Exploring the role of anticipatory postural adjustment duration within APA2 subphase as a potential mediator between clinical disease severity and fall risk in Parkinson's disease.

Introduction: People with Parkinson's Disease (PD) often show reduced anticipatory postural adjustments (APAs) before voluntary steps, impacting their stability. The specific subphase within the APA stage contributing significantly to fall risk remains unclear. Methods: We analyzed center of pressure (CoP) trajectory parameters, including duration, length, and velocity, throughout gait initiation. This examination encompassed both the postural phase, referred to as anticipatory postural adjustment (APA) (APA1, APA2a, APA2b), and the subsequent locomotor phases (LOC). Participants were instructed to initiate a step and then stop (initiating a single step). Furthermore, we conducted assessments of clinical disease severity using the Unified Parkinson's Disease Rating Scale (UPDRS) and evaluated fall risk using Tinetti gait and balance scores during off-medication periods. Results: Freezing of gait (FOG) was observed in 18 out of 110 participants during the measurement of CoP trajectories. The Ramer-Douglas-Peucker algorithm successfully identified CoP displacement trajectories in 105 participants (95.5%), while the remaining 5 cases could not be identified due to FOG. Tinetti balance and gait score showed significant associations with levodopa equivalent daily dose, UPDRS total score, disease duration, duration (s) in APA2a (s) and LOC (s), length in APA1 (cm) and APA2b (cm), mediolateral velocity in APA1 (X) (cm/s), APA2a (X) (cm/s), APA2b (X) (cm/s) and LOC (X) (cm/s), and anterior-posterior velocity in APA2a (Z) (cm/s) and APA2b (Z) (cm/s). Multiple linear regression revealed that only duration (s) in APA2a and UPDRS total score was independently associated with Tinetti gait and balance score. Further mediation analysis showed that the duration (s) in APA2a served as a mediator between UPDRS total score and Tinetti balance and gait score (Sobel test, p = 0.047). Conclusion: APA2 subphase duration mediates the link between disease severity and fall risk in PD, suggesting that longer APA2a duration may indicate reduced control during gait initiation, thereby increasing fall risk.

Baroreflex Sensitivity as a Surrogate Biomarker for Concurrently Assessing the Severity of Arterial Stiffness and Cardiovascular Autonomic Neuropathy in Individuals with Type 2 Diabetes.

This study aimed to investigate whether baroreflex sensitivity (BRS) could serve as a reliable metric for assessing cardiovascular autonomic neuropathy (CAN) and concurrently act as a surrogate biomarker for evaluating the severity of arterial stiffness and CAN in individuals diagnosed with type 2 diabetes mellitus (T2DM). Participants underwent brachial-ankle pulse wave velocity (baPWV) as well as autonomic function evaluations encompassing the Sudoscan-based modified composite autonomic scoring scale (CASS), baroreflex sensitivity, and heart rate variability in time domains and frequency domains. Linear regression analysis was performed to evaluate the influence of independent variables on baPWV and modified CASS. Participants with higher baPWV values were older, with longer diabetes duration, lower body weight, body mass index, waist circumference, elevated systolic and diastolic blood pressure, and mean arterial blood pressure. They also exhibited a higher prevalence of retinopathy as the underlying disease and reduced estimated glomerular filtration rate. Multiple linear regression analysis revealed that age and BRS were significantly associated with baPWV while diabetes duration, UACR, and BRS were significantly associated with modified CASS. Our study confirms the significant association of BRS with baPWV and modified CASS in T2DM, highlighting its pivotal role in linking microvascular and macrovascular complications. This supports BRS as a surrogate marker for assessing both the severity of arterial stiffness and cardiovascular autonomic neuropathy in T2DM, enabling the early identification of complications.

Micro- and nanoplastics in agricultural soils: Assessing impacts and navigating mitigation.

Micro-/nanoplastic contamination in agricultural soils raises concerns on agroecosystems and poses potential health risks. Some of agricultural soils have received significant amounts of micro-/nanoplastics (MNPs) through plastic mulch film and biosolid applications. However, a comprehensive understanding of the MNP impacts on soils and plants remains elusive. The interaction between soil particles and MNPs is an extremely complex issue due to the different properties and heterogeneity of soils and the diverse characteristics of MNPs. Moreover, MNPs are a class of relatively new anthropogenic pollutants that may negatively affect plants and food. Herein, we presented a comprehensive review of the impacts of MNPs on the properties of soil and the growth of plants. We also discussed different strategies for mitigating or eliminating MNP contamination. Moreover, perspectives for future research on MNP contamination in the agricultural soils are also highlighted.

