Evaluating community-wide temporal sampling in passive acoustic monitoring: A comprehensive study of avian vocal patterns in subtropical montane forests.

Background: From passive acoustic monitoring (PAM) recordings, the vocal activity rate (VAR), vocalizations per unit of time, can be calculated and is essential for assessing bird population abundance. However, VAR is subject to influences from a range of factors, including species and environmental conditions. Identifying the optimal sampling design to obtain representative acoustic data for VAR estimation is crucial for research objectives. PAM commonly uses temporal sampling strategies to decrease the volume of recordings and the resources needed for audio data management. Yet, the comprehensive impact of this sampling approach on VAR estimation remains insufficiently explored. Methods: In this study, we used vocalizations extracted from recordings of 12 bird species, taken at 14 PAM stations situated in subtropical montane forests over a four-month period, to assess the impact of temporal sampling on VAR across three distinct scales: short-term periodic, diel, and hourly. For short-term periodic sampling analysis, we employed hierarchical clustering analysis (HCA) and the coefficient of variation (CV). Generalized additive models (GAMs) were utilized for diel sampling analysis, and we determined the average difference in VAR values per minute for the hourly sampling analysis. Results: We identified significant day and species-specific VAR fluctuations. The survey season was divided into five segments; the earliest two showed high variability and are best avoided for surveys. Data from days with heavy rain and strong winds showed reduced VAR values and should be excluded from analysis. Continuous recordings spanning at least seven days, extending to 14 days is optimal for minimizing sampling variance. Morning chorus recordings effectively capture the majority of bird vocalizations, and hourly sampling with frequent, shorter intervals aligns closely with continuous recording outcomes. Conclusions: While our findings are context-specific, they highlight the significance of strategic sampling in avian monitoring, optimizing resource utilization and enhancing the breadth of monitoring efforts.

An acoustic detection dataset of birds (Aves) in montane forests using a deep learning approach.

Background: Long-term monitoring is needed to understand the statuses and trends of wildlife communities in montane forests, such as those in Yushan National Park (YSNP), Taiwan. Integrating passive acoustic monitoring (PAM) with an automated sound identifier, a long-term biodiversity monitoring project containing six PAM stations, was launched in YSNP in January 2020 and is currently ongoing. SILIC, an automated wildlife sound identification model, was used to extract sounds and species information from the recordings collected. Animal vocal activity can reflect their breeding status, behaviour, population, movement and distribution, which may be affected by factors, such as habitat loss, climate change and human activity. This massive amount of wildlife vocalisation dataset can provide essential information for the National Park's headquarters on resource management and decision-making. It can also be valuable for those studying the effects of climate change on animal distribution and behaviour at a regional or global scale. New information: To our best knowledge, this is the first open-access dataset with species occurrence data extracted from sounds in soundscape recordings by artificial intelligence. We obtained seven bird species for the first release, with more bird species and other taxa, such as mammals and frogs, to be updated annually. Raw recordings containing over 1.7 million one-minute recordings collected between the years 2020 and 2021 were analysed and SILIC identified 6,243,820 vocalisations of seven bird species in 439,275 recordings. The automatic detection had a precision of 0.95 and the recall ranged from 0.48 to 0.80. In terms of the balance between precision and recall, we prioritised increasing precision over recall in order to minimise false positive detections. In this dataset, we summarised the count of vocalisations detected per sound class per recording which resulted in 802,670 occurrence records. Unlike data from traditional human observation methods, the number of observations in the Darwin Core "organismQuantity" column refers to the number of vocalisations detected for a specific bird species and cannot be directly linked to the number of individuals.We expect our dataset will be able to help fill the data gaps of fine-scale avian temporal activity patterns in montane forests and contribute to studies concerning the impacts of climate change on montane forest ecosystems on regional or global scales.

Clinical Disease Severity Mediates the Relationship between Stride Length and Speed and the Risk of Falling in Parkinson's Disease.

