Microcirculatory Impairment and Cerebral Injury in Hydrocephalus and the Effects of Cerebrospinal Fluid Diversion.

BACKGROUND AND OBJECTIVES: Hydrocephalus is characterized by progressive enlargement of cerebral ventricles, resulting in impaired microvasculature and cerebral hypoperfusion. This study aimed to demonstrate the microvascular changes in hydrocephalic rats and the effects of cerebrospinal fluid (CSF) release on cerebral blood flow (CBF). METHODS: On postnatal day 21 (P21), male Wistar rats were intracisternally injected with either a kaolin suspension or saline. On P47, Evan's ratio (ER) was measured using MRI. On P49, the arteriolar diameter and vascular density of the pia were quantified using a capillary video microscope. The CBF was measured using laser Doppler flowmetry. The expressions of NeuN and glial fibrillary acidic protein determined by immunochemical staining were correlated with the ER. The CBF and rotarod test performance were recorded before and after CSF release. The expressions of 4-hydroxynonenal (4-HNE) and c-caspase-3 were studied on P56. RESULTS: Ventriculomegaly was induced to varying degrees, resulting in the stretching and abnormal narrowing of pial arterioles, which regressed with increasing ER. Quantitative analysis revealed significant decreases in the arteriolar diameter and vascular density in the hydrocephalic group compared with those in the control group. In addition, the CBF in the hydrocephalic group decreased to 30%-50% of that in the control group. In hydrocephalus, the neurons appear distorted, and the expression of 4-HNE and reactive astrogliosis increase in the cortex. After CSF was released, improvements in the CBF and rotarod test performance were inversely associated with the ER. In addition, the levels of 4-HNE and c-caspase-3 were further elevated. CONCLUSION: Rapid ventricular dilatation is associated with severe microvascular distortion, vascular regression, cortical hypoperfusion, and cellular changes that impair the recovery of CBF and motor function after CSF release. Moreover, CSF release may induce reperfusion injury. This pathophysiology should be taken into account when treating hydrocephalus.

Long-term complications and outcomes of augmentation cystoplasty in children with neurogenic bladder.

Augmentation cystoplasty (AC) is an effective surgical procedure for patients with neurogenic bladder whenever conservative treatments have failed. The present study aimed to determine the risks of metabolic complications, malignancy, long-term outcomes and histopathologic changes of native bladder and the augmented intestine after AC in children with neurogenic bladder. Pediatric patients < 18 years who underwent AC between 2000 and 2020 were enrolled. Early postoperative complications, long-term outcomes and histopathologic changes in mucosal biopsies of native bladder and the augmented intestine after AC were reviewed. Twenty-two patients with a mean age of 7.6 ± 4.4 years were included. The ileum was used in 19 patients and the sigmoid colon in 3 patients. The length of hospital stay was 14.8 ± 6.8 days. Post-operatively, the urinary continence rate improved from 22.7 to 81.8% (p < 0.001). Hydronephrosis resolved in 17 of 19 patients. Vesicoureteral reflux resolved in 16 (64.0%) of the refluxing ureter units and was downgraded in 7 (28.0%). Grades of hydronephrosis and reflux significantly improved following AC (p < 0.001). The estimated glomerular filtration rate also significantly increased (p = 0.012). Formation of urinary tract stones was the most frequent late complication (in 8 patients, 36.4%). Life-threatening spontaneous bladder perforation occurred in 1 patient. After a mean follow-up of 13.4 ± 5.9 years, there were no cases of mortality, new-onset symptomatic metabolic acidosis, or changes in serum electrolytes. Of the 17 patients who were followed for > 10 years, no cases of malignancy or metaplastic changes were identified in the native bladder or augmented bowel epithelium. AC is a safe and effective procedure with low surgical and metabolic complication rates. In addition, AC provides a satisfactory continence rate and long-term protection of renal function, increases functional capacity, and regresses reflux and hydronephrosis. Individualized surveillance is recommended for the early identification of urolithiasis and metabolic disturbances.

Recombinant soluble form of receptor for advanced glycation end products ameliorates microcirculation impairment and neuroinflammation after subarachnoid hemorrhage.

