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.

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.

Predictive value of ankle-brachial index for long-term events of ischemic stroke in hemodialysis patients.

OBJECTIVES: The ankle-brachial index is a noninvasive modality to evaluate atherosclerosis and is a predictive role for future cardiovascular events and mortality. However, few studies have evaluated its relation to long-term future ischemic stroke in hemodialysis patients. Therefore, we examined the relationship between ankle-brachial index and ischemic stroke events among hemodialysis patients in a seven-year follow-up. METHODS: A total of 84 patients were enrolled. Ankle-brachial index was assessed in January 2009. Primary outcomes included ischemic stroke. An ankle-brachial index < 0.9 was considered abnormal and 1.4 ≥ ankle-brachial index ≥ 0.9 to be normal ankle-brachial index. RESULTS: Mean values for ankle-brachial index were 0.98 ± 0.21at study entrance. In addition, 28 patients encountered ischemic stroke in the seven-year follow-up. In univariate Cox regression analysis, old age (hazard ratio (HR): 1.065, 95% confidence interval (CI): 1.030-1.102, p < 0.001), low seven-year averaged serum phosphate levels (HR: 0.473, 95% CI: 0.306-0.730, p = 0.001), and abnormal ankle-brachial index (HR: 0.035, 95% CI: 0.009-0.145, p < 0.001) were risk factors for ischemic stroke. In multivariate Cox regression analysis for significant variables in univariate analysis, abnormal ankle-brachial index (HR: 0.058, 95% CI: 0.012-0.279, p < 0.001) and low seven-year averaged serum phosphate levels (HR: 0.625, 95% CI: 0.404-0.968, p = 0.035) remained the risk factors for ischemic stroke. The risk of ischemic stroke was 3.783-fold in patients with abnormal ankle-brachial index compared with patients with normal ankle-brachial index (HR: 3.783, 95% CI: 1.731-8.269, p = 0.001). CONCLUSIONS: These findings suggest that ankle-brachial index is an impressive predictor of future ischemic stroke among hemodialysis patients.

Oligo(ethylene glycol) side chain effect on the physical properties and molecular arrangement of oligothiophene-isoindigo based conjugated polymers.

Oligo(ethylene glycol) (OEG) side chains are widely used in donor-acceptor conjugated polymers (D-A CPs) and enable the polymers to dissolve and be processed in environmentally friendly and cost-effective nonchlorinated solvents, such as water. However, the OEG effect on the physical properties of D-A CPs has not been thoroughly studied and sometimes the results are controversial. In this study, two oligothiophene-isoindigo based conjugated polymers, P3TI and P4TI, are selected as model polymers to investigate the OEG effect. PnTI has octyl side chains on the oligothiophene unit and 2-hexyldecyl side chains on the isoindigo unit. The replacement of an alkyl side chain with OEG not only changes the optical and thermal properties but also the molecular arrangements of the polymers such as π-π d-spacing, crystallinity, and packing orientation. The domination of the crystallization behavior changes from the oligothiophene unit to the isoindigo unit when the bulky alkyl group is replaced by the flexible and linear OEG. The packing changes from edge-on to face-on orientation. The results are intriguing and provide new insights into this class of polymers.

Low serum phosphate is associated with ischemic stroke in hemodialysis patients.

BACKGROUND: Hemodialysis patients have a high incidence of ischemic stroke. However, the association between serum phosphate levels and ischemic stroke is controversial among hemodialysis patients. The present study is used to evaluate whether serum phosphate levels are associated with ischemic stroke among patients undergoing hemodialysis. METHODS: A total of 84 hemodialysis patients were followed up for 8 years. Data collection included chart reviews and assessments of laboratory records. The ischemic stroke diagnosis was made on the basis of history, physical examination and neuroimaging (computed tomography and/or magnetic resonance imaging) by neurologists. Cox proportional hazard regression models were used to analyze the data. RESULTS: During the follow-up period, 29 patients experienced ischemic stroke. According to Cox proportional hazard regression analysis, the risk of ischemic stroke decreased by 45.5% for each 1-mg/dL increase in averaged serum phosphate (HR 0.545, p = 0.011). The risk of ischemic stroke increased by 4.3% for each 1-year increase in age (HR 1.043, p = 0.018). The risk of ischemic stroke increased by 1.1% increase for each 103/µL increase in averaged blood platelet (HR 1.011, p = 0.009). The risk of ischemic stroke in patients with averaged serum phosphate < 4.5 mg/dL increased 3.40-fold more than patients with averaged serum phosphate ≥ 4.5 mg/dL (HR 3.400, p = 0.025). CONCLUSIONS: Low serum phosphate is a risk factor for developing ischemic stroke in hemodialysis patients. The results suggest that managing serum phosphate ≥ 4.5 mg/dL among hemodialysis patients may reduce the risk of ischemic stroke.

