Peripheral inflammation as a potential mechanism and preventive strategy for perioperative neurocognitive disorder under general anesthesia and surgery.

General anesthesia, as a commonly used medical intervention, has been widely applied during surgical procedures to ensure rapid loss of consciousness and pain relief for patients. However, recent research suggests that general anesthesia may be associated with the occurrence of perioperative neurocognitive disorder (PND). PND is characterized by a decline in cognitive function after surgery, including impairments in attention, memory, learning, and executive functions. With the increasing trend of population aging, the burden of PND on patients and society's health and economy is becoming more evident. Currently, the clinical consensus tends to believe that peripheral inflammation is involved in the pathogenesis of PND, providing strong support for further investigating the mechanisms and prevention of PND.

Effects of buccal acupuncture on postoperative analgesia in elderly patients undergoing laparoscopic radical gastrectomy: a randomized controlled trial.

Objective: This study aimed to evaluate the efficacy and safety of buccal acupuncture on postoperative analgesia, perioperative stress response and adverse events in elderly patients undergoing laparoscopic radical gastrectomy. Methods: It was a prospective, outcome assessor-blinded, randomized controlled trial, involving 90 patients aged 65-80 years who were treated with an elective laparoscopic radical gastrectomy. They were randomly assigned to buccal acupuncture group (Group B) and control group (Group C). Buccal acupuncture was applied to patients of Group B before the induction of general anesthesia, while no additional application was given to those in Group C. Patient-controlled intravenous analgesia (PCIA) with sufentanil was postoperatively performed in both groups. Sufentanil consumption and the Visual Analog Scale (VAS) score within 48 h postoperatively were assessed as primary outcomes. Secondary outcomes included peripheral levels of stress markers, intraoperative consumptions of anesthetic drugs and postoperative recovery. Results: Patients in Group B presented significantly lower VAS scores within 24 h and less consumption of sufentanil within 48 h postoperatively (both p < 0.01). The awaking time, time to extubation and length of stay were significantly shorter in Group B than in Group C (p = 0.005, 0.001 and 0.028, respectively). Compared with Group C, stress response and inflammatory response within 24 h postoperatively were also significantly milder in Group B. Conclusion: The use of buccal acupuncture before general anesthesia induction favors the postoperative analgesic effect and recovery in elderly patients undergoing laparoscopic radical gastrectomy, the mechanism of which involves relieving postoperative stress response and inflammatory response. Clinical trial registration: This study was registered in the Chinese Clinical Trial Registry (www.chictr.org.cn) on 15/06/2023 (ChiCTR2300072500).

[Cloning and functional characterization of oxidosqualene cyclase gene for α-amyrin synthesis].

Ursolic acid has gradually attracted much attention due to its unique pharmacological activities and valuable market value in recent years. Currently, ursolic acid is mostly extracted from loquat leaves, but the plant extraction method has low yield and high cost, and chemical synthesis is not readily available, so the biosynthesis method provides a new source for ursolic acid. α-amyrin acts as the main precursor for the synthesis of ursolic acid, and its yield is positively correlated with ursolic acid yield. Oxidosqualene cyclase(OSC) belongs to a multigene family which can catalyze the common precursor 2,3-oxidosqualene to generate different types of triterpene backbones, and plays a decisive role in the synthesis of triterpenoids. However, there are fewer reported key genes catalyzing the synthesis of α-amyrin in medicinal plants, and the yield and proportion of α-amyrin in the catalyzed products have always been a focus of research. In this study, ItOSC2, MdOSC1, AaOSC2 and CrAS, four enzymes capable of catalyzing the production of α-amyrin from 2,3-oxidosqualene, were cloned from Iris tectorum, Malus domestica, Artemisia annua and Catharanthus roseus, subject to sequence alignment and phylogenetic tree analyses, and transformed into Saccharomyces cerevisiae as plasmids. After 7 days of fermentation, the yield and proportions of α-amyrin, ß-amyrin and ergosterol were measured. Finally, AaOSC2 with the best ability to catalyze the generation of α-amyrin was filtered out, providing a key gene element for the later construction of engineered yeast strains with high production of α-amyrin and ursolic acid.

A scalable and modular computational pipeline for axonal connectomics: automated tracing and assembly of axons across serial sections.

