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The current coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2. Due to the increasing number of confirmed cases and accumulating clinical data, in addition to the predominant respiratory symptoms, a significant proportion of patients with COVID-19 experience neurological complications. Presumedly, several mechanisms, such as direct viral effects on the brain parenchyma and endothelium, and activation of the inflammatory and thrombotic pathways, cause these neurological disorders. Herein, the literature focusing on encephalitis among the central nervous system disorders associated with COVID-19 was reviewed.

BACKGROUND Since arterial supply of the anterior ear was described in 1992 by Park et al, various anatomical studies and surgical techniques have been published in the literatures. Although anatomic studies about the vascular pattern of the ear have been previously reported, most were incomplete to understand the vascular anatomy of the ear and its surgical outcomes. In this report, the authors defined further detailed vascular pattern of the arterial networks and of the main perforators of the anterior ear. METHODS The authors dissected in a total of 11 auricles that had been fixed in 10% formalin solution. Prior to dissection, a red latex solution was injected into the common carotid artery. The anteroauricular and postauricular skin was dissected to expose the arterial network under ×10 microscope magnification. RESULTS There are 2 arterial networks in the anteroauricular surface of the ear: triangular-scapha fossa and concha network. In this study, triangular-scapha fossa network has 2 vascular patterns by a dominant arterial supply: the superficial temporal artery (STA) type (6/11, 54.5%) and the posterior auricular artery (PAA) type (5/11, 45.4%). The STA type is distributed by a subbranch of the ascending helical artery of the STA, whereas the dominant arterial supply of the PAA type is a perforator of the triangular fossa from the PAA. We describe an important inflow to the triangular-scapha fossa network as blood supply from the middle division of the PAA, which directly emerges from the posterior to the anterior surface over the cartilage border at midhelix. CONCLUSIONS The detailed vascular anatomy of this report allows surgeons to perform surgical procedures safely and to develop various flaps in the field of the ear reconstruction.

Background Non-invasive painless signaling therapy (NPST) is an electro-cutaneous treatment that converts endogenous pain information into synthetic non-pain information. This study explored whether pain improvement by NPST in failed back surgery syndrome (FBSS) patients is related to cerebral modulation. Methods Electroencephalography (EEG) analysis was performed in 11 patients with FBSS. Subjects received daily NPST for 5 days. Before the first treatment, patients completed the Brief Pain Inventory (BPI) and Beck Depression Inventory and underwent baseline EEG. After the final treatment, they responded again to the BPI, reported the percent pain improvement (PPI), and then underwent post-treatment EEG. If the PPI grade was zero, they were assigned to the ineffective group, while all others were assigned to the effective group. We used standardized low-resolution brain electromagnetic tomography (sLORETA) to explore the EEG current-source distribution (CSD) associated with pain improvement by NPST. Results The 11 participants had a median age of 67.0 years, and 63.6% were female. The sLORETA images revealed a beta-2 CSD increment in 12 voxels of the right anterior cingulate gyrus (ACG) and the right medial frontal area. The point of maximal CSD changes was in the right ACG. The alpha band CSD increased in 2 voxels of the left transverse gyrus. Conclusions Pain improvement by NPST in FBSS patients was associated with increased cerebral activity, mainly in the right ACG. The change in afferent information induced by NPST seems to be associated with cerebral pain perception.

Luteolin is the most abundant phytochemical phenolic compound contained within peanut hulls and has broad pharmacological characteristics and high bioavailability. In this study, the extraction conditions for luteolin from peanut hulls were optimized. The effects of methanol concentration and reaction temperature on luteolin solubility were determined using the central composite design (CCD) under response surface methodology. Luteolin content within in the extracts increased with increasing temperature and organic solvent-to-water ratios. The optimal conditions for luteolin extraction were 81°C and 87.5% methanol for a predicted extraction value of 174.51 mg/100 g, which was within 1.25% of the experimental value of 172.35 mg/100 g, confirming the predicted model. Additionally, compared to conventional stirring, the luteolin content of reflux-extracted peanut hull had a higher extraction efficiency by 42.50%. The antioxidant compound contents and antioxidant capacity of the extracts were also determined, with the effects of temperature and solvent concentration increasing along with the extracted luteolin. In this study, CCD optimized the conditions for obtaining luteolin from peanut hulls, suggesting that the improved extraction efficiency of the bioactive compound can expand the use of peanut shells in the nutraceutical and food industries.

