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Exosomes are membranous structures measuring between 40-120 nm that are secreted by various cells of the human body into the body fluid system. Exosomes contain proteins, mRNA, miRNA, and signaling molecules, and physiologically they assist in the intercellular transport of proteins and RNA molecules. In this study, we used an immunoaffinity filter paper platform combined with scanning electron microscopy and microfluidic systems to detect the size of exosomes within the aqueous humor. Eight aqueous humor samples showed three distinct sizes of exosomes that were significantly different on scanning electron microscopy( P  < 0.01). We further used nanoparticle tracking analysis to assess the size distribution of exosomes within the aqueous humor. We found significantly different distributions of exosomes between patients with three different ocular diseases and patients with normal cataracts as controls. An obvious peak of exomeres(size around 35 nm)was found in the patients with central retinal vein occlusion and vitreous hemorrhage. Flare-ups of large exosomes(size 90-120 nm)were found in the patients with the inflammatory ocular disease pars planitis. No obvious peaks in exomeres or large exosomes were found in the control group. There was a high association between the distribution of exosomes and the pathogenesis of ocular diseases. After intravitreal anti-vascular endothelial growth factor treatment, the aqueous humor from the patients with neovascular diseases showed a significant reduction in exosomes in nanoparticle tracking analysis. These findings suggest that at least three distinct sizes of exosomes exist in the aqueous humor:(1)exomeres:<35 nm;(2)small exosomes:60-80 nm; and (3)large exosomes:90-120 nm. Different sizes of exosomes may have different implications in normal or diseased eyes.

Transcranial temporal interference stimulation (tTIS) is a promising brain stimulation method that can target deep brain regions by delivering an interfering current from surface electrodes. Most instances of tTIS stimulate the brain with a single-frequency sinusoidal waveform generated by wave interference. Theta burst stimulation is an effective stimulation scheme that can modulate neuroplasticity by generating long-term potentiation- or depression-like effects. To broaden tTIS application, we developed a theta burst protocol using tTIS technique to modulate neuroplasticity in rats. Two cannula electrodes were unilaterally implanted into the intact skull over the primary motor cortex. Electrical field of temporal interference envelopes generated by tTIS through cannula electrodes were recorded from primary motor cortex. Theta burst schemes were characterized, and motor activation induced by the stimulation was also evaluated simultaneously by observing electromyographic signals from the corresponding brachioradialis muscle. After validating the stimulation scheme, we further tested the modulatory effects of theta burst stimulation delivered by tTIS and by conventional transcranial electrical stimulation on primary motor cortex excitability. Changes in the amplitude of motor evoked potentials, elicited when the primary motor cortex was activated by electrical pulses, were measured before and after theta burst stimulation by both techniques. Significant potentiation and suppression were found at 15 to 30 min after the intermittent and continuous theta burst stimulation delivered using tTIS, respectively. However, comparing to theta burst stimulations delivered using conventional form of transcranial electrical stimulation, using tTIS expressed no significant difference in modulating motor evoked potential amplitudes. Sham treatment from both methods had no effect on changing the motor evoked potential amplitude. The present study demonstrated the feasibility of using tTIS to achieve a theta burst stimulation scheme for motor cortical neuromodulation. These findings also indicated the future potential of using tTIS to carry out theta burst stimulation protocols in deep-brain networks for modulating neuroplasticity., (© 2024. The Author(s).)

Background: The current treatment options for overactive bladder (OAB) continue to pose challenges for refractory cases and may involve invasive procedures. To assess the potential benefit of non-invasive repetitive peripheral magnetic stimulation (rPMS) on sacral roots using intermittent theta burst stimulation (iTBS) as treatment option for OAB. The study involved a total of 33 rats, which were divided into three different experimental phases., Materials and Methods: To induce bladder overactivity rats were pretreated with a continuous transvesical infusion of 0.5% acetic acid (AA). During bladder infusion, the intravesical pressure was recorded using cystometrography (CMG) to investigate the effects of AA pretreatment and the therapeutic intervention of acute sacral rPMS using iTBS., Results: Pre-application of rPMS with iTBS at a 100% intensity significantly extended the mean first voiding time (Tv) in normal healthy rats to 132%. Acute rPMS iTBS at a 100% intensity resulted in a significant increase of the inter-contraction interval (ICI) to 121%. An AA model was established with continuous saline infusion after 0.5% AA treatment and resulted in significant reductions of Tv to 42% and ICI to 56% of the corresponding control values. Subsequently, rPMS iTBS at a 100% intensity on the sacral nerve effectively inhibited AA-induced bladder overactivity and significantly increased the ICI to 167%∼222%. No significant changes in maximum bladder pressure (Pmax) were found., Conclusions: Sacral nerve rPMS with iTBS demonstrated the ability to suppress AA-induced bladder overactivity. This promising modality could be developed as an alternative approach to enhance bladder continence in OAB syndrome patients., Competing Interests: Declaration of Competing Interest All authors declare that they have no known competing financial interests or personal relationships that could have potentially influenced the research reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Barrier islands are vital dynamic landforms that not only host ecological resources but often protect coastal ecosystems from storm damage. The Waisanding Barrier (WSDB) in Taiwan has suffered from continuous beach erosion in recent decades. In this study, we developed a SiamUnet network compared to three basic DeepUnet networks with different image sizes to effectively detect barrier waterlines from 207 high-resolution satellite images. The evolution of the barrier waterline shape is obtained to present two special morphologic changes at the southern end and the evolution of the entire waterline. The time periods of separation of the southern end from the main WSDB are determined and discussed. We also show that the southern L-shaped end has occurred recently from the end of 2017 until 2021. The length of the L-shaped end gradually decreases during the summer, but gradually increases during the winter. The L-shaped end obviously has a seasonal and jagged change. The attenuation rate of the land area is analyzed as -0.344 km 2 /year. We also explore two factors that affect the analysis results, which are the number of valid images selected and the deviation threshold from the mean sea level.

Background: Nursing professional health courses have been reported to be very exhaustive and stressful, with most nursing students reporting moderate levels of stress., Purpose: This study was designed to compare the spiritual well-being, coping strategies, psychological well-being, anxiety, depression, and suicidal ideation between Taiwanese and Australian nursing students., Methods: Three hundred eighty-one nursing students (180 from Taiwan and 201 from Australia) were recruited for this cross-sectional comparative research study. The Psychological Well-being Scale, Spiritual Well-being Scale, Coping Strategies Inventory Short-Form, Hamilton Anxiety Scale, Zung Depression Scale, and Brief Screen for Adolescent Depression Scale were used to collect data. SPSS 27.0 was used for data analysis. Descriptive data analysis, chi-square tests, independent t test, Pearson correlations, and stepwise multiple regressions were used to examine the research questions., Results: Students in Australia had higher mean scores than Taiwanese nursing students for psychological well-being, life satisfaction/self-actualization, and using problem-focused disengagement coping strategies, whereas Taiwanese students had higher mean scores for using emotion-focused engagement coping strategies and depression than their Australian nursing students. Spiritual well-being and problem-focused disengagement were shown to be significantly and positively related to psychological well-being and significantly and negatively related to anxiety, depression, and suicidal ideation in both groups. No significant difference between Australian students and Taiwanese students was found in anxiety, suicidal ideation, and negative-emotion-related alcohol use., Conclusions/implications for Practice: The multiple regressions performed in this study support life satisfaction/self-actualization and the emotion-focused disengagement coping strategy as significant predictors of anxiety, depression, and suicidal ideation in both student groups. The findings of this study help nursing program faculty better understand the key factors of influence on nursing student mental health and provide a conceptual framework for using problem-focused coping strategies and spiritual education on students., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc.)