Longitudinal artificial intelligence-based deep learning models for diagnosis and prediction of the future occurrence of polyneuropathy in diabetes and prediabetes.

OBJECTIVE: The objective of this study was to develop artificial intelligence-based deep learning models and assess their potential utility and accuracy in diagnosing and predicting the future occurrence of diabetic distal sensorimotor polyneuropathy (DSPN) among individuals with type 2 diabetes mellitus (T2DM) and prediabetes. METHODS: In 394 patients (T2DM=300, Prediabetes=94), we developed a DSPN diagnostic and predictive model using Random Forest (RF)-based variable selection techniques, specifically incorporating the combined capabilities of the Clinical Toronto Neuropathy Score (TCNS) and nerve conduction study (NCS) to identify relevant variables. These important variables were then integrated into a deep learning framework comprising Convolutional Neural Networks (CNNs) and Long Short-Term Memory (LSTM) networks. To evaluate temporal predictive efficacy, patients were assessed at enrollment and one-year follow-up. RESULTS: RF-based variable selection identified key factors for diagnosing DSPN. Numbness scores, sensory test results (vibration), reflexes (knee, ankle), sural nerve attributes (sensory nerve action potential [SNAP] amplitude, nerve conduction velocity [NCV], latency), and peroneal/tibial motor NCV were candidate variables at baseline and over one year. Tibial compound motor action potential amplitudes were used for initial diagnosis, and ulnar SNAP amplitude for subsequent diagnoses. CNNs and LSTMs achieved impressive AUC values of 0.98 for DSPN diagnosis prediction, and 0.93 and 0.89 respectively for predicting the future occurrence of DSPN. RF techniques combined with two deep learning algorithms exhibited outstanding performance in diagnosing and predicting the future occurrence of DSPN. These algorithms have the potential to serve as surrogate measures, aiding clinicians in accurate diagnosis and future prediction of DSPN.

Predictive value of heart rate variability and electrochemical skin conductance measurements for cardiovascular autonomic neuropathy persistence in type 2 diabetes and prediabetes: A 3-year follow-up study.

OBJECTIVE: The study aimed to explore risk stratification approaches for cardiovascular autonomic neuropathy (CAN) in individuals with prediabetes and type 2 diabetes (T2DM) over a three-year follow-up period. METHODS: Participants underwent evaluations of autonomic function encompassing cardiovascular autonomic reflex tests (CARTs), baroreflex sensitivity (BRS), heart rate variability (HRV) in time domains (standard deviation of all normal RR intervals (SDNN)) and frequency domains (high frequency/low frequency ratio), and electrochemical skin conductance (ESC). The diagnosis of CAN relied on abnormal CART results. Subjects were categorized into 4 groups, based on their assessment of cardiac autonomic function at 3-year follow-up, relative to the presence or absence of CAN at baseline assessment: Persistent absence of CAN; Resolution of CAN; Progression to CAN; and Persistent CAN. RESULTS: Participants with T2DM/prediabetes (n = 91/7) were categorized as: Persistent absence of CAN (n = 25), Resolution of CAN (n = 10), Progression to CAN (n = 18), and Persistent CAN (n = 45) groups. The Persistent absence of CAN group showed significant associations with SDNN. The Resolution of CAN group exhibited notable associations with mean HbA1C (follow-up), while the Progression to CAN group displayed a significant link with baseline estimated glomerular filtration rate. The Persistent CAN group demonstrated significant associations with SDNN and Sudoscan CAN risk score. Screening recommendations involve biennial to annual assessments based on risk levels, aiding in CAN detection and subsequent comprehensive and time-intensive autonomic function tests for confirmation. The study's findings offer improved risk categorization approaches for detecting CAN, which has relevance for shaping public health strategies.

Prognostic value of longitudinal HbA1c variability in predicting the development of diabetic sensorimotor polyneuropathy among patients with type 2 diabetes mellitus: A prospective cohort observational study.

