Utilizing stem cell-secreted molecules as a versatile toolbox for skin regenerative medicine.

Stem cells are recognized as an important target and tool in regenerative engineering. In this study, we explored the feasibility of engineering amniotic fluid-derived mesenchymal stem cell-secreted molecules (afMSC-SMs) as a versatile bioactive material for skin regenerative medicine applications in a time- and cost-efficient and straightforward manner. afMSC-SMs, obtained in powder form through ethanol precipitation, effectively contributed to preserving the self-renewal capacity and differentiation potential of primary human keratinocytes (pKCs) in a xeno-free environment, offering a potential alternative to traditional culture methods for their long-term in vitro expansion, and allowed them to reconstitute a fully stratified epithelium sheet on human dermal fibroblasts. Furthermore, we demonstrated the flexibility of afMSC-SMs in wound healing and hair regrowth through injectable hydrogel and nanogel-mediated transdermal delivery systems, respectively, expanding the pool of regenerative applications. This cell-free approach may offer several potential advantages, including streamlined manufacturing processes, scalability, controlled formulation, longer shelf lives, and mitigation of risks associated with living cell transplantation. Accordingly, afMSC-SMs could serve as a promising therapeutic toolbox for advancing cell-free regenerative medicine, simplifying their broad applicability in various clinical settings.

Automated sleep classification with chronic neural implants in freely behaving canines.

Objective.Long-term intracranial electroencephalography (iEEG) in freely behaving animals provides valuable electrophysiological information and when correlated with animal behavior is useful for investigating brain function.Approach.Here we develop and validate an automated iEEG-based sleep-wake classifier for canines using expert sleep labels derived from simultaneous video, accelerometry, scalp electroencephalography (EEG) and iEEG monitoring. The video, scalp EEG, and accelerometry recordings were manually scored by a board-certified sleep expert into sleep-wake state categories: awake, rapid-eye-movement (REM) sleep, and three non-REM sleep categories (NREM1, 2, 3). The expert labels were used to train, validate, and test a fully automated iEEG sleep-wake classifier in freely behaving canines.Main results. The iEEG-based classifier achieved an overall classification accuracy of 0.878 ± 0.055 and a Cohen's Kappa score of 0.786 ± 0.090. Subsequently, we used the automated iEEG-based classifier to investigate sleep over multiple weeks in freely behaving canines. The results show that the dogs spend a significant amount of the day sleeping, but the characteristics of daytime nap sleep differ from night-time sleep in three key characteristics: during the day, there are fewer NREM sleep cycles (10.81 ± 2.34 cycles per day vs. 22.39 ± 3.88 cycles per night;p< 0.001), shorter NREM cycle durations (13.83 ± 8.50 min per day vs. 15.09 ± 8.55 min per night;p< 0.001), and dogs spend a greater proportion of sleep time in NREM sleep and less time in REM sleep compared to night-time sleep (NREM 0.88 ± 0.09, REM 0.12 ± 0.09 per day vs. NREM 0.80 ± 0.08, REM 0.20 ± 0.08 per night;p< 0.001).Significance.These results support the feasibility and accuracy of automated iEEG sleep-wake classifiers for canine behavior investigations.

Treatment Protocol on Using Microfocused Ultrasound with Visualization for Skin Quality Improvement: The Korean Experience.

Facial skin quality profoundly influences an individual's perceived appearance and is an important aspect of facial rejuvenation. Facial pore enlargement is one of the most common concerns among Asian individuals that adversely impacts perceived skin surface evenness and affects overall skin quality. One of the major causes of enlarged pores is facial skin laxity. Microfocused ultrasound with visualization (MFU-V; Ultherapy; Merz North America, Inc., Raleigh, N.C.) is indicated for lifting and tightening of the face and neck, and improving the appearance of wrinkles on the décolletage. In addition, it is useful for addressing several aspects of facial rejuvenation, including facial pores, skin laxity, skin unevenness, etc., but there is limited literature on these applications. Thus, we present our proposed MFU-V treatment protocol for achieving a harmonious outcome for attractive skin, along with practical strategies for its application, illustrated in patients presenting with enlarged pores as their main concern. Drawing on our collective experience in using MFU-V for facial rejuvenation and the recently published skin quality framework that advocates addressing interrelated attributes of skin quality for optimal outcomes, we developed a treatment protocol for improving skin quality using MFU-V. This MFU-V treatment protocol reliably improves overall skin quality in patients presenting with enlarged pores, through MFU-V's effects on skin lifting and tightening, and consequent improvement in facial pores and skin texture. This treatment protocol can be readily used as part of a multimodal layering approach to yield successful outcomes in patients with various facial skin concerns.