Impaired cerebral microcirculation after subarachnoid hemorrhage (SAH) has been shown to be related to delayed ischemic neurological deficits (DIND). We previously demonstrated the involvement of the receptor for advanced glycation end products (RAGE) in the pathogenesis of SAH related neuronal death. In the present study, we aimed to investigate the therapeutic effects of a recombinant soluble form of RAGE (sRAGE) on microcirculation impairment following SAH. Intrathecal injection of autologous blood in rats, mixed primary astrocyte and microglia cultures exposed to hemolysates and endothelial cells â€‹(ECs) from human brain microvascular exposed to glia-conditioned medium or SAH patient's CSF were used as experimental SAH models in vivo and in vitro. The results indicated that intrathecal administration of recombinant sRAGE significantly ameliorated the vasoconstriction of cortical arterioles and associated perfusion impairment, brain edema, reduced cell death, endothelial dysfunction, and improved motor performance at 24 and 48 â€‹h after SAH induction in rats. The in vitro results further showed that recombinant sRAGE significantly reduced astrocyte swelling and microglia activation, in parallel with decreased mRNA expression levels of pro-inflammatory cytokines including interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) in vitro. Moreover, the in vitro model of SAH-induced p-eNOS and eNOS suppression, along with stress fiber formation in brain microvascular ECs, was effectively reversed by sRAGE treatment and led to a decrease in cleaved-caspase 3 expression. In summary, recombinant sRAGE effectively lessened microcirculation impairment and vascular injury after SAH via the mechanism of anti-inflammation, which may provide a potential therapeutic strategy for SAH.

Does a negative correlation of heme oxygenase-1 with hematoma thickness in chronic subdural hematomas affect neovascularization and microvascular leakage? A retrospective study with preliminary validation.

OBJECTIVE: Chronic subdural hematoma (CSDH) is a common neurological disease among elderly adults. The progression of CSDH is an angiogenic process, involving inflammatory mediators that affect vascular permeability, microvascular leakage, and hematoma thickness. The authors aimed to identify biomarkers associated with angiogenesis and vascular permeability that might influence midline shift and hematoma thickness. METHODS: Medical records and laboratory data of consecutive patients who underwent surgery for CSDH were analyzed. Collected data were basic demographic data, CSDH classification, CSDH thickness, midline shift, heme oxygenase-1 (HO-1) levels in hematomas, and common laboratory markers. Linear regression analysis was used to evaluate the relationship of CSDH thickness with characteristic variables. The chick chorioallantoic membrane (CAM) assay was used to test the angiogenic potency of identified variables in ex ovo culture of chick embryos. RESULTS: In total, 93 patients with CSDH (71.0% male) with a mean age of 71.0 years were included. The mean CSDH thickness and midline shift were 19.7 and 9.8 mm, respectively. The mean levels of HO-1, ferritin, total bilirubin, white blood cells, segmented neutrophils, lymphocytes, platelets, international normalized ratio, and partial thromboplastin time were 36 ng/mL, 14.8 µg/mL, 10.5 mg/dL, 10.3 × 103 cells/µL, 69%, 21.7%, 221.1 × 109 cells/µL, 1.0, and 27.8 seconds, respectively. Pearson correlation analysis revealed that CSDH thickness was positively correlated with midline shift distance (r = 0.218, p < 0.05) but negatively correlated with HO-1 concentration (r = -0.364, p < 0.01) and ferritin level (r = -0.222, p < 0.05). Multivariate linear regression analysis revealed that HO-1 was an independent predictor of CSDH thickness (ß = -0.084, p = 0.006). The angiogenic potency of HO-1 in hematoma fluid was tested with the chick CAM assay; topical addition of CSDH fluid with low HO-1 levels promoted neovascularization and microvascular leakage. Addition of HO-1 in a rescue experiment inhibited CSDH fluid-mediated angiogenesis and microvascular leakage. CONCLUSIONS: HO-1 is an independent risk factor in CSDH hematomas and is negatively correlated with CSDH thickness. HO-1 may play a role in the pathophysiology and development of CSDH, possibly by preventing neovascularization and reducing capillary fragility and hyperpermeability.

Advances in numerical simulation of unit operations for tablet preparation.