Background: Alzheimer’s disease (AD) is characterized by the aggregation of two pathological proteins, amyloid-β (Aβ) and tau, leading to neuronal and cognitive dysfunction. Clearance of either Aβ or tau aggregates by immunotherapy has become a potential therapy, as these aggregates are found in the brain ahead of the symptom onset. Given that Aβ and tau independently and cooperatively play critical roles in AD development, AD treatments might require therapeutic approaches to eliminate both aggregates together. Objective: We aimed to discover a chemical drug candidate from natural sources for direct dissociation of both insoluble Aβ and tau aggregates through in vitro assessments. Methods: We isolated four borrelidin chemicals from a saltern-derived halophilic actinomycete strain of rare genus Nocardiopsis and simulated their docking interactions with Aβ fibrils. Then, anti-cytotoxic, anti-Aβ, and anti-tau effects of borrelidins were examined by MTT assays with HT22 hippocampal cell line, thioflavin T assays, and gel electrophoresis. Results: When HT22 cells were exposed to Aβ aggregates, the treatment of borrelidins alleviates the Aβ-induced toxicity. These anti-cytotoxic effects can be derived from the inhibitory functions of borrelidins against the Aβ aggregation as shown in thioflavin T and gel electrophoretic analyses. Among them, especially borrelidin, which exhibits the highest probability of docking, not only dissociates Aβ aggregates but also directly regulates tau aggregation. Conclusion: Borrelidin dissociates insoluble Aβ and tau aggregates together and our findings support the view that it is possible to develop an alternative chemical approach mimicking anti-Aβ or anti-tau immunotherapy for clearance of both aggregates.

Abnormal deposition of amyloid-β (Aβ) is a major biomarker that is often used to diagnose Alzheimer's disease (AD). The Aβ plaque levels in the cortex and hippocampus are measured by either brain histology or positron emission tomography. Although cerebral plaques are found in several phenotypes, such as dense-core, diffuse, and coronal, imaging probes differentiating these plaques are currently unavailable. Here, we report that fluorescent indolizino[3,2-c]quinoline derivatives (YIQ) distinguish Aβ plaque phenotypes in brains of 5XFAD Alzheimer transgenic mice. We synthesized and screened 64 YIQ compounds through a series of in vitro and ex vivo Aβ staining assays. We found 20 compounds that could stain the Aβ phenotypes, 10 for dense-core plaques, eight for both dense-core and diffuse plaques, and two for solely visualizing only the coronal plaques while leaving the centric core unstained. Among the 20 imaging candidates, five YIQs displaying anti-Aβ aggregation efficacy were confirmed by thioflavin T assays and electrophoretic analyses.

Bacillus genus produces several secondary metabolites with biocontrol ability against various phytopathogens. Bacillus velezensis AK-0 (AK-0), an antagonistic strain isolated from Korean ginseng rhizospheric soil, was found to exhibit antagonistic activity against several phytopathogens. To further display the genetic mechanism of the biocontrol traits of AK-0, we report the complete genome sequence of AK-0 and compared it with complete genome sequences of closely related strains. We report the biocontrol activity of AK-0 against apple bitter rot caused by Colletotrichum gloeosporioides, which could lead to commercialization of this strain as a microbial biopesticide in Korea. To retain its biocontrol efficacy for a longer period, AK-0 has been formulated with ingredients for commercialization, named AK-0 product formulation (AK-0PF). AK-0PF played a role in the suppression of the mycelial growth of the fungicide-resistant pathogen C. gloeosporioides YCHH4 at a greater level than the non-treated control. Moreover, AK-0PF exhibited greater disease suppression of bitter rot in matured under field conditions. Here, we report the complete genome sequence of the AK-0 strain, which has a 3,969,429 bp circular chromosome with 3808 genes and a G+C content of 46.5%. The genome sequence of AK-0 provides a greater understanding of the Bacillus species, which displays biocontrol activity via secondary metabolites. The genome has eight potential secondary metabolite biosynthetic clusters, among which, ituD and bacD genes were expressed at a greater level than other genes. This work provides a better understanding of the strain AK-0, as an effective biocontrol agent (BCA) against phytopathogens, including bitter rot in apple.