Quantitative correlation of the effects of crystallinity and additives on nanomorphology and solar cell performance of isoindigo-based copolymers.

The high power conversion efficiency of bulk heterojunction (BHJ) polymer solar cells can be achieved from either low crystallinity (P3TI) or high crystallinity (P6TI) of isoindigo-based donor-acceptor alternating copolymers blended with PC71BM by controlling nanophase separation using additives. P3TI shows similar device performance regardless of the type of additives, while P6TI is significantly affected by whether the additive is aliphatic or aromatic. To understand the interplays of crystallinity of polymers and the type of additive on the formation of nanomorphology of BHJ, we employed the simultaneous grazing-incidence small- and wide-angle X-ray scattering (GISAXS and GIWAXS) technique to perform the quantitative investigation. By incorporating additives, the PC71BM molecules can be easily intercalated into the P3TI polymer-rich domain and the size of the PC71BM clusters is reduced from about 24 nm to about 5 nm by either aliphatic 1,8-diiodooctane (DIO) or aromatic 1-chloronaphthalene (CN). On comparison, it is found to be more difficult for PC71BM molecules to be intercalated into the highly crystalline P6TI dense domain, and the PC71BM molecules have a higher tendency to be self-aggregated, which results in a larger size of PC71BM clusters of about 58 nm. The clusters can be reduced to about 7 nm by DIO and 13 nm by CN. The presence of crystallites in the P6TI domain can interact with the additive to tailor the crystallization of PC71BM clusters to a size similar to that of P6TI crystallites (∼12 nm) and form a connected network for efficient charge transportation. Thus, the power conversion efficiency of P6TI:PC71BM reaches its maximum of 7.04% using aromatic CN additives. This is a new finding of the effect of crystallinity, which is not observed in the common low crystalline donor-acceptor alternating copolymers such as PTB7. Our results provide a useful guideline to manipulate the desired morphology of BHJ films constructed from alternating copolymer with different crystallinity, which is critical for achieving high power conversion efficiency of solar cells.

Endoplasmic reticulum stress-induced cell death in podocytes.

Endoplasmic reticulum (ER) stress occurs in a variety of pathophysiological mechanisms, and there has been great interest in managing this pathway for the treatment of clinical diseases. Increased ER stress can block integrin-ß1 glycosylation, decrease integrin-ß1 protein expression and enhance cell death in podocytes. Autophagy is closely interconnected with ER stress to counteract the possible injurious effects related to the impairment of protein folding and is one of the intracellular protein degradation systems. Studies have shown that podocytes exhibit a high rate of autophagy to maintain as terminally differentiated cells. We have attempted to induce autophagy in podocytes with ER stress to increase the longevity of proteins and the degradation of damaged organelles. However, regardless of ER stress or autophagy that protects the cells at early stages, cells cannot adapt to this situation when the stress is already well established, and podocytes will undergo severe injury finally. In summary, ER stress may induce cell death in podocyte, and autophagy mediate to salvage the injuries caused by ER stress in the short term. It seems that adequate, but not excessive, autophagy is crucial to help maintain the cell viability of podocytes.

Anti-Platelet Factor 4/Heparin Antibody Plays a Significant Role in Progression of Arterial Stiffness among Hemodialysis Patients.