AIMS/INTRODUCTION: This prospective cohort study aims to identify the optimal measure of glycated hemoglobin (HbA1c) variability and to explore its relationship with the development of new diabetic sensorimotor polyneuropathy (DSPN) in individuals with type 2 diabetes mellitus, building upon previous cross-sectional studies that highlighted a significant association between HbA1c visit-to-visit variability and DSPN. MATERIALS AND METHODS: In a prospective study, 321 participants diagnosed with type 2 diabetes mellitus underwent comprehensive clinical assessments, neurophysiologic studies, and laboratory evaluations at enrollment and follow-up. Various indices, including HbA1c standard deviation (HbA1c SD), coefficient of variation (HbA1c CV), HbA1c change score (HbA1c HVS), and average real variability (HbA1c ARV), were employed to calculate the visit-to-visit variability HbA1c based on 3 month intervals. The investigation focused on examining the associations between these indices and the development of new DSPN. RESULTS: The average follow-up duration was 16.9 ± 6.9 months. The Cox proportional hazards model identified age (P = 0.001), diabetes duration (P = 0.024), and HbA1C ARV (P = 0.031) as the sole factors associated with the development of new DSPN. Furthermore, the cumulative risk of developing DSPN over 1 year demonstrated a significant association with HbA1C ARV (P = 0.03, log-rank test). CONCLUSIONS: Apart from age and diabetes duration, HbA1c variability emerged as a robust predictor for the occurrence of new DSPN. Among the various measures of HbA1c variability evaluated, HbA1c ARV demonstrated the highest potential as a reliable indicator for anticipating the onset of new DSPN.

Sudoscan as substitute for quantitative sudomotor axon reflex test in composite autonomic scoring scale and its correlation with composite autonomic symptom scale 31 in type 2 diabetes.

OBJECTIVE: This study aims to evaluate the feasibility of substituting electrochemical skin conductance measurement using SUDOSCAN for sudomotor function testing in the Composite Autonomic Scoring Scale (CASS) and to correlate the results with the Composite Autonomic Symptom Scale 31 (COMPASS 31) among patients with type 2 diabetes mellitus (T2DM). METHODS: Fifty patients with T2DM underwent cardiovascular autonomic function testing and the SUDOSCAN test and completed the COMPASS 31 questionnaire. We developed a SUDOSCAN-based sudomotor subscore as a substitute for the original sudomotor subscore (based on the quantitative sudomotor axon reflex test [QSART]). The modified CASS score (SUDOSCAN-based sudomotor subscore combined with the adrenergic and cardiovagal subscores) and the original CASS score without suomotor assessment (sum of the adrenergic and cardiovagal subscores) were obtained according to the results of the cardiovascular autonomic function and SUDOSCAN tests. RESULTS: The total COMPASS 31 score was significantly correlated with the modified CASS score (p = 0.019 and 0.037 for the raw and weighted scores, respectively) but not with the CASS score without sudomotor assessment. After adding the SUDOSCAN-based sudomotor subscore, the number of patients identified as having diabetic autonomic neuropathy (DAN) increased from 24 (48 %, based on the CASS score without sudomotor assessment) to 35 (70 %, based on the modified CASS score). The modified CASS score enhances the accuracy of assessing autonomic function and improves the diagnosis of diabetic autonomic neuropathy (DAN) among patients with T2DM. In medical settings where QSART is not accessible, SUDOSCAN testing offers a practical and efficient alternative.

Impacts of Chemerin Levels and Antioxidant Capacity on the Severity of Cardiovascular Autonomic Neuropathy in Patients with Type 2 Diabetes and Prediabetes.

Existing evidence supports an association between chemerin levels and cardiovascular risk, while reduced thiol levels are linked to diabetes mellitus. It is hypothesized that chemerin may contribute to autonomic dysfunction and cardiovascular risk in type 2 diabetes mellitus (T2DM), potentially mediated by the antioxidant capacity of patients with well-controlled T2DM and prediabetes. Comprehensive cardiovascular autonomic testing and biomarker assessments were conducted for all participants. The severity of cardiovascular autonomic neuropathy (CAN) was evaluated using the composite autonomic scoring scale (CASS). A mediation model was employed to explore the potential relationships among chemerin levels, antioxidant capacity (indicated by thiol levels), and CAN severity (indicated by CASS values). A total of 184 participants were enrolled in this study, comprising 143 individuals with T2DM and 40 individuals with prediabetes. The findings reveal a significant negative association between thiols levels (r = -0.38, p < 0.0001) and the CASS values, while a positive association is observed between chemerin levels (r = 0.47, p < 0.0001) and the CASS values. Linear regression analysis identified chemerin and thiols as independent variables significantly associated with CASS values. Subsequent mediation analysis elucidated that thiols levels act as mediators in the relationship between elevated chemerin levels and an increased CASS value. This study shows that poor cardiovascular function, higher chemerin levels, and reduced antioxidant capacity coexist in individuals with T2DM and prediabetes. Mediation analysis suggests a pathophysiological link between high chemerin levels and low antioxidant capacity, adversely impacting CAN severity.

