Beneficial carry-over effects of chronic at-home genital nerve stimulation on incontinence in individuals with spinal cord injury: A pragmatic trial.

BACKGROUND: Genital nerve stimulation (GNS) is a promising, but under-researched, alternative treatment for neurogenic detrusor overactivity (NDO) in those with spinal cord injury (SCI). OBJECTIVES: To investigate the urodynamic, quality-of-life (QOL) and carry-over effects of GNS when applied at home for 2 weeks by participants with incomplete SCI and NDO during activities of daily living. METHODS: Seven men and 1 woman participated in this 1-month protocol study. Urodynamic and QOL data were gathered during week 1 (baseline measurements), followed by 2 weeks of daily GNS at home using a portable device. GNS was applied either on-demand or thrice daily, depending on the individual's sensation. At week 4, post-stimulation tests were repeated to record any carry-over effect from the GNS. Participants maintained voiding diaries throughout the study. Assessments were carried out at the end of each protocol period in a randomized order. Clinical procedures were conducted at Taipei Medical University Hospital (Taipei, Taiwan). RESULTS: Everyone completed the study but only 7 of the 8 participants completed their voiding diary. Two weeks after GNS, average cystometric bladder capacity was increased by 30 % compared to baseline (P< 0.05). A 1-week carry-over effect was demonstrated as this capacity remained, on average, 35 % greater than baseline in week 4 after GNS was stopped (P< 0.05). Incontinence frequency significantly decreased by the end of week 3 (P< 0.05) but no significant improvements were recorded for either detrusor pressure or bladder compliance. CONCLUSIONS: Chronic at-home GNS improved cystometric bladder capacity and reduced urinary incontinence for individuals with incomplete SCI and NDO. A carry-over effect of 1 week was observed following GNS treatment. The use of portable GNS treatment that can be applied by the individual at home merits further investigation as alternative treatment for NDO in those with SCI.

A time-course study of urodynamic analyses in rat models with dopaminergic depletion induced through unilateral and bilateral 6-hydroxydopamine injections.

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.

Relaxing Effects of Breathing Pseudotsuga menziesii and Lavandula angustifolia Essential Oils on Psychophysiological Status in Older Adults.

We evaluated the effects of breathing Pseudotsuga menziesii (P. menziesii) and Lavandula angustifolia (L. angustifolia) essential oils (EOs) during a horticultural activity on older adults. A total number of 92 older adult (71.2 ± 7.7 years old) participants were guided through a leaf printing procedure. In the meantime, water vapor and EOs were diffused in an orderly manner. The heart rate variability-related parameters as well as the brain waves were recorded. In addition, we also collected data for the State-Trait Anxiety Inventory-State (STAI-S) questionnaires before and after the whole indoor natural activity program. The physiological parameters including standard deviation of normal to normal intervals, normalized high frequency (nHF), and high alpha wave increased while the normalized low frequency (nLF), the ratio of LF-to-HF power, high beta wave, and gamma wave decreased following the breathing of P. menziesii and L. angustifolia EOs. These changes indicated a relaxing effect of breathing both EOs during a horticultural activity on older adults. Our results demonstrated a beneficial effect of P. menziesii EO which is as good as a well-known relaxant L. angustifolia EO. This notion was supported by the results of STAI-S. Here we developed an indoor natural activity program for older adults to promote physical and mental health.

Sacubitril Valsartan Enhances Cardiac Function and Alleviates Myocardial Infarction in Rats through a SUV39H1/SPP1 Axis.

Sacubitril valsartan (lcz696) has been demonstrated as a substitute for angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for the treatment of heart failure. This research is aimed at examining the effects of lcz696 and its target molecules on myocardial infarction (MI). A rat model of MI was induced by left anterior descending artery ligation and treated with lcz696. Lcz696 treatment significantly reduced cardiac injury and heart failure, restored the left ventricular fractional shortening and ejection fraction, and reduced oxidative stress and inflammatory responses in rat myocardium. By analyzing the heart failure-related GSE47495 dataset and performing gene ontology (GO) functional enrichment analysis, we obtained histone lysine methyltransferase SUV39H1 and secreted phosphoprotein 1 (SPP1) as two molecules implicated in the oxidative stress and inflammation processes. An elevation of SUV39H1 whereas a decline of SPP1 were detected in cardiac tissues after lcz696 treatment. Enrichments of SUV39H1 and H3K9me3 at the SPP1 promoter were identified by chromatin immunoprecipitation assay. SUV39H1 catalyzed H3K9me3 modification to suppress the expression of SPP1. Preconditioning of SUV39H1 silencing blocked the protective roles of lcz696, but SPP1 silencing alleviated the myocardial injury. In conclusion, this study demonstrates that lcz696 enhances cardiac function and alleviates MI in rats through a SUV39H1/SPP1 axis.

