Comparison for the effects of different components of temperature variability on mortality: A multi-country time-series study.

BACKGROUND: Temperature variability (TV) is associated with increased mortality risk. However, it is still unknown whether intra-day or inter-day TV has different effects. OBJECTIVES: We aimed to assess the association of intra-day TV and inter-day TV with all-cause, cardiovascular, and respiratory mortality. METHODS: We collected data on total, cardiovascular, and respiratory mortality and meteorology from 758 locations in 47 countries or regions from 1972 to 2020. We defined inter-day TV as the standard deviation (SD) of daily mean temperatures across the lag interval, and intra-day TV as the average SD of minimum and maximum temperatures on each day. In the first stage, inter-day and intra-day TVs were modelled simultaneously in the quasi-Poisson time-series model for each location. In the second stage, a multi-level analysis was used to pool the location-specific estimates. RESULTS: Overall, the mortality risk due to each interquartile range [IQR] increase was higher for intra-day TV than for inter-day TV. The risk increased by 0.59% (95% confidence interval [CI]: 0.53, 0.65) for all-cause mortality, 0.64% (95% CI: 0.56, 0.73) for cardiovascular mortality, and 0.65% (95% CI: 0.49, 0.80) for respiratory mortality per IQR increase in intra-day TV0-7 (0.9 °C). An IQR increase in inter-day TV0-7 (1.6 °C) was associated with 0.22% (95% CI: 0.18, 0.26) increase in all-cause mortality, 0.44% (95% CI: 0.37, 0.50) increase in cardiovascular mortality, and 0.31% (95% CI: 0.21, 0.41) increase in respiratory mortality. The proportion of all-cause deaths attributable to intra-day TV0-7 and inter-day TV0-7 was 1.45% and 0.35%, respectively. The mortality risks varied by lag interval, climate area, season, and climate type. CONCLUSIONS: Our results indicated that intra-day TV may explain the main part of the mortality risk related to TV and suggested that comprehensive evaluations should be proposed in more countries to help protect human health.

Effects of a choral program combining wind instrument performance and breathing training on respiratory function, stress, and quality of life in adolescents: A randomized controlled trial.

BACKGROUND: Choral activities are correlated with various health and wellbeing parameters. However, an intervention combining a music program using wind instruments and choral activities has not yet been investigated. Thus, this study aimed to assess the effects of a 12-week intervention combining a wind instrument performance program and a choral program on stress factors, quality of life, and respiratory function in adolescents located in a metropolitan city with exposure to air pollution. METHOD: This randomized controlled trial consisted of 50 adolescents, and the subjects were randomly assigned to a combination wind instrument and choral training group, a choral training group, and a control group. Following a 12-week intervention program, respiratory function, stress factors, and quality of life were compared between the three groups. RESULTS: Regarding respiratory function, with the exception of maximal inspiratory pressure, all measured variables exhibited an interaction to indicate a variation in the pattern of change(p<0.05). Furthermore, regarding stress factors and quality of life, all measured variables exhibited an interaction to indicate a variation in the pattern of change(p<0.05). As a result of the post-hoc analysis, significant differences were found in all variables in experimental group 1 compared to other groups (p<0.05). CONCLUSION: The results showed that the 12-week intervention combining a wind instrument performance program and a choral program had positive effects in improving the respiratory function, stress factors, and quality of life in adolescents. This study findings are expected to support future studies aimed at promoting overall health including respiratory function and psychological factors through various music-based programs.

MRI Scoring Systems for Predicting Isocitrate Dehydrogenase Mutation and Chromosome 1p/19q Codeletion in Adult-type Diffuse Glioma Lacking Contrast Enhancement.