Mining host candidate regulators of schistosomiasis-induced liver fibrosis in response to artesunate therapy through transcriptomics approach.

BACKGROUND: Artesunate (ART) has been reported to have an antifibrotic effect in various organs. The underlying mechanism has not been systematically elucidated. We aimed to clarify the effect of ART on liver fibrosis induced by Schistosoma japonicum (S. japonicum) in an experimentally infected rodent model and the potential underlying mechanisms. METHODS: The effect of ART on hepatic stellate cells (HSCs) was assessed using CCK-8 and Annexin V-FITC/PI staining assays. The experimental model of liver fibrosis was established in the Mongolian gerbil model infected with S. japonicum cercariae and then treated with 20 mg/kg or 40 mg/kg ART. The hydroxyproline (Hyp) content, malondialdehyde (MDA) content, superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities in liver tissue were measured and histopathological changes of liver tissues were observed. Whole-transcriptome RNA sequencing (RNA-seq) of the liver tissues was performed. Differentially expressed genes (DEGs) were identified using bioinformatic analysis and verified by quantitative PCR (qPCR) and western blot assay. RESULTS: ART significantly inhibited the proliferation and induce the apoptosis of HSCs in a dose-dependent manner. In vivo, Hyp content decreased significantly in the ART-H group compared to the model (MOD) group and GPX activity was significantly higher in the ART-H group than in the MOD group. Besides, ART treatment significantly reduced collagen production (p <0.05). A total of 158 DEGs and 44 differentially expressed miRNAs related to ART-induced anti-schistosomiasis liver fibrosis were identified. The qPCR and western blot results of selected DEGs were consistent with the sequencing results. These DEGs were implicated in key pathways such as immune and inflammatory response, integrin-mediated signaling and toll-like receptor signaling pathways. CONCLUSION: ART is effective against liver fibrosis using Mongolian gerbil model induced by S. japonicum infection. We identified host candidate regulators of schistosomiasis-induced liver fibrosis in response to ART through transcriptomics approach.

Enhancing Spiritual Well-Being, Physical Activity, and Happiness in Hospitalized Older Adult Patients with Swallowing Difficulties: A Comparative Study of Thickeners and Swallowing Exercises.

Swallowing difficulties often occur in older adult patients during acute hospitalization, leading to reduced nutritional intake, increased frailty, and various psychosocial challenges. This randomized controlled study aimed to assess the effects of two interventions, thickeners and swallowing exercises, on the spiritual well-being, physical activity, and happiness of older adult patients with swallowing difficulties during acute hospitalization from October 2019 to August 2020. Sample size calculation was performed using a conservative estimate approach, resulting in an estimate-required sample size of 42 participants. The sampling method was a random cluster sampling approach, with three ward rooms assigned to the thickeners group, swallowing exercises group and control group, respectively. Seventy-two participants were assigned to the intervention groups (thickeners or swallowing exercises) or the control group using a 1:1:1 stratified random assignment. Data were collected before and after the intervention, and matched samples were analyzed using t-tests, ANOVA, and generalized estimating equations for statistical analysis. Both intervention groups showed significant improvements in spiritual well-being (p < 0.001), physical activity (p < 0.001), and happiness (p < 0.001) compared to the control group. However, there were no significant differences between the intervention groups. Our findings suggest that interventions involving thickeners and swallowing exercises have positive effects on the spiritual well-being, physical activity, and happiness of older adult patients with swallowing difficulties during acute hospitalization and emphasize the importance of implementing these interventions to enhance the overall well-being and quality of life of this vulnerable patient population.

Quantitative thermal testing as a screening and follow-up tool for diabetic sensorimotor polyneuropathy in patients with type 2 diabetes and prediabetes.

