Association between Physical Function, Mental Function and Frailty in Community-Dwelling Older Adults: A Cross-Sectional Study.

Background: This study examines the relationship between physical and mental function and frailty, independently and in conjunction with polypharmacy, among older adults. Methods: This cross-sectional study consisted of 368 participants aged ≥60 years. The participants were categorized into either robust or frail groups using Fried's frailty phenotype. Physical functions were assessed using grip strength, gait speed, Timed Up and Go (TUG), the Five Chair Sit to Stand Test (FCSST) and the Six-Minute Walk Test (SMWT). Mental functions were assessed using cognitive function and depression. Cognitive function was measured using Mini-Mental State Examination (MMSE). Depression was assessed with the Korean version of the Short Geriatric Depression Scale (SGDS). Results: The mean age of study population was 75.4 years. In this population, we identified 78.8% (n = 290) robust participants and 21.2% (n = 78) frail participants. The study examined frailty status (frail vs. non-frail) and frailty with and without polypharmacy using multivariate logistic regressions, adjusting for age and sex. In the logistic regression model estimating the risk of frailty, after adjustments for age, sex, BMI, and number of medications, individuals with low SMWT showed a significantly increased risk of frailty, with an odds ratio (OR) of 8.66 and a 95% confidence interval (CI) of 4.55-16.48. Additionally, global cognitive function was associated with a 1.97-fold increase in frailty risk (95% CI: 1.02-3.67). Moreover, in models adjusted for age, sex, and BMI to assess frailty risk linked to polypharmacy, the TUG, SMWT, and SGDS all showed increased risks, with ORs of 3.65 (95% CI: 1.07-12.47), 5.06 (95% CI: 1.40-18.32), and 5.71 (95% CI: 1.79-18.18), respectively. Conclusions: Physical function (SMWT, FCSST, TUG) and mental function (depression, cognition) were associated with frailty. By comprehensively examining these factors, we will gain valuable insights into frailty and enable more precise strategies for intervention and prevention.

Clinical and Economic Outcomes of Patients with Osteoporosis Undergoing Spine Fusion Surgery in Japan.

Introduction: Spinal fusion surgery with instrumentation is a treatment of choice for many spinal disorders; however, there is little data related to factors associated with early and late outcomes, especially among patients with poor bone quality (e.g., osteoporosis). We conducted this study to characterize the epidemiology and outcomes of patients undergoing spinal fusion surgery with instrumentation in Japan, especially in patients with poor bone quality and those needing additional fixation methods. Methods: This retrospective observational study used real-world health insurance claims data from the Japanese Medical Data Vision. Adult patients undergoing an index spinal fusion procedure from April 1, 2010, to September 30, 2017, with procedural details, length of stay (LOS), total in-hospital costs, spine-related reoperation, all-cause readmission, and postoperative complications recorded. Data were summarized descriptively overall, by osteoporosis status, and additional fixation method used, and were analyzed in bivariate analyses. Multivariate logistic and linear regressions were used to explore associations between covariates and variables of interest. Results: A total of 22,932 patients (mean age, 67.3 years; 51.2% male) met the study criteria and were included. A total of 5,288 (23.0%) patients had osteoporosis, and 2,507 (10.9%) needed additional fixation methods; these patients were older, more frequently female, and had higher Elixhauser comorbidity index scores. Osteoporosis and additional fixation use were also associated with longer LOS, higher hospital costs, and higher rates of complications. Conclusions: Patients with osteoporosis and those needing additional fixation methods have a higher risk for procedural and postoperative complications, reoperation, longer LOS, and higher total hospital costs.

Long-term impact of weight loss in people with class II obesity on the overall burden of disease: Evidence from the National Health Screening Cohort in Korea.