BACKGROUND: Arterial stiffness is a determinant of cardiovascular disease in end stage renal disease. Hemodialysis patients may develop anti-platelet factor 4/heparin antibody (PF4-H Ab) because of heparin treatment in dialysis. We tested whether PF4-H Ab was associated with progression of arterial stiffness in a 3-year follow-up. METHODS: We enrolled 74 hemodialysis patients and studied their clinical, biochemical and arterial stiffness measurement with brachial-ankle pulse wave velocity (baPWV) over 3 years. Baseline and changes in baPWV after 3 years (ΔbaPWV) were collected and compared with related clinical and biochemical parameters. PF4-H Ab was evaluated by the enzyme-linked immunosorbent assay and titer ≥ 0.4 was defined to have PF4-H Ab. RESULTS: We found a positive PF4-H Ab status in 25 of 74 patients. Mean baPWV was 16.1 ± 3.8 (m/s) at baseline and 17.6 ± 4.0 (m/s) after 3 years. Mean ΔbaPWV was 3.4 ± 2.2 (m/s) in the PF4-H Ab positive group, and 0.6 ± 1.2 (m/s) in the PF4-H Ab negative group. Baseline baPWV was only significantly associated with age (ß = 0.49, p < 0.01). ΔbaPWV was significantly different between the PF4-H Ab positive and negative groups (p < 0.01). In multivariate regression analysis, only PF4-H Ab was positively associated with ΔbaPWV (ß = 0.71, p < 0.01). CONCLUSIONS: Our study concluded that PF4-H Ab was associated with progression of arterial stiffness in hemodialysis patients.

Serum ferritin is associated with progression of peripheral arterial disease in hemodialysis patients.

BACKGROUND: Dialysis patients received intravenous iron to treat anemia and had high prevalence of peripheral artery disease (PAD). We hypothesized that high iron status might associate with the progression of PAD among hemodialysis patients. Therefore, we evaluated the relationship between iron status and progression of PAD. METHODS: We measured iron status in 74 hemodialysis patients and studied the association with clinical, biochemical, and vascular parameters including progression of PAD measured by ankle-brachial index (ABI) over 3 years. RESULTS: Mean baseline ABI was 1.03 ± 0.18. Mean ABI at 3 years was 0.95 ± 0.20. Mean ∆ABI (change in ABI after 3 years) was -0.08 ± 0.14. Serum ferritin was negatively correlated with baseline ABI (r = -0.232, p = 0.046). After 3 years, ∆ABI was negatively associated with 3-year averaged serum ferritin, phosphorus, and calcium-phosphate product (Ca × P) (r = -0.253, p = 0.029; r = -0.278, p = 0.016; r = -0.288, p = 0.013; respectively). After an adjusted model, 3-year averaged serum ferritin and Ca × P remained the significant determinants of ∆ABI (ß = -0.234, p = 0.038; ß = -0.271, p = 0.017; respectively). ∆ABI was significantly different between 3-year averaged serum ferritin level ≥600 and <600 ng/mL (p = 0.032). CONCLUSIONS: In hemodialysis patients, high serum ferritin associates with progression of PAD, especially among those with high Ca x P level.

cis-1-Oxo-heterocyclyl-4-amido cyclohexane derivatives as NPY5 receptor antagonists.

The NPY5 receptor binding and pharmacokinetic properties of a novel series of cis-1-oxo-heterocyclyl-4-amido-cyclohexane derivatives are described.

Ankle-brachial index associates with arteriovenous fistula stenosis.

BACKGROUND: Arteriovenous fistula (AVF) stenosis is associated with pre-existing arterial atherosclerosis of AVF and results in significant morbidity and hospitalization for hemodialysis patients. The ankle brachial index (ABI) is a noninvasive method of assessing atherosclerosis. This study was to examine whether ABI is a significant predictor for AVF stenosis. METHODS: This was a retrospective, longitudinal cohort study. Patients with hemodialysis between 1 January 2016 and 31 December 2022 were reviewed. ABI was assessed in January 2016. AVF stenosis was diagnosed by fistulography. RESULTS: A total of 82 patients were included. Forty-two patients experienced AVF stenosis. The univariate logistic regression analysis showed that AVF stenosis was associated with age (OR: 1.045, p = 0.033), DM status (OR: 5.529, p = 0.013), 7-year averaged cholesterol level (OR: 1.018, p = 0.034), 7-year averaged triglyceride level (OR: 1.007, p = 0.017), and ABI (OR: 0.011, p < 0.001). In multivariate logistic regression analysis, ABI was a strong predictor for AVF stenosis (OR: 0.036, p = 0.023). Then, a cut-off point of ABI with optimal sensitivity and specificity for AVF stenosis was 1.01. An analysis of time to events with adjustment for other variables showed that patients with ABI < 1.01 were significantly associated with AVF stenosis (HR: 3.859, p < 0.001). CONCLUSIONS: ABI below 1.01 was associated with AVF stenosis. This finding may be useful in tailoring surveillance programs for monitoring AVF function.