Development of an integrated microperfusion-EEG electrode for unbiased multimodal sampling of brain interstitial fluid and concurrent neural activity.

Objective. To modify off-the-shelf components to build a device for collecting electroencephalography (EEG) from macroelectrodes surrounded by large fluid access ports sampled by an integrated microperfusion system in order to establish a method for sampling brain interstitial fluid (ISF) at the site of stimulation or seizure activity with no bias for molecular size.Approach. Twenty-four 560µm diameter holes were ablated through the sheath surrounding one platinum-iridium macroelectrode of a standard Spencer depth electrode using a femtosecond UV laser. A syringe pump was converted to push-pull configuration and connected to the fluidics catheter of a commercially available microdialysis system. The fluidics were inserted into the lumen of the modified Spencer electrode with the microdialysis membrane removed, converting the system to open flow microperfusion. Electrical performance and analyte recovery were measured and parameters were systematically altered to improve performance. An optimized device was tested in the pig brain and unbiased quantitative mass spectrometry was used to characterize the perfusate collected from the peri-electrode brain in response to stimulation.Main results. Optimized parameters resulted in >70% recovery of 70 kDa dextran from a tissue analog. The optimized device was implanted in the cortex of a pig and perfusate was collected during four 60 min epochs. Following a baseline epoch, the macroelectrode surrounded by microperfusion ports was stimulated at 2 Hz (0.7 mA, 200µs pulse width). Following a post-stimulation epoch, the cortex near the electrode was stimulated with benzylpenicillin to induce epileptiform activity. Proteomic analysis of the perfusates revealed a unique inflammatory signature induced by electrical stimulation. This signature was not detected in bulk tissue ISF.Significance. A modified dual-sensing electrode that permits coincident detection of EEG and ISF at the site of epileptiform neural activity may reveal novel pathogenic mechanisms and therapeutic targets that are otherwise undetectable at the bulk tissue level.

Physicochemical Properties of Yanggaeng with Added Tempeh Powder.

In this study, we investigated the physicochemical and antioxidative properties of the traditional Korean confectionery, Yanggaeng, when various amounts of tempeh powder (TP) were added. We replaced a portion of the white bean paste in Yanggaeng with TP at percentages of 0% (CON), 2% (TP2), 4% (TP4), and 6% (TP6) by total weight. The proximate composition results showed that TP6 exhibited the highest crude ash and crude protein contents, but its moisture content and carbohydrate content were the lowest compared to the CON. Tempeh addition altered the colorimetric properties by increasing the L* value, b* value, and browning index; however, tempeh addition did not alter the a* value. The results also showed that tempeh addition gradually decreased the pH of Yanggaeng. The Brix value was the highest in TP2; in TP4 and TP6, the Brix value gradually decreased, and these formulations exhibited lower Brix values than the CON. Furthermore, tempeh addition gradually induced antioxidative capacities, as evidenced by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activities. The results of this study demonstrate that the addition of tempeh to Yanggaeng alters its physicochemical properties and antioxidative capacity.

Distributed brain co-processor for tracking spikes, seizures and behaviour during electrical brain stimulation.