Background According to 2021 World Health Organization criteria, adult-type diffuse gliomas include glioblastoma, isocitrate dehydrogenase (IDH)-wildtype; oligodendroglioma, IDH-mutant and 1p/19q-codeleted; and astrocytoma, IDH-mutant, even when contrast enhancement is lacking. Purpose To develop and validate simple scoring systems for predicting IDH and subsequent 1p/19q codeletion status in gliomas without contrast enhancement using standard clinical MRI sequences. Materials and Methods This retrospective study included adult-type diffuse gliomas lacking contrast at contrast-enhanced MRI from two tertiary referral hospitals between January 2012 and April 2022 with diagnoses confirmed at pathology. IDH status was predicted primarily by using T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign, followed by 1p/19q codeletion prediction. A visual rating of MRI features, apparent diffusion coefficient (ADC) ratio, and relative cerebral blood volume was measured. Scoring systems were developed through univariable and multivariable logistic regressions and underwent calibration and discrimination, including internal and external validation. Results For the internal validation cohort, 237 patients were included (mean age, 44.4 years ± 14.4 [SD]; 136 male patients; 193 patients in IDH prediction and 163 patients in 1p/19q prediction). For the external validation cohort, 35 patients were included (46.1 years ± 15.3; 20 male patients; 28 patients in IDH prediction and 24 patients in 1p/19q prediction). The T2-FLAIR mismatch sign demonstrated 100% specificity and 100% positive predictive value for IDH mutation. IDH status prediction scoring system for tumors without mismatch sign included age, ADC ratio, and morphologic characteristics, whereas 1p/19q codeletion prediction for IDH-mutant gliomas included ADC ratio, cortical involvement, and mismatch sign. For IDH status and 1p/19q codeletion prediction, bootstrap-corrected areas under the receiver operating characteristic curve were 0.86 (95% CI: 0.81, 0.90) and 0.73 (95% CI: 0.65, 0.81), respectively, whereas at external validation they were 0.99 (95% CI: 0.98, 1.0) and 0.88 (95% CI: 0.63, 1.0). Conclusion The T2-FLAIR mismatch sign and scoring systems using standard clinical MRI predicted IDH and 1p/19q codeletion status in gliomas lacking contrast enhancement. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Badve and Hodges in this issue.

Totally laparoscopic versus laparoscopy-assisted distal gastrectomy: the KLASS-07, a randomized controlled trial.

BACKGROUNDS: Strong evidence is lacking as no confirmatory randomized controlled trials (RCTs) have compared the efficacy of totally laparoscopic distal gastrectomy (TLDG) with laparoscopy-assisted distal gastrectomy (LADG). We performed an RCT to confirm if TLDG is different from LADG. METHODS: The XXXXX trial is a multicentre, open-label, parallel-group, phase III, RCT of 442 patients with clinical stage I gastric cancer. Patients were enrolled from 21 cancer care centers in South Korea between January 2018 and September 2020 and randomized to undergo TLDG or LADG using blocked randomization with a 1:1 allocation ratio, stratified by the participating investigators. Patients were treated through R0 resections by TLDG or LADG as the full analysis set of the XXXXX trial. The primary endpoint was morbidity within postoperative day 30, and the secondary endpoint was QoL for 1 year. This trial is registered at ClinicalTrials.gov (NCT XXXXXXXX). RESULTS: 442 patients were randomized (222 to TLDG, 220 to LADG), and 422 patients were included in the pure analysis (213 and 209, respectively). The overall complication rate did not differ between the two groups (TLDG vs. LADG: 12.2% vs. 17.2%). However, TLDG provided less postoperative ileus and pulmonary complications than LADG (0.9% vs. 5.7%, P=0.006; and 0.5% vs. 4.3%, P=0.035, respectively). The QoL was better after TLDG than after LADG regarding emotional functioning at 6 months, pain at 3 months, anxiety at 3 and 6 months, and body image at 3 and 6 months (all P<0.05). However, these QoL differences were resolved at 1 year. CONCLUSIONS: The XXXXX trial confirmed that TLDG is not different from LADG in terms of postoperative complication but has advantages to reduce ileus and pulmonary complications. TLDG can be a good option to offer better QoL in terms of pain, body image, emotion, and anxiety at 3-6 months.

Added value of 40 keV virtual monoenergetic images for diagnosing malignant pleural effusion on chest CT.