Anti-PF4/heparin antibodies are associated with arteriovenous fistula thrombosis in non-diabetic hemodialysis patients.

AIM: Anti-platelet factor 4/heparin complex antibodies (anti-PF4/heparin Ab) have been found to cause heparin-induced thrombocytopenia (HIT), a clinical syndrome thrombocytopenia and thrombosis. There is still controversy as to whether the presence of anti-PF4/heparin antibodies in hemodialysis patients augments clot formation in access fistula thrombosis, peripheral artery disease (PAD), and coronary heart disease (CHD). METHODS: We enrolled 111 non-diabetic hemodialysis patients without liver cirrhosis and without an ankle-brachial index (ABI) ≥1.3 (arterial calcification). ABI measurements were performed and patients with an ABI ≤0.9 were defined as having PAD and included in the PAD group. ELISA was used for determination of anti-PF4/heparin Ab. Correlation factors include PAD, native arteriovenous fistula (AVF) thrombosis, platelet count, and CHD. RESULTS: Thirty-seven of 111 patients (33.3%) presented with anti-PF4/heparin Ab. Thirty-eight of 111 patients (34%) had PAD; fourteen of these patients (36.8%) and 23/73 of patients without PAD (31.5%) were anti-PF4/heparin Ab-positive (P = 0.57). Fifty-two of 111 patients (46.8%) had AVF thrombosis; twenty-three of these patients (44.2%) and 14/59 of patients without AVF thrombosis (23.7%) were anti-PF4/heparin Ab-positive (P = 0.02). The odds ratio for AVF thrombosis was 2.55 (95% CI 1.14-5.71) for anti-PF4/heparin Ab-positive patients. Thirty-two of 111 patients (28.8%) had thrombocytopenia (platelet count <140 × 10(3)/µL); eleven of these patients (34.3%) and 26/79 patients without thrombocytopenia (32.9%) were anti-PF4/heparin Ab-positive (P = 0.88). Ten of 111 patients (9%) had CHD; two of these patients (20%) and 35/101 patients without CHD (34.6%) were anti-PF4/heparin Ab-positive (P = 0.49). CONCLUSIONS: We found that anti-PF4/heparin Ab may contribute to an increased risk of AVF thrombosis in non-diabetic hemodialysis patients.

Reduction in hemodialysis catheter-related bloodstream infections after implementation of a novel care program.

BACKGROUND: Catheter-related bloodstream infection (CRBSI) due to dialysis is the major factor causing morbidity and mortality factor for patients undergoing hemodialysis and is associated with additional costs for these patients. This study investigated the effect of a novel care program in terms of reducing CRBSIs for hemodialysis patients with nontunneled (temporary) catheters inserted in their femoral veins. METHODS: This study included dialysis patients (inpatients and outpatients) from July 2018 to September 2019, covering two periods, pre-intervention (baseline period) and intervention with a novel care program (novel care period). The novel care program was initiated on December 1, 2018. The CRBSI rates (/1000 catheter-days) for the baseline and novel care periods were compared, and the characteristics of the pathogens were determined. FINDINGS: Of a total of 72 patients, 33 were from the baseline period and 39 were from the novel care period. Patients in the baseline and novel care periods had the catheter inserted in their femoral veins for a median of 20 and 29 days, respectively. The CRBSI rate decreased by 82.63%, from 8.52/1000 catheter-days in the baseline period to 1.48/1000 catheter-days in the novel care period (p = 0.036). The most common organisms involved in CRBSIs were coagulase-negative staphylococcus and Burkholderia cepacia (26% for both). DISCUSSION: The novel care program reduced the incidence of CRBSIs in patients with temporary catheters inserted in their femoral veins.

Generation of endoplasmic reticulum stress-dependent reactive oxygen species mediates TGF-ß1-induced podocyte migration.