Early implantable epilepsy therapy devices provided open-loop electrical stimulation without brain sensing, computing, or an interface for synchronized behavioural inputs from patients. Recent epilepsy stimulation devices provide brain sensing but have not yet developed analytics for accurately tracking and quantifying behaviour and seizures. Here we describe a distributed brain co-processor providing an intuitive bi-directional interface between patient, implanted neural stimulation and sensing device, and local and distributed computing resources. Automated analysis of continuous streaming electrophysiology is synchronized with patient reports using a handheld device and integrated with distributed cloud computing resources for quantifying seizures, interictal epileptiform spikes and patient symptoms during therapeutic electrical brain stimulation. The classification algorithms for interictal epileptiform spikes and seizures were developed and parameterized using long-term ambulatory data from nine humans and eight canines with epilepsy, and then implemented prospectively in out-of-sample testing in two pet canines and four humans with drug-resistant epilepsy living in their natural environments. Accurate seizure diaries are needed as the primary clinical outcome measure of epilepsy therapy and to guide brain-stimulation optimization. The brain co-processor system described here enables tracking interictal epileptiform spikes, seizures and correlation with patient behavioural reports. In the future, correlation of spikes and seizures with behaviour will allow more detailed investigation of the clinical impact of spikes and seizures on patients.

Bacterially Converted Oat Active Ingredients Enhances Antioxidative and Anti-UVB Photoaging Activities.

Oat (Avena sativa L.) is one of the most widely consumed cereal grains worldwide and is considered as an important cereal crop with high nutritional value and potential health benefits. With different bacterial strains, fermented oat extracts were examined for the antioxidant and antiaging effects on the skin after optimization of extraction conditions. Fermented oats contained high avenanthramides, and its function was investigated on matrix metalloproteinase-1 and collagen expression with human dermal fibroblast cells. After fractionation, butanol layers showed the highest avenanthramides contents. Therefore, the microbial fermentation of oats enhances the quality and content of functional ingredients of oats, which provide natural dietary supplements, antioxidants, and antiaging agents.

Lowering n-6/n-3 Ratio as an Important Dietary Intervention to Prevent LPS-Inducible Dyslipidemia and Hepatic Abnormalities in ob/ob Mice.

Obesity is closely associated with low-grade chronic and systemic inflammation and dyslipidemia, and the consumption of omega-3 polyunsaturated fatty acids (n-3 PUFAs) may modulate obesity-related disorders, such as inflammation and dyslipidemia. An emerging research question is to understand the dietary intervention strategy that is more important regarding n-3 PUFA consumption: (1) a lower ratio of n-6/n-3 PUFAs or (2) a higher amount of n-3 PUFAs consumption. To understand the desirable dietary intervention method of n-3 PUFAs consumption, we replaced lard from the experimental diets with either perilla oil (PO) or corn oil (CO) to have identical n-3 amounts in the experimental diets. PO had a lower n-6/n-3 ratio, whereas CO contained higher amounts of PUFAs; it inherently contained relatively lower n-3 but higher n-6 PUFAs than PO. After the 12-week dietary intervention in ob/ob mice, dyslipidemia was observed in the normal chow and CO-fed ob/ob mice; however, PO feeding increased the high density lipoprotein-cholesterol (HDL-C) level; further, not only did the HDL-C level increase, the low density lipoprotein-cholesterol (LDL-C) and triglyceride (TG) levels also decreased significantly after lipopolysaccharide (LPS) injection. Consequently, extra TG accumulated in the liver and white adipose tissue (WAT) of normal chow- or CO-fed ob/ob mice after LPS injection; however, PO consumption decreased serum TG accumulation in the liver and WAT. PUFAs replacement attenuated systemic inflammation induced by LPS injection by increasing anti-inflammatory cytokines but inhibiting pro-inflammatory cytokine production in the serum and WAT. PO further decreased hepatic inflammation and fibrosis in comparison with the ND and CO. Hepatic functional biomarkers (aspartate aminotransferase (AST) and alanine transaminase (ALT) levels) were also remarkably decreased in the PO group. In LPS-challenged ob/ob mice, PO and CO decreased adipocyte size and adipokine secretion, with a reduction in phosphorylation of MAPKs compared to the ND group. In addition, LPS-inducible endoplasmic reticulum (ER) and oxidative stress decreased with consumption of PUFAs. Taken together, PUFAs from PO and CO play a role in regulating obesity-related disorders. Moreover, PO, which possesses a lower ratio of n-6/n-3 PUFAs, remarkably alleviated metabolic dysfunction in LPS-induced ob/ob mice. Therefore, an interventional trial considering the ratio of n-6/n-3 PUFAs may be desirable for modulating metabolic complications, such as inflammatory responses and ER stress in the circulation, liver, and/or WAT.