The shuffling gait with slowed speed and reduced stride length has been considered classic clinical features in idiopathic Parkinson's disease (PD), and the risk of falling increases as the disease progresses. This raises the possibility that clinical disease severity might mediate the relationship between stride length and speed and the risk of falling in patients with PD. Sixty-one patients with PD patients underwent the clinical scores as well as quantitative biomechanical measures during walking cycles before and after dopamine replacement therapy. Mediation analysis tests whether the direct effect of an independent variable (stride length and speed) on a dependent variable (three-step fall prediction model score) can be explained by the indirect influence of the mediating variable (Unified Parkinson's Disease Rating Scale (UPDRS) total scores). The results demonstrate that decreased stride length, straight walking speed, and turning speed is associated with increased three-step fall prediction model score (r = -0.583, p < 0.0001, r = -0.519, p < 0.0001, and r = -0.462, p < 0.0001, respectively). We further discovered that UPDRS total scores value is negatively correlated with stride length, straight walking, and turning speed (r = -0.651, p < 0.0001, r = -0.555, p < 0.0001, and r = -0.372, p = 0.005, respectively) but positively correlated with the fall prediction model score value (r = 0.527, p < 0.0001). Further mediation analysis shows that the UPDRS total score values serve as mediators between lower stride length, straight walking, and turning speed and higher fall prediction model score values. Our results highlighted the relationship among stride length and speed, clinical disease severity, and risk of falling. As decreased stride length and speed are hallmarks of falls, monitoring the changes of quantitative biomechanical measures along with the use of wearable technology in a longitudinal study can provide a scientific basis for pharmacology, rehabilitation programs, and selecting high-risk candidates for surgical treatment to reduce future fall risk.

Feasibility of Combining Disease-Specific and Balance-Related Measures as Risk Predictors of Future Falls in Patients with Parkinson's Disease.

Evidence supports the view that postural sway in a quiet stance increases with clinical disease severity and dopaminergic therapy in idiopathic Parkinson's disease (PD), which, in turn, increases the risk of falling. This study evaluated the feasibility of combining disease-specific and balance-related measures as risk predictors for future falls in patients with PD. The patients with PD underwent postural sway measurements (area, length, and velocity traveled by the excursion of the center of pressure) and clinical functional scores (Parkinson's Disease Rating Scale [UPDRS] and Tinetti balance and gait score assessment) in both the on- and off-states of dopaminergic therapy. The outcome was defined as the development of a new fall. The sway area, velocity, and length increased after the medication administration. The Cox proportional hazards model showed that only previous fall history, Tinetti balance and gait score (on-state), and levodopa equivalent daily dose (LEDD) were associated with the development of future falls. The cumulative risk of fall development showed that the sway length and velocity were associated with future falls after more than six months. The combined LEDD, Tinetti balance and gait score (on-state), and velocity and length of postural sway (on-state) had the highest diagnostic accuracy (area under the curve = 0.9, p < 0.0001). Dopaminergic therapy can improve clinical functional scores but worsen balance-related measures. Increased sway length and velocity during the medication state are hallmarks of future falls, particularly in advanced PD. Combining disease-specific and balance-related measures can serve as an auxiliary diagnosis as risk predictors for future falls.

Adipose-Derived Stromal Cells and Mineralized Extracellular Matrix Delivery by a Human Decellularized Amniotic Membrane in Periodontal Tissue Engineering.

Periodontitis is a prevalent disease characterized by the loss of periodontal supporting tissues, bone, periodontal ligament, and cementum. The application of a bone tissue engineering strategy with Decellularized Human Amniotic Membrane (DAM) with adipose-derived stromal cells (ASCs) has shown to be convenient and valuable. This study aims to investigate the treatments of a rat periodontal furcation defect model with DAM, ASCs, and a mineralized extracellular matrix (ECM). Rat ASCs were expanded, cultivated on DAM, and with a bone differentiation medium for four weeks, deposited ECM on DAM. Periodontal healing for four weeks was evaluated by micro-computed tomography and histological analysis after treatments with DAM, ASCs, and ECM and compared to untreated defects on five consecutive horizontal levels, from gingival to apical. The results demonstrate that DAM preserves its structure during cultivation and healing periods, supporting cell attachment, permeation, bone deposition on DAM, and periodontal regeneration. DAM and DAM+ASCs enhance bone healing compared to the control on the gingival level. In conclusion, DAM with ASC or without cells and the ECM ensures bone tissue healing. The membrane supported neovascularization and promoted osteoconduction.