Podocyte migration results in proteinuria and glomerulonephropathy. Transforming growth factor-ß1 (TGF-ß1), endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) can mediate podocyte migration; however, the crosstalk between them is unclear. This study determined the relationships between these factors. ER stress biomarkers (GRP78, p-eIF2α or CHOP), intracellular ROS generation, integrin-ß3 and cell adhesion and migration were studied in a treatment of experiment using TGF-ß1 with and without the ER stress inhibitors: 4-phenylbutyric acid (4-PBA, a chemical chaperone), salubrinal (an eIF2α dephosphorylation inhibitor) and N-acetylcysteine (NAC, an antioxidant). ER stress biomarkers (p-eIF2α/eIF2α and GRP78), ROS generation and intergrin-ß3 expression increased after TGF-ß1 treatment. NAC down-regulated the expression of GRP78 after TGF-ß1 treatment. 4-PBA attenuated TGF-ß1-induced p-eIF2α/eIF2α, CHOP, ROS generation and intergrin-ß3 expression. However, salubrinal did not inhibit TGF-ß1-induced p-eIF2α/eIF2α, CHOP, ROS generation or integrin-ß3 expression. NAC abrogated TGF-ß1-induced integrin-ß3 expression. At 24 h after treatment with TGF-ß1, podocyte adhesion and migration increased. Furthermore, NAC, 4-PBA and an anti-interin-ß3 antibody attenuated TGF-ß1-induced podocyte adhesion and migration. This study demonstrated that TGF-ß1-induced ER stress potentiates the generation of intracellular ROS to a high degree through the PERK/eIF2α/CHOP pathway. This intracellular ROS then mediates integrin-ß3 expression, which regulates podocyte migration.

Effects of Electrical Stimulation of Acupoints on Xerostomia for Patients Who Undergo Hemodialysis.

Xerostomia plays a major role in higher interdialytic weight gain (IDWG), which causes cardiovascular complications in patients who undergo hemodialysis. However, few studies have determined a method to manage xerostomia. This study determines the effect of transcutaneous electrical acupoint stimulation (TEAS) on hemodialysis patients with xerostomia and the percentage of IDWG. The study was a single-blind and quasi-experimental study. There are 75 participants: 37 in the TEAS group and 38 in the contrast group. The TEAS group used 250 µs and 50 Hz and the contrast group used 50 µs and 2 Hz three times a week for 3 weeks to stimulate ST 6 and TE17 acupoints. The salivary flow rates, dry mouth, and %IDWG were determined before, during and one week after the program. Compared with the contrast group, the TEAS group showed a significantly improved salivary flow rate (mL/min) (F (2, 123) = 15.28, p < 0.0001), and patients recovered their normal salivary flow rate. However, the results show that both groups showed significant improvement in dry mouth after treatment. The TEAS group demonstrated no effect in terms of %IDWG, as expected. The results show that a TEAS program is an effective means of symptom management for xerostomia patients who undergo hemodialysis. A TEAS program can be used to manage symptoms for xerostomia patients who undergo hemodialysis.

Epidemiology of Aspergillosis in Cancer Patients in Taiwan.

Purpose: The incidence of aspergillosis is increasing, and the risk factors for infection include cancer, admission to the intensive care unit, chronic pulmonary diseases, immunocompromised status, and taking immunomodulatory drugs. There are limited data about the incidence of aspergillosis in patients with different types of cancer. The aim of our study was to survey the incidence of aspergillosis in different cancer types from 2006 to 2017. Patients and Methods: Data were collected from the Taiwan Cancer Registry database and International Classification of Diseases, 9th, 10th Revision, and Clinical Modification codes for diagnosing aspergillosis. Patients with a history of aspergillosis before cancer were excluded, and the secondary outcome was the risk of mortality in cancer patients with and without aspergillosis after 1 year. Results: Among 951 cancer patients with a diagnosis of aspergillosis, there were 614 hematopoietic and reticuloendothelial system patients, 100 lung cancer patients, and 73 lymphoma cancer patients. The overall incidence rates of aspergillosis tended to increase significantly from 2006 to 2017 (from 3.50 to 13.37 per 10,000 person-years, p value: <0.0001). Regarding sex, the incidence rates of aspergillosis in males and females were 12.52 and 7.53 per 10,000 person-years, respectively. Patients with a diagnosis of aspergillosis had a 2.30-fold (95% CI: 2.14-2.48, p value: <0.0001) higher risk of mortality than those without aspergillosis. Conclusion: The incidence of aspergillosis was increased in cancer patients, and cancer patients with aspergillosis had a significantly higher risk of mortality than those without aspergillosis.