Toward a fully implantable ecosystem for adaptive neuromodulation in humans: Preliminary experience with the CorTec BrainInterchange device in a canine model.

This article describes initial work toward an ecosystem for adaptive neuromodulation in humans by documenting the experience of implanting CorTec's BrainInterchange (BIC) device in a beagle canine and using the BCI2000 environment to interact with the BIC device. It begins with laying out the substantial opportunity presented by a useful, easy-to-use, and widely available hardware/software ecosystem in the current landscape of the field of adaptive neuromodulation, and then describes experience with implantation, software integration, and post-surgical validation of recording of brain signals and implant parameters. Initial experience suggests that the hardware capabilities of the BIC device are fully supported by BCI2000, and that the BIC/BCI2000 device can record and process brain signals during free behavior. With further development and validation, the BIC/BCI2000 ecosystem could become an important tool for research into new adaptive neuromodulation protocols in humans.

Thalamic deep brain stimulation modulates cycles of seizure risk in epilepsy.

Chronic brain recordings suggest that seizure risk is not uniform, but rather varies systematically relative to daily (circadian) and multiday (multidien) cycles. Here, one human and seven dogs with naturally occurring epilepsy had continuous intracranial EEG (median 298 days) using novel implantable sensing and stimulation devices. Two pet dogs and the human subject received concurrent thalamic deep brain stimulation (DBS) over multiple months. All subjects had circadian and multiday cycles in the rate of interictal epileptiform spikes (IES). There was seizure phase locking to circadian and multiday IES cycles in five and seven out of eight subjects, respectively. Thalamic DBS modified circadian (all 3 subjects) and multiday (analysis limited to the human participant) IES cycles. DBS modified seizure clustering and circadian phase locking in the human subject. Multiscale cycles in brain excitability and seizure risk are features of human and canine epilepsy and are modifiable by thalamic DBS.

Generation of Induced Nephron Progenitor-like Cells from Human Urine-Derived Cells.

BACKGROUND: Regenerative medicine strategies employing nephron progenitor cells (NPCs) are a viable approach that is worthy of substantial consideration as a promising cell source for kidney diseases. However, the generation of induced nephron progenitor-like cells (iNPCs) from human somatic cells remains a major challenge. Here, we describe a novel method for generating NPCs from human urine-derived cells (UCs) that can undergo long-term expansion in a serum-free condition. RESULTS: Here, we generated iNPCs from human urine-derived cells by forced expression of the transcription factors OCT4, SOX2, KLF4, c-MYC, and SLUG, followed by exposure to a cocktail of defined small molecules. These iNPCs resembled human embryonic stem cell-derived NPCs in terms of their morphology, biological characteristics, differentiation potential, and global gene expression and underwent a long-term expansion in serum-free conditions. CONCLUSION: This study demonstrates that human iNPCs can be readily generated and expanded, which will facilitate their broad applicability in a rapid, efficient, and patient-specific manner, particularly holding the potential as a transplantable cell source for patients with kidney disease.

Physicochemical characteristics of Ethiopian Coffea arabica cv. Heirloom coffee extracts with various roasting conditions.

