitaxel resistance, such as ITGB7, ANPEP, and ST3GAL1. CONCLUSIONS: This PDAC PDO platform allows several therapeutic drugs to be tested within a short time window and opens the possibility for timely personalized medicine as a "patient avatar model" in clinical practice.

Unenhanced Breast MRI With Diffusion-Weighted Imaging for Breast Cancer Detection: Effects of Training on Performance and Agreement of Subspecialty Radiologists.

OBJECTIVE: To investigate whether reader training improves the performance and agreement of radiologists in interpreting unenhanced breast magnetic resonance imaging (MRI) scans using diffusion-weighted imaging (DWI). MATERIALS AND METHODS: A study of 96 breasts (35 cancers, 24 benign, and 37 negative) in 48 asymptomatic women was performed between June 2019 and October 2020. High-resolution DWI with b-values of 0, 800, and 1200 sec/mm² was performed using a 3.0-T system. Sixteen breast radiologists independently reviewed the DWI, apparent diffusion coefficient maps, and T1-weighted MRI scans and recorded the Breast Imaging Reporting and Data System (BI-RADS) category for each breast. After a 2-h training session and a 5-month washout period, they re-evaluated the BI-RADS categories. A BI-RADS category of 4 (lesions with at least two suspicious criteria) or 5 (more than two suspicious criteria) was considered positive. The per-breast diagnostic performance of each reader was compared between the first and second reviews. Inter-reader agreement was evaluated using a multi-rater κ analysis and intraclass correlation coefficient (ICC). RESULTS: Before training, the mean sensitivity, specificity, and accuracy of the 16 readers were 70.7% (95% confidence interval [CI]: 59.4-79.9), 90.8% (95% CI: 85.6-94.2), and 83.5% (95% CI: 78.6-87.4), respectively. After training, significant improvements in specificity (95.2%; 95% CI: 90.8-97.5; P = 0.001) and accuracy (85.9%; 95% CI: 80.9-89.8; P = 0.01) were observed, but no difference in sensitivity (69.8%; 95% CI: 58.1-79.4; P = 0.58) was observed. Regarding inter-reader agreement, the κ values were 0.57 (95% CI: 0.52-0.63) before training and 0.68 (95% CI: 0.62-0.74) after training, with a difference of 0.11 (95% CI: 0.02-0.18; P = 0.01). The ICC was 0.73 (95% CI: 0.69-0.74) before training and 0.79 (95% CI: 0.76-0.80) after training (P = 0.002). CONCLUSION: Brief reader training improved the performance and agreement of interpretations by breast radiologists using unenhanced MRI with DWI.

Calcium pyrophosphate crystal deposition with rotator cuff tear-A case report.

Calcium pyrophosphate dihydrate (CPPD) deposition disease is an inflammatory arthritis induced by calcium pyrophosphate (CPP) crystals and clinically it is called pseudogout. It usually deposits in articular cartilage and in periarticular soft tissues. But no cases of pseudogout in the rotator cuff without cartilage deposition or destruction have been reported so far. We present a case of a 57-year-old woman who was diagnosed as pseudogout with rotator cuff tear.

Activation of Lysosomal Function Ameliorates Amyloid-ß-Induced Tight Junction Disruption in the Retinal Pigment Epithelium.

Accumulation of pathogenic amyloid-ß disrupts the tight junction of retinal pigment epithelium (RPE), one of its senescence-like structural alterations. In the clearance of amyloid-ß, the autophagy-lysosome pathway plays the crucial role. In this context, mammalian target of rapamycin (mTOR) inhibits the process of autophagy and lysosomal degradation, acting as a potential therapeutic target for age-associated disorders. However, efficacy of targeting mTOR to treat age-related macular degeneration remains largely elusive. Here, we validated the therapeutic efficacy of the mTOR inhibitors, Torin and PP242, in clearing amyloid-ß by inducing the autophagy-lysosome pathway in a mouse model with pathogenic amyloid-ß with tight junction disruption of RPE, which is evident in dry age-related macular degeneration. High concentration of amyloid-ß oligomers induced autophagy-lysosome pathway impairment accompanied by the accumulation of p62 and decreased lysosomal activity in RPE cells. However, Torin and PP242 treatment restored the lysosomal activity via activation of LAMP2 and facilitated the clearance of amyloid-ß in vitro and in vivo. Furthermore, clearance of amyloid-ß by Torin and PP242 ameliorated the tight junction disruption of RPE in vivo. Overall, our findings suggest mTOR inhibition as a new therapeutic strategy for the restoration of tight junctions in age-related macular degeneration.