Amyloid-β (Aβ) aggregated forms are highly associated with the onset of Alzheimer's disease (AD). Aβ abnormally accumulates in the brain and induces neuronal damages and symptoms of AD such as cognitive impairment and memory loss. Since an antibody drug, aducanumab, reduces Aβ aggregates and delays clinical decline, clearance of accumulated Aβ in the brain is accounted as a therapeutic approach to treat AD. In this study, we synthesized 17 benzofuran derivatives that may disaggregate Aβ oligomers and plaques into inert monomers. By a series of Aβ aggregation inhibition and aggregates' disaggregation assays utilizing thioflavin T assays and gel electrophoresis, YB-9, 2-((5-methoxy-3-(4-methoxyphenyl)benzofuran-6-yl)oxy)acetic acid, was selected as the final Aβ-disaggregator candidate. When it was orally administered to the 8-month-old male transgenic mouse model with five familial AD mutations (5XFAD) via drinking water daily for two months, Aβ oligomers and plaques in hippocampus were reduced. Consequently, decreased astrogliosis and rescued synaptic dysfunction were observed in the hippocampus of YB-9-treated 5XFAD mice compared with the untreated transgenic control group.

Although the pathological contributions of reactive astrocytes have been implicated in Alzheimer's disease (AD), their in vivo functions remain elusive due to the lack of appropriate experimental models and precise molecular mechanisms. Here, we show the importance of astrocytic reactivity on the pathogenesis of AD using GiD, a newly developed animal model of reactive astrocytes, where the reactivity of astrocytes can be manipulated as mild (GiDm) or severe (GiDs). Mechanistically, excessive hydrogen peroxide (H2O2) originated from monoamine oxidase B in severe reactive astrocytes causes glial activation, tauopathy, neuronal death, brain atrophy, cognitive impairment and eventual death, which are significantly prevented by AAD-2004, a potent H2O2 scavenger. These H2O2--induced pathological features of AD in GiDs are consistently recapitulated in a three-dimensional culture AD model, virus-infected APP/PS1 mice and the brains of patients with AD. Our study identifies H2O2 from severe but not mild reactive astrocytes as a key determinant of neurodegeneration in AD.

Background: Hemorrhoids are a common anal disorder and are more frequent in women than in men. Urinary incontinence (UI) also occurs more frequently in women than in men. Although both diseases share similar risk factors, research on the association between the two diseases is lacking. This study aimed to investigate the relationship between hemorrhoids and UI in adult Korean women. Methods: This study was based on the data of the 2008-2009 Korean National Health and Nutrition Examination Survey. Logistic regression test was performed to determine the relationship between hemorrhoids and UI after adjusting for age, body mass index (BMI), smoking, heavy drinking, physical activity, education level, income, diabetes mellitus, and hypertension. Results: Analysis of the data of 8,139 adult women revealed that the prevalence of hemorrhoids, which were self-reported and diagnosed by a physician, was 17.5% and 7.9%, respectively. Both types of hemorrhoids were more prevalent in older women with spouses, those with a large waist circumference, and those with a high BMI. The prevalence of UI was significantly high in the hemorrhoid group, regardless of whether it was self-reported or diagnosed by a physician. Multiple logistic regression analyses revealed a significant association between the prevalence of UI and hemorrhoids, both of which were found to peak at 19-39 years of age. Conclusions: Our findings demonstrate that hemorrhoids are significantly correlated with UI in adult Korean women. When treating adult women with hemorrhoids, it is, therefore, necessary to consider other pelvic floor diseases such as UI.

Rhizolutin (1) was discovered as a natural product of ginseng-rhizospheric Streptomyces sp. WON17. Its structure features an unprecedented 7/10/6-tricyclic dilactone carbon skeleton composed of dimethylcyclodecatriene flanked by a 7-membered and a 6-membered lactone ring based on spectroscopic analysis. During an unbiased screening of natural product libraries, this novel compound was found to dissociate amyloid-β (Aβ) plaques and tau tangles, which are key pathological hallmarks of Alzheimer's disease (AD). Rhizolutin treatment of APP/PS1 double transgenic mice with AD significantly dissociated hippocampal plaques. In vitro, rhizolutin substantially decreased Aβ-induced apoptosis and inflammation in neuronal and glial cells. Our findings introduce a unique chemical entity that targets Aβ and tau concurrently by mimicking misfolded protein clearance mechanisms of immunotherapy, which is prominently investigated in clinical trials.