Progress in histological methods and in microscope technology has enabled dense staining and imaging of axons over large brain volumes, but tracing axons over such volumes requires new computational tools for 3D reconstruction of data acquired from serial sections. We have developed a computational pipeline for automated tracing and volume assembly of densely stained axons imaged over serial sections, which leverages machine learning-based segmentation to enable stitching and alignment with the axon traces themselves. We validated this segmentation-driven approach to volume assembly and alignment of individual axons over centimeter-scale serial sections and show the application of the output traces for analysis of local orientation and for proofreading over aligned volumes. The pipeline is scalable, and combined with recent advances in experimental approaches, should enable new studies of mesoscale connectivity and function over the whole human brain.

A Summed Score From Cardiopulmonary Exercise Test Parameters Predicts 1-Year Mortality in Newly Diagnosed Interstitial Lung Disease.

BACKGROUND: Cardiopulmonary exercise testing (CPET) is a unique diagnostic tool that assesses the functional capacity of the heart, lungs, and peripheral oxidative system in an integrated manner. However, the clinical utility of CPET for evaluating interstitial lung disease (ILD) remains uncertain. The objective of this study was to determine the predictive value of CPET for mortality in subjects with ILD. METHODS: We prospectively enrolled subjects with ILD who underwent CPET at a tertiary medical center in Taiwan and followed up their survival status for 12 months. Mortality prediction was based on comparing CPET parameters between subjects who survived and those who died. We further analyzed CPET parameters that showed significant differences using receiver operating characteristic curves to identify their optimal cutoff values. RESULTS: A total of 106 newly diagnosed subjects with ILD underwent CPET, and the 1-y mortality rate was 7.5%. Six CPET variables were found to be significant predictors of mortality: peak oxygen consumption, oxygen pulse, end-tidal partial pressure of carbon dioxide, heart rate recovery 1 min after CPET, minute ventilation to carbon dioxide output slope, and functional aerobic impairment. We calculated a summed score by adding the number of CPET variables that exceeded their cutoff values. Subjects with a summed score of 6 had a 1-y survival rate of only 25%, whereas subjects with scores of 0-5 had a survival rate of 98%. CONCLUSIONS: In conclusion, the summed score represents a useful tool for screening patients with ILD who can undergo a CPET to determine their prognosis.

Comparative analysis of machine learning algorithms for Alzheimer's disease classification using EEG signals and genetic information.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory impairments, and behavioral changes. The presence of abnormal beta-amyloid plaques and tau protein tangles in the brain is known to be associated with AD. However, current limitations of imaging technology hinder the direct detection of these substances. Consequently, researchers are exploring alternative approaches, such as indirect assessments involving monitoring brain signals, cognitive decline levels, and blood biomarkers. Recent studies have highlighted the potential of integrating genetic information into these approaches to enhance early detection and diagnosis, offering a more comprehensive understanding of AD pathology beyond the constraints of existing imaging methods. Our study utilized electroencephalography (EEG) signals, genotypes, and polygenic risk scores (PRSs) as features for machine learning models. We compared the performance of gradient boosting (XGB), random forest (RF), and support vector machine (SVM) to determine the optimal model. Statistical analysis revealed significant correlations between EEG signals and clinical manifestations, demonstrating the ability to distinguish the complexity of AD from other diseases by using genetic information. By integrating EEG with genetic data in an SVM model, we achieved exceptional classification performance, with an accuracy of 0.920 and an area under the curve of 0.916. This study presents a novel approach of utilizing real-time EEG data and genetic background information for multimodal machine learning. The experimental results validate the effectiveness of this concept, providing deeper insights into the actual condition of patients with AD and overcoming the limitations associated with single-oriented data.

Application of online to offline teaching mode in the training of non-anesthesiology residents in the department of anesthesiology: a randomized, controlled trial.