High-Definition Transcranial Direct Current with Electrical Theta Burst on Post-Stroke Motor Rehabilitation: A Pilot Randomized Controlled Trial.

BACKGROUND: High-definition transcranial electrical theta burst superimposing direct current stimulation (HD-tDCS-eTBS) not only incorporates the therapeutic advantages of tDCS and TBS but enhances stimulation focality and practicality. However, the applicability of this innovative neuromodulatory device in post-stroke rehabilitation remains uncertain. OBJECTIVE: This study aimed to assess the efficacy and safety of the HD-tDCS-eTBS on upper extremity (UE) motor function in patients with chronic stroke. METHODS: A patient-blinded, randomized controlled study was conducted. Twenty-four participants were randomly assigned into either the active HD-tDCS-eTBS group or sham HD-tDCS-eTBS group. Both groups received 20 minutes of active/sham HD-tDCS-eTBS combined with 30 minutes of conventional UE rehabilitation each time, 3 times a week for 4 weeks. Outcome measures including the Fugl-Meyer Assessment of Upper Extremity, Wolf Motor Function Test, Jebsen-Taylor Hand Function Test, Finger-Nose Test, and Modified Ashworth Scale were assessed before and immediately after the intervention period. RESULTS: Spasticity of shoulder adductor (P = .05), elbow extensor (P = .04), and thumb flexor (P < .01) were significantly reduced in the active HD-tDCS-eTBS group versus the sham group. Nonsignificant trends in the improvements of most other outcome measures were in favor of the active HD-tDCS-eTBS group with moderate to large effect sizes (P = .06-.26, ηp2 = 0.06-0.16). No severe adverse events except for slight skin redness under the stimulus electrode was detected after the HD-tDCS-eTBS. CONCLUSIONS: Our findings support that HD-tDCS-eTBS is safe and has therapeutic potential for post-stroke UE motor rehabilitation. TRIAL REGISTRATION: ClinicalTrials.gov (ID: NCT04278105).

Hemodynamics and Tissue Optical Properties in Bimodal Infarctions Induced by Middle Cerebral Artery Occlusion.

Various infarct sizes induced by middle cerebral artery occlusion (MCAO) generate inconsistent outcomes for stroke preclinical study. Monitoring cerebral hemodynamics may help to verify the outcome of MCAO. The aim of this study was to investigate the changes in brain tissue optical properties by frequency-domain near-infrared spectroscopy (FD-NIRS), and establish the relationship between cerebral hemodynamics and infarct variation in MCAO model. The rats were undergone transient MCAO using intraluminal filament. The optical properties and hemodynamics were measured by placing the FD-NIRS probes on the scalp of the head before, during, and at various time-courses after MCAO. Bimodal infarction severities were observed after the same 90-min MCAO condition. Significant decreases in concentrations of oxygenated hemoglobin ([HbO]) and total hemoglobin ([HbT]), tissue oxygenation saturation (StO2), absorption coefficient (µa) at 830 nm, and reduced scattering coefficient (µs') at both 690 and 830 nm were detected during the occlusion in the severe infarction but not the mild one. Of note, the significant increases in [HbO], [HbT], StO2, and µa at both 690 and 830 nm were found on day 3; and increases in µs' at both 690 and 830 nm were found on day 2 and day 3 after MCAO, respectively. The interhemispheric correlation coefficient (IHCC) was computed from low-frequency hemodynamic oscillation of both hemispheres. Lower IHCCs standing for interhemispheric desynchronizations were found in both mild and severe infarction during occlusion, and only in severe infarction after reperfusion. Our finding supports that sequential FD-NIRS parameters may associated with the severity of the infarction in MCAO model, and the consequent pathologies such as vascular dysfunction and brain edema. Further study is required to validate the potential use of FD-NIRS as a monitor for MCAO verification.

Motor Neuroplastic Effects of a Novel Paired Stimulation Technology in an Incomplete Spinal Cord Injury Animal Model.

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_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.

Designing and Pilot Testing a Novel Transcranial Temporal Interference Stimulation Device for Neuromodulation.

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.