BACKGROUND: Obesity is known to increase overall disease burden but does obesity management actually help reduce disease burden? OBJECTIVES: To investigate the effects of weight loss on disease burden in people with obesity using the National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) in Korea. SETTING: Pure longitudinal observational study using Nationwide cohort database. METHODS: Out of 514,866 NHIS-HEALS cohort, participants with class II obesity in Asia-Pacific region (30 ≤ body mass index [BMI] < 35) who underwent health check-up provided by NHIS during 2003-2004 (index date) were included. All final participants continued to receive a total of 5 biennial health check-ups over the next 10 years without missing. A group-based trajectory model (GBTM) was used to categorize subjects based on 10-year BMI change patterns. The changes of co-morbidities, healthcare resource utilization, and medical cost were analyzed. RESULTS: The final study subjects (9857) were categorized into 3 trajectory clusters based on the pattern of BMI (kg/m2) change: maintenance (57.35%) with an average change of -.02 ± .06, loss (38.65%) with -.04 ± .08, and substantial loss (4.0%) with -.10 ± .18. The annual increases in the number of co-morbidities per subject in each cluster were .18, .18, and .16 (all P < .001), respectively. The increase of healthcare resource utilization over time was lowest for the substantial loss compared to maintenance and loss. With each passing year, the average annual total healthcare cost increased by ₩21,200 ($16.48, P = .034) and ₩10,500 ($8.16, P = .498) in the maintenance and loss, respectively, but decreased by ₩62,500 ($48.59, P = .032) in the substantial loss. CONCLUSIONS: Weight loss in people with obesity was associated with a reduced burden of disease, as evidenced by lower co-morbidity, healthcare resource utilization rate, and decreased medical costs. This study highlights the potential positive long-term impact on Korean society when actively managing weight in individuals with obesity.

Nonlinear Associations between Physical Function, Physical Activity, Sleep, and Depressive Symptoms in Older Adults.

The purpose of this study is to examine how physical function, physical activity, and sleep are related to depressive symptoms in older adults using a nonlinear model. The participants were 283 Korean older adults aged 65 and older who met the study inclusion criteria. Depressive symptoms were measured using the shortened version of the Geriatric Depression Scale in Korean (SGDS-K). Physical activity and sleep time were objectively quantified by continuously monitoring participants over 20 consecutive days using a triaxial accelerometer. Physical function was evaluated using five distinct measurements: grip strength, gait speed, the Timed Up and Go Test (TUG), the Six-Minute Walk Test (SMWT), and the Five Times Sit to Stand Test (FTSST). The SMWT, gait speed, and MVPA exhibited a nonlinear relationship with depressive symptoms. However, other physical functions showed linear relationships. Also, sleep time showed a U-shaped trend starting at approximately 390 min. After adjusting for age, sex, drinking, and smoking in the logistic regression model, SMWT, MVPA, and sleep time were significantly associated with depressive symptoms. The outcomes highlight the importance of considering multiple factors in understanding depression among the elderly, particularly the intricate interactions between these elements and biological rhythms.

Disseminated Nontuberculous Mycobacterial Infection in a Tertiary Referral Hospital in South Korea: A Retrospective Observational Study.

PURPOSE: Disseminated nontuberculous mycobacterial (D-NTM) disease occurs primarily in immunocompromised hosts. However, these cases have rarely been reported in South Korea. This study aimed to describe the clinical manifestations, disease course, and underlying immune deficiencies of patients with D-NTM disease. MATERIALS AND METHODS: We retrospectively reviewed the cases of D-NTM disease from January 2005 to December 2019 at a tertiary referral hospital in South Korea. D-NTM disease was defined as a bloodstream infection or infection of two or more non-contiguous body organs with species identification. RESULTS: Of the 53342 mycobacterial samples from 23338 patients, extrapulmonary NTM was detected in 104 patients, and 3 (2.9%) were diagnosed with D-NTM disease. Mycobacterium avium was isolated from two patients, while M. abscessus subspecies abscessus was identified in one. The patients were aged between 18 and 25 years, and two patients were male. All patients were immunocompromised - one received lung transplantation, one was diagnosed with anhidrotic ectodermal dysplasia with T-cell immune deficiency, and one had monocytopenia and mycobacterial infection syndrome associated with GATA2 mutations. All patients underwent a standard macrolide-based regimen for >5 months, and their sputum tested negative. However, one patient died of bacterial sepsis, while the other two survived. CONCLUSION: D-NTM disease is rare in a tertiary referral center in South Korea. They occur primarily in immunocompromised patients at a relatively young age. Careful investigation of the underlying immune status is required when treating patients with D-NTM disease.