This study aimed to investigate the physicochemical characteristics of Ethiopian Coffea arabica cv. Heirloom coffee extracts with various roasting conditions. Green coffee beans were roasted at four different conditions (Light-medium, Medium, Moderately dark, and Very dark) and used to extract espresso and drip coffee. Moisture content in coffee beans was decreased as the roasting degree increased. The contents of crude fat and ash were lower in the Light-medium roasted coffee beans than in green coffee beans but increased as the roasting degree increased. The values of lightness (L*), redness (a*), yellowness (b*), and browning index of coffee extracts were decreased as the roasting degree increased. Total dissolved solids in espresso coffee were increased with increasing roasting degree but decreased in drip coffee. In both the extracts, the contents of reducing sugar, titratable acidity, organic acids, and chlorogenic acid were decreased, but that of caffeine was increased with the roasting degree increased. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-020-00865-w.

An Exploratory Study of the Relationships Between Diesel Engine Exhaust Particle Inhalation, Pulmonary Inflammation and Anxious Behavior.

Recent technical developments brought negative side effects such as air pollution and large-scale fires, increasingly exposing people to diesel engine exhaust particles (DEP). Testing how DEP inhalation triggers pathophysiology in animal models could be useful in determining how it affects humans. To this end, the aim of this study was to investigate the effects of pulmonary exposure to DEP for seven consecutive days in experimental male C5BL6/N mice. Twenty-four C5BL6/N mice were treated with one of the three test materials: distilled water for control, a low DEP exposure (5 mg/kg), or a high DEP exposure (15 mg/kg). Exposure to DEP induced decreased body weight; however, it gradually increased pulmonary weight in a DEP-dose-dependent manner. DEP exposure significantly elevated soot accumulation in the lungs, with the alteration of pulmonary homeostasis. It also elevated infiltrated immune cells, thus significantly increasing inflammatory cytokine mRNA and protein production in the lungs and broncho-alveolar lavage fluid, respectively. Pulmonary DEP exposure also altered behavioral responses in the open field test (OFT). Low exposure elevated moving distance and speed, while significantly decreasing the number of trials to enter the central zone. Different concentrations of DEP resulted in different behavioral changes; however, while anxiety levels increased, their degree was independent of DEP concentrations. Results suggest that DEP exposure may possess pro-inflammatory responses in the lungs and trigger anxiety.

Semi-supervised Training Data Selection Improves Seizure Forecasting in Canines with Epilepsy.

OBJECTIVE: Conventional selection of pre-ictal EEG epochs for seizure prediction algorithm training data typically assumes a continuous pre-ictal brain state preceding a seizure. This is carried out by defining a fixed duration, pre-ictal time period before seizures from which pre-ictal training data epochs are uniformly sampled. However, stochastic physiological and pathological fluctuations in EEG data characteristics and underlying brain states suggest that pre-ictal state dynamics may be more complex, and selection of pre-ictal training data segments to reflect this could improve algorithm performance. METHODS: We propose a semi-supervised technique to select pre-ictal training data most distinguishable from interictal EEG according to pre-specified data characteristics. The proposed method uses hierarchical clustering to identify optimal pre-ictal data epochs. RESULTS: In this paper we compare the performance of a seizure forecasting algorithm with and without hierarchical clustering of pre-ictal periods in chronic iEEG recordings from six canines with naturally occurring epilepsy. Hierarchical clustering of training data improved results for Time In Warning (TIW) (0.18 vs. 0.23) and False Positive Rate (FPR) (0.5 vs. 0.59) when evaluated across all subjects (p<0.001, n=6). Results were mixed when evaluating TIW, FPR, and Sensitivity for individual dogs. CONCLUSION: Hierarchical clustering is a helpful method for training data selection overall, but should be evaluated on a subject-wise basis. SIGNIFICANCE: The clustering method can be used to optimize results of forecasting towards sensitivity or TIW or FPR, and therefore can be useful for epilepsy management.

Use of the National Early Warning Score for predicting in-hospital mortality in older adults admitted to the emergency department.