Background: Bladder dysfunction is a common non-motor disorder in Parkinson's disease (PD). This study attempted to determine the bladder dysfunction with disease progression in the PD rat model produced from unilateral/bilateral injections of 6-hydroxydopamine (6-OHDA)., Methods: Cystometrographic (CMG) and external urethral sphincter electromyographic (EUS-EMG) measurements were scheduled in a time-course manner to determine the disease timing, onset, and severity. Animals were allotted into normal control, unilateral, bilateral 6-OHDA injected groups and subjected to scheduled CMG, EUS-EMG analyses at weeks 1, 2, and 4., Results: The urodynamic results concluded that voiding efficiency (VE) was reduced in both unilateral and bilateral PD rats at all-time points. VE had decreased from 57 ± 11% to 31 ± 7% in unilateral PD rats and in bilateral PD rats, a decreased VE of 20 ± 6% was observed compared to control and unilateral PD rats. The EMG results in unilateral PD rats indicated declines in bursting period (BP) (3.78-2.94 s), active period (AP) (93.38-88.75 ms), and silent period (SP) (161.62-114.30 ms). A sudden reduction was noticed in BP (3.62-2.82 s), AP (92.21-86.01 ms), and SP (128.61-60.16 ms) of bilateral PD rats than in control and unilateral PD rats. Histological evidence exhibited a progressive dopaminergic neurons (DA) depletion in the substantia nigra (SN) region in 6-OHDA lesioned rats., Conclusion: The experimental outcomes strongly implied that significant variations in bladder function and VE decline were due to the depletion of DA neurons in the SN region of the brain., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article., (Copyright © 2022 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background/purpose: Paired stimulation can cause neuroplasticity in corticospinal and spinal pathways in subjects with a chronic spinal cord injury (SCI). We aimed to know the effects of different waveforms using paired stimulations with bicycling in subjects with a chronic SCI., Methods: Recruited subjects with an SCI underwent three treatment interventions in random order for 4-20 min followed by 30 min of bicycling (control, repetitive transcranial magnetic stimulation (TMS; rTMS) at 20 Hz with transspinal direct current stimulation (tsDCS), and intermittent theta burst stimulation (iTBS) with tsDCS with a 1-week gap period. A TMS method was employed to record the resting motor threshold (RMT), the 90% values of which was used as the stimulation intensity, and the Hoffman (H)-reflex was measured by stimulating the tibial nerve in the popliteal fossa. The RMT, motor evoked potential (MEP) latency, MEP peak-to-peak amplitude, and H-reflex latency as primary variables and lower extremity motor scale (LEMS) and modified Ashworth spasticity scale (MAS) as secondary variables were analyzed before and after the interventions., Results: The MEP latency, MEP amplitude, and LEMS significantly improved with the rTMS-iTBS/tsDCS or the rTMS-20 Hz/tsDCS (p < 0.050) protocols compared to the control intervention. All other outcome measures, including RMT, H-reflex latency, and MAS score showed some changes but did not fully attain a level of significance., Conclusion: The paired stimulation with rTMS-iTBS/tsDCS was equally effective to produce neuroplastic effect in subjects with chronic SCI compared to the conventional TMS-20 Hz/tsDCS intervention., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2022 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Cone cell-enriched macular degeneration is a major cause of functional vision deterioration. Astragaloside IV (Asg IV), an active triterpenoid saponin component with properties of anti-oxidative and anti-apoptotic damage, which benefit retinal tissue and capillaries. But, the nutraceutical therapeutic effects on functional vision have not been fully evaluated. In this study, mice were administrated to high-intensity light exposure after either receiving a vehicle or Asg IV (0.05, 0.5, and 50 mg/kg, BID). During this time, their spatial-visual performance, visual acuity (VA), and visual contrast sensitivity function (VCSF) were measured using the behavioral optomotor reflex method. Morphological changes in the retina were determined by histological examination. High energy light-evoked visual damage was confirmed by the loss in structural tissue integrity in the retina accompanied by a decline in both VA and VCSF, whereas the retina tissue exhibited loss of cone cell density and severe cone-specific opsin misplacement. In contrast, prophylactic oral Asg IV (0.5, and 50 mg/kg, BID)-treated exerted protective and improvement effects against light-evoked deterioration of functional vision. Asg IV treatment significantly improved the thresholds of VA and VCSF. In particular, Asg IV (50 mg/kg, BID) modulated and increased the survival of the photoreceptors, especially the cone cells, which targeted and enhanced the high spatial frequency-characterized VCSF. In contrast, the cellular protective effect of Asg IV (50 mg/kg, BID) on photoreceptors was significantly reversed by synchronous injection of a glucocorticoid receptor (GR) antagonist (mifepristone). This study demonstrated the major neuroretina-protective effect and functional vision-improving effect of Asg IV in vivo., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Paired stimulation of the brain and spinal cord can remodel the central nervous tissue circuitry in an animal model to induce motor neuroplasticity. The effects of simultaneous stimulation vary according to the extent and severity of spinal cord injury. Therefore, our study aimed to determine the significant effects on an incomplete SCI rat brain and spinal cord through 3 min and 20 min stimulations after 4 weeks of intervention. Thirty-three Sprague Dawley rats were classified into six groups: (1) normal, (2) sham, (3) iTBS/tsDCS, (4) iTBS/ts-iTBS, (5) rTMS/tsDCS, and (6) rTMS/ts-iTBS. Paired stimulation of the brain cortex and spinal cord thoracic (T10) level was applied simultaneously for 3−20 min. The motor evoked potential (MEP) and Basso, Beattie, and Bresnahan (BBB) scores were recorded after every week of intervention for four weeks along with wheel training for 20 min. Three-minute stimulation with the iTBS/tsDCS intervention induced a significant (p < 0.050 *) increase in MEP after week 2 and week 4 treatments, while 3 min iTBS/ts-iTBS significantly improved MEP (p < 0.050 *) only after the week 3 intervention. The 20 min rTMS/ts-iTBS intervention showed a significant change only in post&#95;5 min after week 4. The BBB score also changed significantly in all groups except for the 20 min rTMS/tsDCS intervention. iTBS/tsDCS and rTMS/ts-iTBS interventions induce neuroplasticity in an incomplete SCI animal model by significantly changing electrophysiological (MEP) and locomotion (BBB) outcomes.

Intermittent theta burst (iTBS) powered by direct current stimulation (DCS) can safely be applied transcranially to induce neuroplasticity in the human and animal brain cortex. tDCS-iTBS is a special waveform that is used by very few studies, and its safety needs to be confirmed. Therefore, we aimed to evaluate the safety of tDCS-iTBS in an animal model after brain stimulations for 1 h and 4 weeks. Thirty-one Sprague Dawley rats were divided into two groups: (1) short-term stimulation for 1 h/session (sham, low, and high) and (2) long-term for 30 min, 3 sessions/week for 4 weeks (sham and high). The anodal stimulation applied over the primary motor cortex ranged from 2.5 to 4.5 mA/cm 2 . The brain biomarkers and scalp tissues were assessed using ELISA and histological analysis (H&E staining) after stimulations. The caspase-3 activity, cortical myelin basic protein (MBP) expression, and cortical interleukin (IL-6) levels increased slightly in both groups compared to sham. The serum MBP, cortical neuron-specific enolase (NSE), and serum IL-6 slightly changed from sham after stimulations. There was no obvious edema or cell necrosis seen in cortical histology after the intervention. The short- and long-term stimulations did not induce significant adverse effects on brain and scalp tissues upon assessing biomarkers and conducting histological analysis.

Oxygen consumption (VO 2 ) during strength training can be predicted through surface electromyography (sEMG) of local muscles. This research aimed to determine relations between VO 2 and sEMG of upper and lower body muscles to predict VO 2 from sEMG during moderate-intensity strength training exercises. Of the 12 participants recruited, 11 were divided into two groups: untrained ( n = 5; with no training experience) and trained ( n = 6; with 2 months of training experience). On different days, each individual completed six training sessions. Each participant performed training sessions consisting of three types of dumbbell exercises: shoulder press, deadlift, and squat, while wearing a mask for indirect calorimetric measurements of VO 2 using the Cortex Metalyzer 3B. sEMG measurements of the bilateral middle deltoid, lumbar erector spinae, quadriceps (rectus femoris), and hamstring (biceps femoris) muscles were recorded. The VO 2 was predicted from sEMG root mean square (RMS) values of the investigated muscles during the exercise period using generalized estimating equation (GEE) modeling. The predicted models for the three types of exercises for the untrained vs. trained groups were shoulder press [QIC = 102, * p = 0.000 vs. QIC = 82, * p = 0.000], deadlift [QIC = 172, * p = 0.000 vs. QIC = 320, * p = 0.026], and squat [QIC = 76, * p = 0.000 vs. QIC = 348, * p = 0.001], respectively. It was observed that untrained vs. trained groups predicted GEE models [quasi-likelihood under an independence model criterion (QIC) = 368, p = 0.330 vs. QIC = 837, p = 0.058], respectively. The study obtained significant VO 2 prediction models during shoulder press, deadlift, and squat exercises using the right and left middle deltoid, right and left lumbar erector spinae, left rectus femoris, and right and left biceps femoris sEMG RMS for the untrained and trained groups during moderate-intensity strength training exercises.