Systematic Literature Review and Meta-Analysis on the Clinical Outcomes of Spine Surgeries in Patients with Concurrent Osteoporosis.

Background: Osteoporosis is common among elderly patients and can result in vertebral fractures requiring surgical treatment. This study assessed clinical outcomes associated with spinal surgery in patients with osteoporosis/osteopenia with an additional focus on Asian patients. Methods: A PRISMA-compliant systematic review and meta-analysis were conducted using the PubMed and ProQuest databases to identify articles published up to May 27, 2021, that included outcomes for patients with osteoporosis or osteopenia undergoing spinal surgery. Statistical analysis was conducted comparing rates of proximal junctional kyphosis (PJK)/proximal junctional failure (PJF), implant loosening, and revision surgery. A qualitative summary of Asian studies was also conducted. Results: A total of 16 studies comprising 133,086 patients were included; among the 15 studies reporting rates of osteoporosis/osteopenia, 12.1% (16,127/132,302) of patients overall and 38.0% (106/279) of Asian patients (n=4 studies) had osteoporosis/osteopenia. The risks of PJK/PJF (relative risk [RR]=1.89; 95% confidence interval [CI]=1.22-2.92, p=0.004), screw loosening (RR=2.59; 95% CI=1.67-4.01, p<0.0001), and revision surgery (RR=1.65; 95% CI=1.13-2.42, p=0.010) were higher in patients with poor bone quality compared with those with healthy bone. In the qualitative review of Asian studies, all studies found that osteoporosis increased the risk of complications and/or revision for spinal surgery patients. Conclusions: This systematic literature review and meta-analysis indicate that spinal surgery patients with compromised bone quality have more complications and higher healthcare utilization than those with normal bone quality. To our knowledge, this is the first study to focus on the pathophysiology and disease burden among Asian patients. Given the high rate of poor bone quality in this aging population, additional high-quality Asian studies, with uniform definitions and data reporting, are needed.

Development of a method for analysis and risk assessment of residual pesticides in ginseng using liquid and gas chromatography-tandem mass spectrometry.

In this study, we developed a method for detecting 335 pesticides in ginseng using liquid chromatography quadrupole mass spectrometry (LC-MS/MS) and gas chromatography quadrupole mass spectrometry (GC-MS/MS). Additionally, the linearity, sensitivity, selectivity, accuracy, and precision of the method was validated. The limits of detection (LOD) and limits of quantification (LOQ) for the instrument used in these experiments was 0.1-5.8 µg/kg and 0.3-17.5 µg/kg, respectively. The average recovery was 71.6-113.4%. From 2016 to 2019, 467 ginseng samples were analyzed, of which 304 samples detected pesticide residues, but most of them were below the standard. It can be observed that the hazard quotient (HQ) of ginseng for detected pesticides was less than 1, thus implying that the risk was low. Hence, in this study, we developed a specific, reliable, and suitable method for a fast and simultaneous analysis of 335 pesticides in ginseng.

Long-term radiofrequency electromagnetic fields exposure attenuates cognitive dysfunction in 5×FAD mice by regulating microglial function.