Newly isolated Lactobacillus paracasei strain modulates lung immunity and improves the capacity to cope with influenza virus infection.

BACKGROUND: The modulation of immune responses by probiotics is crucial for local and systemic immunity. Recent studies have suggested a correlation between gut microbiota and lung immunity, known as the gut-lung axis. However, the evidence and mechanisms underlying this axis remain elusive. RESULTS: In this study, we screened various Lactobacillus (L.) strains for their ability to augment type I interferon (IFN-I) signaling using an IFN-α/ß reporter cell line. We identified L. paracasei (MI29) from the feces of healthy volunteers, which showed enhanced IFN-I signaling in vitro. Oral administration of the MI29 strain to wild-type B6 mice for 2 weeks resulted in increased expression of IFN-stimulated genes and pro-inflammatory cytokines in the lungs. We found that MI29-treated mice had significantly increased numbers of CD11c+PDCA-1+ plasmacytoid dendritic cells and Ly6Chi monocytes in the lungs compared with control groups. Pre-treatment with MI29 for 2 weeks resulted in less weight loss and lower viral loads in the lung after a sub-lethal dose of influenza virus infection. Interestingly, IFNAR1-/- mice did not show enhanced viral resistance in response to oral MI29 administration. Furthermore, metabolic profiles of MI29-treated mice revealed changes in fatty acid metabolism, with MI29-derived fatty acids contributing to host defense in a Gpr40/120-dependent manner. CONCLUSIONS: These findings suggest that the newly isolated MI29 strain can activate host defense immunity and prevent infections caused by the influenza virus through the gut-lung axis. Video Abstract.

Genetic influences on alcohol flushing in East Asian populations.

BACKGROUND: Although it is known that variation in the aldehyde dehydrogenase 2 (ALDH2) gene family influences the East Asian alcohol flushing response, knowledge about other genetic variants that affect flushing symptoms is limited. METHODS: We performed a genome-wide association study meta-analysis and heritability analysis of alcohol flushing in 15,105 males of East Asian ancestry (Koreans and Chinese) to identify genetic associations with alcohol flushing. We also evaluated whether self-reported flushing can be used as an instrumental variable for alcohol intake. RESULTS: We identified variants in the region of ALDH2 strongly associated with alcohol flushing, replicating previous studies conducted in East Asian populations. Additionally, we identified variants in the alcohol dehydrogenase 1B (ADH1B) gene region associated with alcohol flushing. Several novel variants were identified after adjustment for the lead variants (ALDH2-rs671 and ADH1B-rs1229984), which need to be confirmed in larger studies. The estimated SNP-heritability on the liability scale was 13% (S.E. = 4%) for flushing, but the heritability estimate decreased to 6% (S.E. = 4%) when the effects of the lead variants were controlled for. Genetic instrumentation of higher alcohol intake using these variants recapitulated known associations of alcohol intake with hypertension. Using self-reported alcohol flushing as an instrument gave a similar association pattern of higher alcohol intake and cardiovascular disease-related traits (e.g. stroke). CONCLUSION: This study confirms that ALDH2-rs671 and ADH1B-rs1229984 are associated with alcohol flushing in East Asian populations. Our findings also suggest that self-reported alcohol flushing can be used as an instrumental variable in future studies of alcohol consumption.

Catastrophic rhabdomyolysis following breast reconstruction operation using an abdominal flap: a case report.

Background: Rhabdomyolysis is a potentially fatal clinical syndrome resulting from the damage or breakdown of skeletal muscle, which can also lead to permanent disabilities. Based on our review of studies on rhabdomyolysis after prolonged surgeries, no other cases of rhabdomyolysis caused by muscle injury in the buttock area following breast reconstruction have been reported, making the current report the first to share information related to patient conditions and treatment progress in such cases. Case Description: Here, we present the case of a 57-year-old Asian patient with left breast cancer. We performed immediate breast reconstruction using a deep inferior epigastric perforator (DIEP) flap anastomosed to the internal mammary vessels after a skin-sparing mastectomy with sentinel lymph node biopsy. The surgery exceeded the estimated time because, after anastomosis, severe congestion was observed in the flap and because of the need to perform re-anastomosis and the reconstruction of the internal mammary vein twice. The surgical team eventually re-performed the breast reconstruction using a contralateral pedicled transverse rectus abdominis myocutaneous (TRAM) flap. The patient underwent breast reconstruction in a sitting position to ensure a symmetrical and natural breast shape resembling its original state. Additionally, a brown splint was placed underneath both legs to keep the hip and knees flexed to ensure donor-site closure when using an abdominal-based flap. The patient was closely monitored in the early postoperative period. On postoperative day (POD) 3, patient developed hypotension and was deemed to have experienced a hypovolemic shock. A complete laboratory workup was performed, and a rhabdomyolysis diagnosis was made based on the laboratory results. We believe that rhabdomyolysis resulted from prolonged pressure on the large gluteus maximus muscle located below the site of the pressure sore in the present patient. Conclusions: Postoperative rhabdomyolysis often results from prolonged surgery. Given the possibility of prolonged procedure time in patients undergoing breast reconstruction, the current case emphasizes the need to identify each patient's risk factors for rhabdomyolysis and prepare for possible rhabdomyolysis to prevent ischemic injuries and reduce the risk of complications such as hypovolemic shock.

