Pilot study of using transcranial temporal interfering theta-burst stimulation for modulating motor excitability in rat.

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.

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.

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.

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.

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.

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.

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.

[Application of drug-target prediction technology in network pharmacology of traditional Chinese medicine].

In recent years, network pharmacology has been developed rapidly, and especially, the concept of ″network target″ has brought a new era in the field of traditional Chinese medicine (TCM). The integrity and systematicness emphasized in network pharmacology comply with the characteristics of holistic view and treatment in Chinese medicine. It can provide deeper insights into the underlying mechanisms of TCM theories, including the illustration on action mechanism of Chinese medicine, selection of pharmacodynamic materials and the combination principles of various Chinese herbs, etc. Therefore, this theory is more suitable for TCM academic characteristics and practical conditions. The key problem in network pharmacology is how to efficiently and quickly identify the interactions between large amounts of drugs and target proteins. As an efficient and high throughput way, drug-target prediction technology can reduce costs, quickly predict the component targets, and provide foundation for the application of TCM network pharmacology. In view of the large amount of compounds and target databases, different prediction methods and technologies have been developed, and used to predict the drug-target interactions. Many virtual screening technologies have been successfully applied to network pharmacology. Based on different prediction principles, drug-target prediction technology can be generally divided into four types： ligand-based prediction, receptor-based prediction, machine learning and combined prediction. In this paper, we are going to review the prediction methods of drug-target interactions and give acomprehensive elaboration of their application in network pharmacology of TCM, hoping to provide beneficial references for various Chinese medicine researchers.

[Study on Material Base of Panax ginseng for Treating Brain Ischemia Based on Molecular Docking].

Objective: On the basis of molecular docking,to study the mechanism of Panax ginseng in the treatment of ischemic stroke. Methods: The small molecules of Panax ginseng based on molecular docking technology docked with 20 key targets protein of cerebral ischemia, and multi-component protein target network was established by Cytoscape 3. 1. 1 software. At the same time,the two active molecules of the Panax ginseng of Rb2 and 20( R)-ginsenoside Rg2 were also analyzed by VEGF and Caspase-3,which were the key protein in brain ischemia. Results: There were 31 active molecules of Panax ginseng combined strongly with five or more than five protein targets after molecular docking, and only four active molecules of Panax ginseng combined strongly with ten or more than ten protein targets. The two active molecules of Rb2 and 20( R)-ginsenoside Rg2 in the Panax ginseng had a very strong combination with VEGF and Caspase-3,respectively,and the docking scores were more than 7. 0. Conclusion: Molecular docking technology screening active substances of Panax ginseng plays a practical significance in the treatment of ischemic stroke, which offers the foundation to study the chemical constituents of composite prescription.

Coordination of AUF1 and miR-148a destabilizes DNA methyltransferase 1 mRNA under hypoxia in endometriosis.

STUDY HYPOTHESIS: DNA methylation is regulated by hypoxia in endometriosis. STUDY FINDING: Hypoxia causes global hypomethylation through AU-rich element binding factor 1 (AUF1)/microRNA-148a (miR-148a)-mediated destabilization of DNA methyltransferase 1 (DNMT1) mRNA. WHAT IS KNOWN ALREADY: Eutopic endometrial and ectopic endometriotic stromal cells have the same genetic background, but differ in several cellular and molecular responses. Both hypoxia and DNA methylation regulate several genes involved in the development of endometriosis. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: This laboratory study included 15 patients of reproductive age with endometriosis or normal menstrual cycles. Paired endometrial and endometriotic tissues were collected for assaying the levels of DNMT1, 3a and 3b using quantitative RT-PCR, western blot and immunohistochemical (IHC) staining. Primary cultured endometrial stromal cells maintained in normoxia/hypoxia (1% O2) or treated with hypoxia-mimetic compounds were also assayed. The levels of DNA 5-methylcytosine were assayed by using IHC in clinical specimens and murine tissues, and by ELISA in cultured stromal cells. The 3'-untranslated region reporter assay was used to evaluate the effect of hypoxia, microRNAs (miRNAs) and human antigen R (HuR)/AUF1 on DNMT1 mRNA stability. RNA immunoprecipitation was used to assess the interaction of HuR/AUF1 and miR-148a/DNMT1 mRNA under hypoxia. Finally, a transplant-induced mouse model of endometriosis using 20 mice was used to elucidate the alteration of Dnmt1 levels and DNA methylation in the endometriotic tissues. MAIN RESULTS AND THE ROLE OF CHANCE: Levels of DNMT1 mRNA and protein and 5-methylcytosine were lower in the ectopic stromal cells (P < 0.05) than in the eutopic cells. Treatment with hypoxia and its mimetic compounds recapitulated the reduced levels of DNMT1 and 5-methylcytosine levels (P < 0.05 versus control). Hypoxia treatment destabilized DNMT1 mRNA through recruitment of miR-148a and AUF1. Mutations introduced to the miR-148a targeting site or AU-rich element (ARE) restored the hypoxia-suppressed DNMT1 3'-untranslated region (3'-UTR) reporter activity (P < 0.05 versus control). Levels of proteins of three hypermethylated genes in endometrial stroma cells, GATA6, HOXA3 and SLC16A5, were elevated after 72 h of hypoxia treatment (P < 0.05 versus control). Finally, a transplant-induced model of endometriosis demonstrated the down-regulation of DNMT1 and a decrease in 5-methylcytosine in the endometriotic tissues (P < 0.05, eutopic versus ectopic). LIMITATIONS, REASONS FOR CAUTION: Primary human cell cultures and a murine model were used in this study, and thus the results may not fully represent the situation in vivo. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to elucidate how microenvironmental hypoxia links to the epigenetic effects of DNA methylation in the endometriosis, and to delineate the molecular mechanism of hypoxia-coordinated AUF1/miR-148a interaction and recruitment to DNMT1 mRNA during the pathogenesis of endometriosis. The development of future therapeutics in endometriosis may aim at disrupting this specific interaction and eventually restore the epigenetic regulation. STUDY FUNDING AND COMPETING INTERESTS: This work was supported by the National Science Council of Taiwan (NSC101-2320-B-006-030-MY3). The author declares that there are no conflicts of interest.

