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Background Coronary artery calcium score (CACS) has become an important tool for evaluating cardiovascular disease (CVD). This study evaluated the significance of CACS for future CVD through more than 10 years of follow-up in asymptomatic Korean populations with type 2 diabetes mellitus (T2DM) known to have a relatively low CACS burden. Methods We enrolled 981 asymptomatic T2DM patients without CVD at baseline who underwent CACS evaluation using multidetector computed tomography between January 2008 and December 2014. They were grouped into five predefined CACS categories based on Agatston scores and followed up by August 2020. The primary endpoint was incident CVD events, including coronary, cerebrovascular, and peripheral arterial disease. Results The relative risk of CVD was significantly higher in patients with CACS ≥10, and the significance persisted after adjustment for known confounders. A higher CACS category indicated a higher incidence of future CVD: hazard ratio (95% confidence interval) 4.09 (1.79 to 9.36), 12.00 (5.61 to 25.69), and 38.79 (16.43 to 91.59) for 10≤ CACS

Human norovirus (HNoV) GII.4 and Vibrio parahaemolyticus may be found in sea squirts. Antimicrobial effects of floating electrode-dielectric barrier discharge (FE-DBD) plasma (5–75 min, N2 1.5 m/s, 1.1 kV, 43 kHz) treatment were examined. HNoV GII.4 decreased by 0.11–1.29 log copy/μL with increasing duration of treatment time, and further by 0.34 log copy/μL when propidium monoazide (PMA) treatment was added to distinguish infectious viruses. The decimal reduction time (D1) of non-PMA and PMA-treated HNoV GII.4 by first-order kinetics were 61.7 (R2 = 0.97) and 58.8 (R2 = 0.92) min, respectively. V. parahaemolyticus decreased by 0.16–1.5 log CFU/g as treatment duration increased. The D1 for V. parahaemolyticus by first-order kinetics was 65.36 (R2 = 0.90) min. Volatile basic nitrogen showed no significant difference from the control until 15 min of FE-DBD plasma treatment, increasing after 30 min. The pH did not differ significantly from the control by 45–60 min, and Hunter color in “L” (lightness), “a” (redness), and “b” (yellowness) values reduced significantly as treatment duration increased. Textures appeared to be individual differences but were not changed by treatment. Therefore, this study suggests that FE-DBD plasma has the potential to serve as a new antimicrobial to foster safer consumption of raw sea squirts.

Background: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. Methods: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. Results: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events. Conclusion: The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose. [ABSTRACT FROM AUTHOR]

Background: With longer life spans and medical advancements, the rising number of patients with advanced-stage Parkinson's disease (PD) warrants attention. Current literature predominantly addresses dementia and fall management in these patients. However, exploring the impact of swallowing function on patients with advanced PD is crucial. Previous research has demonstrated notable enhancements in the quality of life related to voice for participants following a group singing-intervention program. To further elucidate the effect of individual singing-induced swallowing exercises, our study aimed to investigate the quantitative and qualitative effects of therapeutic singing on swallowing function in patients with advanced PD in comparison to a matched usual care control group. The hypothesis of this study is that therapeutic singing-induced swallowing exercises can assist to maintain swallowing function in patients with advanced PD. Methods: This prospective matched control study compared the effects of a 6-week therapeutic singing-based swallowing intervention on swallowing function and quality of life in patients with advanced PD. The intervention group received individual sessions with a music therapist and conventional individual physical therapy. The control group received the same standard physical therapy for 6 weeks without music intervention. The primary outcome measure was Video Fluoroscopic Dysphagia Scale (VDS). Results: The study revealed that the intervention group maintained swallowing function, whereas the control group experienced deterioration, indicating significant time-dependent changes in Penetration-Aspiration Scale (PAS), National Institutes of Health-Swallowing Safety Scale (NIH-SSS), and VDS. Analysis of PAS and NIH-SSS liquid food scores in both groups showed significant time effects. However, the intervention group exhibited no significant differences between the pre- and post-tests, indicating preservation of the swallowing function. VDS of liquid food indicated an interaction effect between time and group in the pharyngeal phase and total scores. The Swallowing-Quality of Life showed significant time-effect improvement in the intervention group. Conclusion: Therapeutic singing exercises may help maintain swallowing function in advanced PD patients, potentially enhancing quality of life related to swallowing in those with advanced-stage diseases. [ABSTRACT FROM AUTHOR]