Introduction: The diagnosis and assessment of neuropathy severity of diabetic sensorimotor polyneuropathy (DSPN) are mainly based on clinical neuropathy scores and electrophysiologic studies. This study aimed to determine whether quantitative thermal testing (QTT) can be used as a screening and follow-up tool for DSPN of prediabetes and type 2 diabetes at baseline and at 1-year follow-up. Methods: All patients were assessed using the Toronto Clinical Neuropathy Score (TCNS) and underwent electrophysiological testing, including a nerve conduction study (NCS) and QTT, at baseline and at a 1-year follow-up. The TCNS and the composite scores of nerve conduction were used to assess the severity of DSPN. The DSPN status at the 1-year follow-up was classified as remaining no DSPN, remaining DSPN, regression to no DSPN, or progression to DSPN. Results: Diabetic sensorimotor polyneuropathy was initially diagnosed in 89 patients with prediabetes and type 2 diabetes (22%). The regressed to no DSPN in 29 patients and progressed to DSPN in 20 patients at the 1-year follow-up. TCNS was significantly correlated with composite scores of nerve conduction, hand cold detection threshold (CDT), hand warm detection threshold (WDT), foot CDT, and foot WDT. Stepwise logistic regression demonstrated that the foot CDT (p < 0.0001) was independently associated with the presence of DSPN. The TCNS, composite scores of the nerve conduction, hand WDT, hand CDT, foot WDT, and foot CDT were all statistically significant among the four different DSPN status groups at two different time periods (baseline and the 1-year follow-up). Conclusion: The foot CDT can be used as an initial screening tool for DSPN alternatively. The characteristics of nerve damage after 1 year of DSPN can be progressive or reversible, and the neurological functions of large and small fibers have a parallel trend, which can be objectively measured by NCS and QTT.

Effectiveness of Center of Pressure Trajectory as Anticipatory Postural Adjustment Measurement in Parkinson's Disease With Freezing of Gait History.

BACKGROUND: Evidence showed that patients with Parkinson's disease (PD) who have a history of freezing of gait (FOG) have hypometric anticipatory postural adjustment (APA) during gait initiation (GI) compared to PD without FOG. OBJECTIVES: This study aimed to test the feasibility of center of pressure (COP) displacement during GI as the measure of APA in PD with and without a history of FOG. METHODS: Patients with PD underwent COP trajectory measurements, including duration, length, velocity, and acceleration in different phases of APA (APA1, APA2a, APA2, and LOC), as well as evaluation of New Freezing of Gait Questionnaire (NFOG-Q), Tinetti balance and gait score, and Postural Instability and Gait Difficulty (PIGD) score in the on and off medication states. RESULTS: The duration (seconds) of APA2a, APA2b, and LOC were highest while velocity in mediolateral direction (X) (m/s), including APA1, APA2a, APA2b, and LOC showed lowest in PD with FOG. Velocity in the mediolateral direction in different phases of APA increased in patients with FOG after dopaminergic therapy. APA2a (seconds) and APA2b (X) (m/s) were significantly associated with NFOG-Q part II, APA2b (X) (m/s) was significantly associated with NFOG-Q part III, and APA2a (seconds) was significantly associated with Tinetti balance and gait and PIGD score. CONCLUSIONS: PD with FOG history showed a favorable response of APAs to dopaminergic replacement. The APA parameters by COP trajectory, especially lateral COP shift toward the stance foot (APA2b (X) (m/s) and APA2a (seconds)) are surrogate markers to assess PD with FOG history.

Effect of omega-6 linoleic acid on neurobehavioral development in Caenorhabditis elegans.

Linoleic acid (LA, omega-6), an essential polyunsaturated fatty acid, is supplied by vegetable oils such as corn, sunflower and soybean. Supplementary LA in infants and children is required for normal growth and brain development, but has also been reported to induce brain inflammation and neurodegenerative diseases. This controversial role of LA development requires further investigation. Our study utilized Caenorhabditis elegans (C. elegans) as a model to clarify the role of LA in regulating neurobehavioral development. A mere supplementary quantity of LA in C. elegans larval stage affected the worm's locomotive ability, intracellular ROS accumulation and lifespan. We found that more serotonergic neurons were activated by supplementing LA above 10 µM thereby promoting locomotive ability with upregulation of serotonin-related genes. Supplementation with LA above 10 µM also inhibited the expression of mtl-1, mtl-2 and ctl-3 to accelerate oxidative stress and attenuate lifespan in nematodes; however, enhancement of stress-related genes such as sod-1, sod-3, mtl-1, mtl-2 and cyp-35A2 by supplementary LA under 1 µM decreased oxidative stress and increased the worm's lifespan. In conclusion, our study reveals that supplementary LA possesses both pros and cons in worm physiology and provides new suggestions for LA intake administration in childhood.