Modulation of Interhemispheric Synchronization and Cortical Activity in Healthy Subjects by High-Definition Theta-Burst Electrical Stimulation.

Background: Various forms of theta-burst stimulation (TBS) such as intermittent TBS (iTBS) and continuous TBS (cTBS) have been introduced as novel facilitation/suppression schemes during repetitive transcranial magnetic stimulation (rTMS), demonstrating a better efficacy than conventional paradigms. Herein, we extended the rTMS-TBS schemes to electrical stimulation of high-definition montage (HD-TBS) and investigated its neural effects on the human brain. Methods: In a within-subject design, fifteen right-handed healthy adults randomly participated in 10 min and 2 mA HD-TBS sessions: unilateral (Uni)-iTBS, bilateral (Bi)-cTBS/iTBS, and sham stimulation over primary motor cortex regions. A 20-channel near-infrared spectroscopy (NIRS) system was covered on the bilateral prefrontal cortex (PFC), sensory motor cortex (SMC), and parietal lobe (PL) for observing cerebral hemodynamic responses in the resting-state and during fast finger-tapping tasks at pre-, during, and poststimulation. Interhemispheric correlation coefficient (IHCC) and wavelet phase coherence (WPCO) from resting-state NIRS and concentration of oxyhemoglobin during fast finger-tapping tasks were explored to reflect the symmetry between the two hemispheres and cortical activity, respectively. Results: The IHCC and WPCO of NIRS data in the SMC region under Bi-cTBS/iTBS showed relatively small values at low-frequency bands III (0.06-0.15 Hz) and IV (0.02-0.06), indicating a significant desynchronization in both time and frequency domains. In addition, the SMC activation induced by fast finger-tapping exercise was significantly greater during Uni-iTBS as well as during and post Bi-cTBS/iTBS sessions. Conclusions: It appears that a 10 min and 2 mA Bi-cTBS/iTBS applied over two hemispheres within the primary motor cortex region could effectively modulate the interhemispheric synchronization and cortical activation in the SMC of healthy subjects. Our study demonstrated that bilateral HD-TBS approaches is an effective noninvasive brain stimulation scheme which could be a novel therapeutic for inducing effects of neuromodulation on various neurological disorders caused by ischemic stroke or traumatic brain injuries.

Evaluating interhemispheric synchronization and cortical activity in acute stroke patients using optical hemodynamic oscillations.

Objective.An understanding of functional interhemispheric asymmetry in ischemic stroke patients is a crucial factor in the designs of efficient programs for post-stroke rehabilitation. This study evaluates interhemispheric synchronization and cortical activities in acute stroke patients with various degrees of severity and at different post-stroke stages.Approach.Twenty-three patients were recruited to participate in the experiments, including resting-state and speed finger-tapping tasks at week-1 and week-3 post-stroke. Multichannel near-infrared spectroscopy (NIRS) was used to measure the changes in hemodynamics in the bilateral prefrontal cortex (PFC), the supplementary motor area (SMA), and the sensorimotor cortex (SMC). The interhemispheric correlation coefficient (IHCC) measuring the synchronized activities in time and the wavelet phase coherence (WPCO) measuring the phasic activity in time-frequency were used to reflect the symmetry between the two hemispheres within a region. The changes in oxyhemoglobin during the finger-tapping tasks were used to present cortical activation.Main results.IHCC and WPCO values in the severe-stroke were significantly lower than those in the minor-stroke at low frequency bands during week-3 post-stroke. Cortical activation in all regions in the affected hemisphere was significantly lower than that in the unaffected hemisphere in the moderate-severe stroke measured in week-1, however, the SMC activation on the affected hemisphere was significantly enhanced in week-3 post-stroke.Significance.In this study, non-invasive NIRS was used to observe dynamic synchronization in the resting-state based on the IHCC and WPCO results as well as hemodynamic changes in a motor task in acute stroke patients. The findings suggest that NIRS could be used as a tool for early stroke assessment and evaluation of the efficacy of post-stroke rehabilitation.

Nature-based solutions for securing contributions of water, food, and energy in an urban environment.

There is growing awareness that nature-based solutions (NBS) prevent negative effects and secure ecosystem services. However, the potential of NBS to provide intended benefits has not been rigorously assessed. Water, food, and energy (WFE) are essential for human well-being. This study highlights the importance of NBS in terms of water, food, and energy. A set of on-site NBS that includes permeable pavements, plant microbial fuel cells, bio-filtration basins, and rain gardens is used to determine the contribution of NBS to the environmental and economic development of urban environments. The results of this study show that NBSs benefit an urban environment in terms of water treatment, stormwater retention, food production and energy generation, carbon sequestration, pollination, sedimentation retention, and cultural services dimension. This research highlights an urgent need for the integration of water, food, and energy plans to ensure that NBSs contribute to the environment and for the conservation of ecosystem services.