OBJECTIVE: The National Early Warning Score (NEWS), based on the patients' vital signs, detects clinical deterioration in critically ill patients and is used to reduce the incidence of in-hospital cardiac arrest. However, although mortality prediction based on vital signs may be difficult in older patients, the effectiveness of the NEWS has not yet been evaluated in this population. This study aimed to test the hypothesis that an elevated NEWS at admission increases the mortality risk in older patients admitted to the emergency department (ED). METHODS: We conducted a single-center retrospective study, including patients admitted to the ED between November 2016 and February 2017. We included patients aged >65 years who were admitted to the ED for any medical problem. The NEWS was calculated at the time of ED admission. The primary outcome was in-hospital mortality. RESULTS: In total, 3,169 patients were included in this study. Median age was 75 years (interquartile range [IQR], 70 to 80 years), and 1,557 (49.1%) patients were male. The in-hospital mortality rate was 5.1% (161 patients). Median NEWS was higher in non-survivors than in survivors (5 [IQR, 3-8] vs. 1 [IQR, 0-3], P<0.001). Multivariate logistic analysis showed that the NEWS was associated with in-hospital mortality, after adjusting for other confounders. The area under the curve of the NEWS for predicting in-hospital mortality was 0.820 (95% confidence interval, 0.806 to 0.833). CONCLUSION: Our results show that the NEWS at admission is associated with in-hospital mortality among patients aged >65 years.

Determining nicotine-related behavior changes in juvenile female rats through long-term maternal nicotine exposure.

Nicotine replacement therapy (NRT) has been developed as a drug therapy for smoking cessation and has been considered a safe alternative to smoking during pregnancy. However, the effects of long-term nicotine exposure via NRT on the fetus are still being debated. Here, we determined the effects of long-term maternal nicotine exposure in gestation and lactation on nicotine-related behavior and drug vulnerability in dams and offspring rats. To expose long-term nicotine, on gestation day 14, pregnant rats were implanted with osmotic minipumps releasing nicotine tartrate (6 mg/kg/day, subcutaneously, equivalent to 2 mg nicotine-freebase) for 28 days. The concentration of cotinine in blood was 373.0 ± 109.0 ng/ml in dams and 12.50 ± 1.19 ng/ml in offspring rats. In dams, we found no significant differences in anxiety-like behaviors and various maternal behaviors such as touching, sniffing, pup licking, laying on pups, and retrieval between saline- and nicotine-exposed groups. Adolescent offspring female rats showed no significant differences in anxiety-like behavior and forced alcohol consumption between saline- and nicotine-exposed groups. Nicotine-exposed offspring rats showed more increased nicotine aversion than saline-exposed groups, but the effect was disturbed in the forced alcohol consumption condition on the first day of the nicotine consumption test. Taken together, these results suggest that, in the last gestation and lactation period corresponding to the second and third trimester of human pregnancy, long-term maternal nicotine exposure has a minor effect on dam and female offspring health and does not involve serious pathological changes in rat offspring, despite the presence of nicotine in their blood.

Mapping BOLD Activation by Pharmacologically Evoked Tremor in Swine.

Harmaline-induced tremor is one of the most commonly utilized disease models for essential tremor (ET). However, the underlying neural networks involved in harmaline-induced tremor and the degree to which these are a representative model of the pathophysiologic mechanism of ET are incompletely understood. In this study, we evaluated the functional brain network effects induced by systemic injection of harmaline using pharmacological functional magnetic resonance imaging (ph-fMRI) in the swine model. With harmaline administration, we observed significant activation changes in cerebellum, thalamus, and inferior olivary nucleus (ION). In addition, inter-regional correlations in activity between cerebellum and deep cerebellar nuclei and between cerebellum and thalamus were significantly enhanced. These harmaline-induced effects gradually decreased with repeated administration of drug, replicating the previously demonstrated 'tolerance' effect. This study demonstrates that harmaline-induced tremor is associated with activity changes in brain regions previously implicated in humans with ET. Thus, harmaline-induction of tremor in the swine may be a useful model to explore the neurological effects of novel therapeutic agents and/or neuromodulation techniques for ET.

High frequency electrical stimulation promotes expression of extracellular matrix proteins from human astrocytes.