We have previously found that long-term effects of exposure to radiofrequency electromagnetic fields in 5×FAD mice with severe late-stage Alzheimer's disease reduced both amyloid-ß deposition and glial activation, including microglia. To examine whether this therapeutic effect is due to the regulation of activated microglia, we analyzed microglial gene expression profiles and the existence of microglia in the brain in this study. 5×FAD mice at the age of 1.5 months were assigned to sham- and radiofrequency electromagnetic fields-exposed groups and then animals were exposed to 1950 MHz radiofrequency electromagnetic fields at a specific absorption rate of 5 W/kg for 2 hours/day and 5 days/week for 6 months. We conducted behavioral tests including the object recognition and Y-maze tests and molecular and histopathological analysis of amyloid precursor protein/amyloid-beta metabolism in brain tissue. We confirmed that radiofrequency electromagnetic field exposure for 6 months ameliorated cognitive impairment and amyloid-ß deposition. The expression levels of Iba1 (pan-microglial marker) and colony-stimulating factor 1 receptor (CSF1R; regulates microglial proliferation) in the hippocampus in 5×FAD mice treated with radiofrequency electromagnetic fields were significantly reduced compared with those of the sham-exposed group. Subsequently, we analyzed the expression levels of genes related to microgliosis and microglial function in the radiofrequency electromagnetic fields-exposed group compared to those of a CSF1R inhibitor (PLX3397)-treated group. Both radiofrequency electromagnetic fields and PLX3397 suppressed the levels of genes related to microgliosis (Csf1r, CD68, and Ccl6) and pro-inflammatory cytokine interleukin-1ß. Notably, the expression levels of genes related to microglial function, including Trem2, Fcgr1a, Ctss, and Spi1, were decreased after long-term radiofrequency electromagnetic field exposure, which was also observed in response to microglial suppression by PLX3397. These results showed that radiofrequency electromagnetic fields ameliorated amyloid-ß pathology and cognitive impairment by suppressing amyloid-ß deposition-induced microgliosis and their key regulator, CSF1R.

Comparative Analysis of Protein Folding Stability-Based Profiling Methods for Characterization of Biological Phenotypes.

Recently, a new suite of mass spectrometry-based proteomic methods has been developed that enables evaluation of protein folding stability on the proteomic scale. These methods utilize chemical and thermal denaturation approaches (SPROX and TPP, respectively) as well as proteolysis strategies (DARTS, LiP, and PP) to assess protein folding stability. The analytical capabilities of these technique have been well-established for protein target discovery applications. However, less is known about the relative advantages and disadvantages of using these different strategies to characterize biological phenotypes. Reported here is a comparative study of SPROX, TPP, LiP, and conventional protein expression level measurements using both a mouse model of aging and a mammalian cell culture model of breast cancer. Analyses on proteins in brain tissue cell lysates derived from 1- and 18-month-old mice (n = 4-5 at each time point) and on proteins in cell lysates derived from the MCF-7 and MCF-10A cell lines revealed a majority of the differentially stabilized protein hits in each phenotype analysis had unchanged expression levels. In both phenotype analyses, TPP generated the largest number and fraction of differentially stabilized protein hits. Only a quarter of all the protein hits identified in each phenotype analysis had a differential stability that was detected using multiple techniques. This work also reports the first peptide-level analysis of TPP data, which was required for the correct interpretation of the phenotype analyses performed here. Studies on selected protein stability hits also uncovered phenotype-related functional changes.

Identification of TRPC6 as a Novel Diagnostic Biomarker of PM-Induced Chronic Obstructive Pulmonary Disease Using Machine Learning Models.