Effects of paired stimulation with specific waveforms on cortical and spinal plasticity in subjects with a chronic spinal cord injury.

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.

Oxygen Consumption (VO2) and Surface Electromyography (sEMG) during Moderate-Strength Training Exercises.

Oxygen consumption (VO2) during strength training can be predicted through surface electromyography (sEMG) of local muscles. This research aimed to determine relations between VO2 and sEMG of upper and lower body muscles to predict VO2 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 VO2 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 VO2 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 VO2 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.

Protective Effects of Salicylic Acid and Calcium Chloride on Sage Plants (Salvia officinalis L. and Salviaelegans Vahl) under High-Temperature Stress.

High-temperature stress is a major risk to fresh-market Salvia production, and heat intolerance is a major constraint in sage cultivation, particularly during the hot summer season. Previously, we investigated heat tolerance in five common-market cultivars of sage plants using leaf relative injury (RI) values and found that S. elegans Vahl (SE) and S. officinalis L. (SO) were the most and least heat-tolerant species, respectively. The exogenous applications of salicylic acid (SA) and calcium chloride (CaCl2) to alleviate heat stress in various species have been extensively studied, but reports of the effects of SA and CaCl2 treatments on the heat tolerance of sage plants are scarce. The objective of this study was to investigate how SA and CaCl2 affect the physiology and morphology of SE and SO plants under high-temperature conditions. Potted plants were pretreated with SA (0, 100, 200, 400, and 800 µM) and CaCl2 (0, 5, 10, and 15 mM), alone and combined, exposed to 55 °C and 80% humidity for 30 min, then placed in an environment-controlled chamber at 30 °C for three days and evaluated for changes in phenotypic appearance, RI, spectral reflectance, and chlorophyll fluorescence indices at different time intervals. Plants watered without chemical solutions were used as controls. Our results show that the growth of SO plants pretreated with SA and CaCl2 was more robust, compared with control plants, which were considerably affected by heat stress, resulting in brown, withered leaves and defoliation. The effects of the combined applications of SA (100 µM) and CaCl2 (5 mM) to SO plants were superior to control plants in increasing values of soil-plant analysis development (SPAD), normalized difference vegetation index (NDVI), and the maximal quantum yield of photosystemII photochemistry (Fv/Fm), while reducing RI%. Furthermore, SO plants exhibited higher SPAD and Fv/Fm values and lower RI% than SE plants in combined treatments at all time intervals after heat stress, implying that different genotypes displayed variations in their SPAD, Fv/Fm, and RI%. Thus, a combined treatment of 100 µM of SA and 5 mM of CaCl2 is effective and beneficial to plant appearance and ability to ameliorate heat stress. These indices can be used as indicators to characterize the physiology of these plants and applied on a commercial scale for informing the development of rapid and precise management practices on bedded sage plants grown in plant factories to achieve maximum market benefit.

Designing and pilot testing a novel high-definition transcranial burst electrostimulation device for neurorehabilitation.

Objective.Non-invasive brain stimulation has been promoted to facilitate neuromodulation in treating neurological diseases. Recently, high-definition (HD) transcranial electrical stimulation and a novel electrical waveform combining a direct current (DC) and theta burst stimulation (TBS)-like protocol were proposed and demonstrated high potential to enhance neuroplastic effects in a more-efficient manner. In this study, we designed a novel HD transcranial burst electrostimulation device and to preliminarily examined its therapeutic potential in neurorehabilitation.Approach.A prototype of the transcranial burst electrostimulation device was developed, which can flexibly output a waveform that combined a DC and TBS-like protocol and can equally distribute the current into 4 × 1 HD electrical stimulation by automatic impedance adjustments. The safety and accuracy of the device were then validated in a series ofin vitroexperiments. Finally, a pilot clinical trial was conducted to assess its clinical safety and therapeutic potential on upper-extremity rehabilitation in six patients with chronic stroke, where patients received either active or sham HD transcranial burst electrostimulation combined with occupational therapy three times per week for four weeks.Main results.The prototype was tested, and it was found to comply with all safety requirements. The output parameters were accurate and met the clinical study needs. The pilot clinical study demonstrated that the active HD transcranial burst electrostimulation group had greater improvement in voluntary motor function and coordination of the upper extremity than the sham control group. Additionally, no severe adverse events were noted, but slight skin redness under the stimulus electrode immediately after stimulation was seen.Conclusions.The results demonstrated the feasibility of incorporating the HD electrical DC and TBS-like protocol in our device; and the novel neuromodulatory device produced positive neurorehabilitation outcomes in a safe fashion, which could be the basis for the future clinical implementation for treating neurological diseases.Trial registration:ClinicalTrials.gov Identifier: NCT04278105. Registered on 20 February 2020.