Transcranial temporal interference stimulation (tTIS) has been proposed as a new neuromodulation technology for non-invasive deep-brain stimulation (DBS). However, few studies have detailed the design method of a tTIS device and provided system validation. Thus, a detailed design and validation scheme of a novel tTIS device for animal brain stimulation are presented in this study. In the proposed tTIS device, a direct digital synthesizer (DDS) was used to generate a sine wave potential of different frequencies, which was converted to an adjustable sine wave current. A current transformer was used to produce electrical isolation of different channels, which eliminated the current crosstalk between channels and greatly increased the load capacity by amplifying the output voltage. Several in vitro experiments were first conducted to validate the tTIS device. Our results indicated that the error percentages of the stimulation currents were within ±2%. Current crosstalk between channels was almost completely eliminated. Then, in vivo electric field measurement shows that the 2-pole arrangement may provide better cortical targeting than the 4-pole mode. A pilot animal experiment was conducted in which evoked motion and electromyographic activation of the contralateral forelimb were observed, which indicated that the 2-pole tTIS had successfully activated the primary motor cortex in a rat. Motor activation induced by the 2-pole tTIS demonstrated the feasibility and safety potential when applying our tTIS device for neuromodulation.

Background: The risk of skeletal events is rising in parallel with the burden of chronic kidney disease and mineral bone disorder (CKD-MBD), whilst the role of the fat-bone axis in CKD-MBD remains elusive. Adiponectin derived from adipocytes has emerged as a valid biomarker of low bone mineral density and increased marrow adiposity. We aimed to explore the association between adiponectin and bone fracture (BF) risks in patients with maintenance hemodialysis (MHD)., Methods: Serum concentrations of adiponectin and bio-clinical data were determined at study entry. The Cox proportional hazard regression analyses were used to assess unadjusted and adjusted hazard ratios (aHRs) of adiponectin and various clinical predictors for BF risks. The predictive accuracy of adiponectin for BF events was evaluated by receiver operating characteristic (ROC) curve analysis., Results: Age and serum concentrations of adiponectin, phosphate, and intact parathyroid hormone were significantly associated with higher risks of BF. With respect to the risk of BF events, the cumulative event-free survival curves differed significantly between the high and low concentration groups of adiponectin ( p = 0.02). In multivariable analysis, higher adiponectin levels were associated with an incremental risk of BF (adjusted hazard ratios (aHRs): 1.08 (95% confidence interval (CI): 1.01-1.15, p < 0.05). The ROC analysis of adiponectin cutoff point concentration (18.15 ug/mL) for prediction of BF showed 0.66 (95% CI = 0.49 to 0.84)., Conclusion: Adiponectin was associated with an incremental risk of BF that could serve as a potential predictor of BF in MHD patients. In the high-risk population with hyperphosphatemia, an elevated adiponectin level could alert clinicians to the urgent need to correct mineral dysregulation and undertake further bone survey.

Patients with chronic kidney disease (CKD), especially those undergoing hemodialysis, are at a considerably high risk of bone fracture events. Experimental data indicate that uremic toxins intricately involved in bone-related proteins exert multi-faced toxicity on bone cells and tissues, leading to chronic kidney disease-mineral and bone disorder (CKD-MBD). Nonetheless, information regarding the association between p -cresyl sulfate (PCS), non-hepatic alkaline phosphatase (NHALP) and skeletal events remains elusive. We aim to explore the association between PCS, NHALP and risk of bone fracture (BF) in patients with hemodialysis. Plasma concentrations of PCS and NHALP were ascertained at study entry. Cox proportional hazard regression analyses were used to determine unadjusted and adjusted hazard ratios (aHRs) of PCS for BF risk. In multivariable analysis, NHALP was associated with incremental risks of BFs [aHR: 1.06 (95% CI: 1.01-1.11)]. The association between the highest PCS tertile and BF risk remained robust [aHR: 2.87 (95% CI: 1.02-8.09)]. With respect to BF events, the interaction between NHALP and PCS was statistically significant ( p value for the interaction term < 0.05). In addition to mineral dysregulation and hyperparathyroidism in hemodialysis patients, higher circulating levels of PCS and NHALP are intricately associated with incremental risk of BF events, indicating that a joint evaluation is more comprehensive than single marker. In light of the extremely high prevalence of CKD-MBD in the hemodialysis population, PCS may act as a pro-osteoporotic toxin and serve as a potential surrogate marker for skeletal events.

We investigated the effects of intermittent theta-burst stimulation (iTBS) on locomotor function, motor plasticity, and axonal regeneration in an animal model of incomplete spinal cord injury (SCI). Aneurysm clips with different compression forces were applied extradurally around the spinal cord at T10. Motor plasticity was evaluated by examining the motor evoked potentials (MEPs). Long-term iTBS treatment was given at the post-SCI 5th week and continued for 2 weeks (5 consecutive days/week). Time-course changes in locomotor function and the axonal regeneration level were measured by the Basso Beattie Bresnahan (BBB) scale, and growth-associated protein (GAP)-43 expression was detected in brain and spinal cord tissues. iTBS-induced potentiation was reduced at post-1-week SCI lesion and had recovered by 4 weeks post-SCI lesion, except in the severe group. Multiple sessions of iTBS treatment enhanced the motor plasticity in all SCI rats. The locomotor function revealed no significant changes between pre- and post-iTBS treatment in SCI rats. The GAP-43 expression level in the spinal cord increased following 2 weeks of iTBS treatment compared to the sham-treatment group. This preclinical model may provide a translational platform to further investigate therapeutic mechanisms of transcranial magnetic stimulation and enhance the possibility of the potential use of TMS with the iTBS scheme for treating SCIs., Competing Interests: The authors have no conflicts of interest to disclose.

Lung cancer is the leading cause of cancer-related deaths worldwide. Identifying genetic risk factors and understanding their mechanisms will help reduce lung cancer incidence. The p53 apoptosis effect is related to PMP-22 (PERP), a tetraspan membrane protein, and an apoptotic effector protein downstream of p53. Although historically considered a tumor suppressor, PERP is highly expressed in lung cancers. Stable knockdown of PERP expression induces CL1-5 and A549 lung cancer cell death, but transient knockdown has no effect. Interestingly, relative to the PERP-428GG genotype, PERP-428CC was associated with the highest lung cancer risk (OR = 5.38; 95% CI = 2.12-13.65, p < 0.001), followed by the PERP-428CG genotype (OR = 2.34; 95% CI = 1.55-3.55, p < 0.001). Ectopic expression of PERP-428G, but not PERP-428C, protects lung cancer cells against ROS-induced DNA damage. Mechanistically, PERP-428 SNPs differentially regulate p53 protein stability. p53 negatively regulates the expression of the antioxidant enzymes catalase (CAT) and glutathione reductase (GR), thereby modulating redox status. p53 protein stability is higher in PERP-428C-expressing cells than in PERP-428G-expressing cells because MDM2 expression is decreased and p53 Ser20 phosphorylation is enhanced in PERP-428C-expressing cells. The MDM2 mRNA level is decreased in PERP-428C-expressing cells via PTEN-mediated downregulation of the MDM2 constitutive p1 promoter. This study reveals that in individuals with PERP-428CC, CAT/GR expression is decreased via the PTEN/MDM2/p53 pathway. These individuals have an increased lung cancer risk. Preventive antioxidants and avoidance of ROS stressors are recommended to prevent lung cancer or other ROS-related chronic diseases., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: A cylindrical piezoelectric element and a specific multi-channel circular microelectromechanical systems (MEMS)-transducer array of ultrasonic system were used for ultrasonic energy generation and ablation. A relatively long time is required for the heat to be conducted to the target position. Ultrasound thermal therapy has great potential for treating deep hyperplastic tissues and tumors, such as breast cancer and liver tumors., Methods: Ultrasound ablation technology produces thermal energy by heating the surface of a target, and the heat gradually penetrates to the target's interior. Beamforming was performed to observe energy distribution. A resonance method was used to generate ablation energy for verification. Energy was generated according to the coordinates of geometric graph positions to reach the ablation temperature., Results: The mean resonance frequency of Channels 1-8 was 2.5 MHz, and the cylindrical piezoelectric ultrasonic element of Channel A was 4.2546 Ω at 5.7946 MHz. High-intensity ultrasound has gradually been applied in clinical treatment. Widely adopted, ultrasonic hyperthermia involves the use of high-intensity ultrasound to heat tissues at 42-45 °C for 30-60 min., Conclusion: In the ultrasonic energy method, when the target position reaches a temperature that significantly reduces the cell viability (46.9 °C), protein surface modification occurs on the surface of the target.