Recently, there has been an increase in the use of numerical simulation technology in pharmaceutical preparation processes. Numerical simulation can contribute to a better understanding of processes, reduce experimental costs, optimize preparation processes, and improve product quality. The intermediate material of most dosage forms is powder or granules, especially in the case of solid preparations. The macroscopic behavior of particle materials is controlled by the interactions of individual particles with each other and surrounding fluids. Therefore, it is very important to analyze and control the microscopic details of the preparation process for solid preparations. Since tablets are one of the most widely used oral solid preparations, and the preparation process is relatively complex and involves numerous units of operation, it is especially important to analyze and control the tablet production process. The present paper discusses recent advances in numerical simulation technology for the preparation of tablets, including drying, mixing, granulation, tableting, and coating. It covers computational fluid dynamics (CFD), discrete element method (DEM), population balance model (PBM), finite element method (FEM), Lattice-Boltzmann model (LBM), and Monte Carlo model (MC). The application and deficiencies of these models in tablet preparation unit operations are discussed. Furthermore, the paper provides a systematic reference for the control and analysis of the tablet preparation process and provides insight into the future direction of numerical simulation technology in the pharmaceutical industry.

Dental Pulp Stem Cell-Derived Conditioned Medium Alleviates Subarachnoid Hemorrhage-Induced Microcirculation Impairment by Promoting M2 Microglia Polarization and Reducing Astrocyte Swelling.

Aneurysmal subarachnoid hemorrhage (SAH) can cause severe neurological deficits and high mortality. Early brain edema following SAH contributes to the initiation of microcirculation impairment and may further lead to delayed ischemic neurologic deficit (DIND). This study aimed to investigate whether dental pulp stem cell conditioned medium (DPSC-CM) ameliorates SAH-induced microcirculation impairment and the underlying mechanisms. SAH was induced via intrathecal injection of fresh autologous blood in Wistar male adult rat. DPSC-CM or DPSC-CM + insulin growth factor-1 (IGF-1) antibody was randomly administered by intrathecal route 5 min after SAH induction. To evaluate the underlying mechanisms of DPSC-CM in the treatment of SAH, primary rat astrocyte and microglia co-cultures were challenged with hemolysate or SAH-patient CSF in the presence or absence of DPSC-CM. The results showed that in vivo, DPSC-CM treatment decreased the brain water content, improved microcirculation impairment and enhanced functional recovery at 24 h post-SAH. DPSC-CM treatment also alleviated the expressions of water channel protein aquaporin-4 (AQP4) and pro-inflammatory cytokines, and enhanced the expressions of anti-inflammatory factors in the cortical region. However, all the beneficial effects of DPSC-CM were abrogated after treatment with IGF-1 neutralizing antibody. The in vitro results further showed that DPSC-CM treatment reduced hemolysate/SAH-patient CSF-induced astrocyte swelling and promoted M2 microglia polarization, partially through IGF-1/AKT signaling. The data suggested that DPSC-CM significantly reduced brain edema and rescued microcirculation impairment with concomitant anti-inflammatory benefits after SAH, and may potentially be developed into a novel therapeutic strategy for SAH.

Combination of indirect revascularization and endothelial progenitor cell transplantation improved cerebral perfusion and ameliorated tauopathy in a rat model of bilateral ICA ligation.

OBJECTIVE: Endothelial progenitor cells (EPCs) contribute to the recovery of neurological function after ischemic stroke. Indirect revascularization has exhibited promising effects in the treatment of cerebral ischemia related to moyamoya disease and intracranial atherosclerotic disease. The role of EPCs in augmenting the revascularization effect is not clear. In this study, we investigated the therapeutic effects of indirect revascularization combined with EPC transplantation in rats with chronic cerebral ischemia. METHODS: Chronic cerebral ischemia was induced by bilateral internal carotid artery ligation (BICAL) in rats, and indirect revascularization by encephalo-myo-synangiosis (EMS) was performed 1 week later. During the EMS procedure, intramuscular injection of EPCs and the addition of stromal cell-derived factor 1 (SDF-1), and AMD3100, an SDF-1 inhibitor, were undertaken, respectively, to investigate their effects on indirect revascularization. Two weeks later, the cortical microcirculation, neuronal damage, and functional outcome were evaluated according to the microvasculature density and partial pressure of brain tissue oxygen (PbtO2), regional blood flow, expression of phosphorylated Tau (pTau), TUNEL staining and the rotarod performance test, respectively. RESULTS: The cortical microcirculation, according to PbtO2 and regional blood flow, was impaired 3 weeks after BICAL. These impairments were improved by the EMS procedure. The regional blood flow was further increased by the addition of SDF-1 and decreased by the addition of AMD3100. Intramuscular injection of EPCs further increased the regional blood flow as compared with the EMS group. The rotarod test results showed that the functional outcome was best in the EMS combined with EPC injection group. Western blot analysis showed that the EMS combined with EPC treatment group had significantly decreased expressions of phosphorylated Tau and phosphorylated glycogen synthase kinase 3 beta (Y216 of GSK-3ß). pTau and TUNEL-positive cells were markedly increased at 3 weeks after BICAL induction. Furthermore, the groups treated with EMS combined with SDF-1 or EPCs exhibited marked decreases in the pTau expression and TUNEL-positive cells, whereas AMD3100 treatment increased TUNEL-positive cells. CONCLUSION: The results of this study suggested that indirect revascularization ameliorated the cerebral ischemic changes. EPCs played a key role in augmenting the effect of indirect revascularization in the treatment of chronic cerebral ischemia.