Flavonoid Compounds and Photosynthesis in Passiflora Plant Leaves under Varying Light Intensities.

Functional constituents in the leaves of Passiflora plants contain antidepressant and antianxiety effects which are beneficial to human health and fitness. The objective of this study was to investigate leaf growth, physiological parameters, and secondary metabolite contents of Tainung No. 1 variety (P. edulis × P. edulis f. flavicarpa.) and P. suberosa in response to three light intensity conditions, including 100% light intensity (LI-100), 50% light intensity (LI-50), and 15% light intensity (LI-15) for 2 months. The leaf number, length, width, area, dry weight (DW), minimal fluorescence (Fo), maximal fluorescence (Fm), maximum photochemical efficiency of photosystem II, and soil-plant analysis development (SPAD) values of all tested plants increased with a decreasing light intensity, except for the leaf number and DW of P. suberosa plants. Low values of the net photosynthetic rate, transpiration rate, and stomatal conductance of Tainung No. 1 leaves in the LI-15 treatment showed the acclimation capacity of these plants. These observations together with high values of leaf growth traits of Fo, Fm, SPAD, and the intercellular-to-atmospheric CO2 concentration ratio indicate their physiological plasticity, which is of fundamental importance when cultivating plants in environments with different light availabilities. Wide variations occurred in total phenol (TP), total flavonoid (TF), orientin (OR), and isovitexin (IV) contents of the two Passiflora varieties, and P. suberosa contained higher TP and TF contents than did Tainung No. 1 in each light treatment but IV content of P. suberosa was lower than that of Tainung No. 1 in the LI-15 treatment. Moreover, increases in TF, OR, and IV contents of Tainung No. 1 and P. suberosa were clear in the LI-50 and LI-100 treatments, respectively, compared to LI-15 treatment. Leaf growth, physiological parameters, and secondary metabolite accumulations in Passiflora species can be optimized for commercial production via lighting control technologies, and this approach may also be applicable to leafy vegetables to produce a stable industrial supply of high leaf yields and metabolite contents.

Measurement of Interhemispheric Correlation Coefficient in Rodent Model of Middle Cerebral Artery Occlusion Using Near Infrared Spectroscopy.

Near-infrared spectroscopy (NIRS) is a noninvasive brain imaging technique that measures hemodynamics by determining the optical properties of tissue. Clinical potential of NIRS for monitoring cerebral hemodynamics in cerebrovascular diseases, such as stroke, has been studied. However, inconsistencies in measurements among studies, which are believed to be partly due to anatomical variance and diversity in disease presentation, limit the clinical feasibility of NIRS for stroke monitoring. In the present study, bihemispheric frequency-domain NIRS measurements on middle cerebral artery occlusion rats were performed. The discrepancy in interhemispheric synchronicity in hemodynamic oscillation appeared during the early reperfusion stage is related to the size of infarct that developed three days later. These NIRS parameters may have the potential to be early prognostic biomarkers for long-term stroke monitoring in the future translational investigation.

Modulation of motor excitability by cortical optogenetic theta burst stimulation.