Background: The risk of cardiovascular (CV) and fatal events remains extremely high in patients with maintenance hemodialysis (MHD), and the growth differentiation factor 15 (GDF15) has emerged as a valid risk stratification biomarker. We aimed to develop a GDF15-based risk score as a death prediction model for MHD patients., Methods: Age, biomarker levels, and clinical parameters were evaluated at study entry. One hundred and seventy patients with complete information were finally included for data analysis. We performed the Cox regression analysis of various prognostic factors for mortality. Then, age, GDF15, and robust clinical predictors were included as a risk score model to assess the predictive accuracy for all-cause and CV death in the receiver operating characteristic (ROC) curve analysis., Results: Age, GDF15, and albumin were significantly associated with higher all-cause and CV mortality risk that were combined as a risk score model. The highest tertile of GDF-15 (>1707.1 pg/mL) was associated with all-cause mortality (adjusted hazard ratios (aHRs): 3.06 (95% confidence interval (CI): 1.20-7.82), p < 0.05) and CV mortality (aHRs: 3.11 (95% CI: 1.02-9.50), p < 0.05). The ROC analysis of GDF-15 tertiles for all-cause and CV mortality showed 0.68 (95% CI = 0.59 to 0.77) and 0.68 (95% CI = 0.58 to 0.79), respectively. By contrast, the GDF15-based prediction model for all-cause and CV mortality showed 0.75 (95% CI: 0.67-0.82) and 0.72 (95% CI: 0.63-0.81), respectively., Conclusion: Age, GDF15, and hypoalbuminemia predict all-cause and CV death in MHD patients, yet a combination scoring system provides more robust predictive powers. An elevated GDF15-based risk score warns clinicians to determine an appropriate intervention in advance. In light of this, the GDF15-based death prediction model could be developed in the artificial intelligence-based precision medicine.

The system designed in this study involves a three-dimensional (3D) microelectronic mechanical system chip structure using DNA printing technology. We employed diverse diameters and cavity thickness for the heater. DNA beads were placed in this rapid array, and the spray flow rate was assessed. Because DNA cannot be obtained easily, rapidly deploying DNA while estimating the total amount of DNA being sprayed is imperative. DNA printings were collected in a multiplexer driver microelectronic mechanical system head, and microflow estimation was conducted. Flow-3D was used to simulate the internal flow field and flow distribution of the 3D spray room. The simulation was used to calculate the time and pressure required to generate heat bubbles as well as the corresponding mean outlet speed of the fluid. The "outlet speed status" function in Flow-3D was used as a power source for simulating the ejection of fluid by the chip nozzle. The actual chip generation process was measured, and the starting voltage curve was analyzed. Finally, experiments on flow rate were conducted, and the results were discussed. The density of the injection nozzle was 50, the size of the heater was 105 μm × 105 μm, and the size of the injection nozzle hole was 80 μm. The maximum flow rate was limited to approximately 3.5 cc. The maximum flow rate per minute required a power between 3.5 W and 4.5 W. The number of injection nozzles was multiplied by 100. On chips with enlarged injection nozzle density, experiments were conducted under a fixed driving voltage of 25 V. The flow curve obtained from various pulse widths and operating frequencies was observed. The operating frequency was 2 KHz, and the pulse width was 4 μs. At a pulse width of 5 μs and within the power range of 4.3-5.7 W, the monomer was injected at a flow rate of 5.5 cc/min. The results of this study may be applied to estimate the flow rate and the total amount of the ejection liquid of a DNA liquid.

Bladder dysfunction is a common phenomenon in Parkinson's disease (PD) patients. A research attempt was made to analyze the voiding efficiency (VE) and bladder functions in rats with PD induced by unilateral or bilateral injections of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. PD rats were divided into unilateral- and bilateral-injected groups and subjected to rotation and beam walking tests. Further, the experimental rats underwent cystometric measurements for analyses of bladder dysfunction and VE. Immunohistochemical analysis was performed to analyze the dopaminergic neuron depletion on the target area. Outcomes of the rotation and beam walking tests revealed the extent of parkinsonism in the experimental rats. Urodynamic observations denoted that rats with unilateral PD exhibited a significantly decreased VE (from 68.3±3.5% to 32.7±5.8%), while rats with bilateral PD displayed a much-reduced and substantially lower level of VE of 18.3±5.1% compared to the control value and to that of rats with unilateral PD. Rats with bilateral PD showed more-extensive behavioral deficits and urodynamic changes than did rats with unilateral PD. These significant changes in motor, behavioral, bladder function and VE were due to an extensive degeneration of dopaminergic neurons in the substantia nigra region on both sides of the brain. The obtained results were substantiated with appropriate immunohistochemical results., Competing Interests: The authors have declared that no competing interests exist.

Objective: Traumatic brain injuries (TBIs) are a prime public health challenge with a high incidence of mortality, and also reflect severe economic impacts. One of their severe symptoms is bladder dysfunction. Conventional therapeutic methods are not effective in managing bladder dysfunction. Henceforth, a research endeavor was attempted to explore a new therapeutic approach for bladder dysfunction through deep brain stimulation (DBS) procedures in a TBI animal model., Methods: TBI in this animal model was induced by the weight-drop method. All rats with an induced TBI were housed for 4 weeks to allow severe bladder dysfunction to develop. Subsequently, an initial urodynamic measurement, the simultaneous recording of cystometric (CMG) and external urethral sphincter electromyography (EUS-EMG) activity was conducted to evaluate bladder function. Further, standard DBS procedures with varying electrical stimulation parameters were executed in the target area of the pedunculopontine tegmental nucleus (PPTg). Simultaneously, urodynamic measurements were re-established to compare the effects of DBS interventions on bladder functions., Results: From the variable combinations of electrical stimulation, DBS at 50 Hz and 2.0 V, significantly reverted the voiding efficiency from 39% to 69% in TBI rats. Furthermore, MRI studies revealed the precise localization of the DBS electrode in the target area., Conclusions: The results we obtained showed an insightful understanding of PPTg-DBS and its therapeutic applications in alleviating bladder dysfunction in rats with a TBI. Hence, the present study suggests that PPTg-DBS is an effective therapeutic strategy for treating bladder dysfunction.

Osteogenesis in human arterial smooth muscle cell (HASMC) is a key feature of uremic vascular calcification (UVC). Concerning pro-oxidant properties of p -cresyl sulfate (PCS), the therapeutic effect of reactive oxygen species (ROS) scavenger on PCS triggered inflammatory signaling transduction in osteogenesis was investigated in this translational research. Based on severity level of chronic kidney disease (CKD), arterial specimens with immunohistochemistry stain were quantitatively analyzed for UVC, oxidative injury and osteogenesis along with PCS concentrations. To mimic human UVC, HASMC model was used to explore whether PCS-induced ROS could trigger mitogen-activated protein kinase (MAPK) pathways with nuclear factor-κB (NF-κB) translocation that drive context-specific gene/protein expression, including Runt-related transcription factor 2 ( Runx2 ) and alkaline phosphatase (ALP). In parallel with PCS accumulation, CKD arteries corresponded with UVC severity, oxidative DNA damage (8-hydroxy-2'-deoxyguanosine), Runx2 and ALP. PCS directly phosphorylated extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK)/P38 (pERK/pJNK/pP38) and modulated NF-κB translocation to promote expressions of Runx2 and ALP in HASMC. Notably, intracellular ROS scavenger attenuated pERK signaling cascade and downstream osteogenic differentiation. Collectively, our data demonstrate PCS induces osteogenesis through triggering intracellular ROS, pERK/pJNK/pP38 MAPK pathways and NF-κB translocation to drive Runx2 and ALP expressions, culminating in UVC. Beyond mineral dysregulation, osteocytic conversion in HASMC could be the stimulation of PCS. Thus PCS may act as a pro-osteogenic and pro-calcific toxin. From the perspective of translational medicine, PCS and intracellular ROS could serve as potential therapeutic targets for UVC in CKD patients.

The nephrotoxicity of aristolochic acids (AAs), p-cresyl sulfate (PCS) and indoxyl sulfate (IS) were well-documented, culminating in tubulointerstitial fibrosis (TIF), advanced chronic kidney disease (CKD) and fatal urothelial cancer. Nonetheless, information regarding the attenuation of AAs-induced nephropathy (AAN) and uremic toxin retention is scarce. Propolis is a versatile natural product, exerting anti-oxidant, anti-cancer and anti-fibrotic properties. We aimed to evaluate nephroprotective effects of propolis extract (PE) in a murine model. AAN was developed to retain circulating PCS and IS using C57BL/6 mice, mimicking human CKD. The kidney sizes/masses, renal function indicators, plasma concentrations of PCS/IS, tissue expressions of TIF, α-SMA, collagen IaI, collagen IV and signaling pathways in transforming growth factor-β (TGF-β) family were analyzed among the control, PE, AAN, and AAN-PE groups. PE ameliorated AAN-induced renal atrophy, renal function deterioration, TIF, plasma retention of PCS and IS. PE also suppressed α-SMA expression and deposition of collagen IaI and IV in the fibrotic epithelial-mesenchymal transition. Notably, PE treatment in AAN model inhibited not only SMAD 2/3-dependent pathways but also SMAD-independent JNK/ERK activation in the signaling cascades of TGF-β family. Through disrupting fibrotic epithelial-mesenchymal transition and TGF-β signaling transduction pathways, PE improves TIF and thereby facilitates renal excretion of PCS and IS in AAN. In light of multi-faced toxicity of AAs, PE may be capable of developing a new potential drug to treat CKD patients exposed to AAs.

