High glycated albumin is associated with early neurological deterioration in patients with acute ischemic stroke.

BACKGROUND: Glycated albumin (GA) is an indicator of glycemic variability over the past 2-4 weeks and has suitable characteristics for predicting the prognosis of ischemic stroke during the acute phase. This study evaluated the association between early neurological deterioration (END) and GA values in patients with acute ischemic stroke (AIS). METHODS: We assessed consecutive patients with AIS between 2022 and 2023 at two large medical centers in Korea. END was defined as an increase of ≥ 2 in the total National Institutes of Health Stroke Scale (NIHSS) score or ≥ 1 in the motor NIHSS score within the first 72 h of admission. We evaluated various glycemic parameters including fasting glucose (mg/dL), hemoglobin A1c (%), and GA (%). RESULTS: In total, 531 patients with AIS were evaluated (median age: 69 years, male sex: 66.3%). In the multivariable logistic regression analysis, GA value was positively associated with END (adjusted odds ratio [aOR] = 3.24, 95% confidence interval [CI]: 1.10-9.50). Initial NIHSS score (aOR = 1.04, 95% CI: 1.01-1.08) and thrombolytic therapy (aOR = 2.06, 95% CI: 1.14-3.73) were also associated with END. In a comparison of the predictive power of glycemic parameters for END, GA showed a higher area under the curve value on the receiver operating characteristic curve than fasting glucose and hemoglobin A1c. CONCLUSIONS: High GA values were associated with END in patients with AIS. Furthermore, GA was a better predictor of END than fasting glucose or hemoglobin A1c.

Identifying best fall-related balance factors and robotic-assisted gait training attributes in 105 post-stroke patients using clinical machine learning models.

BACKGROUND: Despite the promising effects of robot-assisted gait training (RAGT) on balance and gait in post-stroke rehabilitation, the optimal predictors of fall-related balance and effective RAGT attributes remain unclear in post-stroke patients at a high risk of fall. OBJECTIVE: We aimed to determine the most accurate clinical machine learning (ML) algorithm for predicting fall-related balance factors and identifying RAGT attributes. METHODS: We applied five ML algorithms- logistic regression, random forest, decision tree, support vector machine (SVM), and extreme gradient boosting (XGboost)- to a dataset of 105 post-stroke patients undergoing RAGT. The variables included the Berg Balance Scale score, walking speed, steps, hip and knee active torques, functional ambulation categories, Fugl- Meyer assessment (FMA), the Korean version of the Modified Barthel Index, and fall history. RESULTS: The random forest algorithm excelled (receiver operating characteristic area under the curve; AUC = 0.91) in predicting balance improvement, outperforming the SVM (AUC = 0.76) and XGboost (AUC = 0.71). Key determinants identified were knee active torque, age, step count, number of RAGT sessions, FMA, and hip torque. CONCLUSION: The random forest algorithm was the best prediction model for identifying fall-related balance and RAGT determinants, highlighting the importance of key factors for successful RAGT outcome performance in fall-related balance improvement.

Triglyceride-Related Parameters and Symptomatic Atherosclerotic Lesions in Patients With Ischemic Stroke.

Objective: Recently, evidence has suggested that the pathophysiology and risk factors of intracranial atherosclerosis (ICAS) differs from those of extracranial atherosclerosis (ECAS). In addition, novel parameters reflecting metabolic conditions, such as insulin resistance or atherogenic dyslipidemia, based on triglycerides (TG) and other biomarkers, have emerged. In this study, we evaluated the association between TG-related parameters and symptomatic cerebral atherosclerosis in patients with acute ischemic stroke resulting from large artery atherosclerosis (LAA). Methods: We assessed consecutive acute LAA-stroke patients between January 2010 and December 2020. Based on the radiological findings, we classified the relevant symptomatic arteries that caused the index stroke into LAA-ICAS and LAA-ECAS. As TG-related parameters, the atherogenic index of plasma (AIP) and TG-glucose (TyG) index were calculated according to the following formulas: AIP = log10 (TG Level/High-density Lipoprotein Cholesterol Level), TyG Index = Ln (TG Level × Glucose Level/2). Results: A total of 519 patients with LAA-stroke were evaluated. In multivariable logistic regression analysis to identify predictors of LAA-ICAS, AIP was significantly associated with LAA-ICAS (adjusted odds ratio [aOR], 3.60; 95% confidence interval [CI], 1.60-8.06). TyG index also showed a statistically significant relationship with LAA-ICAS (aOR, 1.60; 95% CI, 1.11-2.32). However, TG per se did not show a statistical association with LAA-ECAS. Conclusion: TG-related parameters were more closely associated with stroke by ICAS than by ECAS. The metabolic conditions reflected by the AIP or TyG index, rather than hypertriglyceridemia itself, may play a greater role in determining the relevant vessel causally involved in a stroke.