Chronic obstructive pulmonary disease (COPD) was the third most prevalent cause of mortality worldwide in 2010; it results from a progressive and fatal deterioration of lung function because of cigarette smoking and particulate matter (PM). Therefore, it is important to identify molecular biomarkers that can diagnose the COPD phenotype to plan therapeutic efficacy. To identify potential novel biomarkers of COPD, we first obtained COPD and the normal lung tissue gene expression dataset GSE151052 from the NCBI Gene Expression Omnibus (GEO). A total of 250 differentially expressed genes (DEGs) were investigated and analyzed using GEO2R, gene ontology (GO) functional annotation, and Kyoto Encyclopedia of Genes and Genomes (KEGG) identification. The GEO2R analysis revealed that TRPC6 was the sixth most highly expressed gene in patients with COPD. The GO analysis indicated that the upregulated DEGs were mainly concentrated in the plasma membrane, transcription, and DNA binding. The KEGG pathway analysis indicated that the upregulated DEGs were mainly involved in pathways related to cancer and axon guidance. TRPC6, one of the most abundant genes among the top 10 differentially expressed total RNAs (fold change ≥ 1.5) between the COPD and normal groups, was selected as a novel COPD biomarker based on the results of the GEO dataset and analysis using machine learning models. The upregulation of TRPC6 was verified in PM-stimulated RAW264.7 cells, which mimicked COPD conditions, compared to untreated RAW264.7 cells by a quantitative reverse transcription polymerase chain reaction. In conclusion, our study suggests that TRPC6 can be regarded as a potential novel biomarker for COPD pathogenesis.

Education increases COVID-19 vaccine uptake among people in Canadian federal prisons in a prospective randomized controlled trial: The EDUCATE study.

Education is key to behavioural adoption and acceptability of health interventions. We evaluated the impact of an educational intervention administered 1:1 to individuals incarcerated in four Canadian federal prisons on COVID-19 vaccine uptake. Eligible individuals (those who had refused all COVID-19 vaccines) were randomized 2:1 to receive the educational intervention or not (control group); those who received the intervention completed questionnaires assessing COVID-19 vaccine-related knowledge, attitudes, and beliefs pre- and post-educational intervention. The primary and secondary outcome measures were COVID-19 vaccine uptake and vaccine confidence, respectively. Between May 3 and September 9, 2022, 202 participants were randomized to receive the intervention, of whom 127 (63 %) agreed to participate. Participants who were randomized to the intervention had higher COVID-19 vaccine uptake vs. the control group (5 % vs 1 %, p = 0.046). COVID-19 vaccine-related knowledge, attitudes, and beliefs improved post-intervention. Education increases COVID-19 vaccine uptake and confidence among people in Canadian federal correctional facilities.

Phenolic from apple blossom "Hongro" inhibits the expression of proteins related to melanogenesis in B16F10 melanoma cells.

This study aimed to assess apple blossom extracts as potential natural whitening agents due to their ability to inhibit melanogenesis. Ethanol extracts of apple blossom (ABE) were assessed for biological activity in the B16F10 mouse melanoma cell line. ABE toxicity was assessed by thiazolyl blue tetrazolium bromide (MTT) assay. Levels of melanogenic enzyme expression in response to ABE supplementation were assessed by western blotting. Also assessed purified kaempferol, one of the phenolic compounds extracted from apple blossom, was evaluated using western blot analysis. The expression levels of cellular tyrosinase, microphthalmia-associated transcription factor (MITF), tyrosinase-related protein (TRP)-1, and TRP-2 proteins related to melanogenesis decreased in a dose-dependent manner with ABE treatment of cells. Using nuclear magnetic resonance, we identified kaempferol in the ABE. Treatment of cells with purified kaempferol decreased the expression levels of tyrosinase and the MITF protein to a similar degree as that observed with ABE treatment. This suggests that the efficacy of melanogenesis-related inhibition demonstrated by ABE was due to kaempferol. ABE has an inhibitive effect on melanogenic enzymes and potentially can be applied to functional foods and cosmetics having a whitening effect as a natural material.

Twelve-Year Trajectory of Disease Burden and Mortality by Obesity Level in Korea: Analysis of the National Health Insurance Service Database.