Stimulation of median raphe terminals in dorsal CA2 reduces social investigation in male mice specifically investigating social stimulus of ovariectomized female mice.

The cornu ammonis area 2 (CA2) region is essential for social behaviors, especially in social aggression and social memory. Recently, we showed that targeted CA2 stimulation of vasopressin presynaptic fibers from the paraventricular nuclei of hypothalamus strongly enhances social memory in mice. In addition, the CA2 area of the mouse hippocampus receives neuronal inputs from other regions including the septal nuclei, the diagonal bands of Broca, supramammillary nuclei, and median raphe nucleus. However, the functions of these projections have been scarcely investigated. A functional role of median raphe (MR) - CA2 projection is supported by the MR to CA2 projections and 82% reduction of hippocampal serotonin (5-HT) levels following MR lesions. Thus, we investigated the behavioral role of presynaptic fibers from the median raphe nucleus projecting to the dorsal CA2 (dCA2). Here, we demonstrate the optogenetic stimulation of 5-HT projections to dCA2 from the MR do not alter social memory, but instead reduce social interaction. We show that optical stimulation of MR fibers excites interneurons in the stratum radiatum (SR) and stratum lacunosum moleculare (SLM) of CA2 region. Consistent with these observations, we show that bath application of 5-HT increases spontaneous GABA release onto CA2 pyramidal neurons and excites presumed interneurons located in the SR/SLM. This is the first study, to our knowledge, which investigates the direct effect of 5-HT release from terminals onto dCA2 neurons on social behaviors. This highlights the different roles for these inputs (i.e., vasopressin inputs regulating social memory versus serotonin inputs regulating social interaction).

Skin wound healing effects of (+)-syringaresinol from ginseng berry.

Background: Ginseng has been used as a traditional medicine and functional cosmetic ingredients for many years. Recent studies have focused on the potential biological effects of the ginseng berry and its ingredients. (+)-Syringaresinol (SYR) is enriched in ginseng berry and its beneficial effects on the skin have been recently reported. However, little is known about the its effects on the wound healing process of skin. Methods: Here, we evaluated the skin wound healing effect of (+)-SYR using the human fibroblast Hs68 cell and ex vivo pig and human skin tissue model. Scratch wound test and hydrogen peroxide (HPO) induce chemical wound model were employed. Results: (+)-SYR promoted the migration and proliferation of Hs68 cells without significant cytotoxicity at the tested concentrations. Especially, in ex vivo pig and human skin tissue, HPO-induced chemical wound was recovered almost completely by (+)-SYR. In line with the finding in Hs68, the protein expression levels of TGF-ß and PCNA, a proliferation marker were increased, demonstrating the beneficial effects of (+)-SYR on skin wound repair. Conclusion: Collectively, we demonstrated that (+)-SYR from ginseng berry, can enhance the wound healing effect by accelerating cell proliferation and skin regeneration, suggesting the potential utility of (+)-SYR for skin wound repair.

Antiinflammatory effect of the ethanolic extract of Korean native herb Potentilla rugulosa Nakai in Bisphenol-a-stimulated A549 cells.

Potentilla rugulosa Nakai (P. rugulosa) is a perennial herb in the Rosaceae family and found in the Korean mountains. Previously, our findings demonstrated that P. rugulosa contains numerous polyphenols and flavonoids exhibiting important antioxidant and anti-obesity bioactivities. Bisphenol A (BPA) is a xenoestrogen that was shown to produce pulmonary inflammation in humans. However, the mechanisms underlying BPA-induced inflammation remain to be determined. The aim of this study was to examine whether ethanolic extract of P. rugulosa exerted an inhibitory effect on BPA-induced inflammation utilizing an adenocarcinoma human alveolar basal epithelial cell line A549. The P. rugulosa extract inhibited BPA-mediated cytotoxicity by reducing levels of reactive oxygen species (ROS). Further, P. rugulosa extract suppressed the upregulation of various pro-inflammatory mediators induced by activation of the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. In addition, inhibition of the NF-κB and MAPK signaling pathways by P. rugulosa extract was found to occur via decrease in the transcriptional activity of NF-κB. Further, blockade of phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and stress-activated protein kinase/Jun N-terminal kinase (SAPK/JNK) was noted. Thus, our findings suggest that the ethanolic extract of P. rugulosa may act as a natural anti-inflammatory therapeutic agent.