Infrared thermography can be applied in different medical systems, for example it can be used to catch the images of living blood vessels. Far infrared rays can be used in a heating machine, which can be applied in the clinical hemodialysis patients. Infrared electronically sensitized images, which are generated by near-infrared Charge-coupled Device (CCD), are used to detect blood vessels, and used as a long-wavelength external stimulating therapeutic tissue repair system. When an infrared sensor detection and actuator treatment is applied during hemodialysis, a missing needle can be detected, and far infrared rays have a therapeutic effect on blood vessels. Because a far-infrared actuated light source can improve blood circulation, it is currently used to prevent fistula embolism in hemodialysis (HD) patients and reduce vascular occlusion after hemodialysis. Sensors used for sudden changes in heart rate variability (HRV) are used as predictive and evaluation indicators for our new method. Far-infrared actuated radiation can increase sympathetic nerve activity and regulation of parasympathetic and sympathetic nerves. We performed baseline measurements of the low-frequency/high-frequency ratio of autonomic nerve activity before hemodialysis (low frequency (LF), high frequency (HF), LF/HF, before HD) and after hemodialysis (LF/HF, after-HD). Based on data from the HRV continuity tracking report, 35 patients with autonomic nerve activation were treated and evaluated. We have demonstrated that the resulting near-infrared (NIR) sensor imaging and far-infrared actuator illumination can be used for the detection and treatment of hemodialysis patients.

Objective: Systemic hypoperfusion is intricately involved in neurohormone secretion, vascular calcification (VC) related impaired vasodilation, and luminal stenosis. We aimed to conduct a joint evaluation of vasopressin-neurophysin II-copeptin peptide (VP) and advanced aortic arch calcification (AAC) on all-cause and cardiovascular (CV) mortality in maintenance hemodialysis (MHD) patients. Methods: Unadjusted and adjusted hazard ratios (aHRs) of mortality risks were analyzed for different groups of VP and AAC in 167 MHD patients. The modification effect between higher VP and advanced AAC on mortality risk was examined using an interaction product term. Results: Interactions between VP and AAC with respect to all-cause and CV mortality were statistically significant. In multivariable analysis, higher VP predicted all-cause and CV mortality [aHR: 2.2 (95% confidence interval (CI): 1.1-4.5)] and 2.6 (95% CI: 1.1-4.6), respectively. Advanced AAC was associated with incremental risks of all-cause and CV mortality [aHR: 2.1 (95% CI: 1.1-4.0)and 2.5 (95% CI: 1.0-4.3), respectively]. Patients with combined higher VP (>101.5 ng/mL) and advanced AAC were at the greatest risk of all-cause and CV mortality [aHR: 4.7 (95% CI: 1.2-16.2)and 4.9 (95% CI: 1.1-18.9), respectively]. Conclusion: Combined VP and advanced AAC predict not only all-cause but also CV death in MHD patients, and a joint evaluation is more comprehensive than single marker. In light of hypoperfusion and ischemic events in vital organs, VP and AAC could act as more robust dual marker for prognostic assessment., (Copyright © 2020 Chang, Chou, Wu, Chen, Ko, Liou, Hsieh, Lin, Wen, Chang, Tung and Wang.)

Background: Cardiac sympathetic response (CSR) and malnutrition-inflammation syndrome (MIS) score are validated assessment tools for patients' health condition. We aim to evaluate the joint effect of CSR and MIS on all-cause and cardiovascular (CV) mortality in patients with hemodialysis (HD). Methods: Changes in normalized low frequency (ΔnLF) during HD were utilized for quantification of CSR. Unadjusted and adjusted hazard ratios (aHRs) of mortality risks were analyzed in different groups of ΔnLF and MIS score. Results: In multivariate analysis, higher ΔnLF was related to all-cause, CV and sudden cardiac deaths [aHR: 0.78 (95% confidence interval (CI): 0.72-0.85), 0.78 (95% CI: 0.70-0.87), and 0.74 (95% CI: 0.63-0.87), respectively]. Higher MIS score was associated with incremental risks of all-cause, CV and sudden cardiac deaths [aHR: 1.36 (95% CI: 1.13-1.63), 1.33 (95% CI: 1.06 - 1.38), and 1.50 (95% CI: 1.07-2.11), respectively]. Patients with combined lower ΔnLF (≤6.8 nu) and higher MIS score were at the greatest risk of all-cause and CV mortality [aHR: 5.64 (95% CI: 1.14-18.09) and 5.86 (95% CI: 1.64-13.65), respectively]. Conclusion: Our data indicate a joint evaluation of CSR and MIS score to identify patients at high risk of death is more comprehensive and convincing. Considering the extremely high prevalence of cardiac autonomic neuropathy and malnutrition-inflammation cachexia in HD population, a non-invasive monitoring system composed of CSR analyzer and MIS score calculator should be developed in the artificial intelligence-based prediction of clinical events., (Copyright © 2020 Chang, Wu, Hsieh, Li, Wang and Liou.)

Background: Uremic vascular calcification (UVC) is reminiscent of osteogenesis and apoptosis in vascular smooth muscle cell (VSMC). We aimed to identify how circulating procalcific particles dramatically leak into VSMC layer in human tissue models of vascular rings. Methods: According to baseline estimated glomerular filtration rate (eGFR), patients following lower extremity amputation were divided into three groups: normal renal function (eGFR ≧ 60 ml/min), mild-to-moderate (15 ml/min < eGFR ≧ 60 ml/min) and severe chronic kidney disease (CKD) (eGFR ≦ 15 ml/min). Arterial specimens with immunohistochemistry stain were quantitatively analyzed for UVC, internal elastic lamina (EL) disruption, α-SMA, osteogenesis, apoptosis, and oxidative injury. Correlations among UVC severity, eGFR, EL disruption, osteogenesis, and oxidative injury were investigated. Results: CKD arteries were associated with eGFR-dependent EL disruption corresponding to UVC severity. CKD arteries exhibited lower α-SMA, higher expressions of caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), indicative of contractile VSMC loss, and apoptosis. Enhanced expressions of alkaline phosphatase and Runx2 were presented in VSMCs of CKD arteries, indicative of osteogenic differentiation. Above eGFR-dependent UVC and EL disruption correlated expressions of 8-hydroxy-2'-deoxyguanosine (8-OHdG), indicating oxidative EL injury promoted procalcific processes. Conclusions: Circulating uremic milieu triggers vascular oxidative stress, leading to progressive internal EL disruption as a key event in disabling VSMC defense mechanisms and catastrophic mineral ion influx into VSMC layer. Oxidative EL injury begins in early CKD, corresponding with active VSMC re-programming, apoptosis, and ultimately irremediable UVC. In light of this, therapeutic strategies targeting oxidative tissue injury might be of vital importance to hinder the progression of UVC related cardiovascular events., (Copyright © 2020 Chang, Liu, Lu, Ka, Hsieh, Ho, Lin, Wen, Liou, Chang, Wu, Wang and Li.)

We developed a new format for liquid crystal (LC)-based multi-microfluidic immunoassays, hosted on a polydimethylsiloxane substrate. In this design, the orientations of the LCs were strongly affected by the interface between the four microchannel walls and surrounding LCs. When the alignment layer was coated inside a microchannel, the LCs oriented homeotropically and appeared dark under crossed polarizers. After antigens bound to the immobilized antibodies on the alignment layer were coated onto the channel walls, the light intensity of the LC molecules changed from dark to bright because of disruption of the LCs. By employing pressure-driven flow, binding of the antigen/antibody could be detected by optical signals in a sequential order. The multi-microfluidic LC biosensor was tested by detecting bovine serum albumin (BSA) and an immunocomplex of BSA antigen/antibody pairs, a protein standard commonly used in labs. We show that this multi-microfluidic immunoassay was able to detect BSA and antigen/antibody BSA pairs with a naked-eye detection limitation of -0.01 µg/mL. Based on this new immunoassay design, a simple and robust device for LC-based label-free microfluidic immunodetection was demonstrated.