Objective: To explore the effect of applying the online to offline teaching mode in the training of non-anesthesiology residents in department of anesthesiology. Trial design: The randomized controlled trial was performed on non-anesthesiology residents from Affiliated Jiangning Hospital of Nanjing Medical University. Methods: All selected residents were randomly divided into the traditional teaching group (Group T) and the online to offline teaching group (Group O) by the random number table method. Traditional teaching mode was used in Group T, while the online to offline teaching mode was used in Group O. The training period lasted for two months. At the end of the training, theoretical and clinical skills were assessed for all residents, and students' satisfaction scores on teaching were investigated from the aspects of teaching mode, stimulating learning interest, improving learning process and teaching satisfaction. The teaching efficiency was compared and analyzed in the two groups. Results: In total, 39 cases in Group O and 38 cases in Group T were included in the statistical analysis. Compared with Group T, theory test scores, clinical skills test scores, and overall scores improved significantly in Group O (82.2 ± 8.1 vs. 91.3 ± 7.6; 85.1 ± 4.7 vs. 93.3 ± 5.4 and 83.4 ± 6.4 vs. 92.1 ± 6.7, respectively, p < 0.01). Compared with Group T, scores on teaching mode, stimulating learning interest, improving learning process and teaching satisfaction were higher in Group O (81.1 ± 6.9 vs. 93.7 ± 5.2; 83.6 ± 5.8 vs. 91.6 ± 6.4; 82.4 ± 5.3 vs. 90.9 ± 4.8 and 82.1 ± 5.9 vs. 92.1 ± 5.5, respectively, p < 0.01). Conclusion: The online to offline teaching mode can improve the level of professional theory and clinical skill operation, and teaching satisfaction of the non-anesthesiology residents in department of anesthesiology, thus improving the teaching effectiveness.

Sleep deprivation reduces the baroreflex sensitivity through elevated angiotensin (Ang) II subtype 1 receptor expression in the nucleus tractus solitarii.

Introduction: Sleep insufficiency has been linked to an increased risk of high blood pressure and cardiovascular diseases. Emerging studies have demonstrated that impaired baroreflex sensitivity (BRS) is involved in the adverse cardiovascular effects caused by sleep deprivation, however, the underlying mechanisms remain unknown. Therefore, the present study aims to clarify the role of abnormal renin-angiotensin system in the nucleus tractus solitarii (NTS) in impaired BRS induced by sleep deprivation. Methods: Rats were randomly divided into two groups: normal sleep (Ctrl) and chronic sleep deprivation (CSD) group. Rats were sleep deprived by an automated sleep deprivation system. The blood pressure, heart rate, BRS, the number of c-Fos positive cells and the expression of angiotensin (Ang) II subtype 1 receptors (AT1R) in the NTS of rats were assessed. Results: Compared to Ctrl group, CSD group exhibited a higher blood pressure, heart rate, and reduced BRS. Moreover, the number of c-Fos positive cells and local field potential in the NTS in CSD group were increased compared with the Ctrl group. It was shown that the expression of the AT1R and the content of Ang II and the ratio of Ang II to Ang-(1-7) were increased in the NTS of rats in CSD group compared to Ctrl group. In addition, microinjection of losartan into the NTS significantly improved the impaired BRS caused by sleep deprivation. Discussion: In conclusion, these data suggest that the elevated AT1R expression in the NTS mediates the reduced BRS induced by chronic sleep deprivation.

Urine biomarker could be a useful tool for differential diagnosis of a lower urinary tract dysfunction.

A precision diagnosis of lower urinary tract dysfunctions (LUTD) such as bladder outlet obstruction, detrusor overactivity (DO), interstitial cystitis/bladder pain syndrome (IC/BPS), dysfunctional voiding (DV), or detrusor underactivity (DU) needs invasive videourodynamic study. Exploring non-invasive tools to help screening LUTD is necessary for clinicians in their daily practice. This article reviews recently clinical studies of using urinary inflammatory proteins and oxidative stress biomarkers in the identification of specific LUTD among men and women with lower urinary tract symptoms (LUTS). Some important findings have been reported: (1) Using urine chemokines CXCL-1 and interleukin-8 (IL-8), we may discriminate overactive bladder (OAB) symptoms in women between DO and urinary tract infection. (2) Urinary levels of oxidative stress biomarkers such as 8-hydroxydeoxyguanosine (8-OHdG) and 8-isoprostane have a potential being used as a tool to identify women with mixed DO and stress urinary incontinence. (3) Urine levels of total antioxidant capacity (TAC), and prostaglandin E2 (PGE2) are positively correlated with voiding detrusor pressure in patients with DU. (4) Urine levels of brain-derived neurotrophic factor (BDNF) and PGE2 were significantly higher in the DU patients with detrusor function recovery. (5) Women with DV had higher urinary levels of tumor necrosis factor-alpha (TNF-α) and 8-OHdG, and urinary IL-2 level was significantly lower. (6) Urine level of 8-isoprostane was higher in the patients with idiopathic DO and neurogenic DO. (7) Higher urine cytokine levels of monocyte chemoattractant protein-1 (MCP-1), regulated on activation, normal T-cell expressed and secreted (RANTES), CXCL-10, IL-7, and eotaxin-1 in patients with IC/BPS than controls. (8) The urine levels of IL-8, CXCL-10, BDNF, IL-6, and RANTES were significantly higher in patients with Hunner's IC than non-Hunner's IC. (9) Male patients with IC/BPS had a significantly higher level of eotaxin, MCP-1, TNF-α, 8-OHdG, and TAC. Combining a higher eotaxin and a higher TNF-α can provide a satisfactory diagnostic value in discriminating IC/BPS from other LUTD in men. These studies provide evidence that measurement of cluster of urine biomarkers could be used as a diagnostic tool to differentiate different LUTD in patients with similar LUTS.