Influence of Vitamin D Deficiency on the Expression of Genes and Proteins in Patients With Medium Rotator Cuff Tears.

BACKGROUND: Whether vitamin D deficiency is related to rotator cuff muscle and tendon physiology is controversial. PURPOSE: To assess the relationship between vitamin D deficiency and various gene expression patterns in patients with rotator cuff tears. STUDY DESIGN: Controlled laboratory study. METHODS: During arthroscopic surgery, samples from the supraspinatus muscle, deltoid muscle, and supraspinatus tendon were acquired from 12 patients with vitamin D deficiency (serum 25-hydroxyvitamin D concentration <20 ng/dL) and 12 patients with sufficient vitamin D levels (control group, serum 25-hydroxyvitamin D concentration ≥30 ng/dL) who were matched for age, sex, and tear size. Alterations in the expression of genes and proteins associated with myogenesis, muscle atrophy, adipogenesis, inflammation, and apoptosis, as well as in vitamin D receptor expression, were assessed using quantitative reverse transcription polymerase chain reaction, Western blotting, and immunohistochemistry and were compared between the 2 groups. RESULTS: Vitamin D receptor gene expression in the deltoid muscle was significantly lower in the vitamin D deficiency group than in the control group (P = .043). Additionally, in the deltoid muscle, myoDgene expression levels were lower and atrogin levels were higher in the vitamin D deficiency group than in the control group (P = .034 and P = .011, respectively). However, in the supraspinatus muscle, no differences were observed between groups in the expression of myogenesis- or atrophy-related genes (all P > .05). The expression of inflammation-related genes (interleukin (IL)-1ß and IL-6) was significantly higher in the vitamin D deficiency group, in both the deltoid and supraspinatus muscles (all P < .05). The supraspinatus tendon tissue did not show any significant differences in any gene expression evaluated (all P > .05). A correlation between gene and protein expression was observed for atrogin and IL-1ß in the deltoid muscle (P = .019 and P = .037, respectively) and for IL-6 in the supraspinatus muscle (P = .044). CONCLUSION: Vitamin D deficiency was not associated with the expression of myogenesis-related or muscle atrophy-related genes in the supraspinatus muscle of patients with rotator cuff tears, unlike in the deltoid muscle; rather, vitamin D deficiency was associated with increased proinflammatory cytokine expression. CLINICAL RELEVANCE: In patients with rotator cuff tears, vitamin D deficiency was observed to be associated with increased levels of proinflammatory cytokines in the rotator cuff muscles, without significant changes in gene expression related to myogenesis or muscle atrophy.

Comparative study of young-old and old-old people using functional evaluation, gait characteristics, and cardiopulmonary metabolic energy consumption.