Equal Z standard-setting method to estimate the minimum number of panelists for a medical school's objective structured clinical examination in Taiwan: a simulation study

PURPOSE: Undertaking a standard-setting exercise is a common method for setting pass/fail cut scores for high-stakes examinations. The recently introduced equal Z standard-setting method (EZ method) has been found to be a valid and effective alternative for the commonly used Angoff and Hofstee methods and their variants. The current study aims to estimate the minimum number of panelists required for obtaining acceptable and reliable cut scores using the EZ method. METHODS: The primary data were extracted from 31 panelists who used the EZ method for setting cut scores for a 12-station of medical school's final objective structured clinical examination (OSCE) in Taiwan. For this study, a new data set composed of 1,000 random samples of different panel sizes, ranging from 5 to 25 panelists, was established and analyzed. Analysis of variance was performed to measure the differences in the cut scores set by the sampled groups, across all sizes within each station. RESULTS: On average, a panel of 10 experts or more yielded cut scores with confidence more than or equal to 90% and 15 experts yielded cut scores with confidence more than or equal to 95%. No significant differences in cut scores associated with panel size were identified for panels of 5 or more experts. CONCLUSION: The EZ method was found to be valid and feasible. Less than an hour was required for 12 panelists to assess 12 OSCE stations. Calculating the cut scores required only basic statistical skills.

Surface Modifiers on Composite Particles for Direct Compaction.

Direct compaction (DC) is considered to be the most effective method of tablet production. However, only a small number of the active pharmaceutical ingredients (APIs) can be successfully manufactured into tablets using DC since most APIs lack adequate functional properties to meet DC requirements. The use of suitable modifiers and appropriate co-processing technologies can provide a promising approach for the preparation of composite particles with high functional properties. The purpose of this review is to provide an overview and classification of different modifiers and their multiple combinations that may improve API tableting properties or prepare composite excipients with appropriate co-processed technology, as well as discuss the corresponding modification mechanism. Moreover, it provides solutions for selecting appropriate modifiers and co-processing technologies to prepare composite particles with improved properties.

Identification and Functional Prediction of Poplar Root circRNAs Involved in Treatment With Different Forms of Nitrogen.

Circular RNAs (circRNAs) are a class of noncoding RNA molecules with ring structures formed by covalent bonds and are commonly present in organisms, playing an important regulatory role in plant growth and development. However, the mechanism of circRNAs in poplar root responses to different forms of nitrogen (N) is still unclear. In this study, high-throughput sequencing was used to identify and predict the function of circRNAs in the roots of poplar exposed to three N forms [1 mM NO3 - (T1), 0.5 mM NH4NO3 (T2, control) and 1 mM NH4 + (T3)]. A total of 2,193 circRNAs were identified, and 37, 24 and 45 differentially expressed circRNAs (DECs) were screened in the T1-T2, T3-T2 and T1-T3 comparisons, respectively. In addition, 30 DECs could act as miRNA sponges, and several of them could bind miRNA family members that play key roles in response to different N forms, indicating their important functions in response to N and plant growth and development. Furthermore, we generated a competing endogenous RNA (ceRNA) regulatory network in poplar roots treated with three N forms. DECs could participate in responses to N in poplar roots through the ceRNA regulatory network, which mainly included N metabolism, amino acid metabolism and synthesis, response to NO3 - or NH4 + and remobilization of N. Together, these results provide new insights into the potential role of circRNAs in poplar root responses to different N forms.