Feasibility of combining heart rate variability and electrochemical skin conductance as screening and severity evaluation of cardiovascular autonomic neuropathy in type 2 diabetes.

AIMS/INTRODUCTION: Clinical studies show that either heart rate variability (HRV) or electrochemical skin conductance (ESC) alone can serve as a simple and objective method for screening cardiovascular autonomic neuropathy (CAN). We tested the hypothesis that combining these two quantitative approaches can not only reinforce accuracy in CAN screening but also provide a better estimate of CAN severity in patients with type 2 diabetes (T2DM) who had already had CAN in outpatient clinics. MATERIALS AND METHODS: Each patient received a complete battery of cardiovascular autonomic reflex tests (CARTs), with ESC measured by SUDOSCAN, time domain of HRV measured by standard deviation of all normal RR intervals (SDNN) and frequency domain of HRV (low frequency [LF], high frequency [HF], and LF/HF ratio), and peripheral blood studies for vascular risk factors. Severity of CAN was measured by CAN score. RESULTS: The 90 T2DM patients included 50 males and 40 females. Those with more severe CAN had lower values in feet ESC (P = 0.023) and SDNN (P < 0.0001). Multiple linear regression analysis also showed that feet ESC and SDNN value (P = 0.003 and P < 0.0001) were significantly associated with CAN score. Combining SDNN and feet ESC also can increase the diagnostic accuracy of CAN with respective to sensitivity and specificity by using receiver operating characteristic analysis. CONCLUSIONS: Combining the results of SDNN and feet ESC can not only assess, but also quantitatively reflect the progress or improvement of autonomic nerve function (including sympathetic and parasympathetic activity) in patients with T2DM.

Retinal Thickness Asymmetry in Highly Myopic Eyes with Early Stage of Normal-Tension Glaucoma.

PURPOSE: To investigate the retinal thickness asymmetry parameters of circumpapillary retinal nerve fiber layer (cpRNFL) and macular layers measured by spectral-domain optical coherence tomography in highly myopic (HM) patients with an early stage of normal-tension glaucoma (NTG). METHODS: This cross-sectional study included 55 eyes of HM patients with early NTG and 37 eyes of HM normal participants. High myopia was defined as spherical equivalence more myopic than -6 diopters. Thickness differences and asymmetry indices (AIs) of cpRNFL between superior and inferior corresponding parts and thickness differences and AIs of the total macular layer (TML) and inner macular layers between superior and inferior hemispheres were calculated. The areas under the receiver operating characteristic curves (AROCs) were analyzed and compared. RESULTS: In the cpRNFL asymmetry analysis, the thickness differences and AIs of cpRNFL between temporal-superior and temporal-inferior sectors (P < 0.0001 and P < 0.0001, respectively) and between superior and inferior quadrants (P = 0.002 and P < 0.0001, respectively) were significantly different between HM control subjects and HM NTG patients. In the macular asymmetry analysis, the thickness difference and AI of TML were significantly different between superior and inferior hemispheres (P < 0.0001 and P < 0.0001, respectively). The thickness difference and AI of the macular ganglion cell layer (mGCL) were significantly different between superior and inferior hemispheres (P < 0.0001 and P < 0.0001, respectively). The AROCs for thickness difference of TML (0.845) and thickness difference of mGCL (0.773) were comparable to AROCs for average cpRNFL thickness (0.842), macular retinal nerve fiber layer thickness (mRNFL) thickness (0.871), and mGCL thickness (0.822). CONCLUSION: In our study, HM NTG patients had retinal thickness asymmetry in cpRNFL, TML, and mGCL. The diagnostic capabilities for thickness asymmetry of TML and mGCL were comparable to the diagnostic capabilities for cpRNFL thickness, mRNFL thickness, and mGCL thickness. Asymmetry analysis of retinal thickness can be an adjunctive tool for the early detection of HM NTG.

Severity of Cardiovascular Autonomic Neuropathy Is a Predictor Associated With Major Adverse Cardiovascular Events in Adults With Type 2 Diabetes Mellitus: A 6-Year Follow-up Study.

