Caregiving-Related Depression Increases Neuroinflammation in Spousal Caregivers to Individuals with Cognitive Impairment: A Longitudinal Study.

BACKGROUND: The caregiving burden of the spousal caregivers (SCGs) to individuals with cognitive impairment poses public health challenges with adverse psychosocial and physiological effects. However, few studies have investigated the neurobiological impact of caregiving, particularly through the investigation of neuroinflammation and neurodegeneration. METHODS: Using data from a longitudinal cohort at Chungnam National University Hospital, the relationship between caregiving burden, neuroinflammation and neurodegeneration was examined in 38 older adult couples over a 16-month period. Caregiving burden was assessed through a multifaceted approach. For factors related to the care recipient, we assessed cognitive function and neuropsychiatric symptoms. Factors regarding the SCGs included the measurement of perceived depression. Glial fibrillary acidic protein (GFAP) was used as a plasma biomarker for neuroinflammation and neurofilament light chain (NfL) for neurodegeneration. Regression analyses were adjusted for age, sex, apolipoprotein E status, follow-up interval, vascular risk factors, and physical activity. RESULTS: Changes in depression among SCGs were significantly correlated with increased GFAP levels (p = 0.003), indicating that greater depressive symptoms during caregiving are associated with increased neuroinflammation. In contrast, no significant correlations were found between changes in cognitive function or neuropsychiatric symptoms in care recipients and the plasma biomarker levels of SCGs. Additionally, there was no significant association between changes in depression and NfL levels in SCGs. CONCLUSIONS: The psychological stress experienced by SCGs while caring for partners with cognitive impairment actively contributes to neuroinflammation, a well-known risk factor for various diseases. This study emphasizes the need to address psychological stress experienced by older adult caregivers.

Study on Data Preprocessing for Machine Learning Based on Semiconductor Manufacturing Processes.

Various data types generated in the semiconductor manufacturing process can be used to increase product yield and reduce manufacturing costs. On the other hand, the data generated during the process are collected from various sensors, resulting in diverse units and an imbalanced dataset with a bias towards the majority class. This study evaluated analysis and preprocessing methods for predicting good and defective products using machine learning to increase yield and reduce costs in semiconductor manufacturing processes. The SECOM dataset is used to achieve this, and preprocessing steps are performed, such as missing value handling, dimensionality reduction, resampling to address class imbalances, and scaling. Finally, six machine learning models were evaluated and compared using the geometric mean (GM) and other metrics to assess the combinations of preprocessing methods on imbalanced data. Unlike previous studies, this research proposes methods to reduce the number of features used in machine learning to shorten the training and prediction times. Furthermore, this study prevents data leakage during preprocessing by separating the training and test datasets before analysis and preprocessing. The results showed that applying oversampling methods, excluding KM SMOTE, achieves a more balanced class classification. The combination of SVM, ADASYN, and MaxAbs scaling showed the best performance with an accuracy and GM of 85.14% and 72.95%, respectively, outperforming all other combinations.

Multiorgan transplant for therapy-associated lung and liver failure in a patient with stage III lung cancer.

Immunotherapy can significantly improve efficacy of cancer treatments. For locally advanced stage III lung cancers, chemoimmunotherapy in the neoadjuvant setting can achieve complete pathological response in about 40% of cases. However, optimal cancer response in patients receiving immunotherapy is sometimes associated with potentially fatal bystander injury to lung and liver. We report a successful combined double lung and liver transplantation for immunotherapy-associated respiratory failure and cirrhosis in a patient with advanced lung cancer. A 68-year-old male with stage IIIA squamous cell lung cancer, encountered severe interstitial pneumonitis and nodular regenerative hyperplasia of the liver following systemic anti-cancer therapy that included immunotherapy and platinum-based chemotherapy. These adverse events culminated in fulminant end-stage pulmonary fibrosis and cirrhosis, that was treated with simultaneous lung and liver transplantation, complete resection of lung cancer and mediastinal lymphadenectomy. The patient demonstrated promising early outcomes without recurrence of cancer at 12 months. Given that oncologic treatments can induce irreversible solid organ failure despite cancer control, our report suggests that in carefully selected patients without systemic metastasis and in whom complete resection of residual cancer can be performed, organ transplantation can be life-saving.