Latency and amplitude are the measurement parameters of mismatch negativity (MMN). The values of the parameters vary sensitively with the stimulus paradigm. A paradigm using the frequency difference of sounds for the MMN study is well known. This study obtained the reference values of the parameters in healthy young adults by performing the MMN study using the frequency paradigm. The authors recruited ten healthy adults. Their average age was 25.5 years; three were female, and seven were male. On the auditory paradigm for the MMN study, the frequency of sound was 1000 Hz for the standard stimulus, and 1032 Hz for the deviant stimulus. The mean values of latency and amplitude of MMN were 202 ms and 1.88 μV at Fz, 207 ms, and 1.46 μV at Cz, 212 ms, and 1.10 μV at C3, and 214 ms and 1.45 μV at C4. There was no correlation between the latency and amplitude of MMN. This study presented the reference values of the latency and amplitude of the MMN using a standard paradigm that is easy to apply. This information may make the MMN useful for clinical applications and basic research.

Background and purpose The increased demand for donor organs has made it crucial to keep the organs of patients with impending brain death (PWIBDs) suitable for transplantation during the process of determining brain death. This study aimed to identify the time taken to determine brain death (TT-BD) in PWIBDs and the associated influencing factors. Methods This study analyzed data collected by the Korean Organ Donation Agency from 15 hospitals in the Yeongnam region of South Korea. There were 414 PWIBDs eligible for inclusion in this study. The data consisted of the TT-BD for PWIBDs and the potential variables influencing the TT-BD. Results The mean age of the 414 PWIBDs was 48.9 years, and 120 of them were female (29.0%). The mean TT-BD was 8.5 days. The presence of spontaneous movements (SMs) and craniotomy significantly affected the TT-BD. The mean TT-BDs were 13.9 and 8.2 days in the PWIBDs with and without SMs, respectively, and 9.8 and 8.0 days in the PWIBDs with and without craniotomy, respectively. Conclusions The SMs in PWIBDs and a craniotomy performed immediately before starting the process of determining brain death seem to be related to lengthening the TT-BD.

BackgroundThe blood-brain barrier has been a hindrance to developing blood-based diagnostic tests for dementias, as it limits the appearance of brain biomarkers in the blood. Our aim was to see if the natural opening of the blood-brain barrier induced by ischemic stroke would increase serum levels of inflammatory biomarkers known to be elevated in the brains of patients with Alzheimer’s disease and other neurodegenerative dementias.MethodsForty-three patients with acute ischemic stroke presenting to Stony Brook University Hospital were prospectively enrolled in the study. Eight of these patients were clinically diagnosed as having an underlying neurodegenerative dementia. Blood was drawn acutely within 72 h of stroke symptom onset, and serum levels of the classic inflammatory biomarkers, interleukin-6 (IL-6) and C-reactive protein (CRP) were measured, along with levels of S100B protein (S100B) and complement C3 (CC3).ResultsSerum levels of IL-6 and CRP in patients with acute ischemic stroke and underlying dementia (AIS + D) were significantly higher (p = 0.002 and 0.003, respectively) than in patients with acute ischemic stroke alone (AIS). Serum levels of S100B and CC3 did not differ significantly between the groups.ConclusionsThis study supports the possibility that opening of the blood-brain barrier may enhance the blood appearance of brain tissue markers of inflammation associated with neurodegenerative dementia. Further study is warranted to test this possibility, given the recent emergence of methods to open the blood-brain barrier for diagnostic or therapeutic purposes.

We investigated the impact of acute kidney injury (AKI) in elderly deceased-donors (DDs) vs. AKI in young DDs on post-transplant clinical outcomes. A total of 709 kidney transplant recipients (KTRs) from 602 DDs at four transplant centers were enrolled. KTRs were divided into young-DDKT and elderly-DDKT groups according to the age of DD of 60 years. Both groups were subdivided into non-AKI-KT and AKI-KT subgroups according to AKI in DDs. We investigated short-term and long-term clinical outcomes of non-AKI-DDKT and AKI-DDKT subgroups within young-DDKT and elderly-DDKT groups. The incidence of DGF in the AKI-DDKT subgroup was higher and the allograft function within 12 months after KT in the AKI-DDKT subgroup was lower than those in the non-AKI-DDKT subgroup in both young-DDKT and elderly-DDKT groups. Death-censored allograft survival rate was significantly lower in the AKI-elderly-DDKT subgroup than that in the non-AKI-elderly-DDKT subgroup, but it did not differ between AKI-young-DDKT and non-AKI-young-DDKT subgroup. In multivariable analysis, AKI-elderly-DDKT was an independent risk factor for allograft failure (hazard ratio: 2.648, 95% CI: 1.170–5.994, p = 0.019) and a significant interaction between AKI and old age in DDs on allograft failure was observed (p = 0.001). AKI in elderly DDs, but not in young DDs, can significantly affect long-term allograft outcomes of KTRs.