OBJECTIVES: Cardiovascular autonomic function impairment has been reported in patients with type 2 diabetes mellitus and is associated with cardiovascular events. In this study, we test the hypothesis that the severity of cardiovascular autonomic neuropathy is a predictor associated with subsequent 3-point major adverse cardiovascular events (3-P MACE; combined endpoint of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke). METHODS: In this prospective study, we enrolled 168 patients with type 2 diabetes mellitus over a 6-year follow-up period. We constructed the Composite Autonomic Scoring Scale as a measure of the severity of cardiovascular autonomic neuropathy and examined baseline clinical and laboratory data of 168 patients with diabetes. Cardiovascular autonomic testing included heart rate response to deep breathing, Valsalva ratio and baroreflex sensitivity. Therapeutic outcome was defined as 3-P MACE. RESULTS: The overall incidence of new 3-P MACE was 23.2% and overall fatality rate was 9.5% during the 6-year follow-up period. Only underlying coronary heart disease and Composite Autonomic Scoring Scale were independently associated with subsequent 3-P MACE in the Cox proportional hazards model. Any increase of 1 point in Composite Autonomic Scoring Scale would increase the risk of new 3-P MACE by 9.7%. Area under the curve on receiver-operating characteristic curve analysis was 0.72 in predicting subsequent 3-point MACE in combined heart rate response to deep breathing and Valsalva ratio. CONCLUSIONS: Besides underlying coronary heart disease, the severity of cardiovascular autonomic neuropathy is strongly associated with subsequent 3-P MACE. Combined heart rate response to deep breathing and Valsalva ratio testing can increase sensitivity and specificity in predicting subsequent 3-point MACE, and it can serve as a time-effective cardiovascular autonomic screening service in the outpatient clinic sitting.

Computer-Assisted Quantitative Analysis of Drug-Induced Sleep Endoscopy for Obstructive Sleep Apnea/Hypopnea Syndrome.

OBJECTIVES: To use computer-assisted quantitative measurements of upper airway changes during drug-induced sleep endoscopy (DISE) and to correlate these parameters with disease severities and physiologic changes in patients with obstructive sleep apnea/hypopnea syndrome (OSA). DESIGN: A retrospective study. SETTING: Tertiary academic medical center. PATIENTS AND METHODS: A total of 170 patients who failed continuous positive airway pressure therapy and then underwent upper airway surgery were enrolled. All patients received polysomnography and DISE preoperatively. We used ImageJ 1.48v to obtain maximal and minimal measurements, including cross-sectional areas and anterior-posterior and lateral diameters at 4 anatomic levels (retropalatal, oropharyngeal, retroglossal, and retroepiglottic) under DISE, and then computed the percentage changes. We analyzed the clinical values of DISE changes by computer-assisted analysis in patients with OSA and any correlations between these changes and polysomnography parameters. RESULTS: The percentage changes of upper airway showed significant collapses at all 4 anatomic levels (all P < .0001). We also found that the changes at retropalatal levels were significantly greater and that retroglossal levels were significantly smaller, while the changes of anterior-posterior diameters at retroglossal levels showed a significant positive association with apnea-hypopnea index and desaturation index. However, there were no statistically significant correlations between upper airway changes and obesity. CONCLUSION: Computer-assisted quantitative analysis could evaluate upper airway changes of OSA in an objective way and may help identify the sites of obstruction during DISE more accurately. Upper airway showed multilevel collapse with independent significant changes in patients with OSA, with the retropalatal and retroglossal levels playing important roles in particular.

Effects of CPAP for patients with OSA on visual sensitivity and retinal thickness.