Clinical Utility of Plantar Pressure Measurements as Screening in Patients With Parkinson Disease With and Without Freezing of Gait History.

OBJECTIVE: To test the feasibility of objective assessments using the TekScan MatScan pressure mat plantar pressure measurement as a time-effective screening service for Parkinson disease (PD) with and without freezing of gait (FOG) history. DESIGN: Prospective cross-sectional study. SETTING: Largest medical center in southern Taiwan. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Plantar pressure measurements including average peak pressure (PP), contact area (CA), and pressure-time integral (PTI) in static and dynamic conditions as well as clinical scores during off-medication states. PARTICIPANTS: A total of 103 patients with PD and 22 age- and sex-matched volunteers without PD (N=125). RESULTS: Plantar pressure assessment including PP, CA, and PTI on the total foot areas between participants with PD and controls without PD in the static conditions are similar. Patients with PD presented higher PTI on total foot areas as well as hallux, midfoot area, and medial and lateral heels during dynamic conditions than controls without PD. The PP, CA, and PTI during the static condition and CA during the dynamic condition on the hallux showed statistical significance between PD with and without FOG history. Stepwise logistic regression after controlling with age and body mass index showed only PTI on hallux (static conditions) was significantly associated with the presence of FOG. The receiver operating characteristic curve analysis in diagnostic accuracy for FOG in PTI was statistically significant (P=.002; area under the curve, 0.71). CONCLUSIONS: FOG screening using the TekScan MatScan pressure mat plantar pressure measurement could serve as a time-effective screening service at the outpatient clinic. Based on our study, PTI may be valuable in auxiliary diagnosis.

Assessing the Feasibility of Using Electrochemical Skin Conductance as a Substitute for the Quantitative Sudomotor Axon Reflex Test in the Composite Autonomic Scoring Scale and Its Correlation with Composite Autonomic Symptom Scale 31 in Parkinson's Disease.

The Composite Autonomic Scoring Scale (CASS) is a quantitative scoring system that integrates the sudomotor, the cardiovagal, and the adrenergic subscores, and the Composite Autonomic Symptom Scale 31 (COMPASS 31) is based on a well-established comprehensive questionnaire designed to assess the autonomic symptoms across multiple domains. We tested the hypothesis that electrochemical skin conductance (Sudoscan) can be a substitute for the quantitative sudomotor axon reflex test (QSART) in the sudomotor domain and assessed its correlation with COMPASS 31 in patients with Parkinson's disease (PD). Fifty-five patients with PD underwent clinical assessment and cardiovascular autonomic function tests and completed the COMPASS 31 questionnaire. We compared the modified CASS (integrating the Sudoscan-based sudomotor, adrenergic, and cardiovagal subscores) and CASS subscores (the sum of the adrenergic and cardiovagal subscores). The total weighted score of COMPASS 31 was significantly correlated with both the modified CASS and the CASS subscore (p = 0.007 and p = 0.019). The correlation of the total weighted score of COMPASS 31 increased from 0.316 (CASS subscores) to 0.361 (modified CASS). When we added the Sudoscan-based sudomotor subscore, the case numbers for autonomic neuropathy (AN) increased from 22 (40%, CASS subscores) to 40 (72.7%, modified CASS). The modified CASS not only better reflects the exact autonomic function, but also improves the characterization and quantification of AN in patients with PD. In areas in which a QSART facility is not easily available, Sudoscan could be a time-saving substitution.

7,10,13,16-Docosatetraenoic acid impairs neurobehavioral development by increasing reactive oxidative species production in Caenorhabditis elegans.