Chronic ultraviolet irradiation induces memory deficits via dysregulation of the dopamine pathway.

The effects of ultraviolet (UV) radiation on brain function have previously been investigated; however, the specific neurotransmitter-mediated mechanisms responsible for UV radiation-induced neurobehavioral changes remain elusive. In this study, we aimed to explore the mechanisms underlying UV radiation-induced neurobehavioral changes. In a mouse model, we observed that UV irradiation of the skin induces deficits in hippocampal memory, synaptic plasticity, and adult neurogenesis, as well as increased dopamine levels in the skin, adrenal glands, and brain. Chronic UV exposure altered the expression of genes involved in dopaminergic neuron differentiation. Furthermore, chronic peripheral dopamine treatments resulted in memory deficits. Systemic administration of a dopamine D1/D5 receptor antagonist reversed changes in memory, synaptic plasticity, adult neurogenesis, and gene expression in UV-irradiated mice. Our findings provide converging evidence that chronic UV exposure alters dopamine levels in the central nervous system and peripheral organs, including the skin, which may underlie the observed neurobehavioral shifts, such as hippocampal memory deficits and impaired neurogenesis. This study underscores the importance of protection from UV exposure and introduces the potential of pharmacological approaches targeting dopamine receptors to counteract the adverse neurological impacts of UV exposure.

A comparison of random forest-based missing imputation methods for covariates in propensity score analysis.

Propensity score analysis (PSA) is a prominent method to alleviate selection bias in observational studies, but missing data in covariates is prevalent and must be dealt with during propensity score estimation. Through Monte Carlo simulations, this study evaluates the use of imputation methods based on multiple random forests algorithms to handle missing data in covariates: multivariate imputation by chained equations-random forest (Caliber), proximity imputation (PI), and missForest. The results indicated that PI and missForest outperformed other methods with respect to bias of average treatment effect regardless of sample size and missing mechanisms. A demonstration of these five methods with PSA to evaluate the effect of participation in center-based care on children's reading ability is provided using data from the Early Childhood Longitudinal Study, Kindergarten Class of 2010-2011. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Prediction of hospital-acquired influenza using machine learning algorithms: a comparative study.

BACKGROUND: Hospital-acquired influenza (HAI) is under-recognized despite its high morbidity and poor health outcomes. The early detection of HAI is crucial for curbing its transmission in hospital settings. AIM: This study aimed to investigate factors related to HAI, develop predictive models, and subsequently compare them to identify the best performing machine learning algorithm for predicting the occurrence of HAI. METHODS: This retrospective observational study was conducted in 2022 and included 111 HAI and 73,748 non-HAI patients from the 2011-2012 and 2019-2020 influenza seasons. General characteristics, comorbidities, vital signs, laboratory and chest X-ray results, and room information within the electronic medical record were analysed. Logistic Regression (LR), Random Forest (RF), Extreme Gradient Boosting (XGB), and Artificial Neural Network (ANN) techniques were used to construct the predictive models. Employing randomized allocation, 80% of the dataset constituted the training set, and the remaining 20% comprised the test set. The performance of the developed models was assessed using metrics such as the area under the receiver operating characteristic curve (AUC), the count of false negatives (FN), and the determination of feature importance. RESULTS: Patients with HAI demonstrated notable differences in general characteristics, comorbidities, vital signs, laboratory findings, chest X-ray result, and room status compared to non-HAI patients. Among the developed models, the RF model demonstrated the best performance taking into account both the AUC (83.3%) and the occurrence of FN (four). The most influential factors for prediction were staying in double rooms, followed by vital signs and laboratory results. CONCLUSION: This study revealed the characteristics of patients with HAI and emphasized the role of ventilation in reducing influenza incidence. These findings can aid hospitals in devising infection prevention strategies, and the application of machine learning-based predictive models especially RF can enable early intervention to mitigate the spread of influenza in healthcare settings.