Genome-Wide Identification and Characterization of Long Noncoding RNAs in Populus × canescens Roots Treated With Different Nitrogen Fertilizers.

Nitrate (NO3 -) and ammonium (NH4 +) are the primary forms of inorganic nitrogen acquired by plant roots. LncRNAs, as key regulators of gene expression, are a class of non-coding RNAs larger than 200 bp. However, knowledge about the regulatory role of lncRNAs in response to different nitrogen forms remains limited, particularly in woody plants. Here, we performed strand-specific RNA-sequencing of P. × canescens roots under three different nitrogen fertilization treatments. In total, 324 lncRNAs and 6,112 mRNAs were identified as showing significantly differential expression between the NO3 - and NH4NO3 treatments. Moreover, 333 lncRNAs and 6,007 mRNAs showed significantly differential expression between the NH4 + and NH4NO3 treatments. Further analysis suggested that these lncRNAs and mRNAs have different response mechanisms for different nitrogen forms. In addition, functional annotation of cis and trans target mRNAs of differentially expressed lncRNAs indicated that 60 lncRNAs corresponding to 49 differentially expressed cis and trans target mRNAs were involved in plant nitrogen metabolism and amino acid biosynthesis and metabolism. Furthermore, 42 lncRNAs were identified as putative precursors of 63 miRNAs, and 28 differentially expressed lncRNAs were potential endogenous target mimics targeted by 96 miRNAs. Moreover, ceRNA regulation networks were constructed. MSTRG.6097.1, MSTRG.13550.1, MSTRG.2693.1, and MSTRG.12899.1, as hub lncRNAs in the ceRNA networks, are potential candidate lncRNAs for studying the regulatory mechanism in poplar roots under different nitrogen fertilization treatments. The results provide a basis for obtaining insight into the molecular mechanisms of lncRNA responses to different nitrogen forms in woody plants.

Immersive virtual reality (VR) training increases the self-efficacy of in-hospital healthcare providers and patient families regarding tracheostomy-related knowledge and care skills: A prospective pre-post study.

BACKGROUND: Virtual reality (VR)-based simulation in hospital settings facilitates the acquisition of skills without compromising patient safety. Despite regular text-based training, a baseline survey of randomly selected healthcare providers revealed deficiencies in their knowledge, confidence, comfort, and care skills regarding tracheostomy. This prospective pre-post study compared the effectiveness of regular text- and VR-based intervention modules in training healthcare providers' self-efficacy in tracheostomy care skills. METHODS: Between January 2018 and January 2020, 60 healthcare providers, including physicians, nurses, and respiratory therapists, were enrolled. For the intervention, a newly developed head-mounted display (HMD) and web VR materials were implemented in training and clinical services. Subsequently, in-hospital healthcare providers were trained using either text or head-mounted display virtual reality (HMD-VR) materials in the regular and intervention modules, respectively. For tracheostomy care skills, preceptors directly audited the performance of trainees and provided feedback. RESULTS: At baseline, the degree of trainees' agreement with the self-efficacy-related statements, including the aspects of familiarity, confidence, and anxiety about tracheostomy-related knowledge and care skills, were not different between the control and intervention groups. At follow-up stage, compared with the regular group, a higher percentage of intervention group' trainees reported that they are "strongly agree" or "somewhat agree" that the HMD-VR simulation increases their self-efficacy, including the aspects of familiarity and confidence, and reduced their anxiety about tracheostomy-related knowledge and care skills. After implementation, a higher degree of trainees' average satisfaction with VR-based training and VR materials was observed in the intervention group than in the regular group. Most reported that VR materials enabled accurate messaging and decreased anxiety. The increasing trend of the average written test and hands-on tracheostomy care skills scores among the intervention group trainees was significant compared to those in the regular group. The benefits of HMD-VR simulations and web-VR material-based clinical services for in-hospital healthcare providers and patient families persisted until 3 to 4 weeks later. CONCLUSION: The current study suggests that VR materials significantly enhance trainees' self-efficacy (increased familiarity, increased confidence, and reduced anxiety) and their satisfaction with the training, while motivating them to use acquired knowledge and skills in clinical practice.