A composite score based on cardiovascular parameters can predict the mortality risk of patients with newly diagnosed interstitial lung disease: A prospective observational study.

BACKGROUND: It is crucial to identify factors that can predict the risk of mortality in patients newly diagnosed with interstitial lung disease (ILD). This study sought to develop and assess a composite scoring system for mortality prediction among ILD patients based on cardiovascular parameters, which were previously reported as predictors of survival. METHODS: We prospectively enrolled patients with newly diagnosed ILD and monitored their survival status for 24 months. Surviving and deceased patients were compared regarding their baseline characteristics including clinical, pulmonary, and cardiovascular parameters. A system of composite scores was established based on significant cardiovascular parameters and the Gender-Age-Physiology (GAP) score. Receiver operating characteristic curves were generated to identify their optimal cut-off values. Univariate as well as multiple multivariate regression models were built to investigate the mortality prediction of different individual and combined parameters. RESULTS: Ninety-six patients newly diagnosed with ILD underwent cardiovascular evaluation. In univariate analysis, three cardiovascular parameters were identified as significant predictors of mortality risk in ILD patients, either individually or as a combination of composite scores: tricuspid regurgitation velocity > 3.1 m/s; N-terminal pro-B-type natriuretic peptide level > 300 pg/ml and computed tomography pulmonary artery/ascending aorta diameter ratio > 0.9. In multivariate analysis, a composite score of those parameters [hazard ratio (HR) = 2.37 (confidence interval [CI]:1.06-5.33); p = 0.037; Score 1] and GAP score [HR = 1.62 (CI: 1.11-2.36); p = 0.012] were the most significant predictors for mortality among ILD patients. Combination of Score 1 and GAP score (Score 2) can increase the accuracy of survival predictions (area under the curve 0.83; p < 0.001). CONCLUSIONS: A composite score based on cardiovascular parameters and the GAP score can be used to predict the risk of mortality of patients with ILD. Such a score achieved better diagnostic accuracy than the GAP score alone. Nevertheless, further larger-scale randomized controlled trials are required for evaluation of the newly proposed score and confirmation of our results.

Combination of urinary biomarkers and machine-learning models provided a higher predictive accuracy to predict long-term treatment outcomes of patients with interstitial cystitis/bladder pain syndrome.

PURPOSE: To identify predictive factors for satisfactory treatment outcome of the patients with IC/BPS using urine biomarkers and machine-learning models. METHODS: The IC/BPS patients were prospectively enrolled and provide urine samples. The targeted analytes included inflammatory cytokines, neurotrophins, and oxidative stress biomarkers. The patients with overall subjective symptom improvement of ≥ 50% were considered to have satisfactory results. Binary logistic regression, receiver-operating characteristic (ROC) curve, machine-learning decision tree, and random forest models were used to analyze urinary biomarkers to predict satisfactory results. RESULTS: Altogether, 57.4% of the 291 IC/BPS patients obtained satisfactory results. The patients with satisfactory results had lower levels of baseline urinary inflammatory cytokines and oxidative biomarkers than patients without satisfying results, including interleukin-6, monocyte chemoattractant protein-1 (MCP-1), C-X-C motif chemokine 10 (CXCL10), oxidative stress biomarkers 8-hydroxy-2'-deoxyguanosine (8-OHDG), 8-isoprostane, and total antioxidant capacity (TAC). Logistic regression and multivariable analysis revealed that lower levels of urinary CXCL10, MCP-1, 8-OHDG, and 8-isoprostane were independent factors. The ROC curve revealed that MCP-1 level had best area under curve (AUC: 0.797). In machine-learning decision tree model, combination of urinary C-C motif chemokine 5, 8-isoprostane, TAC, MCP-1, and 8-OHDG could predict satisfactory results (accuracy: 0.81). The random forest model revealed that urinary 8-isoprostance, MCP-1, and 8-OHDG levels had the most important influence on accuracy. CONCLUSION: Machine learning decision tree model provided a higher accuracy for predicting treatment outcome of patients with IC/BPS than logistic regression, and levels of 8-isoprostance, MCP-1, and 8-OHDG had the most important influence on accuracy.