Outcomes of non-vitamin K oral anticoagulants for secondary prevention in ischemic stroke with atrial fibrillation.

Previous studies have rarely investigated the role of non-vitamin K oral anticoagulants (NOAC) and warfarin in the secondary prevention of ischemic stroke patients with nonvalvular atrial fibrillation (NVAF). In this study, we compared the effectiveness and safety of NOAC and warfarin for secondary prevention in Korean ischemic stroke patients with NVAF. Based on the Korean National Health Insurance Service Database, this study included 21,064 oral anticoagulants-naïve acute ischemic stroke patients with NVAF between July 2015 and June 2019. The main study outcomes included ischemic stroke, systemic embolism, major bleeding, and death. During the observational periods, NOAC users had a significantly decreased risk of ischemic stroke + systemic embolism (adjusted hazard ratio [aHR] 0.86; 95% confidence interval [CI] 0.78-0.95), ischemic stroke (aHR 0.89; 95% CI 0.81-0.99), major bleeding (aHR 0.78; 95% CI 0.68-0.89), and all-cause death (aHR 0.87; 95% CI 0.81-0.93). Standard-dose NOAC users had a lower risk of ischemic stroke, systemic embolism, and major bleeding events than warfarin users. In contrast, low-dose NOAC users did not differ in risk from warfarin users for all outcomes. In conclusion, NOACs were associated with a lower risk of secondary thromboembolic events and bleeding complications in Korean ischemic stroke patients with NVAF than warfarin.

SHP2 regulates GluA2 tyrosine phosphorylation required for AMPA receptor endocytosis and mGluR-LTD.

Posttranslational modifications regulate the properties and abundance of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors that mediate fast excitatory synaptic transmission and synaptic plasticity in the central nervous system. During long-term depression (LTD), protein tyrosine phosphatases (PTPs) dephosphorylate tyrosine residues in the C-terminal tail of AMPA receptor GluA2 subunit, which is essential for GluA2 endocytosis and group I metabotropic glutamate receptor (mGluR)-dependent LTD. However, as a selective downstream effector of mGluRs, the mGluR-dependent PTP responsible for GluA2 tyrosine dephosphorylation remains elusive at Schaffer collateral (SC)-CA1 synapses. In the present study, we find that mGluR5 stimulation activates Src homology 2 (SH2) domain-containing phosphatase 2 (SHP2) by increasing phospho-Y542 levels in SHP2. Under steady-state conditions, SHP2 plays a protective role in stabilizing phospho-Y869 of GluA2 by directly interacting with GluA2 phosphorylated at Y869, without affecting GluA2 phospho-Y876 levels. Upon mGluR5 stimulation, SHP2 dephosphorylates GluA2 at Y869 and Y876, resulting in GluA2 endocytosis and mGluR-LTD. Our results establish SHP2 as a downstream effector of mGluR5 and indicate a dual action of SHP2 in regulating GluA2 tyrosine phosphorylation and function. Given the implications of mGluR5 and SHP2 in synaptic pathophysiology, we propose SHP2 as a promising therapeutic target for neurodevelopmental and autism spectrum disorders.

Changes in dementia treatment patterns associated with changes in the National Policy in South Korea among patients with newly diagnosed Alzheimer's disease between 2011 and 2017: results from the multicenter, retrospective CAPTAIN study.