Background: Interactions and early warning effects of non-hepatic alkaline phosphatase (NHALP) and high-sensitivity C-reactive protein (hs-CRP) on the progression of vertebral fractures (VFs) in patients with rheumatoid arthritis (RA) remain unclear. We aim to explore whether serum concentrations of NHALP and hs-CRP could serve as a promising dual biomarker for prognostic assessment of VF progression., Methods: Unadjusted and adjusted hazard ratios (aHRs) of VF progression were calculated for different categories of serum NHALP and hs-CRP using the Cox regression model in RA patients. The modification effect between serum NHALP and hs-CRP on VF progression was determined using an interaction product term., Results: During 4489 person-years of follow-up, higher NHALP (>125 U/L) and hs-CRP (>3.0 mg/L) were robustly associated with incremental risks of VF progression in RA patients (aHR: 2.2 (95% confidence intervals (CIs): 1.2⁻3.9) and 2.0 (95% CI: 1.3⁻3.3) compared to the lowest HR category, respectively). The interaction between NHALP and hs-CRP on VF progression was statistically significant ( p < 0.05). In the stratified analysis, patients with combined highest NHALP and hs-CRP had the greatest risk of VF progression (aHR: 4.9 (95% CI: 2.5⁻9.6)) compared to the lowest HR group (NHALP < 90 U/L and hs-CRP < 1 mg/L)., Conclusions: In light of underdiagnoses of VFs and misleading diagnosis by single test, NHALP and hs-CRP could serve as compensatory biomarkers to predict subclinical VF progression in RA patients.

Background: Interactions and joint effects of galectin-3 and vascular cell adhesion molecule 1 (VCAM-1) on risks of all-cause and cardiovascular (CV) mortality remain unclear in patients with maintenance hemodialysis (MHD)., Methods: Unadjusted and adjusted hazard ratios (aHRs) of mortality risks were analyzed between higher and lower concentration groups of serum galectin-3 and VCAM-1. The modification effect between serum galectin-3 and VCAM-1 on mortality risk was investigated using an interaction product term., Results: During follow-up, galectin-3 and VCAM-1 were associated with incremental risks of all-cause mortality (aHR: 1.038 (95% confidence interval (CI): 1.001⁻1.077) and 1.002 (95% CI: 1.001⁻1.003), respectively). Nonetheless, VCAM-1 but not galectin-3 predicted CV mortality (aHR: 1.043 (95% CI: 0.993⁻1.096) and 1.002 (95% CI: 1.001⁻1.003), respectively). In the interaction analysis, patients with combined higher galectin-3 (>29.5 ng/mL) and VCAM-1 (>1546.9 ng/mL) were at the greatest risk of all-cause and CV mortality (aHR: 4.6 (95% CI: 1.6⁻13.4), and 4.2 (95% CI: 1.3⁻14.4), respectively). The interactions between galectin-3 and VCAM-1 with respect to all-cause and CV mortality were statistically significant ( p < 0.01 and < 0.05, respectively)., Conclusion: Galectin-3 and VCAM-1 could serve as a promising dual biomarker for prognostic assessment, considering their joint effects on pathogenesis of leukocyte trafficking and atherothrombosis.

Molecular mechanisms and pathological features of p-Cresyl sulfate (PCS)-induced uremic lung injury (ULI) in chronic kidney disease (CKD) remain unclear. We analyzed pleural effusions (PE) from CKD and non-CKD patients for uremic toxins, reactive oxygen species (ROS), and chemotactic cytokines. Correlations between PE biomarkers and serum creatinine were also studied. Cell viability and inflammatory signaling pathways were investigated in PCS-treated human alveolar cell model. To mimic human diseases, CKD-ULI mouse model was developed with quantitative comparison of immunostaining and morphometric approach. PE from CKD patients enhance expressions of uremic toxins, hydroxyl radicals, and IL-5/IL-6/IL-8/IL-10/IL-13/ENA-78/GRO α/MDC/thrombopoietin/VEGF. PE concentrations of ENA-78/VEGF/IL-8/MDC/PCS/indoxyl sulphate correlate with serum creatinine concentrations. In vitro, PCS promotes alveolar cell death, cPLA2/COX-2/aquaporin-4 expression, and NADPH oxidase/mitochondria activation-related ROS. Intracellular ROS is abrogated by non-specific ROS scavenger N-acetyl cysteine (NAC), inhibitors of NADPH oxidase and mitochondria-targeted superoxide scavenger. However, only NAC protects against PCS-induced cell death. In vivo, expressions of cPLA2/COX2/8-OHdG, resident alveolar macrophages, recruited leukocytes, alveolar space, interstitial edema and capillary leakage increase in lung tissues of CKD-ULI mice, and NAC pretreatment ameliorates alveolar⁻capillary injury. PCS causes alveolar⁻capillary injury through triggering intracellular ROS, downstream prostaglandin pathways, cell death, and activating leukocytes to release multiplex chemoattractants and extracellular ROS. Thus PCS and nonspecific ROS serve as potential therapeutic targets.

Emerging roles of exosomes in the pathogenesis of major blindness-threatening diseases, such as age-related macular degeneration, glaucoma, and corneal dystrophy, were discovered by aqueous humor analysis. A new diagnostic method using cellulose-based devices and microfluidic chip techniques for the isolation of exosomes from aqueous humor is less cumbersome and saves time. This method will enable more investigations for aqueous humor analysis in the future., Competing Interests: The authors declare no conflict of interest.

In this study, we demonstrate and investigate a new droplet injection design. We create a thermal inkjet (TIJ) printhead using an application-specific integrated circuit system and bulk micromachining technology (microelectromechanical systems). We design inkjet printhead chips with a new structure and investigate their properties. For the new structure, the integration of complementary metal-oxide-semiconductors (MOSs) and enhancement-mode devices, as well as power switches and a TIJ heater transducer, enables logic functions to be executed on-chip. This capability is used in the proposed design to address individual jets with even fewer input lines than in matrix addressing. A high number of jets (at least 896) can be addressed with only 11 input lines. E1 (Enable 1) and E2 (Enable 2) are set up dependently, and they have the ability to reverse their signals in relation to each other (i.e., if E1 is disabled, E2 is enabled and vice versa). The E1 and E2 signals each service 448 jets. If one of the MOSs is turned on, then it corresponds to a power line with a similar function. If an addressing gate terminal of the other MOS has a discharge action, then we can control a different heater to generate heating bubbles in the jet inks. The operating frequency for addressing these measurements is 18 kHz in normal mode, 26 kHz in draft mode, and 16 kHz in best mode., Competing Interests: The authors declare no conflict of interest.

Purpose: Uveitic inflammatory injury can cause irreversible visual loss; however, no single animal model recapitulates all the characteristics of human uveitis. Ultraviolet radiation (UVR) is one of the risk factors for uveitis, but the role of UVR in the pathogenesis of uveitic injury is unclear. The aim of this study was to elucidate whether UVB promotes the initiation of, and subsequently contributes to, uveitic inflammatory injury., Methods: Mice were assigned to either a blank control group or one of three UVB treatment groups: no protection, protection with Nelfilcon A contact lens (Food and Drug Administration [FDA] class II, about 46.8% UVB transmittance), or protection with Etafilcon A contact lens (FDA class IV, about 0.55% UVB transmittance). The contact lenses acted as blocking barriers against UVR. After the application of UVR, pathologic injuries were determined with slit-lamp microscopy and histologic examination., Results: Compared with the intact status of the controls, the anterior eyes of the UVB groups showed pathologic alterations in physiologic properties and tissue integrity. UVR promoted anterior uveitic inflammatory injury, with expansion of the hyperemic iris vessels, over-production of aqueous humor protein, disruption of the blood-aqueous barrier, and embedding of infiltrative leukocytes inside the iridocorneal angle. However, blockage of UVR in vivo retarded the progression of uveitic inflammatory injury. The highest level of UV protection in the Etafilcon A group resulted in greater inhibition of uveitic inflammatory injury than that in the Nelfilcon A group., Conclusions: This study demonstrates that UVB initiated and promoted uveitic inflammatory injury. UV protection is needed for the clinical management of anterior uveitis. The Etafilcon A lenses provide better protection of the anterior segment of the eye against UVB damage compared with the Nelfilcon A lenses.