OBJECTIVE: Obstructive sleep apnea/hypopnea syndrome (OSA) could compromise oxygenation of the optic nerve and cause glaucomatous optic neuropathy; there has been no study to investigate the microstructure changes of the optic nerve and retina in OSA patients before and after continuous positive airway pressure (CPAP) therapy. In this study, we assess whether treatment with CPAP might improve visual sensitivity and retinal thickness in patients with OSA. METHODS: Patients with OSA were prospectively recruited and referred for ophthalmologic evaluation at baseline and three months after CPAP treatment. Each patient underwent an ophthalmological exam, standard automated perimetry (SAP), and optical coherence tomography (OCT) exam. Peripapillary retinal nerve fiber layer (RNFL) and macular layer (ML) thickness parameters were measured. The SAP, RNFL, and ML thickness parameters before and after treatment were compared. RESULTS: A total of 32 OSA patients were consecutively enrolled. At baseline, the mean deviation (MD) of SAP was -2.15 ± 1.90 dB (dB). After CPAP treatment, the MD was -1.38 ± 1.37 dB (p = 0.017). Regarding the OCT parameters, the inferior quadrant and nasal-inferior sector of RNFL thickness significantly improved after treatment (p = 0.025 and 0.004, respectively). The ML thickness in the superior-inner sector, inferior-outer sector, nasal-outer sector, superior hemisphere, and inferior hemisphere were also significantly improved after treatment. Improvement of ML thickness in the superior-inner sector positively correlated with the apnea/hypopnea index (r = 0.405, p = 0.022) and desaturation index (r = 0.473, p = 0.006) on pre-treatment polysomnography. CONCLUSION: The treatment of CPAP could improve visual sensitivity and increase retinal thickness in patients with OSA.

Sural nerve sensory response in diabetic distal symmetrical polyneuropathy.

INTRODUCTION: The sural sensory nerve action potential (SNAP) amplitude is a measure of the number of axons. We tested the hypothesis that sural SNAP amplitude can be used as a marker in screening, severity evaluation, and follow-up of diabetic distal symmetrical polyneuropathy (DSPN). METHODS: Patients with type 2 diabetes underwent nerve conduction studies and were followed for 6 years. Composite amplitude scores (CASs) were determined to evaluate DSPN severity. RESULTS: Sural SNAP amplitudes were negatively correlated with CAS (r = -.790, P < .0001), and changes in sural SNAP amplitudes were negatively correlated with those of CAS after controlling for follow-up duration (r = -.531, P = .028). DISCUSSION: When a patient's baseline sural SNAP amplitude is above zero, it can be used as one measure of DSPN in screening, severity evaluation, and follow-up. However, if the patient's sural SNAP value is zero, CAS can be used as a follow-up measure.

Effects of OSA Surgery on Ophthalmological Microstructures.

OBJECTIVE: Obstructive sleep apnea/hypopnea syndrome (OSA) could compromise oxygenation of the optic nerve and cause glaucomatous optic neuropathy; however, there were no studies to investigate the changes of visual function and retinal microstructures in OSA patients after upper airway surgery. We aim to assess the changes in the visual sensitivity and retinal fiber layer thickness in OSA patients before and after surgery. METHODS: This prospective single-blind study enrolled patients with OSA from a tertiary academic medical center who had unsuccessful conservative therapy and then underwent surgery. The patients were referred for comprehensive ophthalmologic evaluation at baseline and 6 months after OSA surgery. The polysomnographic findings were collected pre- and postoperatively. Visual sensitivities on standard automated perimetry (SAP) were assessed. Peripapillary retinal nerve fiber layer (RNFL) thickness and macular layer (ML) thickness parameters were measured by spectral-domain optical coherence tomography (OCT). RESULTS: A total of 108 OSA patients were enrolled. Six months after surgery, the major parameters of polysomnography (PSG), mean deviation, and pattern standard deviation of SAP significantly improved in these OSA patients. Regarding the OCT parameters, thickness of ML in the nasal-outer, superior-inner, temporal-inner, inferior-inner, nasal-inner sectors, and total ML thickness significantly increased 6 months after upper airway surgery in the severe OSA group (apnea/hypopnea index ⩾30 per hour). CONCLUSION: The visual sensitivities on SAP, ML thickness on OCT, and oxygenation status on PSG significantly improved 6 months after upper airway surgery in patients with severe OSA. Upper airway surgery may ameliorate the microstructures of the retina in patients with severe OSA.

Endothelial progenitor cells, rosuvastatin and valsartan have a comparable effect on repair of balloon-denudated carotid artery injury.