BACKGROUND: The South Korean government has been actively involved in plans to combat dementia, implementing a series of national strategies and plans since 2008. In July 2014, eligibility for mandatory long-term care insurance (LTCI) was extended to people with dementia enabling access to appropriate long-term care including the cognitive function training program and home nursing service. This study aimed to investigate changes in treatment patterns for Alzheimer's disease (AD) between July 2011 and June 2017 which spanned the 2014 revision. METHODS: This multicenter, retrospective, observational study of patients with newly diagnosed AD analyzed electronic medical records from 17 general hospitals across South Korea. Based on their time of AD diagnosis, subjects were categorized into Cohort 1 (1 July 2011 to 30 June 2014) and Cohort 2 (1 July 2014 to 30 June 2017). RESULTS: Subjects (N=3,997) divided into Cohorts 1 (n=1,998) and 2 (n=1,999), were mostly female (66.4%) with a mean age of 84.4 years. Cohort 1 subjects were significantly older (P<0.0001) and had a lower number of comorbidities (P=0.002) compared with Cohort 2. Mean Mini-Mental State Examination (MMSE) scores in Cohorts 1 and 2 at the time of AD diagnosis or start of initial treatment were 16.9 and 17.1, respectively (P=0.2790). At 1 year, mean MMSE scores in Cohorts 1 and 2 increased to 17.9 and 17.4, respectively (P=0.1524). Donepezil was the most frequently administered medication overall (75.0%), with comparable rates between cohorts. Rates of medication persistence were ≥98% for acetylcholinesterase inhibitor or memantine therapy. Discontinuation and switch treatment rates were significantly lower (49.7% vs. 58.0%; P<0.0001), and mean duration of initial treatment significantly longer, in Cohort 2 vs. 1 (349.3 vs. 300.2 days; P<0.0001). CONCLUSIONS: Comparison of cohorts before and after revision of the national LTCI system for dementia patients found no significant difference in mean MMSE scores at the time of AD diagnosis or start of initial treatment. The reduction in the proportion of patients who discontinued or changed their initial treatment, and the significant increase in mean duration of treatment, were observed following revision of the LTCI policy which enabled increased patient access to long-term care.

Heat conduction in live tissue during radiofrequency electrosurgery.

In this paper, we propose a method to model radiofrequency electrosurgery to capture the phenomena at higher temperatures and present the methods for parameter estimation. Experimental data taken from our surgical trials performed on in vivo porcine liver show that a non-Fourier Maxwell-Cattaneo-type model can be suitable for this application when used in combination with an Arrhenius-type model that approximates the energy dissipation in physical and chemical reactions. The resulting model structure has the advantage of higher accuracy than existing ones, while reducing the computation time required.

Intrinsic plasticity of Purkinje cell serves homeostatic regulation of fear memory.

Two forms of plasticity, synaptic and intrinsic, are neural substrates for learning and memory. Abnormalities in homeostatic plasticity cause severe neuropsychiatric diseases, such as schizophrenia and autism. This suggests that the balance between synaptic transmission and intrinsic excitability is important for physiological function in the brain. Despite the established role of synaptic plasticity between parallel fiber (PF) and Purkinje cell (PC) in fear memory, its relationship with intrinsic plasticity is not well understood. Here, patch clamp recording revealed depression of intrinsic excitability in PC following auditory fear conditioning (AFC). Depressed excitability balanced long-term potentiation of PF-PC synapse to serve homeostatic regulation of PF-evoked PC firing. We then optogenetically manipulated PC excitability during the early consolidation period resulting in bidirectional regulation of fear memory. Fear conditioning-induced synaptic plasticity was also regulated following optogenetic manipulation. These results propose intrinsic plasticity in PC as a novel mechanism of fear memory and elucidate that decreased intrinsic excitability in PC counterbalances PF-PC synaptic potentiation to maintain fear memory in a normal range.

Homogeneity- and Stoichiometry-Induced Electrical and Optical Properties of Cu-Se Thin Films by RF Sputtering Power.

P-type Cu-Se thin films were deposited on glass substrates at room temperature using radio frequency magnetron sputtering by a single multi-component CuSe2 target. When using a multi-component target, the impact of the sputtering power on the homogeneity and stoichiometry within the thin films should be investigated in the depth direction to demonstrate a secondary effect on the electrical and optical properties of the thin films. Systematic characterization of the Cu-Se thin films, including the morphology, microstructure, chemical composition, and depth-directional chemical bonding state and defect structure of the thin films, revealed that the sputtering power played an important role in the homogeneity and stoichiometry of the thin films. At very low and very high sputtering power levels, the Cu-Se thin films exhibited more deviations from stoichiometry, while an optimized sputtering power resulted in more homogenous thin films with improved stoichiometry across the entire thin film thickness in the X-ray photoelectron spectroscopy depth profile, despite showing Se deficiency at all depths. A rapid decrease in carrier concentration, indicating a reduction in the net effect of total defects, was obtained at the optimized sputtering power with less deviation from stoichiometry in the Cu-Se thin films and the closest stoichiometric ratio at an intermediate depth.

