Predicting patient-reported outcome of activities of daily living in stroke rehabilitation: a machine learning study.

BACKGROUND: Machine Learning is increasingly used to predict rehabilitation outcomes in stroke in the context of precision rehabilitation and patient-centered care. However, predictors for patient-centered outcome measures for activities and participation in stroke rehabilitation requires further investigation. METHODS: This study retrospectively analyzed data collected for our previous studies from 124 participants. Machine Learning models were built to predict postintervention improvement of patient-reported outcome measures of daily activities (i.e, the Motor Activity Log and the Nottingham Extended Activities of Daily Living) and participation (i.e, the Activities of Daily Living domain of the Stroke Impact Scale). Three groups of 18 potential predictors were included: patient demographics, stroke characteristics, and baseline assessment scores that encompass all three domains under the framework of International Classification of Functioning, Disability and Health. For each target variable, classification models were built with four algorithms, logistic regression, k-nearest neighbors, support vector machine, and random forest, and with all 18 potential predictors and the most important predictors identified by feature selection. RESULTS: Predictors for the four target variables partially overlapped. For all target variables, their own baseline scores were among the most important predictors. Upper-limb motor function and selected demographic and stroke characteristics were also among the important predictors across the target variables. For the four target variables, prediction accuracies of the best-performing models with 18 features ranged between 0.72 and 0.96. Those of the best-performing models with fewer features ranged between 0.72 and 0.84. CONCLUSIONS: Our findings support the feasibility of using Machine Learning for the prediction of stroke rehabilitation outcomes. The study was the first to use Machine Learning to identify important predictors for postintervention improvement on four patient-reported outcome measures of activities and participation in chronic stroke. The study contributes to precision rehabilitation and patient-centered care, and the findings may provide insights into the identification of patients that are likely to benefit from stroke rehabilitation.

K-Rod: An Innovative Method of Personalized Rib Splinting for Expeditious Management of Flail Chest in Acute Care Settings.

Flail chest is a severe type of multiple rib fracture that can cause ventilation problems and respiratory complications. Historically, flail chest has been mainly managed through pain control and ventilatory support as needed. Operative fixation has recently become popular for the condition, and some studies have revealed its potentially positive effects on the outcomes of patients with flail chest. However, for those for whom surgery is unsuitable, few treatment options, other than simply providing analgesia, are available. Herein, we introduce our innovative method of applying personalized rib splinting for quick management of flail chest, which is easy, tailor-made, and has significant effects on pain reduction.

Palladium-Catalyzed Intramolecular Allylic Amidation via Decarboxylative Aromatization: Synthesis of N-Allyl-N-aryl Sulfonamides.

A protocol in the preparation of functionalized N-allyl-N-aryl sulfonamides via palladium-catalyzed intramolecular decarboxylative N-allylation reaction is presented. The alkylated 2,5-cyclohexadienyl ketoesters reacted with arylsulfonamides in the presence of titanium tetrachloride and pyridine, which allows the formation of alkylated 2,5-cyclohexadienyl sulfonyl iminoesters which then undergo a palladium-catalyzed intramolecular allylic amidation through decarboxylative aromatization to provide functionalized N-allyl-N-aryl sulfonamides. This allylation protocol proceeds with good regioselectivity. Moreover, we have also shown that N-allyl-N-aryl sulfonamide can be transformed into 4-aryl-1,2,3,4-tetrahydroquinoline and nitrogen-containing ß-hydroxysulfide bioactives.

[Factors Influencing the Recovery of Walking Ability in Older Adults After Hospital Discharge].