AIMS: To investigate human breast milk (HBM) lipids that may adversely affect infant neurodevelopment. MAIN METHODS: We performed multivariate analyses that combined lipidomics and psychologic Bayley-III scales to identify which HBM lipids are involved in regulating infant neurodevelopment. We observed a significant moderate negative correlation between 7,10,13,16-docosatetraenoic acid (omega-6, C22H36O2, the common name adrenic acid, AdA) and adaptive behavioral development. We further studied the effects of AdA on neurodevelopment by using Caenorhabditis elegans (C. elegans) as a model. Worms from larval stages L1 to L4 were supplemented with AdA at 5 nominal concentrations (0 µM [control], 0.1 µM, 1 µM, 10 µM, and 100 µM) and subjected to behavioral and mechanistic analyses. KEY FINDINGS: Supplementation with AdA from larval stages L1 to L4 impaired neurobehavioral development, such as locomotive behaviors, foraging ability, chemotaxis behavior, and aggregation behavior. Furthermore, AdA upregulated the production of intracellular reactive oxygen species. AdA-induced oxidative stress blocked serotonin synthesis and serotoninergic neuron activity and inhibited expression of daf-16 and the daf-16-regulated genes mtl-1, mtl-2, sod-1, and sod-3, resulting in attenuation of the lifespan in C. elegans. SIGNIFICANCE: Our study reveals that AdA is a harmful HBM lipid that may have adverse effects on infant adaptive behavioral development. We believe this information may be critical for AdA administration guidance in children's health care.

The Effects of Indoxyl Sulfate and Oxidative Stress on the Severity of Peripheral Nerve Dysfunction in Patients with Chronic Kidney Diseases.

Pieces of evidence support the view that the accumulation of uremic toxins enhances oxidative stress and downstream regulation of signaling pathways, contributing to both endothelial microangiography and cell dysfunction. This study is to address the impact of protein-binding uremic toxins on the severity of peripheral nerve function in patients with chronic kidney disease (CKD). Fifty-four patients with CKD were included in the Toronto Clinical Neuropathy Score (TCNS), nerve conduction study (NCS), and laboratory studies including protein-binding uremic toxin (indoxyl sulfate [IS] and p-cresyl sulfate [PCS]), oxidative stress (Thiol and thiobarbituric acid reacting substances [TBARS]), and endothelial dysfunction (serum intercellular adhesion molecule 1 [sICAM-1] and serum vascular adhesion molecule 1 [sVCAM-1]) at enrollment. We used composite amplitude scores (CAS) to analyze the severity of nerve conductions on peripheral nerve function. TCNS and CAS were higher in the diabetic CKD group (p = 0.02 and 0.01, respectively). The NCS revealed the compound muscle action potential of ulnar and peroneal nerves and the sensory nerve action potential of ulnar and sural nerves (p = 0.004, p = 0.004, p = 0.004, and p = 0.001, respectively), which was found to be significantly low in the diabetic group. CAS was significantly correlated with age (r = 0.27, p = 0.04), urine albumin-creatinine ratio (UACR) (r = 0.29, p = 0.046), free-form IS (r = 0.39, p = 0.009), sICAM-1 (r = 0.31, p = 0.02), sVCAM-1 (r = 0.44, p < 0.0001), TBARS (r = 0.35, p = 0.002), and thiols (r = −0.28, p = 0.045). Linear regression revealed that only TBARS and free-form IS were strongly associated with CAS. The mediation analysis shows that the sVCAM-1 level serves as the mediator between higher IS and higher CAS. IS and oxidative stress contribute to the severity of peripheral nerve dysfunction in patients with CKD, and chronic glycemic impairment can worsen the conditions.

The Utilization of Chinese Herbal Products for Hyperthyroidism in National Health Insurance System (NHIRD) of Taiwan: A Population-Based Study.

Background: Traditional Chinese Medicine (TCM) relieves associated symptoms of hyperthyroidism such as heat intolerance, palpitations, tremor, anxiety, weight loss, increased frequency of bowel movements, and shortness of breath. However, there are no studies regarding the core prescription patterns of herbal formula and single herbs for hyperthyroidism in Taiwan. Materials and Methods: This is a retrospective, observational study using the National Health Insurance Research Database (NHIRD) in Taiwan to analyze the prescription patterns of TCM. Demographic factors, such as sex, age, occupational status, and residential area, and the risk factors for hyperthyroidism were also studied. Results: The outpatient or/and inpatient services for hyperthyroidism receive 17,707 cases in a year. Overall, there were 13,394 newly diagnosed patients. TCM was used in 73% of the patients, and 77.3% of the patients were females. The acceptability of TCM was higher among female patients. Most patients were diagnosed with hyperthyroidism between the ages of 30 and 49 years. The most common comorbidity identified was diabetes mellitus. The most commonly prescribed Chinese herbal product (CHP) formula was Jia-Wei-Xia-Yao-San, while Xia-Ku-Cao was the most commonly prescribed single CHP. There was a high coprescription rate for Xuan-Shen, Bei-Mu, and Mu-Li. Conclusion: This study describes the core prescription pattern of TCM used in the treatment of patients with hyperthyroidism in Taiwan. The most frequently used CHPs could be potential candidates for future pharmacologic studies or clinical trials.