Modulation of osteoblastogenesis by NRF2: NRF2 activation suppresses osteogenic differentiation and enhances mineralization in human bone marrow-derived mesenchymal stromal cells.

Mesenchymal stromal stem cells (MSCs) or skeletal stem cells (SSCs) play a major role in tissue repair due to their robust ability to differentiate into osteoblasts, chondrocytes, and adipocytes. Complex cell signaling cascades tightly regulate this differentiation. In osteogenic differentiation, Runt-related transcription factor 2 (RUNX2) and ALP activity are essential. Furthermore, during the latter stages of osteogenic differentiation, mineral formation mediated by the osteoblast occurs with the secretion of a collagenous extracellular matrix and calcium deposition. Activation of nuclear factor erythroid 2-related factor 2 (NRF2), an important transcription factor against oxidative stress, inhibits osteogenic differentiation and mineralization via modulation of RUNX2 function; however, the exact role of NRF2 in osteoblastogenesis remains unclear. Here, we demonstrate that NRF2 activation in human bone marrow-derived stromal cells (HBMSCs) suppressed osteogenic differentiation. NRF2 activation increased the expression of STRO-1 and KITLG (stem cell markers), indicating NRF2 protects HBMSCs stemness against osteogenic differentiation. In contrast, NRF2 activation enhanced mineralization, which is typically linked to osteogenic differentiation. We determined that these divergent results were due in part to the modulation of cellular calcium flux genes by NRF2 activation. The current findings demonstrate a dual role for NRF2 as a HBMSC maintenance factor as well as a central factor in mineralization, with implications therein for elucidation of bone formation and cellular Ca2+ kinetics, dystrophic calcification and, potentially, application in the modulation of bone formation.

Recurrence-Independent Progressive Inner-Retinal Thinning After Optic Neuritis: A Longitudinal Study.

BACKGROUND: Longitudinal changes in the inner retina in patients with optic neuritis (ON) may be helpful in monitoring patients and determining maintenance treatment. The aim of this study was to investigate longitudinal changes in the inner retina after subsiding of acute demyelinating ON and to identify the factors associated with such changes. METHODS: In this multicenter retrospective observational study, we reviewed the medical records of 77 patients with ON, including 23 with neuromyelitis optica spectrum disorder with aquaporin 4 (AQP4)-immunoglobulin G (IgG) (AQP4 group), 23 with myelin oligodendrocyte glycoprotein (MOG)-antibody-associated disease (MOG group), 18 with multiple sclerosis (MS group), and 13 with idiopathic ON (iON group). We measured the thickness of the peripapillary retinal nerve fiber layer (pRNFL) and the macular ganglion cell-inner plexiform layer (mGCIPL) using optical coherence tomography (OCT) at baseline and at follow-up examinations (mean follow-up duration, 29.6 ± 8.6 months; mean number of OCT, 4.2 ± 1.2) in the absence of ON recurrence. RESULTS: The estimated rate of pRNFL thinning in the AQP4, MOG, MS, and iON groups was 0.66 (95% confidence interval, 0.35-0.97), 0.35 (0.04-0.66), 0.53 (0.16-0.90), and 0.25 (-0.18 to 0.68) µm/year, respectively, indicating that, in the iON group in contrast to the other groups, there was no significant decrease of pRNFL thickness. Among the AQP4, MOG, and MS groups, there was no significant difference in the rate of pRNFL thinning (P = 0.560). The rate of mGCIPL thinning in the AQP4 and MOG groups was 0.25 (0.04-0.46) µm/year and 0.38 (0.23-0.53) µm/year, respectively. Meanwhile, the rate of mGCIPL change in the MS and iON groups was 0.04 (-0.12 to 0.19) and 0.00 (-0.17 to 0.16) µm/year, respectively, which indicates that there was no significant mGCIPL thinning in the latter 2 groups. Between the AQP4 and MOG groups, meanwhile, the rate of mGCIPL change did not significantly differ (P = 0.295). Age older than 40 years was associated with significant progression of mGCIPL thinning (P = 0.005). CONCLUSIONS: We noted inner retina thinning progression independent of relapse activity in AQP4-ON, MOG-ON, and MS-ON. Because subclinical neuroaxonal damage continues to be incurred after an acute attack of ON subsides despite suppression of new attacks, long-term follow-up and neuroprotection should be considered to be integral to the treatment of patients with ON.