BACKGROUND: Functional decline is a common complication in hospitalized older adults, and decline in the ability to walk is often the first change in physical functioning in this population. Decline in walking ability leads to a loss of independence in the activities of daily living in older adults after discharge from the hospital. PURPOSE: To explore the factors associated with the recovery of walking ability in older adults after discharge from the hospital. METHODS: This study used a longitudinal research design. Potential participants were recruited from a tertiary medical center in southern Taiwan. Patients were eligible for inclusion if they were at least 65 years old and were affected by a decline in walking ability at discharge. The data collected at discharge included: demographic information, Charlson Comorbidity Index, Modified Katz Index of Independence in Activities of Daily Living (walking item), Mini Nutritional Assessment, Mini-Mental State Examination, and ambulation during hospital stay. The follow-up data collected at three months after discharge included: Modified Katz Index of Independence in Activities of Daily Living (walking item), exercise habit, rehabilitation, and social support. RESULTS: A total of 78 older adults were enrolled as participants. Three-quarters (75.64%) of the participants had regained their ability to walk at three months after discharge. Moreover, nutritional status, cognitive function, and exercise habit were significantly associated with the recovery of walking ability. The results of multiple logistic regression analysis showed having an exercise habit to be significantly associated with the recovery of walking ability at three months after discharge (OR = 10.212, p = .004). CONCLUSIONS / IMPLICATIONS FOR PRACTICE: In addition to treating the acute medical issues of older patients, healthcare professionals should screen and provide them with appropriate nutritional, cognitive, and physical care plans. Moreover, emphasizing the importance of an exercise habit in nursing discharge plans is also important. This effort may help older adults recover their walking ability and maintain their independence.

Microbubble-facilitated ultrasound pulsation promotes direct α-synuclein gene delivery.

Intra-neuronal α-synuclein (αSNCA) aggregation are the leading cause of dopaminergic neuron degeneration in Parkinson's disease (PD). Most PD patients is linked with αSNCA gene mutations. Gene therapy shows therapeutic potential by packing gene into viral vectors to improve gene expression through stereotactic brain injections. However, through intracranial injection, the gene expression is typically limited with tissue distribution tightly adjacent to the injection track, when expressing therapeutic genes for a wider CNS region is preferable. We use microbubble-facilitated ultrasound pulsations (MB-USP) as a new gene delivering tool to enhance the limit gene delivery of local injection in brain and evaluate the feasibility using αSNCA as model gene. We demonstrate that MB-USP can transfect naked constructs DNA of αSNCA gene into two types of neuron cells and enhance the gene expression. We confirm α-synuclein fusion protein functionality, showing that α-synuclein fusion protein significantly reduce the mitochondrial activity. We show MB-USP improves in vivo gene transfer in the brain with naked construct local injection, significantly enhances α-synuclein expression level to 1.68-fold, and broaden its distribution to 25-fold. In vivo fused α-synuclein protein aggregation is also found in gene-injected mice brains by MB-USP. MB-USP provides an alternative to α-synuclein over expression in vitro and in vivo model for investigation of α-synuclein related PD therapeutic strategies.

Immobilization of Chlamydomonas reinhardtii CLH1 on APTES-Coated Magnetic Iron Oxide Nanoparticles and Its Potential in the Production of Chlorophyll Derivatives.

Recombinant Chlamydomonas reinhardtii chlorophyllase 1 (CrCLH1) that could catalyze chlorophyll hydrolysis to chlorophyllide and phytol in vitro was successfully expressed in Escherichia coli. The recombinant CrCLH1 was immobilized through covalent binding with a cubic (3-aminopropyl) triethoxysilane (APTES) coating on magnetic iron oxide nanoparticles (MIONPs), which led to markedly improved enzyme performance and decreased biocatalyst costs for potential industrial application. The immobilized enzyme exhibited a high immobilization yield (98.99 ± 0.91 mg/g of gel) and a chlorophyllase assay confirmed that the immobilized recombinant CrCLH1 retained enzymatic activity (722.3 ± 50.3 U/g of gel). Biochemical analysis of the immobilized enzyme, compared with the free enzyme, showed higher optimal pH and pH stability for chlorophyll-a hydrolysis in an acidic environment (pH 3-5). In addition, compared with the free enzyme, the immobilized enzyme showed higher activity in chlorophyll-a hydrolysis in a high temperature environment (50-60 °C). Moreover, the immobilized enzyme retained a residual activity of more than 64% of its initial enzyme activity after 14 cycles in a repeated-batch operation. Therefore, APTES-coated MIONP-immobilized recombinant CrCLH1 can be repeatedly used to lower costs and is potentially useful for the industrial production of chlorophyll derivatives.