OBJECTIVE: This study aimed to evaluate the added value of 40 keV virtual mono-energetic images (VMIs) obtained from dual-layer detector CT (DLCT) for diagnosing malignant pleural effusion (MPE) in patients presenting with unilateral pleural effusion on chest CT. MATERIALS AND METHODS: This retrospective study included 75 patients with unilateral pleural effusion who underwent contrast-enhanced chest CT scans using DLCT. Quantitative and qualitative assessments of the visibility of pleural thickening were conducted on both conventional 120 kVp images and 40 keV VMIs. Two independent radiologists reviewed chest CT scans with or without 40 keV VMIs to detect pleural nodules or nodular thickening for the diagnosis of MPE. Diagnostic performances were compared and independent predictors of MPE were identified through multivariate logistic regression analysis using CT and clinicopathologic findings. RESULTS: Pleural thickening associated with MPE demonstrated a higher contrast-to-noise ratio value and greater visual conspicuity in 40 keV VMIs compared to benign effusions (p < 0.05). For both readers, the use of 40 keV VMIs significantly improved (p < 0.05) the diagnostic performance in terms of sensitivity and area under the curve (AUC) for diagnosing MPE through the detection of pleural nodularity. Inter-observer agreements between the two readers were substantial for both 120 kVp images alone and the combined use of 40 keV VMIs. Initial cytology results and pleural nodularity at 40 keV were identified as independent predictors of MPE. CONCLUSION: The use of 40 keV VMIs from DLCT can improve diagnostic performance of readers in detecting MPE among patients with unilateral pleural effusion.

Non-destructive assessment of cannabis quality during drying process using hyperspectral imaging and machine learning.

Cannabis sativa L. is an industrially valuable plant known for its cannabinoids, such as cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), renowned for its therapeutic and psychoactive properties. Despite its significance, the cannabis industry has encountered difficulties in guaranteeing consistent product quality throughout the drying process. Hyperspectral imaging (HSI), combined with advanced machine learning technology, has been used to predict phytochemicals that presents a promising solution for maintaining cannabis quality control. We examined the dynamic changes in cannabinoid compositions under diverse drying conditions and developed a non-destructive method to appraise the quality of cannabis flowers using HSI and machine learning. Even when the relative weight and water content remained constant throughout the drying process, drying conditions significantly influenced the levels of CBD, THC, and their precursors. These results emphasize the importance of determining the exact drying endpoint. To develop HSI-based models for predicting cannabis quality indicators, including dryness, precursor conversion of CBD and THC, and CBD : THC ratio, we employed various spectral preprocessing methods and machine learning algorithms, including logistic regression (LR), support vector machine (SVM), k-nearest neighbor (KNN), random forest (RF), and Gaussian naïve Bayes (GNB). The LR model demonstrated the highest accuracy at 94.7-99.7% when used in conjunction with spectral pre-processing techniques such as multiplicative scatter correction (MSC) or Savitzky-Golay filter. We propose that the HSI-based model holds the potential to serve as a valuable tool for monitoring cannabinoid composition and determining optimal drying endpoint. This tool offers the means to achieve uniform cannabis quality and optimize the drying process in the industry.

Cognition and Functional Capacity: An Initial Comparison of Veteran and Non-Veteran Older Adults.