Self-Aggregating Tau Fragments Recapitulate Pathologic Phenotypes and Neurotoxicity of Alzheimer's Disease in Mice.

In tauopathy conditions, such as Alzheimer's disease (AD), highly soluble and natively unfolded tau polymerizes into an insoluble filament; however, the mechanistic details of this process remain unclear. In the brains of AD patients, only a minor segment of tau forms ß-helix-stacked protofilaments, while its flanking regions form disordered fuzzy coats. Here, it is demonstrated that the tau AD nucleation core (tau-AC) sufficiently induced self-aggregation and recruited full-length tau to filaments. Unexpectedly, phospho-mimetic forms of tau-AC (at Ser324 or Ser356) show markedly reduced oligomerization and seeding propensities. Biophysical analysis reveal that the N-terminus of tau-AC facilitates the fibrillization kinetics as a nucleation motif, which becomes sterically shielded through phosphorylation-induced conformational changes in tau-AC. Tau-AC oligomers are efficiently internalized into cells via endocytosis and induced endogenous tau aggregation. In primary hippocampal neurons, tau-AC impaired axon initial segment plasticity upon chronic depolarization and is mislocalized to the somatodendritic compartments. Furthermore, it is observed significantly impaired memory retrieval in mice intrahippocampally injected with tau-AC fibrils, which corresponds to the neuropathological staining and neuronal loss in the brain. These findings identify tau-AC species as a key neuropathological driver in AD, suggesting novel strategies for therapeutic intervention.

Dysregulation of the Wnt/ß-catenin signaling pathway via Rnf146 upregulation in a VPA-induced mouse model of autism spectrum disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with impaired social behavior and communication, repetitive behaviors, and restricted interests. In addition to genetic factors, environmental factors such as prenatal drug exposure contribute to the development of ASD. However, how those prenatal factors induce behavioral deficits in the adult stage is not clear. To elucidate ASD pathogenesis at the molecular level, we performed a high-resolution mass spectrometry-based quantitative proteomic analysis on the prefrontal cortex (PFC) of mice exposed to valproic acid (VPA) in utero, a widely used animal model of ASD. Differentially expressed proteins (DEPs) in VPA-exposed mice showed significant overlap with ASD risk genes, including differentially expressed genes from the postmortem cortex of ASD patients. Functional annotations of the DEPs revealed significant enrichment in the Wnt/ß-catenin signaling pathway, which is dysregulated by the upregulation of Rnf146 in VPA-exposed mice. Consistently, overexpressing Rnf146 in the PFC impaired social behaviors and altered the Wnt signaling pathway in adult mice. Furthermore, Rnf146-overexpressing PFC neurons showed increased excitatory synaptic transmission, which may underlie impaired social behavior. These results demonstrate that Rnf146 is critical for social behavior and that dysregulation of Rnf146 underlies social deficits in VPA-exposed mice.

Effects of 20-hydroxyecdysone on UVB-induced photoaging in hairless mice.

We recently reported that exposure of skin to ultraviolet B (UVB) irradiation for 2 weeks induces stress and accelerates skin aging. Interestingly, aldosterone synthase is known to be crucial in generating UVB-induced stress-related responses, suggesting that drugs that regulate its activity can be used as skin antiaging agents. Through extensive drug screening, we have identified 20-hydroxyecdysone (20E), a steroidal prohormone secreted by the prothoracic glands of insects, as a potent inhibitor of UVB-induced aging. Although 20E has been shown to exert antistress and anti-collagenase effects in vitro, its effects in vivo remain unexplored. Furthermore, the pharmacological and physiological effects of 20E on UVB-mediated photoaging are poorly understood. Therefore, in this study, we investigated the effects of 20E on aldosterone synthase and UVB-induced photoaging and skin lesions in hairless mice, focusing on the stress-related hypothalamic-pituitary-adrenal axis. We confirmed that 20E inhibited aldosterone synthase and reduced corticosterone levels. When applied to a UV-induced skin aging animal model, it ameliorated UV-induced stress and protected against the decrease in collagen levels. Importantly, when the aldosterone synthase inhibitor osilodrostat, an FDA-approved drug, was applied to the UV-induced skin aging model, the stress-reducing and antiaging effects of 20E were not observed. Thus, we conclude that 20E inhibits UVB-induced skin aging by blocking aldosterone synthase and is a potential candidate to prevent skin aging.