[Using active surveillance in the early detection of methicillin-resistant Staphylococcus aureus colonization].

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the principal pathogens implicated in hospital-acquired infections. Active surveillance of patients with MRSA colonization at admission may reduce the spread of the MRSA through contact precautions. PURPOSE: This study applies active surveillance to the early detection of MRSA colonization and to the determination of the risk factors of MRSA colonization. METHODS: A prospective cohort study was conducted at a medical center in North Taiwan from March 2010 to August 2010. Participants were recruited from among patients admitted to an infection department who were under active surveillance for culture within the 24-hour period following admission. Nose and environment samplings were taken every Monday and Thursday until participants were transferred, discharged, or expired. RESULTS: This study enrolled 239 patients, with 182 included in data analysis. Positive nasal cultures were found on 53.3% of admitted patients during the initial 24-hour period, with 7.1% generating positive environmental cultures. During the nose and environment sampling phase, 27.4% and 19.2% of participants, respectively, generated positive nasal and positive environmental cultures. The average number of days required to provide a positive culture were 9.2 days for nasal cultures and 11.4 days for environmental cultures. Incidence density of nosocomial MRSA infections reduced by 0.47‰ to 0.19‰. Univariate analysis identified using a nasogastric tube and using steroids as two statistically significant risk factors for positive nasal MRSA colonization (p < .05). A multivariate analysis of risk factors showed a 2.68-times higher risk in participants admitted with pressure sores and 2.81-times higher risk in those who used steroids. The risk of participants acquiring MRSA during their stay was 6% per day. CONCLUSIONS: Active surveillance facilitates the early detection of MRSA colonization. Healthcare professionals should wear gloves and adhere to hand-hygiene and contact-precaution protocols when caring for damaged skin, especially pressure sores. Further, healthcare professionals should implement clean environment practices to control the spread of MRSA.

Responsiveness and construct validity of two outcome measures of bilateral upper limb function in patients with chronic stroke.

Background: Stroke is a leading cause of long-term disability among stroke survivors. Despite the availability of numerous stroke rehabilitative therapies, such as mirror therapy, bilateral arm training, and robot-assisted therapy, the recovery of motor function after stroke remains incomplete. Bilateral arm function is a key component in stroke patients to perform activities of daily living and to reflect their functional autonomy. Objective: This clinimetric study investigated and compared the construct validity and responsiveness of 2 bimanual activity outcome measures, the Chedoke Arm and Hand Activity Inventory (CAHAI) and the ABILHAND Questionnaire, in individuals receiving stroke rehabilitation. Methods: The present study is a secondary analysis following the framework of the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). Individuals with chronic stroke (N = 113) were recruited from outpatient rehabilitation settings. Participants received 18 to 20 sessions of robot-assisted therapy, mirror therapy, combined therapy, or conventional rehabilitation for 4 to 6 weeks. The CAHAI, ABILHAND Questionnaire, and a comparison instrument, the Motor Activity Log (MAL), were administered twice at a 4- to 6-week interval to all participants. ABILHAND scores, in logits, were converted from raw ordinal scores into a linear measure. Results: There was medium to large correlation of the CAHAI and the MAL (ρ = 0.60-0.62, p < 0.01) as well as the ABILHAND Questionnaire and the MAL (ρ = 0.44-0.51, p < 0.01). Change scores from the initial measurement to the post-intervention measurement demonstrated small to medium correlation of the CAHAI and the MAL (ρ = 0.27-0.31, p < 0.01) and medium to large correlation of the ABILHAND Questionnaire and the MAL (ρ = 0.37-0.41, p < 0.01). Overall, 7 of 8 hypotheses were supported. The hypothesis testing regarding the construct validity and responsiveness of the CAHAI and ABILHAND Questionnaire was confirmed. Conclusion: The CAHAI and ABILHAND Questionnaire are both responsive and suitable to detect changes in bilateral arm functional daily activities in individuals with chronic stroke. Patient-reported outcome measures are recommended to use along with therapist-rated outcome measures for upper limb capacity evaluation in stroke rehabilitation. Further study with a prospective study design to capture specific clinical features of participants and the use of body-worn sensors, such as the arm accelerometer, is suggested.