INTRODUCTION: The U.S. Military Veterans aged 65 and older comprise an estimated 43% of the 22 million living Veterans in the United States. Veterans have high rates of physical, psychiatric, and social challenges, but it is not known whether Veteran status confers additional risk for cognitive or functional impairments in later life. Thus, this investigation specifically compared older Veterans with their non-Veteran peers in cognitive functioning and performance-based functional capacity. MATERIALS AND METHODS: Participants (N = 110; 29 Veterans and 81 non-Veterans) were part of a larger longitudinal study on biopsychosocial functioning in independently living older adult residents of a Continuing Care Senior Housing Community. The University of California San Diego Institutional Review Board approved the study and all participants provided written informed consent. Participants provided demographic and mental health information and were administered a comprehensive neuropsychological battery. Functional capacity was assessed using the UCSD Performance-Based Skills Assessment-Brief (UPSA-B), which uses financial and communication role-plays to assess everyday functioning skills. Neuropsychological scores were appropriately normed prior to analysis. Multivariate Analyses of Variances with post hoc t-tests and an Analysis of Covariance were used to examine neuropsychological and functional capacity differences, respectively, between Veterans and non-Veterans. RESULTS: Veterans did not differ from non-Veterans in educational attainment (16.4 years versus 15.5 years, P = 0.110), but they were significantly older (mean age 86.9 years ± 5.7, versus 81.74 years ± 6.53; P < 0.001) and were more likely to be male (X2 [1, N = 110] = 62.39, P < 0.001). Thus, though neuropsychological norms already accounted for demographic differences in our participants, age and sex were controlled in the Analysis of Covariance predicting UPSA-B score from Veteran status. Results suggested that, compared to non-Veterans, Veterans had significantly worse performance in the list learning portion of a test of verbal memory (Hopkins Verbal Learning Test-Revised, Total Recall; t = 2.56, P = 0.012, d = 0.56). Veterans and non-Veterans did not significantly differ in performance on the delayed recall portion of the verbal learning test and did not differ on a cognitive screening test (Montreal Cognitive Assessment) or on measures of premorbid intellectual functioning (Wide Range Achievement Test-4 Reading), language (Boston Naming Test, Verbal Fluency), visual memory (Brief Visuospatial Memory Test-Revised), attention/working memory (WAIS-IV Digit Span), processing speed (WAIS-IV Digit Symbol Coding), executive function (Delis-Kaplan Executive Function System Trails and Color-Word Test), or functional capacity (UPSA-B). Because our examination of multiple outcomes might have inflated Type I error, we performed a post hoc adjustment of P values using Benjamini-Hochberg procedures and the group difference in verbal learning remained significant. CONCLUSIONS: Despite largely similar function in most domains, Veterans performed significantly more poorly in verbal list learning than their non-Veteran peers. Additional attention should be given to the understanding, assessment, and possible treatment of learning and memory differences in older Veterans, as this may be an area in which Veteran status confers additional risk or vulnerability to decline. This is the first study to compare objective neuropsychological and functional performance between older (age 65+) US Veterans and non-Veterans.

Ensuring spatial scalability with temporal-wise spatial attentive pooling for temporal action detection.

Recent temporal action detection models have focused on end-to-end trainable approaches to utilize the representational power of backbone networks. Despite the advantages of end-to-end trainable methods, these models still employ a small spatial resolution (e.g., 96 × 96) due to the inefficient trade-off between computational cost and spatial resolution. In this study, we argue that a simple pooling method (e.g., adaptive average pooling) acts as a bottleneck at the spatial aggregation part, restricting representational power. To address this issue, we propose a temporal-wise spatial attentive pooling (TSAP), which alleviates the bottleneck between the backbone and the detection head using a temporal-wise attention mechanism. Our approach mitigates the inefficient trade-off between spatial resolution and computational cost, thereby enhancing spatial scalability in temporal action detection. Moreover, TSAP is adaptable to previous end-to-end approaches by simply replacing the spatial pooling part. Our experiments demonstrated the essential role of spatial aggregation, and consistent improvements are observed by incorporating TSAP into previous end-to-end methods.

In vitro characterization of [125I]HY-3-24, a selective ligand for the dopamine D3 receptor.

Introduction: Dopamine D3 receptor (D3R) ligands have been studied for the possible treatment of neurological and neuropsychiatric disorders. However, selective D3R radioligands for in vitro binding studies have been challenging to identify due to the high structural similarity between the D2R and D3R. In a prior study, we reported a new conformationally-flexible benzamide scaffold having a high affinity for D3R and excellent selectivity vs. D2R. In the current study, we characterized the in vitro binding properties of a new radioiodinated ligand, [125I]HY-3-24. Methods: In vitro binding studies were conducted in cell lines expressing D3 receptors, rat striatal homogenates, and rat and non-human primate (NHP) brain tissues to measure regional brain distribution of this radioligand. Results: HY-3-24 showed high potency at D3R (Ki = 0.67 ± 0.11 nM, IC50 = 1.5 ± 0.58 nM) compared to other D2-like dopamine receptor subtypes (D2R Ki = 86.7 ± 11.9 nM and D4R Ki > 1,000). The Kd (0.34 ± 0.22 nM) and Bmax (38.91 ± 2.39 fmol/mg) values of [125I]HY-3-24 were determined. In vitro binding studies in rat striatal homogenates using selective D2R and D3R antagonists confirmed the D3R selectivity of [125I]HY-3-24. Autoradiography results demonstrated that [125I]HY-3-24 specifically binds to D3Rs in the nucleus accumbens, islands of Calleja, and caudate putamen in rat and NHP brain sections. Conclusion: These results suggest that [125I]HY-3-24 appears to be a novel radioligand that exhibits high affinity binding at D3R, with low binding to other D2-like dopamine receptors. It is anticipated that [125I]HY-3-24 can be used as the specific D3R radioligand.