Intravesical Botulinum Toxin Injection Plus Hydrodistention Is More Effective in Patients with Bladder Pain-Predominant Interstitial Cystitis/Bladder Pain Syndrome.

Intravesical botulinum toxin A (BoNT-A) injections are included in the interstitial cystitis/bladder pain syndrome (IC/BPS) treatment guidelines. However, the IC phenotype suitable for treatment with BoNT-A has not been clarified. Therefore, we identified the factors influencing treatment outcomes for intravesical BoNT-A injections in patients with non-Hunner IC/BPS (NHIC). This retrospective study included patients with NHIC who underwent 100 U BoNT-A intravesical injections over the past two decades. Six months after treatment, treatment outcomes were assessed using the Global Response Assessment (GRA). Outcome endpoints included GRA, clinical symptoms, urodynamic parameters, urine biomarkers, and the identification of factors contributing to satisfactory treatment outcomes. The study included 220 patients with NHIC (42 men, 178 women). The satisfactory group (n = 96, 44%) had significantly higher pain severity scores and IC symptoms index, larger maximum bladder capacity (MBC), and lower 8-isoprostane levels at baseline. Logistic regression revealed that larger MBC (≥760 mL) and bladder pain predominance were associated with satisfactory outcomes after BoNT-A injection. Subjective parameters and pain severity scores improved significantly in patients with bladder pain-predominant IC/BPS after BoNT-A injection. Thus, NHIC patients with bladder or pelvic pain are more likely to experience satisfactory outcomes following intravesical BoNT-A injections.

Construction of a label-free fluorescent biosensor for homogeneous detection of m6A eraser FTO in breast cancer tissues.

Fat mass and obesity-associated protein (FTO) is a crucial eraser of RNA N6- methyladenosine (m6A) modification, and abnormal FTO expression level is implicated in pathogenesis of numerous cancers. Herein, we demonstrate the construction of a label-free fluorescent biosensor for homogeneous detection of m6A eraser FTO in breast cancer tissues. When FTO is present, it specifically erases the methyl group in m6A, inducing the cleavage of demethylated DNA by endonuclease DpnII and the generation of a single-stranded DNA (ssDNA) with a 3'-hydroxyl group. Subsequently, terminal deoxynucleotidyl transferase (TdT) promotes the incorporation of dTTPs into the ssDNA to obtain a long polythymidine (T) DNA sequence. The resultant long poly (T) DNA sequence can act as a template to trigger hyperbranched strand displacement amplification (HSDA), yielding numerous DNA fragments that may be stained by SYBR Gold to produce an enhanced fluorescence signal. This biosensor processes ultrahigh sensitivity with a detection limit of 1.65 × 10-10 mg/mL (2.6 fM), and it can detect the FTO activity in a single MCF-7 cell. Moreover, this biosensor can screen the FTO inhibitors, evaluate enzyme kinetic parameters, and discriminate the FTO expression levels in the tissues of breast cancer patients and healthy persons.

High-pressure Hydrodynamic Injection as a Method of Establishing Hepatitis B Virus Infection in Mice.

Among several existing mouse models for hepatitis B virus (HBV) infection, the high-pressure hydrodynamic injection (HDI) method is frequently used in HBV research due to its economic advantages and ease of implementation. The use of the HDI method is influenced by factors such as mouse genetic background, age, sex, and the type of HBV plasmid used. This overview provides a multidimensional analysis and comparison of various factors that influence the effectiveness of the HBV mouse model established through HDI. The goal is to provide a summary of information for researchers who create HBV models in mice.