INTRODUCTION: Despite increases in obesity prevalence, awareness of obesity as a disease requiring active treatment remains lacking in Korea. We investigated differences in medical problems and expenditures and mortality across obesity categories using 12-year data from the National Health Insurance Service. MATERIALS AND METHODS: Individuals aged 40-79 years who underwent medical examinations during 2003-2004 (n = 415,201) were divided based on Asian body mass index (kg/m2) criteria: normal weight (18.5 to < 23.0, 36.4%), overweight (23.0 to < 25.0, 28.3%), obesity (25.0 to < 30.0, 32.5%), and severe obesity (≥ 30.0, 2.8%). Medical problems and expenditures were fitted to linear mixed models. Mortality was analyzed via Cox proportional-hazards model. RESULTS: More severe obesity was associated with a higher rate of medical problems, relative to normal weight: coefficient = 0.31 (95% confidence interval [CI], 0.30-0.32) for overweight, 0.61 (0.60-0.61) for obesity, and 1.07 (1.04-1.09) for severe obesity. A similar association was observed for medical expenditure: coefficient = 8.85 (95%CI, 6.80-10.89) for overweight, 20.04 (18.07-22.01) for obesity, and 48.76 (43.66-53.86) for severe obesity. Relative to overweight participants, those with normal weight and severe obesity exhibited a higher mortality risk (hazard ratio [HR] 1.21 [95%CI, 1.18-1.25] for normal; 1.27 [1.19-1.36] for severe obesity). In age-specific analyses, mortality risk was the highest for participants with severe obesity, aged < 60 years (HR, 1.58 [95%CI, 1.41-1.77]). CONCLUSION: Disease burden including medical problems and expenditure, and mortality in middle-aged adults, increased proportionally to the degrees of obesity. Health policies and medical systems aimed at reducing the burden of obesity may help reduce the burden of disease on society.

Clinical characteristics and outcomes of invasive and non-invasive fusariosis in South Korea.

BACKGROUND: Invasive fusariosis mainly affects immunocompromised patients including haematopoietic stem cell transplant recipients and those with haematologic malignancy. There are limited studies on invasive fusariosis in the Asia-Pacific region. OBJECTIVE: To describe the clinical characteristics and outcomes of invasive and non-invasive fusariosis in South Korea. PATIENTS/METHODS: From 2005 to 2020, patients with fusariosis who met the revised European Organisation for Research and Treatment of Cancer and the Mycoses Study Group criteria for the definition of proven or probable invasive fusariosis, and those with non-invasive fusariosis were retrospectively reviewed in a tertiary medical centre in Seoul, South Korea. RESULTS: Overall, 26 and 75 patients had invasive and non-invasive fusariosis, respectively. Patients with invasive fusariosis commonly had haematologic malignancy (62%), were solid organ transplant recipients (23%), and had a history of immunosuppressant usage (81%). In non-invasive fusariosis, diabetes mellitus (27%) and solid cancer (20%) were common underlying conditions. Disseminated fusariosis (54%) and invasive pulmonary disease (23%) were the most common clinical manifestations of invasive fusariosis; skin infection (48%) and keratitis (27%) were the most common manifestations of non-invasive fusariosis. Twenty-eight-day and in-hospital mortalities were high in invasive fusariosis (40% and 52%, respectively). In multivariate analysis, invasive fusariosis (adjusted odds ratio, 9.6; 95% confidence interval 1.3-70.8; p = .03) was an independent risk factor for 28-day mortality. CONCLUSIONS: Patients with invasive fusariosis were frequently immunocompromised, and more than half had disseminated fusariosis. Invasive fusariosis was associated with poor prognosis.

Feasibility of facial nerve monitoring using adhesive surface electrodes during parotidectomy: a comparative study with needle electrodes.