Endothelial cell (EC) dysfunction plays a crucial role for arterial obstructive disease. This study tested the therapeutic role of autologous endothelial progenitor cells (EPCs)/rosuvastatin-(Rosu)/valsartan-(Val) on repair of injured carotid ECs. Male Sprague-Dawley rats (n = 60) were categorized into five groups [sham-control (SC), left common carotid artery injury induced by balloon denudation (LCABD), LCABD + Rosu (10 mg/kg/day), LCABD + Val (20 mg/kg/day), and LCABD + EPC (1.2 × 106)]. By day 5, the LCA was harvested from each rat (n = 6/each time interval in group) after the procedure. Carotid-ring angiogenesis was significantly lower in LCABD than the other groups (all P < 0.001). Compared with LCABD, the number of EC was significantly higher in LCABD treated with adipose-derived mesenchymal stem cells (ADMSCs) and more significantly higher in LCABD treated with EPCs (all P < 0.001). Gene expression of EC (CD31/vWF), EPC (SDF-1α/CXCR4) and angiogenesis (VEGF/VEGF-receptor/angiopoietin/eNOS) and EC intercellular junction (VE-cadherin) biomarkers were significantly lower in LCABD than in groups LCABD + Rosu to LCABD + EPC (all P < 0.001). Conversely, the gene expression of inflammatory (VCAM-1/MMP-9/TNF-α), oxidative-stress (NOX-1/NOX-2), apoptosis (cleaved caspase-3/PARP) and thrombin cofactor (thrombomodulin) biomarkers were significantly higher in LCABD than in other groups (all P < 0.001). By day 14, the neointimal-layer area and cellular expressions of (CD40+/CD68+) were highest in LCABD, lowest in SC, significantly higher in LCABD + Val than in LCABD + Rosu and LCABD + EPC (all P < 0.001). In conclusion, EPCs were comparable to rosuvastatin and valsartan in upregulation of angiogenesis and repair of injured carotid ECs.

Clinical Prediction Model for Obstructive Sleep Apnea among Adult Patients with Habitual Snoring.

OBJECTIVE: To identify standard clinical parameters that may predict the presence and severity of obstructive sleep apnea/hypopnea syndrome (OSA). DESIGN: Case series with chart review. SETTING: Tertiary academic medical center. SUBJECTS AND METHODS: A total of 325 adult patients (274 men and 51 women; mean age, 44.2 years) with habitual snoring completed comprehensive polysomnography and anthropometric measurements, including modified Mallampati grade (also known as updated Friedman's tongue position [uFTP]), tonsil size grading, uvular length, neck circumference, waist circumference, hip circumference, and body mass index (BMI). RESULTS: When the aforementioned physical parameters were correlated singly with the apnea/hypopnea index (AHI), we found that sex, uFTP, tonsil size grading, neck circumference, waist circumference, hip circumference, thyroid-mental distance, and BMI grade were reliable predictors of OSA. When all important factors were considered in a multiple stepwise regression analysis, an estimated AHI can be formulated by factoring sex, uFTP, tonsil size grading, and BMI grade as follows: -43.0 + 14.1 × sex + 12.8 × uFTP + 5.0 × tonsil size + 8.9 × BMI grade. Severity of OSA can be predicted with a receiver operating characteristic curve. Predictors of OSA can be further obtained by the "OSA score." CONCLUSION: This study has distinguished the correlations between sex, uFTP, tonsil size, and BMI grade and the presence and severity of OSA. An OSA score might be beneficial in identifying patients who should have a full sleep evaluation.

Urinary Uromodulin/Creatinine Ratio as a Potential Clinical Biomarker for Chronic Kidney Disease Patients with Gout: A Pilot Study.