Background: Intrathecal baclofen (ITB) therapy, a viable alternative for unsuitable candidates of conventional spasticity medications, is a preferred method of administration over the oral route. Owing to its enhanced bioavailability, ITB ensures a more effective delivery at the target site. Objective: There is a lack of conclusive evidence regarding the use of ITB treatment in managing ambulatory patients with spastic dystonia. Before ITB pump implantation, patients commonly undergo an ITB bolus injection trial to rule out potential adverse reactions and verify the therapeutic effects on hypertonic issues. In this report, we highlight a case of spastic dystonia, particularly focusing on an ambulatory patient who demonstrated significant improvement in both the modified Ashworth scale (MAS) score and gait pattern following the ITB injection trial. Case report: This case report outlines the medical history of a 67-year-old male diagnosed with left-side hemiplegia and spastic dystonia, resulting from his second episode of intracranial hemorrhage in the right thalamus. An ITB injection trial was initiated because the patient was not suitable for continued botulinum toxin injections and oral medications. This was due to the persistent occurrence of spastic dystonia in both the upper and lower extremities. The patient underwent a four-day ITB injection trial with progressively increasing doses, resulting in improved MAS scores and gait parameters, including cadence, step length, step time, stride length, and stride time were increased. Particularly, kinematic gait analysis demonstrates a substantial improvement of increased knee flexion in the swing phase in stiff knee gait pattern. These findings indicated a gradual reduction in spasticity-related symptoms, signifying the positive effect of the ITB injection trial. The patient eventually received an ITB pump implantation. Conclusion: In this post-stroke patient with spastic dystonia, ITB therapy has demonstrated effective and substantial management of spasticity, along with improvement in gait patterns. [ABSTRACT FROM AUTHOR]

Abstract Osteoarthritis (OA) is a degenerative disease of the joints, prevalent worldwide. Polydeoxyribonucleotide (PDRN) is used for treating knee OA. However, the role of PDRN in IL-1β-induced inflammatory responses in human bone marrow-derived mesenchymal stem cells (hBMSCs) remains unknown. Here, we investigated the role of PDRN in IL-1β-induced impairment of chondrogenic differentiation in hBMSCs. hBMSCs treated with PDRN showed a large micromass, enhanced safranin O and alcian blue staining intensity, and increased expression of chondrogenic genes in IL-1β-induced inflammatory responses, in addition to regulation of catabolic and anabolic genes. In addition, PDRN treatment suppressed the expression of inflammatory cytokines and mitigated IL-1β-induced apoptosis in hBMSCs. Mechanistically, PDRN treatment increased the formation of cyclic adenosine monophosphate (cAMP) and upregulated the phosphorylation of cAMP-dependent protein kinase A (PKA)/cAMP response element binding protein (CREB) through the adenosine A2A receptor in hBMSCs and thus blocked the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling pathway. Thus, IL-1β-induced expression of inflammatory cytokines in hBMSCs was directly reduced by adenosine A2A receptor activation. Based on our results, we suggest that PDRN may be a promising MSC-based therapeutic agent for OA.

Background: Antiadhesion products are essential for postoperative care in patients after thyroidectomy by providing a physical barrier to cover the exposed tissue and thus preventing abnormal adhesion of adjacent tissues. Since thyroidectomy may result in swallowing difficulties arising from damage or inflammation of the surrounding tissues, the use of antiadhesion agents such as MegaShield ® or Guardix-SG ® will help reduce scar formation. This may thus improve postoperative swallowing function in patients. Methods: Patients were enrolled and followed up between October 4, 2018, and March 26, 2020. Patients during the postoperative follow-up sessions were randomly allocated to the standard care with Guardix-SG ® and clinical trial medical device application group with MegaShield ® (test group) in a 1:1 ratio by the permuted block randomization method. Patient performance on penetration aspiration scale (PAS), National Institutes of Health-Swallow Safety Scale (NIH-SSS), videofluoroscopic dysphagia scale (VDS), Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) based on Videofluoroscopic swallowing study (VFSS) were collected. Nonadhesion-reducing agent patient data were used as a control group. Results: No statistical significance was shown ( P > .05) between the 2 groups of MegaShield ® and Guardix-SG ® in various phases from thick semisolid, thin semisolid to liquid for both PAS and NIH-SSS. Several statistical significances were reported in the results comparing various criteria of PAS, NIH-SSS, VDS at different oral and pharyngeal phases, and DIGEST in all 3 stages among MegaShield ® , Guardix-SG ® , and nonadhesion-reducing agent group. Conclusions: These results prove the noninferiority of MegaShield ® compared with Guardix-SG ® as an antiadhesion agent in postthyroidectomy care.