Predicting Arm Nonuse in Individuals with Good Arm Motor Function after Stroke Rehabilitation: A Machine Learning Study.

Many stroke survivors demonstrate arm nonuse despite good arm motor function. This retrospective secondary analysis aims to identify predictors of arm nonusers with good arm motor function after stroke rehabilitation. A total of 78 participants were categorized into 2 groups using the Fugl-Meyer Assessment Upper Extremity Scale (FMA-UE) and the Motor Activity Log Amount of Use (MAL-AOU). Group 1 comprised participants with good motor function (FMA-UE ≥ 31) and low daily upper limb use (MAL-AOU ≤ 2.5), and group 2 comprised all other participants. Feature selection analysis was performed on 20 potential predictors to identify the 5 most important predictors for group membership. Predictive models were built with the five most important predictors using four algorithms. The most important predictors were preintervention scores on the FMA-UE, MAL-Quality of Movement, Wolf Motor Function Test-Quality, MAL-AOU, and Stroke Self-Efficacy Questionnaire. Predictive models classified the participants with accuracies ranging from 0.75 to 0.94 and areas under the receiver operating characteristic curve ranging from 0.77 to 0.97. The result indicates that measures of arm motor function, arm use in activities of daily living, and self-efficacy could predict postintervention arm nonuse despite good arm motor function in stroke. These assessments should be prioritized in the evaluation process to facilitate the design of individualized stroke rehabilitation programs to reduce arm nonuse.

Coupled dynamics of energy budget and population growth of tilapia in response to pulsed waterborne copper.

The impact of environmentally pulsed metal exposure on population dynamics of aquatic organisms remains poorly understood and highly unpredictable. The purpose of our study was to link a dynamic energy budget model to a toxicokinetic/toxicodynamic (TK/TD). We used the model to investigate tilapia population dynamics in response to pulsed waterborne copper (Cu) assessed with available empirical data. We mechanistically linked the acute and chronic bioassays of pulsed waterborne Cu at the scale of individuals to tilapia populations to capture the interaction between environment and population growth and reproduction. A three-stage matrix population model of larva-juvenile-adult was used to project offspring production through two generations. The estimated median population growth rate (λ) decreased from 1.0419 to 0.9991 under pulsed Cu activities ranging from 1.6 to 2.0 µg L(-1). Our results revealed that the influence on λ was predominately due to changes in the adult survival and larval survival and growth functions. We found that pulsed timing has potential impacts on physiological responses and population abundance. Our study indicated that increasing time intervals between first and second pulses decreased mortality and growth inhibition of tilapia populations, indicating that during long pulsed intervals tilapia may have enough time to recover. Our study concluded that the bioenergetics-based matrix population methodology could be employed in a life-cycle toxicity assessment framework to explore the effect of stage-specific mode-of-actions in population response to pulsed contaminants.

Predictors for Upper-Limb Functional Recovery Trajectory in Individuals Receiving Stroke Rehabilitation: A Secondary Analysis of Data from Randomized Controlled Trials.