OBJECTIVE: Recent studies have reported that reduced excretion of urinary uromodulin is associated with renal tubular function and risks of progressive kidney disease. Gouty nephropathy is usually seen in patients with gout. Patients with chronic gouty nephropathy are characterized by the deposition of monosodium urate crystals primarily involving the collecting ducts in the medulla. We postulated that this correlation may be specific to gout and may serve as a useful biomarker for chronic kidney disease (CKD). MATERIALS AND METHODS: A total of 114 Taiwanese patients diagnosed with gout (n = 72), CKD (n = 26), or healthy volunteers (n = 16) were prospectively enrolled for this study from the Rheumatology and Nephrology Outpatient Clinics of our institution. We obtained urine and blood samples on patient visits to the outpatient clinics. Demographic data were obtained from medical records. RESULTS: In patients with gout, the spot urinary uromodulin/creatinine ratio (uUMCR; mg/g) in patients with CKD was significantly lower than that in those without CKD (CKD group: 2.2; non-CKD group: 5.6, p = 0.005). Multivariate analysis revealed that patients with CKD and gout had a lower uUMCR than those with gout alone (p = 0.028). A significant association was not observed in our non-gout cohort. CONCLUSION: The association of decreased uUMCR with CKD status was identified only in patients with gout in the present study. We believe that uUMCR might serve as an indicator of differential CKD in patients with gout.

Early administration of empagliflozin preserved heart function in cardiorenal syndrome in rat.

This study tested the hypothesis that early administration of empagliflozin (Empa), an inhibitor of glucose recycling in renal tubules, could preserve heart function in cardiorenal syndrome (CRS) in rat. Chronic kidney disease (CKD) was caused by 5/6 subtotal nephrectomy and dilated cardiomyopathy (DCM) by doxorubicin (DOX) treatment. In vitro results showed that protein expressions of cleaved-caspase3 and autophagy activity at 24 h/48 h in NRK-52P cells were significantly upregulated by para-Creso treatment; these were significantly downregulated by Empa treatment. Flow cytometric analysis showed that annexin-V (i.e., early/late apoptosis) in NRK-52P cells expressed an identical pattern to cleaved-caspase3 between the two groups (all p < 0.001). Adult-male-SD rats (n = 18) were equally categorized into group 1 (sham-control), group 2 (CRS) and group 3 [CRS + Empa; 20 mg/kg/day]. By day-42 after CRS induction, left-ventricular ejection fraction (LVEF) level exhibited an opposite pattern, whereas LV end-diastolic dimension and creatinine level displayed the same pattern, to cleaved-caspase3 among the three groups (all p < 0.0001). In LV tissues, protein expressions of inflammatory (tumor-necrosis factor-α/nuclear-factor-κB/interleukin-1ß/matrix-metalloprotianse-9), oxidative stress (NOX-1/NOX-2/oxidized protein), apoptotic (mitochondrial-Bax/cleaved-caspase-3/cleaved-PARP), fibrotic (transforming-growth factor-ß/Smad3), DNA/mitochondrial-damage (γ-H2AX/cytosolic-cytochrome-C) and heart failure (brain natriuretic peptide (BNP) levels displayed an opposite pattern to LVEF among the three groups (all p < 0.0001). Additionally, cellular expressions of DNA-damage/heart-failure (γ-H2AX+//XRCC1+CD90+//BNP+) biomarkers and histopathological findings of fibrotic/condensed collagen-deposition areas and apoptotic nuclei showed an identical pattern, whereas connexin43 and small-vessel number exhibited an opposite pattern, to inflammation among the three groups (all p < 0.0001). In conclusion, Empa therapy protected heart and kidney against CRS injury.

Inducible pluripotent stem cell-derived mesenchymal stem cell therapy effectively protected kidney from acute ischemia-reperfusion injury.

This study tested whether inducible pluripotent stem cell (iPSC)-derived mesenchymal stem cell (MSC) therapy could effectively protect kidney from acute ischemia (1 h) - reperfusion (5 day) injury (IRI). Male-adult SD-rats (n = 24) were equally categorized into groups 1 (sham-control), 2 [sham-control + iPSC-MSC (1.2 × 106 cells/rat)], 3 (IR only) and 4 (IR + iPSC-MSC). Blood urine nitrogen/creatinine levels and ratio of urine protein to creatinine, kidney weight and expressions of inflammation (TNF-α/NF-κB), oxidative-stress (NOX-1/NOX-2/oxidized protein) and apoptosis (mitochondrial-Bax/cleaved caspase-3/PARP) were significantly higher in group 3 than in groups 1, 2 and 4 and significantly higher in group 4 than in groups 1 and 2 (all P<0.0001), but showed no differences between groups 1 and 2, whereas the protein expressions of anti-inflammation (IL-4/IL-10) and endothelial (CD31/vWF) markers exhibited an opposite pattern to inflammation among the four groups (all P<0.0001). Protein expressions of angiogenesis (VEGF/CXCR4/SDF-1α) markers progressively increased from groups 1 to 4 (all P<0.0001). Cellular expressions of kidney injury score/DNA-damage (γ-H2AX)/apoptotic nuclei and glomerulus-tubular-damage (KIM/FSP-1) displayed an identical pattern to inflammation, whereas the cellular expressions of glomerulus-tubular-integrity (dystroglycan/podocin/p-cadherin/synaptopodin/ZO-1/fibronectin) revealed an opposite pattern to inflammation among the four groups (all P<0.0001). In conclusion, iPSC-derived MSC therapy effectively protected kidney against IRI.