Association between heat and hospital admissions in people with disabilities in South Korea: a nationwide, case-crossover study.

BACKGROUND: Despite extensive findings on the hazardous impacts of environmental heat exposure, little is known about the effect on people with disabilities. This study aimed to estimate the association between environmental heat exposure and emergency department admissions for people with disabilities compared with people without disabilities. METHODS: In this nationwide, case-crossover study, we linked data on emergency department admissions (cases) for any cause in the warm season in South Korea from the Korean National Health Insurance Service (NHIS)-National Sample Cohort database (a nationally representative database of 1 million systematically sampled beneficiaries covering all ages) from Jan 1, 2002, to Dec 31, 2019, and short-term daily mean temperature exposure (measured via Google Earth Engine at a 9 km spatial grid, aggregated to district). We defined beneficiaries with disabilities as those who were registered as disabled in the NHIS; disabilities included in our study were physical disability, brain lesion disorders, blindness or vision loss, and deafness or hearing loss. Other types of disability were not included for confidentiality reasons. A time-stratified case-crossover design, in which participants served as their own control, was used with conditional logistic regression to estimate the association between heat and emergency department admissions in people with and without disabilities. FINDINGS: 23 792 emergency department admissions were recorded for 59 527 people with disabilities. Of these 23 792 admissions, 10 234 (43·0%) individuals were female and 13 558 (57·0%) were male. The odds ratio (OR) of emergency department admissions associated with heat (99th temperature percentile vs 75th percentile) was 1·15 (95% CI 1·07-1·24) in people with disabilities and 1·06 (1·04-1·09) in people without disabilities. The annual excess number of emergency department admissions attributable to heat per 100 000 persons-years was 27·81 admissions (95% CI 9·20-45·69) and excess medical costs were US$638 739·47 (95% CI 201 900·12-1 059 641·87) in people with disabilities; these values were more than four times that of the non-disabled population. People with brain lesion disorders, people with severe physical disabilities, female individuals, and those aged 65 years or older showed higher heat risks. The risks of emergency department admissions due to mental disorder (1·89, 95% CI 1·18-3·00) and respiratory diseases (1·34, 1·06-1·70) also showed higher heat risks than for the other two analysed causes of admission (cardiovascular and genitourinary diseases). INTERPRETATION: Heat was associated with increased risk of emergency department admissions for people with and without disabilities, but the risk appeared to be higher for those with disabilities. These results can inform policy makers when establishing action plans for people with disabilities. FUNDING: National Research Foundation of Korea, the South Korean Ministry of Environment, and the South Korean Ministry of Education.

[Analysis of Short-Term Results after Introduction of Robotic Gastrectomy for Gastric Cancer at Our Hospital].

BACKGROUND: Robotic gastrectomy(RG)for gastric cancer(GC)has been covered by health insurance since 2018. In this study, we examined the results of RG for GC at our hospital during the initial period of its introduction. MATERIALS AND METHOD: From August 2022 to May 2023, we retrospectively examined the surgical outcomes and short-term postoperative outcomes of the first 9 patients who underwent RG for GC at our hospital. RESULTS: The median patient age was 77(67-82) years, gender was 4 males and 5 females, and distal gastrectomy was performed in all patients. The median operative time was 410(323-486)min, blood loss was 5(1-140)mL, postoperative hospital stay was less than 9 days in all patients, and there was no conversion to laparoscopic or open surgery. There were no postoperative complications of Clavien-Dindo Grade Ⅱ or above. CONCLUSION: In this study, RG for GC was performed safely without intraoperative or postoperative complications.

Heat and hospital admission via the emergency department for people with intellectual disability, autism, and mental disorders in South Korea: a nationwide, time-stratified, case-crossover study.