Background: No large epidemiological study has been conducted to investigate the interaction and joint effects of periodontal pocket depth and hyperglycemia on progression of chronic kidney disease in patients with periodontal diseases., Methods: Periodontal pocket depth was utilized for the grading severity of periodontal disease in 2831 patients from January 2002 to June 2013. Progression of chronic kidney disease was defined as progression of color intensity in glomerular filtration rate and albuminuria grid of updated Kidney Disease-Improving Global Outcomes guidelines. Multivariable-adjusted hazard ratios (aHR) in various models were presented across different levels of periodontal pocket depth and hemoglobin A1c (HbA1c) in forest plots and 3-dimensional histograms., Results: During 7621 person-years of follow-up, periodontal pocket depth and HbA1C levels were robustly associated with incremental risks for progression of chronic kidney disease (aHR 3.1; 95% confidence interval [CI], 2.0-4.6 for periodontal pocket depth >4.5 mm, and 2.5; 95% CI, 1.1-5.4 for HbA1C >6.5%, respectively). The interaction between periodontal pocket depth and HbA1C on progression of chronic kidney disease was strong (P <.01). Patients with higher periodontal pocket depth (>4.5 mm) and higher HbA1C (>6.5%) had the greatest risk (aHR 4.2; 95% CI, 1.7-6.8) compared with the lowest aHR group (periodontal pocket depth ≤3.8 mm and HbA1C ≤6%)., Conclusion: Our study identified combined periodontal pocket depth and HbA1C as a valuable predictor of progression of chronic kidney disease in patients with periodontal diseases. While considering the interaction between periodontal diseases and hyperglycemia, periodontal survey and optimizing glycemic control are warranted to minimize the risk of worsening renal function., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Clinical Introduction: A 60-year-old man had a long history of chronic hepatitis C. He presented to the emergency department with 2 days of progressive dyspnoea. Clinical manifestations included respiratory distress, cyanosis, digital clubbing, spider naevi on the upper chest and shifting dullness in the abdomen (see online supplementary figure S1). The ECG showed sinus tachycardia and left axis deviation. The chest radiography depicted blunting of right costophrenic angle with small pleural effusions and bilateral prominent pulmonary vascular markings (see online supplementary figure S2). The dyspnoea was exacerbated by upright posture and improved with recumbency. The hypoxaemia could not be corrected with administration of 100% oxygen. Contrast-enhanced transthoracic echocardiography was performed with injection of agitated saline (see figure 1 and online supplementary video). CT scan of the chest revealed some vascular abnormalities (see online supplementary figure S3-S6)., Question: Which of the following is the next best step in management?Catheter-based closure of intracardiac shuntLiver transplantationPulmonary angiography and embolisationThoracentesisTransjugular intrahepatic portosystemic shunt., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objectives: Acute cardiomyopathy is a health problem worldwide. Few studies have shown an association between acute cardiomyopathy and low vitamin D status. Paricalcitol, a vitamin D receptor activator, clinically benefits patients with advanced kidney disease. The effect of paricalcitol supplement on cardiac remodeling in cardiomyopathic rats is unknown. This experimental study investigated the effect of paricalcitol in rats with cardiomyopathy induced by isoproterenol., Design: Prospective, randomized, controlled experimental study., Setting: Hospital-affiliated animal research institution., Subjects: Eight-week-old male Wistar-Kyoto rats., Interventions: Male Wistar-Kyoto rats were first injected intraperitoneally with isoproterenol to create a rat model of acute cardiomyopathy. Then paricalcitol was administered intraperitoneally to isoproterenol-injected rats at a dosage of 200 ng three times a week for 3 weeks. Relevant cardiomyopathy-related variables were measured regularly in three groups of rats, controls, isoproterenol, and isoproterenol plus paricalcitol. Rat hearts were obtained for evaluation of cardiac fibrosis using Masson trichrome staining and commercially available software, and evaluation of cell transition using immunofluorescence staining analysis., Measurements and Main Results: Isoproterenol infusions generated significant cardiac fibrosis (p < 0.001). Subsequent paricalcitol treatment attenuated the isoproterenol-induced cardiac fibrosis (p = 0.006). Fluorescence showed colocalization of endothelial and fibroblast cell markers (cluster differentiation 31 and α-smooth muscle actin, respectively) in the isoproterenol-treated hearts. Paricalcitol injections attenuated the isoproterenol-induced fluorescence intensity of two cell markers (p < 0.01)., Conclusions: Paricalcitol injections may ameliorate isoproterenol-induced cardiac fibrosis possibly through regulating cell transition.

This paper describes studies leading to the development of an acoustic instrument for measuring properties of micrometeoroids and other dust particles in space. The instrument uses a pair of easily penetrated membranes separated by a known distance. Sensors located on these films detect the transient acoustic signals produced by particle impacts. The arrival times of these signals at the sensor locations are used in a simple multilateration calculation to measure the impact coordinates on each film. Particle direction and speed are found using these impact coordinates and the known membrane separations. This ability to determine particle speed, direction, and time of impact provides the information needed to assign the particle's orbit and identify its likely origin. In many cases additional particle properties can be estimated from the signal amplitudes, including approximate diameter and (for small particles) some indication of composition/morphology. Two versions of this instrument were evaluated in this study. Fiber optic displacement sensors are found advantageous when very thin membranes can be maintained in tension (solar sails, lunar surface). Piezoelectric strain sensors are preferred for thicker films without tension (long duration free flyers). The latter was selected for an upcoming installation on the International Space Station.

Phytoplasmas are bacterial phytopathogens that release virulence effectors into sieve cells and act systemically to affect the physiological and morphological state of host plants to promote successful pathogenesis. We show here that transgenic Nicotiana benthamiana lines expressing the secreted effector SAP11 from Candidatus Phytoplasma mali exhibit an altered aroma phenotype. This phenomenon is correlated with defects in the development of glandular trichomes and the biosynthesis of 3-isobutyl-2-methoxypyrazine (IBMP). IBMP is a volatile organic compound (VOC) synthesized by an O-methyltransferase, via a methylation step, from a non-volatile precursor, 3-isobutyl-2-hydroxypyrazine (IBHP). Based on comparative and functional genomics analyses, NbOMT1, which encodes an O-methyltransferase, was found to be highly suppressed in SAP11-transgenic plants. We further silenced NbOMT1 through virus-induced gene silencing and demonstrated that this enzyme influenced the accumulation of IBMP in N. benthamiana In vitro biochemical analyses also showed that NbOMT1 can catalyse IBHP O-methylation in the presence of S-adenosyl-L-methionine. Our study suggests that the phytoplasma effector SAP11 has the ability to modulate host VOC emissions. In addition, we also demonstrated that SAP11 destabilized TCP transcription factors and suppressed jasmonic acid responses in N. benthamiana These findings provide valuable insights into understanding how phytoplasma effectors influence plant volatiles., (© The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

A self-powered complementary electrochromic device (CECD) driven by a high open-circuit voltage InGaN/GaN multiple quantum well (MQW) solar cell has been designed. The coloration and bleaching time of the system were 5 and 8 s, respectively.

Purpose: Excessive exposure to sunlight may be a risk factor for ocular diseases and reduced visual performance. This study was designed to examine the ability of an ultraviolet (UV)-blocking spectacle lens to prevent visual acuity decline and ocular surface disorders in a mouse model of UVB-induced photokeratitis., Methods: Mice were divided into 4 groups (10 mice per group): (1) a blank control group (no exposure to UV radiation), (2) a UVB/no lens group (mice exposed to UVB rays, but without lens protection), (3) a UVB/UV400 group (mice exposed to UVB rays and protected using the CR-39™ spectacle lens [UV400 coating]), and (4) a UVB/photochromic group (mice exposed to UVB rays and protected using the CR-39™ spectacle lens [photochromic coating]). We investigated UVB-induced changes in visual acuity and in corneal smoothness, opacity, and lissamine green staining. We also evaluated the correlation between visual acuity decline and changes to the corneal surface parameters. Tissue sections were prepared and stained immunohistochemically to evaluate the structural integrity of the cornea and conjunctiva., Results: In blank controls, the cornea remained undamaged, whereas in UVB-exposed mice, the corneal surface was disrupted; this disruption significantly correlated with a concomitant decline in visual acuity. Both the UVB/UV400 and UVB/photochromic groups had sharper visual acuity and a healthier corneal surface than the UVB/no lens group. Eyes in both protected groups also showed better corneal and conjunctival structural integrity than unprotected eyes. Furthermore, there were fewer apoptotic cells and less polymorphonuclear leukocyte infiltration in corneas protected by the spectacle lenses., Conclusions: The model established herein reliably determines the protective effect of UV-blocking ophthalmic biomaterials, because the in vivo protection against UV-induced ocular damage and visual acuity decline was easily defined.

Background: To investigate the association between metabolic syndrome, including its factors, and gallstone disease (GSD) in a Taiwanese population., Methods: We conducted a cross-sectional study during 2011 ~ 2012. A total of 12050 subjects who completed a questionnaire and underwent physical examination, laboratory tests and abdominal ultrasonography formed the study population., Results: The prevalences of metabolic syndrome and gallstone disease were 24.09% and 6.16%. In an age- and sex-adjusted logistic regression model, metabolic syndrome was associated with gallstone disease (OR = 1.61; P < 0.0001). Age, abdominal obesity, and lower high-density lipoprotein cholesterol were associated with gallstone disease after adjusting for other factors. Females had a higher odds ratio than males in waist circumference for GSD, whereas males had a lower odds ratio than females in HDL-C for GSD., Conclusions: The present study suggests that metabolic syndrome is related to gallstone disease. Waist circumference and high-density lipoprotein cholesterol are all associated with GSD. Men and women may possibly have different priorities and strategies to reduce the burden of GSD.