How to Achieve Further Progress of Journal of Korean Neurosurgical Society (JKNS) - Improve the Impact Factor (IF) and Maintain It Continuously.

Journal of Korean Neurosurgical Society (JKNS), which has a history of over 50 years, has made great progress recently. In order to continue this progress in the future, we need to think about the strategies we will take and put them into practice. The progress of JKNS is an important opportunity to publicize the achievements of Korean neurosurgery to the world and for Korea to contribute further to global neurosurgery. We also need to think about and implement various measures to improve the inflow of papers of high quality from various countries and to establish an appropriate merit system for reviewers.

Novel Variant of FDXR as a Molecular Etiology of Postlingual Post-synaptic Auditory Neuropathy Spectrum Disorder via Mitochondrial Dysfunction: Reiteration of the Correlation between Genotype and Cochlear Implantation Outcomes.

OBJECTIVES: FDXR encodes mitochondrial ferredoxin reductase, which is associated with auditory neuropathy spectrum disorder (ANSD) and optic atrophy. To date, only two studies have described FDXR-related hearing loss. The auditory rehabilitation outcomes of this disease entity have not been investigated, and the pathophysiological mechanisms remain incompletely understood. Here we report a hearing-impaired individual with co-segregation of the FDXR variant and post-synaptic type ANSD, who underwent cochlear implantation (CI) with favorable outcomes. We suggest a possible pathophysiological mechanism of adult-onset ANSD involving mitochondrial dysfunction. METHODS: A 35-year-old woman was ascertained to have ANSD. Exome sequencing identified the genetic cause of hearing loss, and a functional study measuring mitochondrial activity was performed to provide molecular evidence of pathophysiology. Expression of FDXR in the mouse cochlea was evaluated by immunohistochemistry. Intraoperatively, electrically evoked compound action potential (ECAP) responses were measured, and the mapping parameters were adjusted accordingly. Audiological outcomes were monitored for over 1 year. RESULTS: In lymphoblastoid cell lines (LCLs) carrying a novel FDXR variant, decreased ATP levels, reduced mitochondrial membrane potential, and increased reactive oxygen species levels were observed compared to control LCLs. These dysfunctions were restored by administering mitochondria isolated from umbilical cord mesenchymal stem cells, confirming the pathogenic potential of this variant via mitochondrial dysfunction. Partial ECAP responses during CI and FDXR expression in the mouse cochlea indicate that FDXR-related ANSD is post-synaptic. As a result of increasing the pulse width during mapping, the patient's CI outcomes showed significant improvement over 1-year post-CI. CONCLUSION: A novel FDXR variant associated with mitochondrial dysfunction and post-synaptic ANSD was first identified in a Korean individual. Additionally, 1-year post-CI outcomes were reported for the first time in the literature. Excellent audiologic. RESULTS: were obtained, and our. RESULTS: reiterate the correlation between genotype and CI outcomes in ANSD.

Moderate capsaicin-containing kochujang alleviates memory impairment through the gut-brain axis in rats with scopolamine-induced amnesia.