BACKGROUND: Walking is an important factor in daily life. Among older adults, gait function declines with age. In contrast to the many studies revealing gait differences between young adults and older adults, few studies have further divided older adults into groups. The purpose of this study was to subdivide an older adult population by age to identify age-related differences in functional evaluation, gait characteristics and cardiopulmonary metabolic energy consumption while walking. METHODS: This was a cross-sectional study of 62 old adult participants who were classified into two age groups of 31 participants each as follows: young-old (65-74 years) and old-old (75-84 years) group. Physical functions, activities of daily living, mood state, cognitive function, quality of life, and fall efficacy were evaluated using the Short Physical Performance Battery (SPPB), Four-square Step Test (FSST), Timed Up and Go Test (TUG), Korean Version of the Modified Barthel Index, Geriatric Depression Scale (GDS), Korean Mini-mental State Examination, EuroQol-5 Dimensions (EQ-5D) questionnaire, and the Korean version of the Fall Efficacy Scale. A three-dimensional motion capture system (Kestrel Digital RealTime System®; Motion Analysis Corporation, Santa Rosa, CA, USA) and two force plates (TF-4060-B; Tec Gihan, Kyoto, Japan) were used to investigate spatiotemporal gait parameters (velocity, cadence, stride length, stride width, step length, single support, stance phase, and swing phase), kinematic variables (hip, knee, and ankle joint angles), and kinetic variables (hip, knee, and ankle joint moment and power) of gait. A portable cardiopulmonary metabolic system (K5; Cosmed, Rome, Italy) was used to measure cardiopulmonary energy consumption. RESULTS: The old-old group showed significantly lower SPPB, FSST, TUG, GDS-SF, and EQ-5D scores (p < 0.05). Among spatiotemporal gait parameters, velocity, stride length, and step length were significantly lower in the old-old group than in the young-old group (p < 0.05). Among the kinematic variables, the knee joint flexion angles during initial contact and terminal swing phase were significantly higher in the old-old than the young-old group (P < 0.05). The old-old group also showed a significantly lower ankle joint plantarflexion angle during the pre- and initial swing phases (P < 0.05). Among the kinetic variables, the hip joint flexion moment and knee joint absorption power in the pre-swing phase were significantly lower in the old-old than the young-old group (P < 0.05). CONCLUSION: This study demonstrated that participants 75-84 years of age had less functional gaits than their young-old counterparts (65-74 years old). As the walking pace of old-old people diminishes, driving strength to move ahead and pressure on the knee joint also tend to decrease together with stride length. These differences in gait characteristics according to age among older adults could improve our understanding of how aging causes variations in gait that increase the risk of falls. Older adults of different ages may require customized intervention plans, such as gait training methods, to prevent age-related falls. TRIAL REGISTRATION: Clinical trials registration information: ClinicalTrials.gov Identifier: NCT04723927 (26/01/2021).

Automated 3-dimensional MRI segmentation for the posterosuperior rotator cuff tear lesion using deep learning algorithm.

INTRODUCTION: Rotator cuff tear (RCT) is a challenging and common musculoskeletal disease. Magnetic resonance imaging (MRI) is a commonly used diagnostic modality for RCT, but the interpretation of the results is tedious and has some reliability issues. In this study, we aimed to evaluate the accuracy and efficacy of the 3-dimensional (3D) MRI segmentation for RCT using a deep learning algorithm. METHODS: A 3D U-Net convolutional neural network (CNN) was developed to detect, segment, and visualize RCT lesions in 3D, using MRI data from 303 patients with RCTs. The RCT lesions were labeled by two shoulder specialists in the entire MR image using in-house developed software. The MRI-based 3D U-Net CNN was trained after the augmentation of a training dataset and tested using randomly selected test data (training: validation: test data ratio was 6:2:2). The segmented RCT lesion was visualized in a three-dimensional reconstructed image, and the performance of the 3D U-Net CNN was evaluated using the Dice coefficient, sensitivity, specificity, precision, F1-score, and Youden index. RESULTS: A deep learning algorithm using a 3D U-Net CNN successfully detected, segmented, and visualized the area of RCT in 3D. The model's performance reached a 94.3% of Dice coefficient score, 97.1% of sensitivity, 95.0% of specificity, 84.9% of precision, 90.5% of F1-score, and Youden index of 91.8%. CONCLUSION: The proposed model for 3D segmentation of RCT lesions using MRI data showed overall high accuracy and successful 3D visualization. Further studies are necessary to determine the feasibility of its clinical application and whether its use could improve care and outcomes.

Exercise with a wearable hip-assist robot improved physical function and walking efficiency in older adults.

Wearable assistive robotics has emerged as a promising technology to supplement or replace motor functions and to retrain people recovering from an injury or living with reduced mobility. We developed delayed output feedback control for a wearable hip-assistive robot, the EX1, to provide gait assistance. Our purpose in this study was to investigate the effects of long-term exercise with EX1 on gait, physical function, and cardiopulmonary metabolic energy efficiency in elderly people. This study used parallel experimental (exercise with EX1) and control groups (exercise without EX1). A total of 60 community-dwelling elderly persons participated in 18 exercise intervention sessions during 6 weeks, and all participants were assessed at 5 time points: before exercise, after 9 exercise sessions, after 18 sessions, and 1 month and 3 months after the last session. The spatiotemporal gait parameters, kinematics, kinetics, and muscle strength of the trunk and lower extremities improved more after exercise with EX1 than in that without EX1. Furthermore, the effort of muscles over the trunk and lower extremities throughout the total gait cycle (100%) significantly decreased after exercise with EX1. The net metabolic energy costs during walking significantly improved, and functional assessment scores improved more in the experimental group than in the control group. Our findings provide evidence supporting the application of EX1 in physical activity and gait exercise is effective to improve age-related declines in gait, physical function, and cardiopulmonary metabolic efficiency among older adults.