BACKGROUND: The objective of the study was to determine predictors for upper-limb functional recovery trajectory after occupational therapy in a population with chronic stroke. METHODS: In this retrospective secondary analysis, Fugl-Meyer Assessment-Upper Extremity (FMA-UE) scores before and after intervention and at the 3-month follow-up were used to divide 105 participants with chronic stroke into three groups of recovery trajectories: fast (participants who reached an improvement of 7 after intervention), extended (those who reached an improvement of 7 at follow-up), and limited (those who did not reach an improvement of 7) recovery. Comparisons among the three groups were made in demographics, stroke characteristics, and baseline assessment scores. Logistic regression analyses were performed to determine predictors for group membership. RESULTS: Time after onset of stroke and the baseline scores of FMA-UE, Stroke Impact Scale-Hand (SIS-Hand), Wolf Motor Function Test (WMFT)-Quality, WMFT-Time scores, Motor Activity Log-Amount of Use (MAL-AOU), and Motor Activity Log-Quality of Movement (MAL-QOM) scores were significantly different among the three groups. Univariate logistic regressions confirmed that SIS-Hand, WMFT-Quality, WMFT-Time, MAL-AOU, and MAL-QOM were significant predictors for both the fast versus limited recovery group membership and the extended versus limited group membership. Time after stroke onset and baseline FMA-UE were additional predictors for the fast versus limited recovery group membership. CONCLUSION: These findings may assist healthcare professionals in making optimal therapeutic decisions and in informing clients and caregivers about the outcomes of stroke recovery.

Simvastatin induces heme oxygenase-1 expression but fails to reduce inflammation in the capsule surrounding a silicone shell implant in rats.

BACKGROUND: Statins are lipid-lowering agents that are widely used in medical practice. Some studies have demonstrated that statins reduce proinflammatory signaling and have antioxidant and anti-inflammatory effects. The inducible heme oxygenase-1 (HO-1) catalyzes the stepwise degradation of heme to produce equimolar quantities of biliverdin, iron, and carbon monoxide; it has also been suggested to promote the important cholesterol-independent cytoprotective action of statins against oxidative insults. However, overexpression of HO-1 may have dual effects under oxidative stress, and the overaccumulation of ferric iron from heme may result in detrimental rather than cytoprotective effects. This study was designed to investigate the effect of a specific statin, simvastatin, and the role of HO-1 on the inflammatory status of the capsule surrounding a silicone shell implant in rats. METHODS: Sprague-Dawley rats were randomly assigned to different groups according to the indicated implantation time (1 , 2 wk, 1 , 2 , and 3 mo postimplant) and the presence or absence of additional treatment (2 mg/kg oral simvastatin daily and/or 2 mg/kg HO inhibitor zinc protoporphyrin (ZnPP) by intraperitoneal injection daily). The formed de novo capsular tissue around the silicone implant was dissected away at the indicated time of sacrifice for experiments regarding the HO-1 expression and the inflammatory status. RESULTS: We found a biphasic pattern of inflammation of the capsule with increased production of TNF-α, IL-1ß, and COX-2, and activation of NF-κB at 1 wk and again at 1 mo postimplantation. Numerous CD68+monocytes or macrophages were diffusely distributed in the capsule in the early stage but not in the late stage postimplantation. In addition, the implantation procedure induced HO-1 expression, which was significantly up-regulated in the first 2 wk but decreased after 1 mo. Although daily feeding of the rats with simvastatin at 2 mg/kg induced HO-1 expression in the capsule throughout the experimental period, simvastatin treatment failed to reduce the production of TNF-α, IL-1ß, and COX-2, or limit NF-κB activation in the early or late stages after implantation. Additionally, simvastatin treatment did not decrease the amount of CD68+cells distributed in the capsule at 1 wk postimplantation. HO-1 up-regulation by simvastatin treatment or down-regulation by additional injection of ZnPP did not demonstrate significant correlation with the inflammatory status of the capsule. CONCLUSION: Simvastatin failed to reduce inflammation of the capsule surrounding a silicone shell implant. Although simvastatin induced HO-1 expression throughout the experimental time, up-regulated HO-1 expression could not be attributed to the inflammatory status of the capsule.

Identification of the potential target genes of microRNA-146a induced by PMA treatment in human microvascular endothelial cells.