Intermittent theta burst stimulation (iTBS) and continuous theta burst stimulation (cTBS) are protocols used in repetitive transcranial magnetic stimulation (rTMS) or cortical electrical stimulation (CES) to facilitate or suppress corticospinal excitability. However, rTMS and CES excite all types of neuron in the target cortex probed by the coil or electrode, making it difficult to differentiate the effect of TBS on specific neural circuits involved in motor plasticity. In this study, TBS protocols were converted into an optogenetic model to achieve focalized and cell-type-specific cortical modulation. Light-sensitive channelrhodopsin-2 (ChR2) was expressed in the glutamatergic neuron in the primary motor cortex (M1) driven by the CaMKIIα promoter. A custom-made optrode comprising an optical fiber and a metal cannula electrode was fabricated to achieve optogenetic stimulation and simultaneous local field potential (LFP) recording. Single-pulse CES was delivered into M1 to elicit motor-evoked potential (MEP), which served as an indicator of motor excitability, before and after TBS intervention. Results show that both CES-iTBS and optogenetic iTBS (Opto-iTBS) can potentiate MEP activity. However, CES-cTBS suppressed MEP activity whereas Opto-cTBS enhanced it. This discrepancy may have resulted from the different neural networks targeted by the two TBS modalities, with CES-cTBS exciting all types of neuron and Opto-cTBS targeting excitatory neuron specifically. The results support the idea that intra-cortical networks determine the variation of TBS-induced neuroplasticity. This study shows that focalized and cell-type-specific brain stimulation using the optogenetic approach is viable and can be extended for further exploration of neuroplasticity.

Risk of incident active tuberculosis disease in patients treated with non-steroidal anti-inflammatory drugs: a population-based study.

BACKGROUND: Mycobacterium tuberculosis (TB) is one of the world's most devastating public health threats. Our goal is to evaluate whether the use of non-steroidal anti-inflammatory drugs (NSAIDs) affect the risk of new incident active TB disease. METHODS: We conducted a nested case-control analysis by using a 1 million longitudinally followed cohort, from Taiwan's national health insurance research database. Effects of NSAIDs on active TB were estimated by conditional logistic regression and adjusted using a TB-specific disease risk score (DRS). NSAIDs exposures were defined as having a prescription record of NSAIDs ≧ 7 days that ended between 31 and 90 days prior to the index date. RESULTS: A total of 123,419 users of traditional NSAIDs, 16,392 users of cyclooxygenase-2 selective inhibitor (Coxibs), and 4706 incident cases of active TB were identified. Compared with nonusers, use of traditional NSAIDs was associated with an increased risk of TB in the unadjusted analysis ([RR], 1.39; 95% [CI], 1.24 - 1.57 and DRS adjusted analysis ([ARR], 1.30; 95% [CI], 1.15- 1.47). However, use of Coxibs was not associated with a significant increase in the risk of TB after DRS adjustment ([ARR], 1.23; 95% [CI], 0.89 - 1.70). CONCLUSIONS: In this large population-based study, we found that subjects using traditional NSAIDs were associated with increased risk for active TB. We did not find evidence for a causative mechanism between traditional NSAIDs and TB, and more research is required to verify whether the association between traditional NSAIDs and TB is causal, or simply reflects an increased use of anti-inflammatory drugs in the early phases of TB onset.

Resveratrol attenuates ICAM-1 expression and monocyte adhesiveness to TNF-α-treated endothelial cells: evidence for an anti-inflammatory cascade mediated by the miR-221/222/AMPK/p38/NF-κB pathway.

Resveratrol, an edible polyphenolic phytoalexin, improves endothelial dysfunction and attenuates inflammation. However, the mechanisms have not been thoroughly elucidated. Therefore, we investigated the molecular basis of the effects of resveratrol on TNF-α-induced ICAM-1 expression in HUVECs. The resveratrol treatment significantly attenuated the TNF-α-induced ICAM-1 expression. The inhibition of p38 phosphorylation mediated the reduction in ICAM-1 expression caused by resveratrol. Resveratrol also decreased TNF-α-induced IκB phosphorylation and the phosphorylation, acetylation, and translocation of NF-κB p65. Moreover, resveratrol induced the AMPK phosphorylation and the SIRT1 expression in TNF-α-treated HUVECs. Furthermore, TNF-α significantly suppressed miR-221/-222 expression, which was reversed by resveratrol. miR-221/-222 overexpression decreased p38/NF-κB and ICAM-1 expression, which resulted in reduced monocyte adhesion to TNF-α-treated ECs. In a mouse model of acute TNF-α-induced inflammation, resveratrol effectively attenuated ICAM-1 expression in the aortic ECs of TNF-α-treated wild-type mice. These beneficial effects of resveratrol were lost in miR-221/222 knockout mice. Our data showed that resveratrol counteracted the TNF-α-mediated reduction in miR-221/222 expression and decreased the TNF-α-induced activation of p38 MAPK and NF-κB, thereby suppressing ICAM-1 expression and monocyte adhesion. Collectively, our results show that resveratrol attenuates endothelial inflammation by reducing ICAM-1 expression and that the protective effect was mediated partly through the miR-221/222/AMPK/p38/NF-κB pathway.