Clinical significance of D-dimer levels during acute period in ischemic stroke.

BACKGROUND: Initial D-dimer level is a well-known prognostic parameter in patients with acute ischemic stroke (AIS). However, there have been no studies on the clinical significance of follow-up D-dimer levels. In this study, we evaluated the association between initial and follow-up D-dimer levels and early neurological deterioration (END) in patients with AIS. METHODS: We included consecutive patients with AIS who had a positive initial D-dimer test (> 0.55 mg/L) between March 2021 and November 2022. The follow-up D-dimer test was performed on the 7th day after hospitalization and on the day of discharge if discharged earlier. END was defined as an increase of ≥ 2 in the total NIHSS score, or ≥ 1 in the motor NIHSS score within the first 7 days of admission. As medical conditions closely associated with the initial and follow-up D-dimer levels in AIS patients, we also evaluated the history of cancer, active cancer, and venous thromboembolism (VTE) that occurred during hospitalization together. RESULTS: A total of 246 patients with AIS were evaluated (median age: 87 years, male: 56.5%). In multivariable logistic regression analysis, the initial D-dimer level was closely associated with END after adjusting for confounders (adjusted odds ratio [aOR]: 1.48, 95% CI: 1.06-2.05). The follow-up D-dimer level also showed a close correlation with END (aOR: 1.60, 95% CI: 1.16-2.20). Regarding the analysis of the association between D-dimer levels and underlying cancer or VTE, the initial D-dimer level showed a statistically significant positive relationship only with active cancer (P = 0.024). On the other hand, the follow-up D-dimer level was found to be statistically significantly associated with a history of cancer (P = 0.024), active cancer (P = 0.001), and VTE (P = 0.001). CONCLUSIONS: Initial and follow-up D-dimer levels were associated with END in AIS patients. Particularly, the follow-up D-dimer level showed a clear correlation not only with END but also with the underlying cancer or the occurrence of VTE during the acute period.

Effectiveness and safety of secondary prevention of non-vitamin K oral anticoagulants use by drug type in Asian patients.

BACKGROUND: Although widely used in clinical fields, real-world data on the role of warfarin and non-vitamin K oral anticoagulants (NOACs) for the secondary prevention of thromboembolic complications in ischemic stroke patients with nonvalvular atrial fibrillation (NVAF) are scarce. AIMS: This retrospective cohort study compared the effectiveness and safety of secondary prevention of NOAC and warfarin in ischemic stroke patients with NVAF. METHODS: From the Korean National Health Insurance Service Database, we included 16,762 oral anticoagulants-naive acute ischemic stroke patients with NVAF between July 2016 and June 2019. The main outcomes included ischemic stroke, systemic embolism, major bleeding, and all-cause of death. RESULTS: In total, 1717 warfarin and 15,025 NOAC users were included in the analysis. After 1:8 propensity score matching, during the observation period, all types of NOACs had a significantly lower risk of ischemic stroke and systemic embolism than warfarin (edoxaban: adjusted hazard ratio [aHR], 0.80; 95% confidence interval [CI], 0.68-0.93, rivaroxaban: aHR, 0.82; 95% CI, 0.70-0.96, apixaban: aHR, 0.79; 95% CI, 0.69-0.91, and dabigatran: aHR, 0.82; 95% CI, 0.69-0.97). Edoxaban (aHR, 0.77; 95% CI, 0.62-0.96), apixaban (aHR, 0.73; 95% CI, 0.60-0.90), and dabigatran (aHR, 0.66; 95% CI, 0.51-0.86) had lower risks of major bleeding and all-cause of death. CONCLUSIONS: All NOACs were more effective than warfarin in the secondary prevention of thromboembolic complications in ischemic stroke patients with NVAF. Except for rivaroxaban, most NOACs demonstrated a lower risk of major bleeding and all-cause of death than warfarin.