This study investigated the efficacy and mechanism of traditionally made kochujang(TMK) with different capsaicin levels to alleviate memory impairment in rats with scopolamine-induced amnesia. Sprague-Dawley male rats were administered scopolamine (2 mg/kg bw/day) intraperitoneally to suppress the parasympathetic nervous system(PNS) and induce memory impairment. The rats were divided into four experimental groups, each consuming a diet containing 1 % kochujang in a 43-energy% high-fat diet(HFD) for 8 weeks. The TMK samples used for the study were categorized according to their capsaicin(CPS) content as follows: Low-CPS(0.5 mg%), medium-CPS(1.2 mg%), and high-CPS(1.7 mg%). In addition, factory-made kochujang (FMK; 1.1 mg% capsaicin) was also tested. The effects of kochujang were compared with the Control group(scopolamine), Positive-control(scopolamine+donepezil), and Normal-control(saline) fed HFD. Kochujang consumption reduced body weight and fat mass compared to the Control group. Compared to the Control, memory function measured using passive avoidance, water maze, and novel object recognition tests was enhanced in kochujang-fed rats, especially in the Medium-CPS group, similar to Positive-control. The Medium-CPS and Positive-control groups also exhibited inhibition of hippocampal cell death and increased cholesterol and triglyceride contents and mRNA expression of TNF-α and IL-1ß in the brain tissue compared to the Control group. Additionally, TMK elevated short-chain fatty acid, particularly, butyrate concentration in the portal vein. Scopolamine disturbed large intestine cell morphology and gut microbiota composition, and kochujang improved them. Kochujang in the medium-CPS (1.2 mg%) had a more significant impact on the gut microbiota in the interaction analysis between gut microbiota and memory function. In conclusion, kochujang, especially with medium-CPS (1.2 mg%), is a potential dietary intervention to mitigate memory impairment and promote overall cognitive health through improving eubiosis, potentially linked to the gut-brain axis in PNS-suppressed rats.

Reliability and Validity of a Tablet-Based Neuropsychological Test (the Hellocog) for Screening Dementia.

OBJECTIVE: To address the gap in timely diagnosis of dementia due to limited screening tools, we investigated the validity and reliability of the Hellocog, computerized neuropsychological test based on tablets for screening dementia. The higher the probability score on the Hellocog, the higher the likelihood of dementia. METHODS: This study included 100 patients with dementia and 100 individuals with normal cognition who were aged 60 years or older and free of other major psychiatric, neurological, or medical conditions. They administered the Hellocog on a tablet under the supervision of a neuropsychologist. To determine test-retest reliability, 20 took the Hellocog again after 4 weeks. Diagnostic performance was assessed using the receiver operator characteristics (ROC) analysis. RESULTS: The Hellocog showed adequate internal consistency (Cronbach's alpha=0.69) and good test-retest reliability (intraclass correlation coefficient=0.86, p<0.001). Participants with dementia scored higher on the Hellocog than those with normal cognition (p<0.001), confirming its high criterion validity. Strong correlations with the Mini-Mental Status Examination (MMSE) score and the total score of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery (CERAD-TS) highlight the concurrent validity of the Hellocog. The area under the ROC curve for dementia of the Hellocog was excellent (0.971) and comparable to that of the MMSE and CERAD-TS. The sensitivity and specificity for dementia were 0.945 and 0.872%, respectively, which were slightly better than those of the MMSE and CERAD-TS. CONCLUSION: Hellocog stands out as a valid and reliable tool for self-administered dementia screening, with promise for improving early detection of dementia.

Wet tissue adhesive polymeric powder hydrogels for skeletal muscle regeneration.

Volumetric muscle loss (VML) frequently results from traumatic incidents and can lead to severe functional disabilities. Hydrogels have been widely employed for VML tissue regeneration, which are unfortunately ineffective because of the lack of intimate contact with injured tissue for structural and mechanical support. Adhesive hydrogels allow for strong tissue connections for wound closure. Nevertheless, conventional adhesive hydrogels exhibit poor tissue adhesion in moist, bleeding wounds due to the hydration layer at the tissue-hydrogel interfaces, resulting in insufficient performance. In this study, we developed a novel, biocompatible, wet tissue adhesive powder hydrogel consisting of dextran-aldehyde (dex-ald) and gelatin for the regeneration of VML. This powder absorbs the interfacial tissue fluid and buffer solution on the tissue, spontaneously forms a hydrogel, and strongly adheres to the tissue via various molecular interactions, including the Schiff base reaction. In particular, the powder composition with a 1:4 ratio of dex-ald to gelatin exhibited optimal characteristics with an appropriate gelation time (258 s), strong tissue adhesion (14.5 kPa), and stability. Dex-ald/gelatin powder hydrogels presented strong adhesion to various organs and excellent hemostasis compared to other wet hydrogels and fibrin glue. A mouse VML injury model revealed that the dex-ald/gelatin powder hydrogel significantly improved muscle regeneration, reduced fibrosis, enhanced vascularization, and decreased inflammation. Consequently, our wet-adhesive powder hydrogel can serve as an effective platform for repairing various tissues, including the heart, muscle, and nerve tissues.