Comparison of OSCE performance between 6- and 7-year medical school curricula in Taiwan.

BACKGROUND: The year 2013 marks a watershed in the history of medical education in Taiwan. Following Taiwan's Taskforce of Medical School Curriculum Reform recommendations, the medical school curriculum was reduced from 7 to 6 years. This study aimed to analyze the impact of medical school curriculum reform on medical students' performance in objective structured clinical examinations (OSCEs). METHODS: We retrospectively analyzed the OSCE records at Taipei Veterans General Hospital (Taipei VGH), one of Taiwan's largest tertiary medical centers, between November 2016 and July 2020. The eligibility criteria were medical students receiving a full one-year clinical sub-internship training at Taipei VGH and in their last year of medical school. All medical students received a mock OSCE-1 at the beginning of their sub-internship, a mock OSCE-2 after six months of training, and a national OSCE at the end of their sub-internship. The parameters for performance in OSCEs included "percentage of scores above the qualification standard" and "percentage of qualified stations." RESULTS: Between November 2016 and July 2020, 361 undergraduates underwent clinical sub-internship training at Taipei VGH. Among them, 218 were taught under the 7-year curriculum, and 143 were instructed under the 6-year curriculum. Based on baseline-adjusted ANCOVA results, medical students under the 7-year curriculum had a higher percentage of scores above the qualification standard than those under the 6-year curriculum at the mock OSCE-1 (7-year curriculum vs. 6-year curriculum: 33.8% [95% CI 32.0-35.7] vs. 28.2% [95% CI 25.9-30.4], p < 0.001), and mock OSCE-2 (7-year curriculum vs. 6-year curriculum: 89.4% [95% CI 87.4-91.4] vs. 84.0% [95% CI 81.5-86.4], p = 0.001). Moreover, medical students in the 7-year curriculum had a higher percentage of qualified stations in mock OSCE-1 (7-year curriculum vs. 6-year curriculum: 89.4% [95% CI 87.4-91.4] vs. 84.0% [95% CI 81.5-86.4], p = 0.001) and mock OSCE-2 (7-year curriculum vs. 6-year curriculum: 91.9% [95% CI 90.1-93.8] vs. 86.1% [95% CI 83.8-88.3], p = 0.001). After clinical sub-internship training, there were no differences in the percentage of scores above the qualification standard (7-year curriculum vs. 6-year curriculum: 33.5% [95% CI 32.2-34.9] vs. 34.6 [95% CI 32.9-36.3], p = 0.328) and percentage of qualified stations (7-year curriculum vs. 6-year curriculum: 89.4% [95% CI 88.1-90.7] vs. 90.2% [95% CI 88.6-91.8], p = 0.492). CONCLUSIONS: At the beginning of the sub-internship, medical students under the 7-year curriculum had better OSCE performance than those under the 6-year curriculum. After the clinical sub-internship training in Taipei VGH, there was no difference in the national OSCE score between the 6- and 7-year curricula. Our study suggests that clinical sub-internship is crucial for the development of clinical skills and performance in the national OSCE.

3,6'-Dithiopomalidomide Ameliorates Hippocampal Neurodegeneration, Microgliosis and Astrogliosis and Improves Cognitive Behaviors in Rats with a Moderate Traumatic Brain Injury.

Traumatic brain injury (TBI) is a leading cause of disability and mortality worldwide. It can instigate immediate cell death, followed by a time-dependent secondary injury that results from disproportionate microglial and astrocyte activation, excessive inflammation and oxidative stress in brain tissue, culminating in both short- and long-term cognitive dysfunction and behavioral deficits. Within the brain, the hippocampus is particularly vulnerable to a TBI. We studied a new pomalidomide (Pom) analog, namely, 3,6'-dithioPom (DP), and Pom as immunomodulatory imide drugs (IMiD) for mitigating TBI-induced hippocampal neurodegeneration, microgliosis, astrogliosis and behavioral impairments in a controlled cortical impact (CCI) model of TBI in rats. Both agents were administered as a single intravenous dose (0.5 mg/kg) at 5 h post injury so that the efficacies could be compared. Pom and DP significantly reduced the contusion volume evaluated at 24 h and 7 days post injury. Both agents ameliorated short-term memory deficits and anxiety behavior at 7 days after a TBI. The number of degenerating neurons in the CA1 and dentate gyrus (DG) regions of the hippocampus after a TBI was reduced by Pom and DP. DP, but not Pom, significantly attenuated the TBI-induced microgliosis and DP was more efficacious than Pom at attenuating the TBI-induced astrogliosis in CA1 and DG at 7D after a TBI. In summary, a single intravenous injection of Pom or DP, given 5 h post TBI, significantly reduced hippocampal neurodegeneration and prevented cognitive deficits with a concomitant attenuation of the neuroinflammation in the hippocampus.