Therapeutic benefits of deep brain stimulation (DBS), a neurosurgical treatment for certain movement disorders and other neurologic conditions, are well documented, but DBS mechanisms remain largely unexplained. DBS is thought to modulate pathological neural activity. However, although astrocytes, the most numerous cell type in the brain, play a significant role in neurotransmission, chemical homeostasis and synaptic plasticity, their role in DBS has not been fully examined. To investigate astrocytic function in DBS, we applied DBS-like high frequency electrical stimulation for 24 h to human astrocytes in vitro and analyzed single cell transcriptome mRNA profile. We found that DBS-like high frequency stimulation negatively impacts astrocyte metabolism and promotes the release of extracellular matrix (matricellular) proteins, including IGFBP3, GREM1, IGFBP5, THBS1, and PAPPA. Our results suggest that astrocytes are involved in the long-term modulation of extra cellular matrix environments and that they may influence persistent cell-to-cell interaction and help maintain neuromodulation over time.

Bioactivity of Fermented Green Coffee Bean Extract Containing High Chlorogenic Acid and Surfactin.

Chlorogenic acid (CGA) is a major component of green coffee beans. Surfactin, a cyclic lipopeptide, is produced and secreted by Bacillus subtilis strains. In this study, bioactivities of fermented green coffee bean extract (FGCBE) and the individual compounds, CGA and surfactin. were compared in HepG2 cells. The concentration of surfactin and CGA in the FGCBE and non-fermented green coffee bean extract (NFGCBE) were determined to be 9.2 and 7.33 and 0.72 and 0.53 mg·mL-1, respectively. The FGCBE contained about 20% and 26% more CGA and surfactin than the NFGCBE. Although CGA and surfactin exhibited cytotoxicity at concentrations more than 100 and 20 µg respectively, the FGCBE 50 containing CGA (460 µg·mL-1) and surfactin (720 µg·mL-1) effectively prevented cell death by oxidative stress and also strongly activated the proliferation of cells incubated with under 50 µM H2O2. The CGA and surfactin in FGCBE were 9.2 and 72 times higher than the CGA and surfactin compounds (50 and 10 µg·mL-1). The relative proliferation of the FGCBE-treated cells also was 3.3 and 8.8 times higher than the CGA and surfactin compounds treated the oxidative stressed cells with 50 µM H2O2. These results suggest that the single compounds such as CGA and surfactin generally have cytotoxicity at low concentration of them but FGCBE contained them acted as strong antioxidants, activators of cell proliferation, inhibitors of cell apoptosis. Various bioactive compounds in fermented coffee bean also seem to help cell proliferation and decreasing of cytotoxicity by CGA and surfactin in coffee bean.

Integrating Brain Implants With Local and Distributed Computing Devices: A Next Generation Epilepsy Management System.

Brain stimulation has emerged as an effective treatment for a wide range of neurological and psychiatric diseases. Parkinson's disease, epilepsy, and essential tremor have FDA indications for electrical brain stimulation using intracranially implanted electrodes. Interfacing implantable brain devices with local and cloud computing resources have the potential to improve electrical stimulation efficacy, disease tracking, and management. Epilepsy, in particular, is a neurological disease that might benefit from the integration of brain implants with off-the-body computing for tracking disease and therapy. Recent clinical trials have demonstrated seizure forecasting, seizure detection, and therapeutic electrical stimulation in patients with drug-resistant focal epilepsy. In this paper, we describe a next-generation epilepsy management system that integrates local handheld and cloud-computing resources wirelessly coupled to an implanted device with embedded payloads (sensors, intracranial EEG telemetry, electrical stimulation, classifiers, and control policy implementation). The handheld device and cloud computing resources can provide a seamless interface between patients and physicians, and realtime intracranial EEG can be used to classify brain state (wake/sleep, preseizure, and seizure), implement control policies for electrical stimulation, and track patient health. This system creates a flexible platform in which low demand analytics requiring fast response times are embedded in the implanted device and more complex algorithms are implemented in offthebody local and distributed cloud computing environments. The system enables tracking and management of epileptic neural networks operating over time scales ranging from milliseconds to months.