Risk factors for hyponatremia associated with desmopressin use.

Background: Nocturia is a urinary symptom that can significantly impact a patient's quality of life. Desmopressin is prescribed for adults with nocturia. However, desmopressin use is associated with hyponatremia. The objective of this study was to assess the rate of hyponatremia in patients prescribed desmopressin and associated risk factors. Methods: Study subjects were patients who were newly prescribed desmopressin 0.1 mg (tablet) between January 1, 2015 (the start of available data) and December 1, 2020. Factors such as patients' baseline characteristics, comorbidities, and concomitant medications were analyzed to compare risk factors for hyponatremia (≤135 mmol/dL). Results: A total of 918 adults were included in this study. The rate of hyponatremia was 4.4 % in patients with desmopressin. The hyponatremia group was older than non-hyponatremia group (71.0 vs. 61.6 years, P<0.001). The hyponatremia group had a higher prevalence of hypertension as a comorbidity. Although hypertension was more common in males than in females, the difference was not statistically significant (4.6% in male vs. 3.5% in female, P=0.65). Patients with hyponatremia were more likely to be taking angiotensin receptor blockers or thiazides than those without hyponatremia. Conclusions: Hyponatremia occurred in 4.4% of patients with desmopressin. Risk factors of hyponatremia were age, comorbidities, concurrent medication and decreased estimated glomerular filtration rate (eGFR) level. Thus, care should be taken when administering desmopressin to these patients.

Anti-Inflammatory Effect of Korean Soybean Sauce (Ganjang) on Mice with Induced Colitis.

Inflammatory bowel disease (IBD), characterized by chronic inflammation of the gut, is caused by several factors. Among these factors, microbial factors are correlated with the gut microbiota, which produces short-chain fatty acids (SCFAs) via anaerobic fermentation. Fermented foods are known to regulate the gut microbiota composition. Ganjang (GJ), a traditional fermented Korean soy sauce consumed worldwide, has been shown to exhibit antioxidant, anticancer, anti-colitis, and antihypertensive activities. However, its effects on the gut microbiota remain unknown. In the present study, we aimed to compare the anti-inflammatory effects of GJ manufactured using different methods and investigate its effect on SCFA production in the gut. To evaluate the anti-inflammatory effects of GJ in the gut, we performed animal experiments using a mouse model of dextran sulfate sodium (DSS)-induced colitis. All GJ samples attenuated DSS-induced colitis symptoms, including reduced colonic length, by suppressing the expression of inflammatory cytokines. In addition, GJ administration modulated SCFA production in the DSS-induced colitis model. Overall, GJ exerted anti-inflammatory effects by reducing DSS-induced symptoms via regulation of inflammation and modulation of SCFA levels in a DSS-induced colitis model. Thus, GJ is a promising fermented food with the potential to prevent IBD.

Korean urobiome platform (KUROM) study for acute uncomplicated sporadic versus recurrent cystitis in women: Clinical significance.

PURPOSE: To investigate urine microbiome differences among healthy women, women with recurrent uncomplicated cystitis (rUC), and those with sporadic/single uncomplicated cystitis (sUC) to challenge traditional beliefs about origins of these infections. MATERIALS AND METHODS: Patients who underwent both conventional urine culture and next-generation sequencing (NGS) of urine were retrospectively reviewed. Symptom-free women with normal urinalysis results as a control group were also studied. Samples were collected via transurethral catheterization. RESULTS: In the control group, urine microbiome was detected on NGS in 83.3%, with Lactobacillus and Prevotella being the most abundant genera. The sensitivity of urine NGS was significantly higher than that of conventional urine culture in both the sUC group (91.2% vs. 32.4%) and the rUC group (82.4% vs. 16.4%). In urine NGS results, Enterobacterales, Prevotella, and Escherichia/Shigella were additionally found in the sUC group, while the recurrent urinary tract infection (rUTI)/rUC group exhibited the presence of Lactobacillus, Prevotella, Enterobacterales, Escherichia/Shigella, and Propionibacterium. Moreover, distinct patterns of urine NGS were observed based on menopausal status and ingestion of antibiotics or probiotics prior to NGS test sampling. CONCLUSIONS: Urine microbiomes in control, sUC, and rUTI/rUC groups exhibited distinct characteristics. Notably, sUC and rUC might represent entirely separate pathological processes, given their distinct urine microbiomes. Consequently, the use of urine NGS might be essential to enhancing sensitivity compared to conventional urine culture in both sUC and rUTI/rUC groups.