BACKGROUND: Given the anticipated increase in ambient temperature due to climate change, the hazardous effects of heat on health have been extensively studied; however, its impact on people with intellectual disability, autism, and mental illness is largely unknown. We aimed to estimate the association between heat and hospitalisation through the emergency department (ED) among people with these mental disorders. METHODS: In this nationwide study, we used data from the National Health Insurance Database (NHID) of the National Health Insurance Service, the single universal insurer in South Korea, the claims data for which is based on the ICD-10. We included individuals with identified intellectual disability, autism, and mental disorders (including schizophrenia, bipolar disorder, recurrent depressive disorder, schizoaffective disorder and persistent obsessive-compulsive disorder, Tourette's disorder, and narcolepsy) and we established two control groups of people without these disorders: one including 1 million systematically sampled individuals, and one matched to the cohort based on sex, age, and income group. Data on hospital admission via the ED were obtained from the NHID, including the primary cause of admission and corresponding medical costs, for the warm season (June-September) of the period 2006-2021. We used the Google Earth Engine with the ERA5-Land dataset to collect data on the daily mean temperature. We applied a time-stratified case-crossover design using a distributed lag non-linear model and performed a conditional logistic regression. The risk ratio was estimated as the odds ratio (OR) with calculated odds at the 99th percentile temperature compared with that at the local 75th percentile temperature. We did not include people with lived experience of mental illness in this study. FINDINGS: Of the 456 946 people with intellectual disability, autism, or mental disorder in the NHID records, 99 845 were admitted to the ED, including 59 821 (59·9%) males and 40 024 (40·1%) females, and including 29 192 people with intellectual disability, 1428 people with autism, and 69 225 people with mental disorders. We were not able to collect data on ethnicity. The mean age at ED admission was 42·1 years (SD 17·9, range 0-102) for people with intellectual disability, 18·6 years (SD 10·4, range 1-72) for people with autism, and 50·8 years (SD 11·9, range 2-94) for people with mental disorders. The heat OR (odds at the 99th percentile vs 75th percentile of temperature) of ED admission was 1·23 (95% CI 1·11-1·36) for intellectual disability, 1·06 (0·68-1·63) for autism, and 1·20 (1·12-1·29) for mental disorders. People with intellectual disability, female individuals, people living in rural areas, or those with a low-income status were at increased risk of ED admission due to heat. The risk of ED admission due to genitourinary diseases was higher than that from other causes. Annual increase in medical costs attributable to heat among people with intellectual disability, autism, and mental disorders was US$ 224 970 per 100 000 person-years (95% empirical CI 139 784-305 770). INTERPRETATION: People with intellectual disability, autism, and mental disorders should be included in groups considered at a high-risk for heat exposure, and heat adaptation policies should be implemented with consideration of these groups and their needs. FUNDING: The National Research Foundation of Korea, Korean Ministry of Environment, and Korean Ministry of Education. TRANSLATION: For the Korean translation of the abstract see Supplementary Materials section.

Triphenylphosphonium-functionalized dimeric BODIPY-based nanoparticles for mitochondria-targeting photodynamic therapy.

The dimerization of boron dipyrromethene (BODIPY) moieties is an appealing molecular design approach for developing heavy-atom-free triplet photosensitizers (PSs). However, BODIPY dimer-based PSs generally lack target specificity, which limits their clinical use for photodynamic therapy. This study reports the synthesis of two mitochondria-targeting triphenylphosphonium (TPP)-functionalized meso-ß directly linked BODIPY dimers (BTPP and BeTPP). Both BODIPY dimers exhibited solvent-polarity-dependent singlet oxygen (1O2) quantum yields, with maximum values of 0.84 and 0.55 for BTPP and BeTPP, respectively, in tetrahydrofuran. The compact orthogonal geometry of the BODIPY dimers facilitated the generation of triplet excited states via photoinduced charge separation (CS) and subsequent spin-orbit charge-transfer intersystem crossing (SOCT-ISC) processes and their rates were dependent on the energetic configuration between the frontier molecular orbitals of the two BODIPY subunits. The as-synthesized compounds were amphiphilic and hence formed stable nanoparticles (∼36 nm in diameter) in aqueous solutions, with a zeta potential of ∼33 mV beneficial for mitochondrial targeting. In vitro experiments with MCF-7 and HeLa cancer cells indicated the effective localization of BTPP and BeTPP within cancer-cell mitochondria. Under light irradiation, BTPP and BeTPP exhibited robust photo-induced therapeutic effects in both cell lines, with half-maximal inhibitory concentration (IC50) values of ∼30 and ∼55 nM, respectively.