Phorbol 12-myristate 13-acetate (PMA) is known to activate protein kinase C (PKC) and increase angiogenesis in cultured endothelial cells. Using a microRNA (miRNA) array, we found that PMA induced miR-146a expression in human microvascular endothelial cells. The miR-146a expression was dependent on dose and time and independent of PKC activation. Using a combined approach involving predictions using miRanda algorithm and whole genome microarray experiments with or without inhibition of miR-146a expression by LNA-antimir-146a or LNA-control, 29 potential target genes of miR-146a were identified. Because endothelial cell S phase progression is an early event in the induction of angiogenesis, we evaluated 5 cell cycle-related genes from the 29 target genes and found that the transcripts of 3 genes (CCNA2, PA2G4, and BRCA1) were downregulated after PMA treatment, but their expression was rescued upon miR-146a inhibition. However, inhibition of miR-146a expression failed to alter the cell cycle distribution or angiogenesis induced by PMA treatment. By using a combined approach involving computational prediction and a whole genome microarray experiment in the presence or absence of antimir, the observations in this presented article raise the possibility that antimir strategies might be used to identify the potential miRNA targets.

Altered expression of the microRNAS and their potential target genes in the soleus muscle after peripheral denervation and reinnervation in rats.

BACKGROUND: To profile the expression of microRNAs (miRNAs) and their potential target genes in the soleus muscles after denervation and reinnervation of the sciatic nerve in rats. MATERIALS AND METHODS: The 4 months denervated and reinnervated soleus muscles were analyzed with Agilent Rat miRNA array to detect the expressed miRNAs against those from the sham control. These differentially expressed miRNAs were applied for hierarchical cluster analysis using average linkage and Pearson correlation as a measure of similarity. A combined approach using computational prediction by the miRanda algorithm and the Agilent Whole Rat Genome 4× 44K oligo microarray experiment was performed to identify the potential target genes of these up-regulated miRNAs. Gene ontology (GO) analysis of these potential target genes into one of the three ontologies, biological process, molecular function, or cellular component, was performed and compared between the denervated and reinnervated muscles. RESULTS: Thirty-six and 39 miRNAs of 350 rat miRNAs tested were significantly up-regulated in the denervated and reinnervated muscles, respectively. The expressed miRNAs in these two groups were similar but with different folds, and the unsupervised hierarchy clustering was able to separate the samples into denervation and reinnervation groupings. In the GO analysis, all three categories indicated a considerable reduced number of the potential target genes of the up-regulated miRNAs and less fraction of differentially expressed genes in most of the GO terms in the reinnervated muscle. CONCLUSIONS: This study demonstrated a different involvement of miRNAs and their potential target genes in the soleus muscle after denervation and after reinnervation of the sciatic nerve in a rat model.

Assessing abalone growth inhibition risk to cadmium and silver by linking toxicokinetics/toxicodynamics and subcellular partitioning.

The purpose of this study was to link toxicokinetics/toxicodynamics and subcellular partitioning for assessing the susceptibility and the growth inhibition risks of abalone Haliotis diversicolor supertexta exposed to waterborne and foodborne cadmium (Cd) and silver (Ag). We reanalyzed published data on growth inhibition and subcellular partitioning associated with the present mechanistic model to explore the correlations among elimination (k (e)), detoxification (k (d)), and recovery (k (r)) rate constants and to assess the growth inhibition risk. We found a positive correlation among k (e), k (d), and k (r) in abalone exposed to Ag. We also employed a life-stage based probabilistic assessment model to estimate the growth inhibition risk of abalone to environmentally relevant Cd (5-995 µg l(-1)) and Ag (0.05-9.95 µg l(-1)) concentrations in Taiwan. The results showed that abalone had a minimum 20% probability of the growth inhibition risk exposed to Cd, whereas Ag exposure was not likely to pose the risk. The maximum biomasses were estimated to be 0.0039 and 0.0038, 61.61 and 43.87, and 98.88 and 62.97 g for larvae, juveniles, and adults of abalone exposed to the same levels of Cd and Ag, respectively. Our study provides a useful tool to detect potential growth biomass of abalone populations subjected to Cd and Ag stresses and mechanistic implications for a long-term ecotoxicological risk assessment in realistic situations.

Autophagy modulation as a potential targeted cancer therapy: From drug repurposing to new drug development.