PURPOSE: Electrophysiological monitoring of the facial nerve during parotidectomy has been reported as an adjunctive method to prevent facial nerve injury. Classically, a needle electrode is used to obtain electromyographic (EMG) signals from facial muscles during facial nerve monitoring (FNM) of parotid surgery, likewise adhesive surface electrodes. This study aimed to investigate the feasibility of performing FNM with surface electrodes during parotid surgery and to compare EMG values with needle electrodes. METHODS: Thirty patients who underwent parotidectomy under FNM using adhesive surface and needle electrodes were included. Two pairs of adhesive surface electrodes and needle electrodes were used for FNM during parotid surgery. Mean amplitudes were collected after electrical facial nerve stimulation at 1 mA after specimen removal. RESULTS: The mean amplitude of the adhesive surface electrodes was 226.50 ± 118.44 µV (orbicularis oculi muscle) and 469.6 ± 306.06 µV (orbicularis oris muscle), respectively. The mean amplitude of the needle electrodes was 449.85 ± 248.10 µV (orbicularis oculi muscle) and 654.66 ± 395.71 µV (orbicularis oris muscle), respectively. The mean amplitude of the orbicularis oris muscle was significantly greater than that of the orbicularis oculi. The amplitude values measured in the orbicularis oculi muscle showed significant differences between the needle and skin electrodes. CONCLUSIONS: Facial nerve monitoring (FNM) using adhesive surface electrodes is feasible in parotid surgery. Although the mean amplitude value of the surface electrode was relatively lower than that of the needle electrode, the surface electrode is considered a feasible and safe EMG recording device for FNM in parotid surgery.

Current Uses of Mushrooms in Cancer Treatment and Their Anticancer Mechanisms.

Cancer is the leading cause of mortality worldwide. Various chemotherapeutic drugs have been extensively used for cancer treatment. However, current anticancer drugs cause severe side effects and induce resistance. Therefore, the development of novel and effective anticancer agents with minimal or no side effects is important. Notably, natural compounds have been highlighted as anticancer drugs. Among them, many researchers have focused on mushrooms that have biological activities, including antitumor activity. The aim of this review is to discuss the anticancer potential of different mushrooms and the underlying molecular mechanisms. We provide information regarding the current clinical status and possible modes of molecular actions of various mushrooms and mushroom-derived compounds. This review will help researchers and clinicians in designing evidence-based preclinical and clinical studies to test the anticancer potential of mushrooms and their active compounds in different types of cancers.

Amelioration of pathologic α-synuclein-induced Parkinson's disease by irisin.

Physical activity provides clinical benefit in Parkinson's disease (PD). Irisin is an exercise-induced polypeptide secreted by skeletal muscle that crosses the blood-brain barrier and mediates certain effects of exercise. Here, we show that irisin prevents pathologic α-synuclein (α-syn)-induced neurodegeneration in the α-syn preformed fibril (PFF) mouse model of sporadic PD. Intravenous delivery of irisin via viral vectors following the stereotaxic intrastriatal injection of α-syn PFF cause a reduction in the formation of pathologic α-syn and prevented the loss of dopamine neurons and lowering of striatal dopamine. Irisin also substantially reduced the α-syn PFF-induced motor deficits as assessed behaviorally by the pole and grip strength test. Recombinant sustained irisin treatment of primary cortical neurons attenuated α-syn PFF toxicity by reducing the formation of phosphorylated serine 129 of α-syn and neuronal cell death. Tandem mass spectrometry and biochemical analysis revealed that irisin reduced pathologic α-syn by enhancing endolysosomal degradation of pathologic α-syn. Our findings highlight the potential for therapeutic disease modification of irisin in PD.

Cannabidiol Regulates PPARγ-Dependent Vesicle Formation as well as Cell Death in A549 Human Lung Cancer Cells.