Therapeutic Effect of Schwann Cell-Like Cells Differentiated from Human Tonsil-Derived Mesenchymal Stem Cells on Diabetic Neuropathy in db/db Mice.

BACKGROUND: Diabetic neuropathy (DN) is the most common complication of diabetes, and approximately 50% of patients with this disease suffer from peripheral neuropathy. Nerve fiber loss in DN occurs due to myelin defects and is characterized by symptoms of impaired nerve function. Schwann cells (SCs) are the main support cells of the peripheral nervous system and play important roles in several pathways contributing to the pathogenesis and development of DN. We previously reported that human tonsil-derived mesenchymal stem cells differentiated into SCs (TMSC-SCs), named neuronal regeneration-promoting cells (NRPCs), which cells promoted nerve regeneration in animal models with peripheral nerve injury or hereditary peripheral neuropathy. METHODS: In this study, NRPCs were injected into the thigh muscles of BKS-db/db mice, a commonly used type 2 diabetes model, and monitored for 26 weeks. Von Frey test, sensory nerve conduction study, and staining of sural nerve, hind foot pad, dorsal root ganglia (DRG) were performed after NRPCs treatment. RESULTS: Von Frey test results showed that the NRPC treatment group (NRPC group) showed faster responses to less force than the vehicle group. Additionally, remyelination of sural nerve fibers also increased in the NRPC group. After NRPCs treatment, an improvement in response to external stimuli and pain sensation was expected through increased expression of PGP9.5 in the sole and TRPV1 in the DRG. CONCLUSION: The NRPCs treatment may alleviate DN through the remyelination and the recovery of sensory neurons, could provide a better life for patients suffering from complications of this disease.

Surgeon Preference Regarding Wound Dressing Management in Lumbar Fusion Surgery: An AO Spine Global Cross-Sectional Study.

OBJECTIVE: To evaluate the global practice pattern of wound dressing use after lumbar fusion for degenerative conditions. METHODS: A survey issued by AO Spine Knowledge Forums Deformity and Degenerative was sent out to AO Spine members. The type of postoperative dressing employed, timing of initial dressing removal, and type of subsequent dressing applied were investigated. Differences in the type of surgery and regional distribution of surgeons' preferences were analyzed. RESULTS: Right following surgery, 60.6% utilized a dry dressing, 23.2% a plastic occlusive dressing, 5.7% glue, 6% a combination of glue and polyester mesh, 2.6% a wound vacuum, and 1.2% other dressings. The initial dressing was removed on postoperative day 1 (11.6%), 2 (39.2%), 3 (20.3%), 4 (1.7%), 5 (4.3%), 6 (0.4%), 7 or later (12.5%), or depending on drain removal (9.9%). Following initial dressing removal, 75.9% applied a dry dressing, 17.7% a plastic occlusive dressing, and 1.3% glue, while 12.1% used no dressing. The use of no additional coverage after initial dressing removal was significantly associated with a later dressing change (p < 0.001). Significant differences emerged after comparing dressing management among different AO Spine regions (p < 0.001). CONCLUSION: Most spine surgeons utilized a dry or plastic occlusive dressing initially applied after surgery. The first dressing was more frequently changed during the first 3 postoperative days and replaced with the same type of dressing. While dressing policies tended not to vary according to the type of surgery, regional differences suggest that actual practice may be based on personal experience rather than available evidence.

Choroidal manifestations of non-ocular sarcoidosis: an enhanced depth imaging OCT study.