Transcranial electrostimulation with special waveforms enhances upper-limb motor function in patients with chronic stroke: a pilot randomized controlled trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) and intermittent theta burst stimulation (iTBS) were both demonstrated to have therapeutic potentials to rapidly induce neuroplastic effects in various rehabilitation training regimens. Recently, we developed a novel transcranial electrostimulation device that can flexibly output an electrical current with combined tDCS and iTBS waveforms. However, limited studies have determined the therapeutic effects of this special waveform combination on clinical rehabilitation. Herein, we investigated brain stimulation effects of tDCS-iTBS on upper-limb motor function in chronic stroke patients. METHODS: Twenty-four subjects with a chronic stroke were randomly assigned to a real non-invasive brain stimulation (NIBS; who received the real tDCS + iTBS output) group or a sham NIBS (who received sham tDCS + iTBS output) group. All subjects underwent 18 treatment sessions of 1 h of a conventional rehabilitation program (3 days a week for 6 weeks), where a 20-min NIBS intervention was simultaneously applied during conventional rehabilitation. Outcome measures were assessed before and immediately after the intervention period: Fugl-Meyer Assessment-Upper Extremity (FMA-UE), Jebsen-Taylor Hand Function Test (JTT), and Finger-to-Nose Test (FNT). RESULTS: Both groups showed improvements in FMA-UE, JTT, and FNT scores after the 6-week rehabilitation program. Notably, the real NIBS group had greater improvements in the JTT (p = 0. 016) and FNT (p = 0. 037) scores than the sham NIBS group, as determined by the Mann-Whitney rank-sum test. CONCLUSIONS: Patients who underwent the combined ipsilesional tDCS-iTBS stimulation with conventional rehabilitation exhibited greater impacts than did patients who underwent sham stimulation-conventional rehabilitation in statistically significant clinical responses of the total JTT time and FNT after the stroke. Preliminary results of upper-limb functional recovery suggest that tDCS-iTBS combined with a conventional rehabilitation intervention may be a promising strategy to enhance therapeutic benefits in future clinical settings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04369235. Registered on 30 April 2020.

Virtual reality-based preprocedural education increases preparedness and satisfaction of patients about the catheter ablation of atrial fibrillation.

BACKGROUND: A recent study suggested to develop and implement more interacted material for preprocedural education to decrease patients' anxiety about the atrial fibrillation (AF) ablation. This study compared the effectiveness of using either newly developed virtual reality (VR) materials (VR group) or paper-based materials (paper group) on giving AF preprocedural education. METHODS: This study consequentially enrolled 33 AF patients preparing for ablation from November 2019 to October 2020. After enrollment, patients were randomized as either paper (n = 22) or VR (n = 11) groups. RESULTS: In comparison with the baseline stage, at the posteducation stage, the degree of improvement in patients' self-assessed self-efficacy on AF ablation knowledge was higher among VR group patients than those in the paper group. At the posteducation stage, the patients' satisfaction to preprocedural education and used materials were higher among the VR group than that among the paper group. In addition to meet their needs and give accurate medical information, VR group patients reported that VR materials increased the effectiveness of education, increased their preparedness for AF catheter ablation, achieved paperless purposes, and willing to recommend VR materials to others. Operators subjectively reported that the periprocedure cooperation was increased both among paper and VR group patients after preprocedural education for the details of procedure. Better preparedness of VR group patients was supported by less periprocedure pain, anxiety, and impatience than those among paper group patients. CONCLUSION: Interactive VR-based materials are superior to the paper-based materials to provide patients immerse and imagine the journey and detail knowledge of AF catheter ablation before the procedure and better prepared patients for the procedure.

Virtual reality simulation increases Chinese physicians' and lab technicians' familiarity and confidence regarding proper clinical wastes segregation/disposal: a 2-year pilot study.