DNA Sequencing from Subcritical Concentration of Cell-Free DNA Extracted from Electrowetting-on-Dielectric Platform.

Electro-Wetting-On-Dielectric (EWOD) based digital operations have demonstrated outstanding potential in actuating and manipulating liquid droplets. Here, we adapted the EWOD for extracting femtogram quantities of cell-free DNA (cf-DNA) from 1 µL of KSOM mouse embryo culture medium. Our group extracted the femtogram quantity of cf-DNA from 1 µL of mouse embryo culture medium in our previous work. Here, we initially explain a modification from our previous extraction protocol, which improves the extraction percentage to 36.74%. Though the modified extraction protocol improves the extraction percentage from our previously reported work, the quantity is still in the femtogram range. The cf-DNA in femtogram quantity is in subcritical/subthreshold concentration for any further analysis, such as sequencing. To the best of our knowledge, we need a minimum of picogram/nanogram DNA quantities for further analysis. We demonstrated a ground-breaking mechanism of this subcritical concentration of cf-DNA amplification to the nanogram range and performed DNA sequencing. Basic Local Alignment Search Tool (BLAST) is used as a sequence similarity search program to confirm the identity percentage between query and subject. More than 97% of nucleotide identities between query and subject sequences have been obtained from the sequencing result. Hence, we can use the methodology to amplify the subcritical concentration of extracted DNA for further analytics. Moreover, as we extract the cf-DNA from the embryo culture medium, the natural growth of the embryo has not been disrupted. This entire mechanism will pave a new path towards the lab-on-a-chip (LOC) concept.

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).

Image-guided intensity modulated radiotherapy with helical tomotherapy for postoperative treatment of high-risk oral cavity cancer.

BACKGROUND: The aim of this study was to assess the treatment results and toxicity profiles of helical tomotherapy (HT) for postoperative high-risk oral cavity cancer. METHODS: From December 6, 2006 through October 9, 2009, 19 postoperative high-risk oral cavity cancer patients were enrolled. All of the patients received HT with (84%) or without (16%) chemotherapy. RESULTS: The median follow-up time was 17 months. The 2-year overall survival, disease-free survival, locoregional control, and distant metastasis-free rates were 94%, 84%, 92%, and 94%, respectively. The package of overall treatment time > 13 wk, the interval between surgery and radiation ≤ 6 wk, and the overall treatment time of radiation ≤ 7 wk was 21%, 84%, and 79%, respectively. The percentage of grade 3 mucositis, dermatitis, and leucopenia was 42%, 5% and 5%, respectively. CONCLUSIONS: HT achieved encouraging clinical outcomes for postoperative high-risk oral cavity cancer patients with high compliance. A long-term follow-up study is needed to confirm these preliminary findings.

Mechanistic study of silver nanoparticle formation on conducting polymer surfaces.

Conducting polymer (polyaniline) sheets are shown to be active substrates to promote the growth of nanostructured silver thin films with highly tunable morphologies. Using the spontaneous electroless deposition of silver, we show that a range of nanostructured metallic features can be controllably and reproducibly formed over large surface areas. The structural morphology of the resulting metal-polymer nanocomposite is demonstrated to be sensitive to experimental parameters such as ion concentration, temperature, and polymer processing and can range from densely packed oblate nanosheets to bulk crystalline metals. The deposition mechanisms are explained using a diffusion-limited aggregation (DLA) model to describe the semi-fractal-like growth of the metal nanostructures. We find these composite films to exhibit strong surface-enhanced Raman (SERS) activity, and the nanostructured features are optimized with respect to SERS activity using a self-assembled monolayer of mercapto-benzoic acid as a model Raman reporter. SERS enhancements are estimated to be on the order of 10(7). Through micro-Raman SERS mapping, these materials are shown to exhibit uniform SERS responses over macroscopic areas. These metal-polymer nanocomposites benefit from the underlying polymer's processability to yield SERS-active materials of almost limitless shape and size and show significant promise for future SERS-based sensing and detection schemes.