Teal-light absorbing cyanobacterial phytochrome superfamily provides insights into the diverse mechanisms of spectral tuning and facilitates the engineering of photoreceptors for optogenetic tools.

Cyanobacteriochromes (CBCRs) are distinctive tetrapyrrole (bilin)-binding photoreceptors exclusively found in cyanobacteria. Unlike canonical phytochromes, CBCRs require only a GAF (cGMP-phosphodiesterase/adenylate cyclase/FhlA) domain for autolyase activity to form a bilin adduct via a Cys residue and cis-trans photoisomerization. Apart from the canonical Cys, which attaches covalently to C31 in the A-ring of the bilin, some GAF domains of CBCRs contain a second-Cys in the Asp-Xaa-Cys-Phe (DXCF) motif, responsible for isomerization of phycocyanobilin (PCB) to phycoviolobilin (PVB) and/or for the formation of a reversible 2nd thioether linkage to the C10. Unlike green/teal-absorbing GAF proteins lacking ligation activity, the second-Cys in another teal-absorbing lineage (DXCF blue/teal group) exhibits both isomerization and ligation activity due to the presence of the Tyr instead of His next to the canonical Cys. Herein, we discovered an atypical CBCR GAF protein, Tpl7205g1, belonging to the DXCF blue/teal group, but having His instead of Tyr next to the first-Cys. Consistent with its subfamily, the second-Cys of Tpl7205g1 did not form a thioether linkage at C10 of PCB, showing only isomerization activity. Instead of forming 2nd thioether linkage, this novel GAF protein exhibits a pH-dependent photocycle between protonated 15Z and deprotonated 15E. Site-directed mutagenesis to the GAF scaffolds revealed its combined characteristics, including properties of teal-DXCF CBCRs and red/green-absorbing CBCRs (XRG CBCRs), suggesting itself as the evolutionary bridge between the two CBCR groups. Our study thus sheds light on the expanded spectral tuning characteristics of teal-light absorbing CBCRs and enhances feasibility of engineering these photoreceptors.

[Analysis of the Adequacy of Nurse Staffing Level through the Estimation of Nursing Activity Hours and Implementation of Focus Group Interviews in a Tertiary Hospital: Using a Mixed-Method Design].

PURPOSE: This study aimed to examine the adequacy of current nurse staffing levels by identifying nursing activities and workload. METHODS: The study used a mixed-method design. A nursing activity survey was conducted using the work sampling method over 2 working days with 119 general ward nurses. A focus group interview was conducted with 12 nurses. Quantitative and qualitative data were analyzed using SPSS 20.0 and content analysis, respectively. RESULTS: The most amount of time was spent on medication (in direct nursing) and electronic medical record documentation (in indirect nursing). The appropriate nurse-to-patient ratio is 1:7.7 for the day shift, 1:9.0 for the evening shift, and 1:11.9 for the night shift. However, the current nurse-to-patient ratio is 1:9.4, 1:11.0, and 1:13.8 for the day, evening, and night shifts, respectively. Therefore, the current nurse staffing level is insufficient for the workload. In the focus group interview, the main reasons cited for being unable to complete tasks within working hours were communication and coordination, and the nursing electronic medical record. The essential nursing activities of basic nursing and emotional support were overlooked owing to a heavy workload. Therefore, an adequate nurse staffing level should be higher than the measured quantitative workload. CONCLUSION: These results suggest the general wards of tertiary hospitals should evaluate the adequacy of their current nurse staffing and allocate sufficient nurses to improve patient safety and nursing care quality.

Fermented Yak-Kong using Bifidobacterium animalis derived from Korean infant intestine effectively relieves muscle atrophy in an aging mouse model.