Intra-carotid arterial transfusion of autologous circulatory derived CD34+ cells for old ischemic stroke patients - a phase I clinical trial to evaluate safety and tolerability.

This phase I clinical trial tested the hypothesis that circulatory CD34+ cell therapy might be safe for old ischemic stroke (IS) (defined as IS>6 months) patients and also to evaluate the neurological function after the therapy. Nine old IS patients (with mean IS interval: 8.6 ± 6.4 years) were consecutively enrolled and received intra-carotid artery transfusion of circulatory-derived autologous CD34+ cells (3.0×107 cells/patient) into the ipsilateral brain infarct area at catheterization room by Catheter Looping Technique, after subcutaneous G-CSF injection (5 µg/kg twice a day for 4 days). The results showed that procedural safety was 100% with all patients uneventfully discharged. The circulating number of EPCs and angiogenesis (i.e., by Matrigel assay) were significantly higher at post than at prior to G-CSF treatment (all P<0.001). Time courses (0/5/10/30 minutes) of blood samplings from right-internal jugular vein exhibited significantly increased in levels of SDF-1α and EPCs numbers in time points of 5/10/30 minutes than in the baseline (0 minute) (all P<0.05). Barthel index was increased (defined as ≥5 scores) in 44.4% (4/9) and CASI score was notably improved (all P<0.01) at 6-month follow-up after the cell therapy as compared to the baseline. No recurrent IS or any tumorigenesis was found in these patients with a mean follow-up time interval of 16.5 ± 6.2 months. All of these patients remain survive and are followed up at outpatient department. In conclusion, CD34+ cell therapy is safe and might offer some benefit to old IS patients.

Effects of Upper Airway Surgery on Daytime Sleepiness in Nonobese Patients with Obstructive Sleep Apnea/Hypopnea Syndrome.

INTRODUCTION:: The aim of this study was to evaluate the effects of upper airway surgery on daytime sleepiness in nonobese patients with obstructive sleep apnea/hypopnea syndrome (OSA). METHODS:: This retrospective study included 121 consecutive adult nonobese patients with OSA from a tertiary academic medical center. Patients with OSA who refused continuous positive airway pressure therapy, or in whom it was unsuccessful, and then underwent OSA surgery were enrolled. Evaluations of excessive daytime sleepiness using the Epworth Sleepiness Scale (ESS) and major parameters of objective full-night polysomnography were collected preoperatively and at least 3 months postoperatively. Statistical analysis was performed using the Wilcoxon signed rank test and Wilcoxon rank sum test. RESULTS:: When pre- and postoperative ESS and polysomnographic parameters were compared in all patients, ESS scores, apnea/hypopnea index, and snoring index showed statistically significant improvements ( P = .007, P < .001, and P < .001, respectively). When patients were classified into mild, moderate, and severe OSA groups, snoring index had statistically significant improvements in all 3 groups, and apnea/hypopnea index had statistically significant decreases in the moderate and severe OSA groups. Although reductions in ESS scores were found in all 3 groups, the most statistically significant improvement was noted only in the severe OSA group. CONCLUSIONS:: OSA surgery can improve daytime sleepiness in nonobese patients with OSA, especially for patients with severe OSA. This study elucidates the effects of OSA surgery on daytime sleepiness by excluding the major confounding factor of obesity. This study adds to the literature on the effects of upper airway surgery for nonobese patients with OSA on daytime quality of life.