Purpose: Translesional pressure ratio (TLPR) indicating fractional flow reserve has been applied to physiological assessment of moderate coronary stenosis. The role of TLPR in hemodialysis (HD) patients with arteriovenous graft (AVG) outflow stenosis undergoing percutaneous transluminal angioplasty (PTA) is unclear. The purpose of the study was to assess the validation of TLPR in such patients undergoing PTA., Methods: Patients with pure AVG outflow stenosis confirmed by angiography were prospectively enrolled. A TLPR defined as a ratio of the mean pressure downstream to the lesion(s) to the vein-sided intragraft pressure was measured using a catheter pullback method. Relationship among TLPR, angiographic result and clinical outcome within 6 months was detected., Results: Of 65 PTAs, the post-PTA TLPR significantly increased (from 0.28±0.10 to 0.50±0.11; p<0.0001). A significantly greater pre-PTA TLPR was observed in the simple lesions at baseline compared with the complex lesions (0.32±0.09 vs. 0.20±0.06; p<0.0001). Post-PTA TLPR ≥0.5 was powerfully related to angiographic success (p<0.0001). The group with angiographic success plus post-PTA TLPR ≥0.5 had a longer PTA-free patency (208.7±188.7 vs. 109.8±67.7 days; p=0.013) compared with that with angiographic nonsuccess plus post-PTA TLPR <0.5., Conclusions: Our data show that TLPR correlates well with lesion properties and angiographic results, and helps predict following unassisted patency. The study suggests TLPR as a hemodynamic indicator during PTA.

Neuropathic pain is characterized by spontaneous pain, hyperalgesia, and allodynia. The aim of this study was to investigate whether KMUP-1 (7-[2-[4-(2-chlorobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine) could improve pain hypersensitivity and reduce inflammatory mediators, and also explore possible mechanisms in the rat sciatic nerve using bilateral chronic constriction injury (CCI) to induce neuropathic pain. Sprague-Dawley rats were randomly divided into four groups: Sham, Sham+KMUP-1, CCI, and CCI+KMUP-1. KMUP-1 (5 mg/kg/day) was injected intraperitoneally starting at day 1 after surgery. Mechanical and thermal responses were assessed before surgery and at days 3, 7, and 14 after CCI. Sciatic nerves around the injury site were isolated for Western blots and enzyme-linked immunosorbent assay to analyze protein and cytokine levels. The results show that thermal hyperalgesia and mechanical allodynia were reduced in the KMUP-1 treated group as compared to that in the CCI group. Inflammatory proteins (COX2, iNOS, and nNOS) and proinflammatory cytokines (TNF-α and IL-1β) induced by CCI were decreased in the KMUP-1 treated group at day 7 after surgery. KMUP-1 also inhibited neuropathic pain-related mechanisms, including p38 and ERK activation, but not JNK. Furthermore, KMUP-1 blocked IκB phosphorylation (p-IκB) and phospho-nuclear factor κB (p-NF-κB) translocation to nuclei. Double immunofluorescent staining further demonstrated that p-IκB (an indicator of activated NFκB) and p-NFκB proteins were almost abolished by KMUP-1 in peripheral macrophages and spinal microglia cells at day 7 after surgery. On the basis of these findings, we concluded that KMUP-1 has antiinflammatory and antihyperalgesia properties in CCI-induced neuropathic pain via decreases in MAPKs and NF-κB activation.

The purpose of this study was to examine the prevalence and predictors of suicidal behavior among Mongolian high school students. Females were more likely to have suicidal behavior than males. No close friends, feelings of loneliness, insomnia, self perception of underweight or overweight, carrying a weapon were significant predictors of students' suicidal behavior. Missing school without permission, being bullied and going hungry were also important risk factors of suicidal ideation. Families and Schools are important environments to prevent high students' suicide. Improving students' psychological well being, quality of relationship with people, and support resources are critical to prevent suicidal behavior.

Recent clinical studies found that fructose intake leads to insulin resistance and hypertension. Fructose consumption promotes protein fructosylation and formation of superoxide. In a previous study, we revealed that inhibition of superoxide production in the nucleus tractus solitarii (NTS) reduces blood pressure. Caffeine displays significant antioxidant ability in protecting membranes against oxidative damage and can lower the risk of insulin resistance. However, the mechanism through which caffeine improves fructose-induced insulin resistance is unclear. The aim of this study was to investigate whether caffeine consumption can abolish superoxide generation to enhance insulin signaling in the NTS, thereby reducing blood pressure in rats with fructose-induced hypertension. Treatment with caffeine for 4 weeks decreased blood pressure, serum fasting glucose, insulin, homeostatic model assessment-insulin resistance, and triglyceride levels and increased the serum direct high-density lipoprotein level in fructose-fed rats but not in control rats. Caffeine treatment resulted in the recovery of fructose-induced decrease in nitric oxide production in the NTS. Immunoblotting and immunofluorescence analyses further showed that caffeine reduced the fructose-induced phosphorylation of insulin receptor substrate 1 (IRS1(S307)) and reversed Akt(S473) and neuronal nitric oxide synthase phosphorylation. Similarly, caffeine was able to improve insulin sensitivity and decrease insulin levels in the NTS evoked by fructose. Caffeine intake also reduced the production of superoxide and expression of receptor of advanced glycation end product in the NTS. These results suggest that caffeine may enhance insulin receptor substrate 1-phosphatidylinositol 3-kinase-Akt-neuronal nitric oxide synthase signaling to decrease blood pressure by abolishing superoxide production in the NTS.

In this study, the Mo-electrode thin films were deposited by a two-stepped process, and the high-purity copper indium selenide-based powder (CuInSe2, CIS) was fabricated by hydrothermal process by Nanowin Technology Co. Ltd. From the X-ray pattern of the CIS precursor, the mainly crystalline phase was CIS, and the almost undetectable CuSe phase was observed. Because the CIS powder was aggregated into micro-scale particles and the average particle sizes were approximately 3 to 8 μm, the CIS power was ground into nano-scale particles, then the 6 wt.% CIS particles were dispersed into isopropyl alcohol to get the solution for spray coating method. Then, 0.1 ml CIS solution was sprayed on the 20 mm × 10 mm Mo/glass substrates, and the heat treatment for the nano-scale CIS solution under various parameters was carried out in a selenization furnace. The annealing temperature was set at 550°C, and the annealing time was changed from 5 to 30 min, without extra Se content was added in the furnace. The influences of annealing time on the densification, crystallization, resistivity (ρ), hall mobility (μ), and carrier concentration of the CIS absorber layers were well investigated in this study.

Objective: To explore the role of far infrared (FIR) radiation therapy for hemodialysis (HD) access maintenance after percutaneous transluminal angioplasties (PTA)., Methods: This was a prospective observational study. Eligible patients were those who received repeated PTA with the last PTA successfully performed within 1 week before the study enrollments. Consecutively enrolled patients undergoing successful HD treatments after PTA were randomly assigned to the FIR-radiated group or control group without radiation. FIR-radiated therapy meaning 40-minute radiation at the major lesion site or anastomosed site three times a week was continued until an end-point defined as dysfunction-driven re-PTA or the study end was reached., Results: Of 216 participants analyzed, including 97 with arteriovenous grafts (AVG) (49 FIR-radiated participants and 48 control participants) and 119 with arteriovenous fistulas (AVF) (69 FIR-radiated participants and 50 control participants), the FIR-radiated therapy compared with free-radiated usual therapy significantly enhanced PTA-unassisted patency at 1 year in the AVG subgroup (16.3% vs. 2.1%; p < .01), but not the AVF subgroup (25.0% vs. 18.4%; p = .50), and this accounted for the overall improved patency rates (21.4% vs. 10.3%; p = .02)., Conclusions: This study suggests FIR-radiated therapy improves PTA-unassisted patency in patients with AVG who have undergone previous PTA., (Copyright © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

A 25-year-old woman presented with severe dyspnoea at an emergency care unit on her postpartum day 7. Her O2 saturation level was low. Blood tests showed a high blood D-dimer level; echocardiography showed a high pulmonary artery pressure. Initially, heparin was administered for suspicion of pulmonary embolism. After transfer to the intensive care unit, she suffered respiratory failure. A three-dimensional (3D) reconstruction CT angiography then revealed a giant patent ductus arteriosus. Extracorporeal membrane oxygenation was performed owing to low O2 saturation after ventilator use. After 1 month, she died of multiple organ failure. In postpartum patients with congenital heart disease, a diagnosis of pulmonary embolism should be immediately confirmed by 3D reconstruction CT angiography to rule out patent ductus arteriosus.