Fundamental Properties and Clinical Application of 3D-Printed Bioglass Porcelain Fused to Metal Dental Restoration.

The purpose of this study is to evaluate the mechanical properties and clinical fitness of 3D-printed bioglass porcelain fused to metal (PFM) dental crowns. To evaluate the mechanical properties, tensile strength, Vickers microhardness, shear bond strength, and surface roughness tests of the SLM printed Co-Cr alloy was conducted. A right mandibular 1st molar tooth was prepared for a single dental crown (n = 10). For a three-unit metal crown and bridge, the right mandibular first premolar and first molar were prepared. Bioglass porcelain was fired to fabricate PFM dental restorations. A clinical gap was observed and measured during each of the four times porcelain was fired. A statistical analysis was conducted. The SLM technique showed the largest statistically significant tensile strength and a 0.2% yield strength value. The milling technique had the lowest statistically significant compressive strength value. The shear bond strength and surface roughness showed no statistically significant difference between the fabricated method. There was a statistically significant change in marginal discrepancy according to the porcelain firing step. The casting technique showed the greatest statistically significant margin discrepancy value. The SLM method showed better fitness than the traditional casting method and showed better mechanical properties as a dental material.

Minimally Invasive Live Tissue High-Fidelity Thermophysical Modeling Using Real-Time Thermography.

We present a novel thermodynamic parameter estimation framework for energy-based surgery on live tissue, with direct applications to tissue characterization during electrosurgery. This framework addresses the problem of estimating tissue-specific thermodynamics in real-time, which would enable accurate prediction of thermal damage impact to the tissue and damage-conscious planning of electrosurgical procedures. Our approach provides basic thermodynamic information such as thermal diffusivity, and also allows for obtaining the thermal relaxation time and a model of the heat source, yielding in real-time a controlled hyperbolic thermodynamics model. The latter accounts for the finite thermal propagation time necessary for modeling of the electrosurgical action, in which the probe motion speed often surpasses the speed of thermal propagation in the tissue operated on. Our approach relies solely on thermographer feedback and a knowledge of the power level and position of the electrosurgical pencil, imposing only very minor adjustments to normal electrosurgery to obtain a high-fidelity model of the tissue-probe interaction. Our method is minimally invasive and can be performed in situ. We apply our method first to simulated data based on porcine muscle tissue to verify its accuracy and then to in vivo liver tissue, and compare the results with those from the literature. This comparison shows that parameterizing the Maxwell-Cattaneo model through the framework proposed yields a noticeably higher fidelity real-time adaptable representation of the thermodynamic tissue response to the electrosurgical impact than currently available. A discussion on the differences between the live and the dead tissue thermodynamics is also provided.

Cerebellar nuclei neurons projecting to the lateral parabrachial nucleus modulate classical fear conditioning.

Multiple brain regions are engaged in classical fear conditioning. Despite evidence for cerebellar involvement in fear conditioning, the mechanisms by which cerebellar outputs modulate fear learning and memory remain unclear. We identify a population of deep cerebellar nucleus (DCN) neurons with monosynaptic glutamatergic projections to the lateral parabrachial nucleus (lPBN) (DCN→lPBN neurons) in mice. While optogenetic suppression of DCN→lPBN neurons impairs auditory fear memory, activation of DCN→lPBN neurons elicits freezing behavior only after auditory fear conditioning. Moreover, auditory fear conditioning potentiates DCN-lPBN synapses, and subsequently, auditory cue activates lPBN neurons after fear conditioning. Furthermore, DCN→lPBN neuron activation can replace the auditory cue but not footshock in fear conditioning. These findings demonstrate that cerebellar nuclei modulate auditory fear conditioning via transmitting conditioned stimuli signals to the lPBN. Collectively, our findings suggest that the DCN-lPBN circuit is a part of neuronal substrates within interconnected brain regions underscoring auditory fear memory.