Extracts of phytocannabinoids from Cannabis sativa have been studied for therapeutic purposes. Although nonpsychoactive CBD has been studied as a promising anticancer drug because it induces apoptosis in many cancer cells, it is also known to induce several physiological changes. In this study, we clarify the functional role it plays in the morphological characteristics of intracellular vesicle formation as well as apoptosis in A549 human lung cancer cells. CBD treatment shows growth inhibition at concentrations above 20 µM, but FACS analysis shows low efficacy in terms of cell death. Microscopic observations suggest that multiple vesicles were detected in the cytoplasmic region of CBD-treated A549 cells. CBD treatment upregulates apoptosis-related proteins, such as p53, PARP, RIP1, RIP3, Atg12, and Beclin, indicating that CBD regulates several types of cell death. CBD treatment also induced E-cadherin, PPARγ, clathrin, ß-adaptin, and Tsg101, also known to be cellular-differentiation inducers or vesicle-formation components. Treatment combining CBD with GW9662, a PPARγ inhibitor, reduced CBD-induced cytoplasmic vesicle formation. This indicates that PPARγ regulates the vesicle-formation mechanism. However, CBD-treated E-cad KO clones did not show this regulatory mechanism. These results elucidate the pharmacological and molecular networks associated with CBD in PPARγ-dependent vesicle formation and the induction of apoptosis.

Patulous eustachian tube after balloon eustachian tuboplasty in a post-radiation patient.

BACKGROUND: Balloon eustachian tuboplasty (BET) is a minimally invasive surgical treatment that is effective and safe for obstructive eustachian tube dysfunction. However, BET complications include excessive widening of the eustachian tube, causing a patulous eustachian tube (PET). Herein, we report a case of PET following BET in a patient who underwent radiation therapy and reviewed the literature on considerations for reducing complications after BET. CASE PRESENTATION: A 63-year-old woman complained of bilateral ear fullness after concurrent chemoradiation therapy for nasopharyngeal lymphoma. BET was performed on the left side because the left-sided serous otitis media persisted. A left-sided PET was performed two weeks after the BET, along with eustachian tube silicone plug insertion on the left side. The patient became asymptomatic immediately after the surgery, with no recurrence reported after a 12-month follow-up period. CONCLUSIONS: To our knowledge, there has been no report of PET following BET in a post-radiation patient, and it was successfully treated via ET silicone plug insertion.

Risk factors and economic burden of postoperative anastomotic leakage related events in patients who underwent surgeries for colorectal cancer.

BACKGROUND: Nationwide research about the clinical and economic burden caused by anastomotic leakage (AL) has not been published yet in Korea. This study assessed the AL rate and quantified the economic burden using the nationwide database. METHODS: This real world evidence study used health claims data provided by the Korean Health Insurance Review and Assessment Service (HIRA, which showed that 156,545 patients underwent anterior resection (AR), low anterior resection (LAR), or ultra-low anterior resection (uLAR) for colorectal cancer (CRC) between January 1, 2007 and January 31, 2020. The incidence of AL was identified using a composite operational definition, a composite of imaging study, antibacterial drug use, reoperation, or image-guided percutaneous drainage. Total hospital costs and length of stay (LOS) were evaluated in patients with AL versus those without AL during index hospitalization and within 30 days after the surgery. RESULTS: Among 120,245 patients who met the eligibility criteria, 7,194 (5.98%) patients had AL within 30 days after surgery. Male gender, comorbidities (diabetes, metastatic disease, ischemic heart disease, ischemic stroke), protective ostomy, and multiple linear stapler use, blood transfusion, and urinary tract injury were associated with the higher odds of AL. Older age, rectosigmoid junction cancer, AR, LAR, and laparoscopic approach were related with the reduced odds of AL. Patients with AL incurred higher costs for index hospitalization compared to those without AL (8,991 vs. 7,153 USD; p<0.0001). Patients with AL also required longer LOS (16.78 vs. 14.22 days; p<0.0001) and readmissions (20.83 vs. 13.93 days; p<0.0001). CONCLUSION: Among patients requiring resection for CRC, the occurrence of AL was associated with significantly increased costs and LOS. Preventing AL could not only produce superior clinical outcomes, but also reduce the economic burden for patients and payers.