BACKGROUND: Although choroidal thickening was reported as a sign of active inflammation in ocular sarcoidosis, there has been no research on the choroidal changes in non-ocular sarcoidosis (defined as systemic sarcoidosis without overt clinical signs of ocular involvement). Therefore, this study aimed to investigate choroidal structural changes in patients with non-ocular sarcoidosis. METHODS: This retrospective case-control study was conducted at Asan Medical Center, a tertiary referral center. We evaluated 30 eyes with non-ocular sarcoidosis and their age- and spherical equivalent-matched healthy control eyes. The subfoveal choroidal thickness, area ratio (Sattler layer-choriocapillaris complex [SLCC] area to Haller layer [HL] area), and choroidal vascularity index (CVI, luminal area to choroidal area) were analyzed using enhanced depth imaging in optical coherence tomography. Systemic and ocular factors associated with the choroidal thickness were investigated. RESULTS: Compared with the healthy control group, the non-ocular sarcoidosis group had significantly thicker subfoveal choroid (total and all sublayers [SLCC and HL]) and lower area ratio. There were no significant differences in the CVIs at all sublayers between groups. In the non-ocular sarcoidosis group, eyes under oral steroid treatment had thinner choroid than eyes under observation. In the control group, eyes with older age and more myopic spherical equivalent had thinner choroidal thickness. CONCLUSION: Total and all sublayers of the subfoveal choroid were significantly thicker without significant vascularity changes in non-ocular sarcoidosis eyes than in healthy control eyes. The degree of choroidal thickening was disproportionally greater at HL than at SLCC. These characteristic choroidal changes may be the subclinical manifestations in non-ocular sarcoidosis.

De novo design of protein minibinder agonists of TLR3.

Toll-like Receptor 3 (TLR3) is a pattern recognition receptor that initiates antiviral immune responses upon binding double-stranded RNA (dsRNA). Several nucleic acid-based TLR3 agonists have been explored clinically as vaccine adjuvants in cancer and infectious disease, but present substantial manufacturing and formulation challenges. Here, we use computational protein design to create novel miniproteins that bind to human TLR3 with nanomolar affinities. Cryo-EM structures of two minibinders in complex with TLR3 reveal that they bind the target as designed, although one partially unfolds due to steric competition with a nearby N-linked glycan. Multimeric forms of both minibinders induce NF-κB signaling in TLR3-expressing cell lines, demonstrating that they may have therapeutically relevant biological activity. Our work provides a foundation for the development of specific, stable, and easy-to-formulate protein-based agonists of TLRs and other pattern recognition receptors.

A dual role of the conserved PEX19 helix in safeguarding peroxisomal membrane proteins.

Accurate localization of membrane proteins is essential for proper cellular functioning and the integrity of cellular membranes. Post-translational targeting of peroxisomal membrane proteins (PMPs) is mediated by the cytosolic chaperone PEX19 and its membrane receptor PEX3. However, the molecular mechanisms underlying PMP targeting are poorly understood. Here, using biochemical and mass spectrometry analysis, we find that a conserved PEX19 helix, αd, is critical to prevent improper exposure of the PEX26 transmembrane domain (TMD) to cytosolic chaperones. Furthermore, the αd helix of PEX19 interacts with the cytosolic domain of the PEX3 receptor, thereby triggering PEX26 release at the correct destination membrane. The peroxisome-deficient PEX3-G138E mutant completely abolishes this secondary interaction, leading to lack of PEX3-induced PEX26 release from PEX19. These findings elucidate a dual molecular mechanism that is essential to membrane protein protection and destination-specific release by a molecular chaperone.

Isoegomaketone exhibits potential as a new Mycobacterium abscessus inhibitor.

Although the incidence of Mycobacterium abscessus infection has recently increased significantly, treatment is difficult because this bacterium is resistant to most anti-tuberculosis drugs. In particular, M. abscessus is often resistant to available macrolide antibiotics, so therapeutic options are extremely limited. Hence, there is a pressing demand to create effective drugs or therapeutic regimens for M. abscessus infections. The aim of the investigation was to assess the capability of isoegomaketone (iEMK) as a therapeutic option for treating M. abscessus infections. We determined the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of iEMK for both reference and clinically isolated M. abscessus strains. In addition to time-kill and biofilm formation assays, we evaluated iEMK's capability to inhibit M. abscessus growth in macrophages using an intracellular colony counting assay. iEMK inhibited the growth of reference and clinically isolated M. abscessus strains in macrophages and demonstrated effectiveness at lower concentrations against macrophage-infected M. abscessus than when used to treat the bacteria directly. Importantly, iEMK also exhibited anti-biofilm properties and the potential to mitigate macrolide-inducible resistance, underscoring its promise as a standalone or adjunctive therapeutic agent. Overall, our results suggest that further development of iEMK as a clinical drug candidate is promising for inhibiting M. abscessus growth, especially considering its dual action against both planktonic bacteria and biofilms.