Cystoscopic characteristic findings of interstitial cystitis and clinical implications.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory bladder disease of unknown etiology, characterized by bladder pain and frequency urgency symptoms. Based on the cystoscopic findings after hydrodistention under anesthesia, the phenotype of IC/BPS includes no glamerulation, characteristic glomerulation, and with Hunner's lesion. IC is specifically defined if there are characteristic Hunner's lesion appeared in cystoscopy or after hydrodistention. If there are glomerulations without Hunner's lesion, BPS should be considered. The definition of Hunner's lesion and glomerulations differs based on different definition and observations. Currently, there has been no clear description and grading of the glomerulations and Hunner's lesion. Because the classification of IC/BPS has an impact on the treatment strategy and associated with therapeutic outcome, it is unmet to have a clear definition and consensus on the characteristic cystoscopic findings of IC/BPS. This article reviews the literature and presents the figures of Hunner's lesions and description of different mucosal lesions after cystoscopic hydrodistention.

Test-Retest Reliability, Criterion-Related Validity, and Ecological Validity of the Test of Visual-Motor Skills, Third Edition, in Kindergarten Children With Developmental Coordination Disorder.

IMPORTANCE: Establishing empirical evidence on the psychometric properties of the Test of Visual-Motor Skills (3rd ed.; TVMS-3) is helpful for guiding its use as an assessment of visual-motor integration (VMI) skills in kindergarten children with developmental coordination disorder (DCD). OBJECTIVE: To investigate the test-retest reliability, criterion-related validity, and ecological validity of the TVMS-3 in Taiwanese kindergarten children with DCD. DESIGN: A nonexperimental, descriptive, correlational design. SETTING: A hospital in Central Taiwan. PARTICIPANTS: Fifty-seven kindergarten children with DCD were recruited in the study. OUTCOMES AND MEASURES: Intraclass correlation coefficient, percentage of minimal detectable change, and paired t test (Wilcoxon signed rank test) were used to investigate the test-retest reliability of the TVMS-3. The correlations (Pearson's r) between the TVMS-3 accuracy score and the scores of each of the four domains and the adaptive behavior composite score of the Vineland Adaptive Behavior Scales (3rd ed.; Vineland-3) were calculated, respectively, to examine criterion-related validity and ecological validity. RESULTS: The accuracy score of the TVMS-3 had excellent test-retest reliability and acceptable random measurement error. Moreover, it showed good criterion-related validity and sufficient ecological validity with the Vineland-3 in Taiwanese kindergarten children with DCD. CONCLUSIONS AND RELEVANCE: The accuracy score of the TVMS-3 is applicable to Taiwanese kindergarten children with DCD in clinical and research settings. Plain-Language Summary: The accuracy score of the Test of Visual-Motor Skills (3rd ed.; TVMS-3) is a useful assessment tool to detect deficits in visual-motor integration for Taiwanese kindergarten children with developmental coordination disorder. The TVMS-3 has excellent test-retest reliability, good criterion-related validity, and sufficient ecological validity.

Multidisciplinary-derived clinical score for accurate prediction of long-term mortality in fibrotic lung disease patients.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) stands out as one of the most aggressive forms of interstitial lung diseases (ILDs), currently without a definitive cure. Multidisciplinary discussion (MDD) is now considered a cornerstone in diagnosing and differentiating ILD subtypes. The Gender-Age-Physiology (GAP) score, developed to assess IPF prognosis based on sex, age, forced vital capacity, and diffusion capacity for carbon monoxide (DLCO), is limited in not considering dyspnea and functional impairment during the walking test. We proposed a MDD-based clinical score for mortality prediction among those patients. METHODS: From December 2018 to December 2019, we enrolled ILD patients with IPF and non-IPF and followed-up them till December 2020. Based on DLCO, modified Medical Research Council (mMRC) Dyspnea Scale, and six-minute walking test (6MWT) distance, a functional score was developed for mortality prediction. RESULTS: We enrolled 104 ILD patients, 12 (11.5%) died by the one-year follow-up. In receiver operating characteristic (ROC) curve analysis, DLCO (% predicted) was the most accurate variable predicting one-year mortality with an area under curve (AUC) of 0.88 (95% confidence interval [CI] = 0.80-0.94), followed by mMRC Dyspnea Score (AUC = 0.82 [95% CI = 0.73-0.89]), 6MWT distance (AUC = 0.80 [95% CI = 0.71-0.88]), and GAP score (AUC = 0.77 [95% CI = 0.67-0.84]). Only the GAP score (hazard ratio [HR] = 1.55, 95% CI = 1.03-2.34, p = 0.0.37) and functional score (HR = 3.45, 95% CI = 1.11-10.73, p = 0.032) were significantly associated with one-year mortality in multivariable analysis. CONCLUSION: The clinical score composite of DLCO, mMRC Dyspnea Scale, and 6MWT distance could provide an accurate prediction for long-term mortality in ILD patients, laying out a helpful tool for managing and following these patients.