Does procalcitonin, C-reactive protein, or interleukin-6 test have a role in the diagnosis of severe infection in patients with febrile neutropenia? A systematic review and meta-analysis.

PURPOSE: The study aims to determine the usefulness of procalcitonin (PCT) and other blood markers for identification of bacterial infection among patients with febrile neutropenia (FN). METHODS: The Medline, EMBASE, and Cochrane databases were searched for articles from 1966 to December 2012. We performed a search to identify articles that examined the diagnostic accuracy of PCT in patients with FN. Statistical analyses (fixed- or random-effect models) were conducted to summarize and calculate the sensitivity, specificity, likelihood ratios, and 95 % confidence intervals (CIs). RESULTS: Twenty-seven studies were included (1960 febrile episodes) for PCT analysis, 13 (1712 febrile episodes) for C-reactive protein (CRP) analysis, and five (314 febrile episodes) for interleukin (IL)-6 analysis. Increased PCT levels (odds ratio [OR] 11.5; 95 % CI 7.6 to 17.3), raised CRP levels (3.3; 2.7 to 4.2), and raised IL-6 levels (10.0; 5.5 to 18.0) were significantly associated with bacterial infection. Overall positive likelihood ratio was 5.49 (4.04-7.45) for PCT, 1.82 (1.42-2.33) for CRP, and 3.68 (2.41-5.60) for IL-6. Overall negative likelihood ratio was 0.40 (0.31-0.51) for PCT, 0.40 (0.26-0.61) for CRP, and 0.33 (0.23-0.46) for IL-6. CONCLUSIONS: Of the three potentially useful markers, PCT had the best positive likelihood ratio and can be used to confirm the diagnosis of bacterial infections in patients with FN. Due to unacceptably high negative likelihood ratio, medical decision for stopping antibiotics based on PCT alone in this high-risk population may not be possible.

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.

Sacral Magnetic Neuromodulation with Intermittent Theta Burst Waveform Enhances Overactive Bladder: In Vivo Study.

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.

Role of procalcitonin in the diagnosis of infective endocarditis: a meta-analysis.

BACKGROUND: Infective endocarditis (IE) is a diagnostic challenge. We aimed to systemically summarize the current evidence on the diagnostic value of procalcitonin (PCT) in identifying IE. METHODS: We searched EMBASE, MEDLINE, Cochrane database, and reference lists of relevant articles with no language restrictions through September 2012 and selected studies that reported the diagnostic performance of PCT alone or compare with other biomarkers to diagnose IE. We summarized test performance characteristics with the use of forest plots, hierarchical summary receiver operating characteristic curves, and bivariate random effects models. RESULTS: We found 6 qualifying studies that included 1006 episodes of suspected infection with 216 (21.5%) confirmed IE episodes from 5 countries. Bivariate pooled sensitivity, specificity, positive likelihood ratios, and negative likelihood ratios were 64% (95% confidence interval [CI], 52%-74%), 73% (95% CI 58%-84%), 2.35 (95% CI 1.40-3.95), and 0.50 (95% CI 0.35-0.70), respectively. Of the 5 studies examining C-reactive protein (CRP), the pooled sensitivity, specificity, positive likelihood ratios, and negative likelihood ratios were 75% (95% CI 62%-85%), 73% (95% CI 61%-82%), 2.81 (95% CI 1.70-4.65), and 0.34 (95% CI 0.19-0.60), respectively. The global measures of accuracy, area under the receiver operating characteristic curve (AUC) and diagnostic odds ratio (dOR), showed CRP (AUC 0.80, dOR 8.55) may have higher accuracy than PCT (AUC 0.71, dOR 4.67) in diagnosing IE. CONCLUSIONS: Current evidence does not support the routine use of serum PCT or CRP to rule in or rule out IE in patients suspected to have IE.

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.

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.

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.

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.

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.

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).