Autophagy is an evolutionarily conserved signaling pathway to deliver dysfunctional proteins or organelles into lysosomes for degradation and recycling, which is an important pathway for normal homeostasis. Autophagy dysfunction can lead to various diseases, particularly cancer. Autophagy not only plays a role in tumor suppression, but it also serves as a tumor promoter in cancer malignancy. In this review, we summarize the involvement of autophagy-related (ATG) proteins in autophagy signaling and the role of autophagy in cancer progression. The effectiveness of US Food and Drug Administration-approved drugs in regulating autophagic flux and suppressing cancer cells is also discussed. Moreover, since clinically available drugs do not specifically target ATG proteins, there is little doubt that their cancer suppression function is autophagy dependent. Therefore, this review also discusses several inhibitors against ATG proteins, such as ULK1/2, ATG4, and VPS34 to suppress cancer cells. Autophagy modulators can be either used alone or combined with chemotherapy or radiation therapy to enhance the efficacy of current treatments for certain types of cancer. This review summarizes current autophagy modulation used as a potential strategy for targeted cancer therapy.

Neuronavigation-guided focused ultrasound for transcranial blood-brain barrier opening and immunostimulation in brain tumors.

Focused ultrasound (FUS) in the presence of microbubbles can transiently open the blood-brain barrier (BBB) to increase therapeutic agent penetration at the targeted brain site to benefit recurrent glioblastoma (rGBM) treatment. This study is a dose-escalating pilot trial using a device combining neuronavigation and a manually operated frameless FUS system to treat rGBM patients. The safety and feasibility were established, while a dose-dependent BBB-opening effect was observed, which reverted to baseline within 24 hours after treatment. No immunological response was observed clinically under the applied FUS level in humans; however, selecting a higher level in animals resulted in prolonged immunostimulation, as confirmed preclinically by the recruitment of lymphocytes into the tumor microenvironment (TME) in a rat glioma model. Our findings provide preliminary evidence of FUS-induced immune modulation as an additional therapeutic benefit by converting the immunosuppressive TME into an immunostimulatory TME via a higher but safe FUS dosage.

Effects of potential shift and efficiency of charge collection on nanotube-based porphyrin-sensitized solar cells with conjugated links of varied length.

For dye-sensitized solar-cell devices fabricated from porphyrin sensitizers with links of varied length (PE1-PE4) adsorbed on anodic titanium-oxide nanotube arrays, we measured induced photocurrent and photovoltage decays under constant bias illumination; the evaluated efficiencies of charge collection of the devices show a systematic trend PE4 > PE3 > PE2 > PE1 at a large short-circuit current, implying that a long link would improve the charge separation if the electrons were effectively injected into the semiconductor.

Effects of aggregation and electron injection on photovoltaic performance of porphyrin-based solar cells with oligo(phenylethynyl) links inside TiO(2) and Al(2)O(3) nanotube arrays.

Porphyrins with phenylethynyl links of varied length (PE1-PE4) were sensitized on vertically oriented, anodic titanium-oxide (ATO) nanotube arrays for application as dye-sensitized solar cells (DSSC). The efficiency of power conversion decreased systematically from the dye with a short link to the dye with a long link. We measured the efficiency of conversion of incident photons to current (IPCE), the photocurrent decay of the devices, and steady-state and time-resolved fluorescence spectra of the thin-film samples to understand how the cell performance depends on the length of the link. Measurements of femtosecond fluorescence confirmed that the efficiency of electron injection depended on length because of dye aggregation that significantly increased the rate of aggregate-induced energy transfer for porphyrins with a long link. The rate of electron injection depended on the length of the link with an attenuation factor beta approximately 0.1 A(-1). Resonant energy transfer (RET) kinetics of porphyrins sensitized on anodic aluminium-oxide (AAO) nanotube arrays were performed with picosecond time-correlated single-photon counting and four molecular densities for each porphyrin. The kinetic data of PE1 and PE2 are described satisfactorily according to a Förster model, whereas those of PE3 and PE4 conform to a Dexter formula. A formation of clusters is proposed to rationalize the observed density-dependent kinetics for the RET of porphyrins on semiconductor films.