Factors influencing long-term outcomes in fibrotic interstitial lung disease (F-ILD) diagnosed through multidisciplinary discussion (MDD): a prospective cohort study.

BACKGROUND: The diagnostic process for fibrotic interstitial lung disease (F-ILD) is notably intricate, necessitating a multidisciplinary discussion to achieve consensus based on both clinical and radiological features. This study investigated the shared and distinctive long-term mortality predictors among the two primary phenotypes of F-ILD, namely idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated interstitial lung disease (CTD-ILD). METHODS: We included patients with F-ILD diagnosed from December 2018 to December 2019 and conducted follow-up assessments until February 2023. Age, gender, usual interstitial pneumonia (UIP) pattern, gender-age-physiology (GAP) score, modified Medical Research Council (mMRC) dyspnea score, antifibrotic agent use, pulmonary function test parameters, and six-minute walking test (6MWT) parameters were recorded at baseline and used as mortality predictors in a multivariate Cox regression model. RESULTS: We enrolled 104 ILD patients. The survival rate of non-IPF patients was more than twice that of IPF patients (78.9% vs. 34%, p < 0.001), and the survival rate of patients with a GAP score of 0-2 was more than twice that of patients with a score of > 2 (93.2% vs. 36.6%, p < 0.001). Older age, male gender, definite UIP pattern, higher GAP score, higher mMRC dyspnea score, lower forced expiratory volume in one second/forced vital capacity (FEV1/FVC), shorter 6MWT distance, and lower initial and final SpO2 were also associated with higher long-term mortality (p < 0.05). In multivariable analysis, only a GAP score of > 2 (hazard ratio [HR]:16.7; 95% confidence interval [CI] 3.28-85.14; p = 0.001) and definite UIP pattern (HR: 4.08; 95% CI 1.07-15.5; p = 0.039) were significantly associated with overall mortality. CONCLUSION: The long-term mortality rate of IPF patients was higher than that of CTD-ILD patients. The GAP score and UIP patterns were significant mortality predictors for both IPF and CTD-ILD patients.

A presynaptic source drives differing levels of surround suppression in two mouse retinal ganglion cell types.

In early sensory systems, cell-type diversity generally increases from the periphery into the brain, resulting in a greater heterogeneity of responses to the same stimuli. Surround suppression is a canonical visual computation that begins within the retina and is found at varying levels across retinal ganglion cell types. Our results show that heterogeneity in the level of surround suppression occurs subcellularly at bipolar cell synapses. Using single-cell electrophysiology and serial block-face scanning electron microscopy, we show that two retinal ganglion cell types exhibit very different levels of surround suppression even though they receive input from the same bipolar cell types. This divergence of the bipolar cell signal occurs through synapse-specific regulation by amacrine cells at the scale of tens of microns. These findings indicate that each synapse of a single bipolar cell can carry a unique visual signal, expanding the number of possible functional channels at the earliest stages of visual processing.

Multimodal therapies and strategies for the treatment of interstitial cystitis/bladder pain syndrome in Taiwan.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic disease characterized by bladder pain, frequency, and nocturia. The most common pathologies include chronic inflammation and bladder urothelium dysfunction. According to the bladder condition with or without Hunner's lesions, IC/BPS can be divided into "IC" in patients with Hunner's lesion (HIC) and "BPS" in those without Hunner's lesion (NHIC). Previous studies have reported greater central sensitization and interorgan cross-talk in patients with NHIC. Multimodal treatments have been recommended in clinical guidelines under the biopsychosocial model. The bladder-gut-brain axis has also been speculated, and multimodal therapies are necessary. Unfortunately, currently, no treatment has been reported durable for IC/BPS. Patients with IC/BPS usually experience anxiety, depression, holistic physical responses, and even threats to social support systems. The lack of durable treatment outcomes might result from inadequate diagnostic accuracy and differentiation of clinical phenotypes based on the underlying pathophysiology. Precision assessment and treatment are essential for optimal therapy under definite IC/BPS phenotype. This article reviewed currently available literature and proposed a diagnosis and treatment algorithm. Based on bladder therapy combined with suitable physical and psychological therapies, a well-grounded multimodal therapy and treatment algorithm for IC/BPS following a diagnostic protocol are indispensable.