Abstract Spinal cord injury (SCI) leads to motor and sensory impairment below the site of injury, thereby necessitating rehabilitation. An enriched environment (EE) increases social interaction and locomotor activity in a mouse model, similar to human rehabilitation. However, the impact of EE on presynaptic plasticity in gene expression levels remains unclear. Hence, this study aimed to investigate the therapeutic potential of EE in an SCI mouse model. Mice with spinal cord contusion were divided into two groups: those housed in standard cages (control) and those in EE conditions (EE). Each group was housed separately for either 2- or 8-weeks post-injury, after which RNA sequencing was performed and compared to a sham group (receiving only a dorsal laminectomy). The synaptic vesicle cycle (SVC) pathway and related genes showed significant downregulation after SCI at both time points. Subsequently, we investigated whether exposure to EE for 2- and 8-weeks post-SCI could modulate the SVC pathway and its related genes. Notably, exposure to EE for 8 weeks resulted in a marked reversal effect of SVC-related gene expression, along with stimulation of axon regeneration and mitigation of locomotor activity loss. Thus, prolonged exposure to EE increased presynaptic activity, fostering axon regeneration and functional improvement by modulating the SVC in the SCI mouse model. These findings suggest that EE exposure proves effective in inducing activity-dependent plasticity, offering a promising therapeutic approach akin to rehabilitation training in patients with SCI.

Abstract Osteoporosis is a common skeletal disease that results in an increased risk of fractures. However, there is no definitive cure, warranting the development of potential therapeutic agents. 3′-Sialyllactose (3′-SL) in human milk regulates many biological functions. However, its effect on bone metabolism remains unknown. This study aimed to investigate the molecular mechanisms underlying the effect of 3′-SL on bone homeostasis. Treatment of human bone marrow stromal cells (hBMSCs) with 3′-SL enhanced osteogenic differentiation and inhibited adipogenic differentiation of hBMSCs. RNA sequencing showed that 3′-SL enhanced laminin subunit gamma-2 expression and promoted osteogenic differentiation via the phosphatidylinositol 3‑kinase/protein kinase B signaling pathway. Furthermore, 3′-SL inhibited the receptor activator of nuclear factor κB ligand-induced osteoclast differentiation of bone marrow-derived macrophages through the nuclear factor κB and mitogen‑activated protein kinase signaling pathway, ameliorated osteoporosis in ovariectomized mice, and positively regulated bone remodeling. Our findings suggest 3′-SL as a potential drug for osteoporosis.

Background: The gut microbiome, which is the collection of microorganisms living in the gastrointestinal tract, has been shown to play a significant role in the development of metabolic disorders such as obesity and type 2 diabetes mellitus (T2DM). Studies have found that the ratio of Firmicutes to Bacteroidetes (F/B) is higher in obese individuals compared to lean individuals and tends to decrease with weight loss. However, the relationship between the F/B ratio and T2DM in Korean individuals, with or without obesity, is not fully understood. Objective: The objective of this study is to compare the F/B ratios and metabolic profiles of lean and obese Korean individuals with T2DM. Methods: In this study, 36 individuals with type 2 diabetes mellitus (T2DM) were recruited and classified into four groups (I, II, III, and IV) based on their body mass index (BMI). Group I had a BMI of less than 23.0, group II had a BMI between 23.0 and 24.9, group III had a BMI between 25.0 and 29.9, and group IV had a BMI of 30 kg/m2 or greater. Fecal samples were collected from all participants and sent to Chunlab Inc. (located in Seoul, Republic of Korea) for analysis. The changes in the major microbial phyla within the samples were investigated using quantitative real-time PCR. The collected data were then statistically analyzed using the SPSS program. Results: The levels of triglycerides and alanine transaminase in group I were significantly lower than in the other three groups. The amount of Actinobacteria in group IV was the highest among all four groups. The ratio of Firmicutes to Bacteroidetes increased as BMI increased, and this ratio was positively correlated with AST activity. Conclusions: Our study showed that there is a correlation between the degree of obesity in individuals with diabetes and their gut microbiome. Additionally, the ratio of Firmicutes to Bacteroidetes (F/B ratio) may play a role in the metabolic effects of fatty liver disease, as it may contribute to obesity.