Yak-Kong (YK) is a small black soybean widely cultivated in Korea. It is considered to have excellent health functionality, as it has been reported to have better antioxidant efficacy than conventional black or yellow soybeans. Since YK has been described as good for the muscle health of the elderly in old oriental medicine books, this study sought to investigate the effect of fermented YK with Bifidobacterium animalis subsp. lactis LDTM 8102 (FYK) on muscle atrophy. In C2C12 mouse myoblasts, FYK elevated the expression of MyoD, total MHC, phosphorylated AKT, and PGC1α. In addition, two kinds of in vivo studies were conducted using both an induced and normal aging mouse model. The behavioral test results showed that in the induced aging mouse model, FYK intake alleviated age-related muscle weakness and loss of exercise performance. In addition, FYK alleviated muscle mass decrease and improved the expression of biomarkers including total MHC, myf6, phosphorylated AKT, PGC1α, and Tfam, which are related to myoblast differentiation, muscle protein synthesis, and mitochondrial generation in the muscle. In the normal aging model, FYK consumption did not increase muscle mass, but did upregulate the expression levels of biomarkers related to myoblast differentiation, muscle hypertrophy, and muscle function. Furthermore, it mitigated age-related declines in skeletal muscle force production and functional limitation by enhancing exercise performance and grip strength. Taken together, the results suggest that FYK has the potential to be a new functional food material that can alleviate the loss of muscle mass and strength caused by aging and prevent sarcopenia.

A 3D printed esophageal atresia-tracheoesophageal fistula thorascopy simulator for young surgeons.

We developed a 3D-printed thoracoscopic surgery simulator for esophageal atresia with tracheoesophageal fistula (EA-TEF) and assessed its effectiveness in educating young pediatric surgeons. Prototype production and modifications were repeated five times before producing the 3-D printed final product based on a patient's preoperative chest computed tomography. A 24-item survey was used to rate the simulator, adapted from a previous report, with 16 young surgeons with an average of 6.2 years of experience in pediatric surgery for validation. Reusable parts of the thoracic cage were printed to combine with replaceable parts. Each structure was fabricated using diverse printing materials, and subsequently affixed to a frame. In evaluating the simulator, the scores for each factor were 4.33, 4.33, 4.27, 4.31, 4.63, and 4.75 out of 5, respectively, with the highest ratings in value and relevance. The global rating was 3.38 out of 4, with ten stating that it could be used with slight improvements. The most common comment from participants was that the esophageal anastomosis was close to the actual EA-TEF surgery. The 3D-printed thoracoscopic EA-TEF surgery simulator was developed and reflected the actual surgical environment. It could become an effective method of training young pediatric surgeons.

Cytosine Deaminase-Overexpressing hTERT-Immortalized Human Adipose Stem Cells Enhance the Inhibitory Effects of Fluorocytosine on Tumor Growth in Castration Resistant Prostate Cancer.

A promising de novo approach for the treatment of Castration-resistant prostate cancer (CRPC) exploits cell-mediated enzyme prodrug therapy comprising cytosine deaminase (CD) and fluorouracil (5-FC). The aim of this study was to determine the potential of bacterial CD-overexpressing hTERT-immortalized human adipose stem cells (hTERT-ADSC.CD) to suppress CRPC. A lentiviral vector encoding a bacterial CD gene was used to transfect and to generate the hTERT-ADSC.CD line. The ability of the cells to migrate selectively towards malignant cells was investigated in vitro. PC3 and hTERT-ADSC.CD cells were co-cultured. hTERT-ADSC.CD and 1 × 106 PC3 cells were administered to nude mice via intracardiac and subcutaneous injections, respectively, and 5-FC was given for 14 days. hTERT-ADSC.CD were successfully engineered. Enhanced in vitro hTERT-ADSC.CD cytotoxicity and suicide effect were evident following administration of 5 µM 5-FC. hTERT-ADSC.CD, together with 5-FC, augmented the numbers of PC3 cells undergoing apoptosis. In comparison to controls administered hTERT-ADSC.CD monotherapy, hTERT-ADSC.CD in combination with 5-FC demonstrated a greater suppressive effect on tumor. In CPRC-bearing mice, tumor suppression was enhanced by the combination of CD-overexpressing ADSC and the prodrug 5-FC. Stem cells exhibiting CD gene expression are a potential novel approach to treatment for CRPC.