Radiotherapy Is Associated with an Accelerated Risk of Carotid Atherosclerosis in Patients with Nasopharyngeal Carcinoma: A Nine-Year Prospective Follow-Up Study.

Radiation-related extracranial vasculopathy is a common late effect after radiation in patients with nasopharyngeal carcinoma (NPC). We proposed the hypothesis that radiation-related extracranial vasculopathy is a progressive process that can begin immediately after radiotherapy and persist for a longer period, and inflammation and oxidative stress may play a pivotal role in this process. Thirty-six newly diagnosed NPC patients were assessed with B-mode ultrasound for the common carotid artery (CCA) intima media thickness (IMT) measurement as well as surrogate markers at three different stages (baseline, immediately after concurrent chemoradiation therapy (CCRT), and 9 years after enrollment). A healthy control group was also recruited for comparison. Surrogate markers including a lipid profile, HbA1c, inflammation, oxidative stress, and platelet activation markers were assessed. The mean CCA IMT in the NPC group were increased immediately after CCRT (p = 0.043). The mean CCA IMT value after a 9-year follow-up also showed a significant increase in NPC and control group, respectively (p < 0.0001 and p < 0.0001, paired t test). The annual increase mean CCA IMT (mm) was 0.053 ± 0.025 and 0.014 ± 0.013 in NPC and control group, respectively (p < 0.0001). The baseline high sensitivity CRP (hs-CRP), thiol, TBARS, and CD63 level were significantly higher in the NPC group (hs-CRP, p = 0.001, thiol, p < 0.0001, TBARS, p = 0.05, and CD63 level, p = 0.04). The thiol and TBARS levels were significantly lower in NPC patients immediately after CCRT (thiol, p < 0.0001, and TBARS, p = 0.043). The CD62P level was significantly higher while the thiol level was significantly lower in the NPC group after a 9-year follow-up (CD62P level, p = 0.007; and thiol level, p = 0.004). Radiation-related extracranial vasculopathy is a progressive process that begins immediately after radiotherapy with significantly increased carotid IMT compared to the control group during the 9-year follow-up. Chronic inflammation and oxidative stress might serve to drive the process and also contribute to increased platelet activation.

Concurrent chemoradiation therapy is associated with an accelerated risk of cardiovascular autonomic dysfunction in patients with nasopharyngeal carcinoma: A 9-year prospective follow-up study.

BACKGROUND: Concurrent chemoradiation therapy (CCRT) is the mainstay treatment for patients with nasopharyngeal carcinoma (NPC). Baroreflex impairment can be a late sequela in patients after neck radiotherapy. We hypothesized that cardiovascular autonomic dysfunction is a progressive process that can begin after CCRT and persists for a longer period. METHODS: Cardiovascular autonomic function was assessed in 29 newly diagnosed patients with NPC using standardized measures including heart rate response to deep breathing (HRDB), Valsalva ratio (VR), baroreflex sensitivity (BRS), and analyses of heart rate variability (HRV), biomarkers of oxidative stress, and inflammation at three different time points (baseline, immediately after CCRT, and 9 years after enrollment). A healthy control group was recruited for the comparison. RESULTS: Although there was an aging effect on autonomic parameters in both groups during the 9 years of follow-up, the between-group comparison showed that there was a significant decrease in HRDB, VR, and HRV at the 9th year of follow-up in the NPC group. Repeated measures ANOVA after controlling for age and sex showed that both HRDB and triangle index of HRV had statistically significant differences between the two groups. CONCLUSION: Based on our results, cardiovascular autonomic dysfunction after CCRT is a progressive and dynamic process. Cardiovagal impairment occurs in the early phase and persists in decline, while adrenergic dysfunction is significant only after a 9-year follow-up. In contrast to the current opinion, our study showed that both afferent and efferent baroreflex pathways can be involved after CCRT.