Objective To compare the kinematic effects of two widely-used prefabricated ankle–foot orthoses (AFOs), the Dyna Ankle (DA) and UD Flex (UD), on the gait cycle of patients with hemiplegia due to cerebral palsy or acquired brain injury. Methods This was a retrospective cohort study involving 29 patients. Gait analysis results were assessed under three conditions: barefoot, with the DA, and with the UD. Friedman tests and post hoc analysis with Bonferroni correction were performed to assess differences between the three conditions. Results The DA significantly improved ankle dorsiflexion during the mid-swing phase, making it more effective in correcting foot drop compared with the UD (DA: 2.28°, UD: 0.44°). Conversely, the UD was more effective in preventing knee flexion during the loading response (DA: 28.11°, UD: 26.72°). Conclusions The DA improved ankle dorsiflexion during the swing phase significantly more than that with the UD in patients with hemiplegia. Compared with the DA, the UD more effectively prevented increased knee flexion during the loading response. The choice to prescribe these orthoses should consider individual patient characteristics.

Central nervous system diseases, particularly neurodegenerative disorders, pose significant challenges in medicine. These conditions, characterized by progressive neuronal loss, have remained largely incurable, exacting a heavy toll on individuals and society. In recent years, in vivo reprogramming using Yamanaka factors has emerged as a promising approach for central nervous system regeneration. This technique involves introducing transcription factors, such as Oct4, Sox2, Klf4, and c-Myc, into adult cells to induce their conversion into neurons. This review summarizes the current state of in vivo reprogramming research in the central nervous system, focusing on the use of Yamanaka factors. In vivo reprogramming using Yamanaka factors has shown promising results in several animal models of central nervous system diseases. Studies have demonstrated that this approach can promote the generation of new neurons, improve functional outcomes, and reduce scar formation. However, there are still several challenges that need to be addressed before this approach can be translated into clinical practice. These challenges include optimizing the efficiency of reprogramming, understanding the cell of origin for each transcription factor, and developing methods for reprogramming in non-subventricular zone areas. Further research is needed to overcome the remaining challenges, but this approach has the potential to revolutionize the way we treat central nervous system disorders.

Appropriate rehabilitation of stroke patients at a very early phase results in favorable outcomes. However, the optimal strategy for very early rehabilitation is at present unclear due to the limited knowledge on the effects of very early initiation of rehabilitation based on voluntary exercise (VE). Environmental enrichment (EE) is a therapeutic paradigm for laboratory animals that involves complex combinations of physical, cognitive, and social stimuli, as well as VE. Few studies delineated the effect of EE on apoptosis in very early stroke in an experimental model. Although a minimal benefit of early rehabilitation in stroke models has been claimed in previous studies, these were based on a forced exercise paradigm. The aim of this study is to determine whether very early exposure to EE can effectively regulate Fas/FasL-mediated apoptosis following hypoxic–ischemic (HI) brain injury and improve neurobehavioral function. C57Bl/6 mice were housed for 2 weeks in either cages with EE or standard cages (SC) 3 h or 72 h after HI brain injury. Very early exposure to EE was associated with greater improvement in motor function and cognitive ability, reduced volume of the infarcted area, decreased mitochondria-mediated apoptosis, and decreased oxidative stress. Very early exposure to EE significantly downregulated Fas/FasL-mediated apoptosis, decreased expression of Fas, Fas-associated death domain, cleaved caspase-8/caspase-8, cleaved caspase-3/caspase-3, as well as Bax and Bcl-2, in the cerebral cortex and the hippocampus. Delayed exposure to EE, on the other hand, failed to inhibit the extrinsic pathway of apoptosis. This study demonstrates that very early exposure to EE is a potentially useful therapeutic translation for stroke rehabilitation through effective inhibition of the extrinsic and intrinsic apoptotic pathways.

BackgroundPatients with acquired brain injury (ABI) suffer from deficits in fine motor function in hands which affect independent self-care function in daily life. This study aimed to examine the effects of movement-specific keyboard playing for improved hand function in adolescents and young adults with ABI.MethodA total of 23 patients with ABI participated in this study. Twelve were assigned to the intervention group and eleven to the control group. The intervention group engaged in movement-specific keyboard playing three to four times a week for 3 weeks in addition to standard care, while the control group received only standard care.ResultsThe results of a mixed model of repeated measures ANOVA showed that the time effects were significant in the functional independence measure, key-pressing force, and most of the hand function tests measured. In terms of the interaction effect between group and time, a significant effect was found only in the checker-stacking task as a subtest of the Jebsen-Talyor Hand Function Test.DiscussionThese results indicate that the specified movements required to play the keyboard may involve more precise and dexterous manipulation with hands and fingers. These results also suggest that movement-specific keyboard playing has potential in optimizing the intervention effect of keyboard playing while maximizing the benefits of music for motivating young patients with ABI.