Although they receive regular training, the survey we administered to our junior physicians and lab technicians revealed that they lack familiarity and confidence regarding the proper segregation/disposal of clinical wastes. In this pilot prospective study, carried out between September 2017 and September 2019, we developed a virtual reality (VR) simulation and integrated it into the steps of Gangen's training flow. Next, we analysed objective performance, recorded by the App in the VR system as well as the subjective self-assessments of 96 junior physicians and lab technicians after two practices of VR games. Before receiving training, lab technicians' self-assessed familiarity and confidence regarding proper clinical wastes segregation/disposal were higher than among physicians. Compared with the first VR game, we noted greater improvement in accuracy as well as a higher percentage of shortened time to complete 10 actions of segregation/disposal of VR clinical wastes, among junior physicians/male trainees, that of junior lab technicians/female trainees in the second VR game. Most of the trainees (81%-88%) reported that they found the VR game-based training to be useful, in contrast to poster-mass media-based training. Our initial positive results indicated the possibility of applying this VR game-based simulation system to regular institution-wide staff education in future.

Virtual reality informative aids increase residents' atrial fibrillation ablation procedures-related knowledge and patients' satisfaction.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia, and increasing numbers of patients receive AF ablation nowadays. Therefore, in the cardiology division, residents need to be familiar with the AF ablation procedure-related knowledge for primary care. This study evaluated the baseline residents and patients' self-efficacy to the AF ablation procedure-related knowledge, developed the specific virtual reality (VR) informative aids, and evaluated the effects of VR training and resident-led VR aids-based patient education on their self-efficacy, in the aspects of familiarity, confidence and anxiety, and satisfaction. METHODS: From 2019, April to 2020, April, this 1-year prospective prestudy and poststudy was undergone in the cardiology division. Between 2019, April and 2019, December, the experienced physicians were invited to develop VR informative aids for AF ablation procedure-related knowledge. Between January 2020 and April 2020, newly developed VR informative aids were implemented in the educational program of training rotated residents for giving patient education. RESULT: A total of 20 residents and 32 patients were enrolled. The baseline self-reported self-efficacy and knowledge scores were relatively low among rotated residents and their patients. In addition to the high level of satisfaction, self-efficacy and knowledge scores of residents and their patients were increased after VR aids-based training and resident-led patient education. Higher degree of improvement in self-efficacy was noted among patients with depression/anxiety history than those without history. The follow-up assessments among residents showed that the positive effects of VR aids were sustained until 2 weeks later. CONCLUSION: Overall, residents and patients reported that the VR aids increase the effectiveness of patient education, achieve the purpose of a paperless environment, and motivate them to recommend it to others. The implementation of resident-to-patient education has a positive impact on trainees and patients understanding about AF ablation procedures-related knowledge.

Designing and Implementing an Implantable Wireless Micromanometer System for Real-Time Bladder Pressure Monitoring: A Preliminary Study.

Many mini-implantable devices have been developed and fabricated for diagnostic and treatment purposes. Wireless implantable biomicrosystems provide a desirable approach for long-term physiological signal monitoring. In this study, we implemented a wireless implantable biomicrosystem for bladder-cavity pressure measurements in a freely moving rabbit. To manage the power more effectively, a magnetic reed switch was applied to turn on/off the implantable module using a neodymium-iron-boron (NdFeB) magnet. The measured bladder pressure signal was wirelessly transmitted from the implantable module to a host unit. Our results indicated that the implantable biomicrosystem exhibited satisfactory performance and safety, as evidenced by an error percentage of less than ±1% for pressure measurements and less than 2 °C of a temperature rise under normal operation. The wireless biomicrosystem was implanted into the bladder cavity of a rabbit. Bladder pressure was simultaneously measured by both the biomicrosystem and conventional cystometry in the animal. The two signals were similar during the voiding phase, with a correlation coefficient of 0.885. Additionally, the biomicrosystem coated with polydimethylsiloxane in this study showed no cytotoxicity, which confirmed its biocompatibility. In conclusion, we demonstrated a good biocompatible wireless biomicrosystem which showed good reproducibility with respect to pressure monitoring by conventional cystometry. Further studies are needed to confirm the results of this preliminary feasibility study for actual clinical applications.