Objective: To evaluate the effect of different extracts of Diospyros lotus leaves in atopic dermatitis Methods: Diospyros lotus leaves were extracted in ethanol and treated with or without hydrochloric acid or α-rhamnosidase to obtain three different extracts-ethanol, acid-hydrolyzed, and enzyme-hydrolyzed leaf extracts of date plum. The myricitrin content in all samples was measured using HPLC analysis. In vitro antioxidant and anti-inflammatory activities of the extracts were determined by measuring DPPH radical scavenging activities and nitric oxide production in RAW264.7 cells, respectively. Seven- week-old male hairless mice were used to evaluate the anti-atopic dermatitis effects of three extracts in vivo. Splenocytes and mast cells were used to further determine the anti-atopic dermatitis effects of the major compound in the ethanol leaf extract. Results: Enzyme-hydrolyzed leaf extract showed significant in vitro antioxidant and anti-inflammatory activities, and attenuated atopic dermatitis-like skin symptoms and clinical signs more significantly than ethanol and acid-hydrolyzed leaf extracts in 1-fluoro-2,4- dinitrobenzene and house dust mite antigen-treated hairless mice. Enzyme-hydrolyzed leaf extract also suppressed the serum level of immunoglobulin E, interleukin (IL)-4, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, thymic stromal lymphopoietin, and thymus and activation-regulated chemokine in mice with atopic dermatitis. Furthermore, histological analysis revealed that enzyme- hydrolyzed leaf extract suppressed the increased epidermal thickness, dermal infiltration of inflammatory cells, and infiltration and degranulation of mast cells more markedly than the other two extracts in atopic dermatitis-like skin lesions. In addition, this extract effectively inhibited the production of IFN-γ, IL-4,and thymus and activation-regulated chemokine compared with the other two extracts in concanavalin A-stimulated splenocytes. Myricitrin, a major compound of enzyme-hydrolyzed leaf extract, suppressed atopic dermatitis biomarkers in stimulated mouse splenocytes and HMC-1 human mast cells. Conclusions: These results suggest that enzyme-hydrolyzed leaf extract might be a potential candidate to treat atopic dermatitis.

Immunoglobulin M nephropathy (IgMN) is an idiopathic glomerulonephritis characterized by diffuse deposits of IgM in the glomerular mesangium. However, its renal prognosis remains unknown. We compared renal outcomes of IgMN patients with those of patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), or mesangial proliferative glomerulonephritis (MsPGN) from a prospective observational cohort, with 1791 patients undergoing native kidney biopsy in eight hospitals affiliated with The Catholic University of Korea between December 2014 and October 2020. IgMN had more mesangial proliferation and matrix expansion than MsPGN and more tubular atrophy and interstitial fibrosis than MCD. IgMN patients had decreased eGFR than MCD patients in the earlier follow-up. However, there was no significant difference in urine protein or eGFR among all patients at the last follow-up. When IgMN was divided into three subtypes, patients with FSGS-like IgMN tended to have lower eGFR than those with MCD-like or MsPGN-like IgMN but higher proteinuria than MsPGN-like IgMN without showing a significant difference. The presence of hypertension at the time of kidney biopsy predicted ≥20% decline of eGFR over two years in IgMN patients. Our data indicate that IgMN would have a clinical course and renal prognosis similar to MCD, FSGS, and MsPGN.

Purpose Disruption of the tumor-brain barrier in meningioma is a crucial factor in peritumoral brain edema (PTBE). We previously reported the possible effect of osteoporosis on the integrity of the arachnoid trabeculae because both the bone and the arachnoid trabeculae are composed of type 1 collagen. We hypothesized that osteoporotic conditions may be associated with PTBE occurrence after radiation treatment in patients with meningioma. Methods A receiver operating characteristic curve analysis was used to identify the optimal cut-off values of mean skull Hounsfield unit for predicting osteopenia and osteoporosis in patients from our registry. Multivariate Cox regression analysis was used to determine whether possible osteoporosis independently predicted PTBE development in patients with meningioma after radiation. Results A total of 106 intracranial meningiomas were included for the study. All patients received linear accelerator-based radiation therapy in our hospital over an approximate 6-year period. Multivariate Cox regression analysis identified that hypothetical osteoporosis was an independent predictive factor for the development of PTBE in patients with meningioma after linear accelerator-based radiation treatment (hazard ratio 5.20; 95% confidence interval 1.11–24.46; p = 0.037). Conclusions Our study suggests that possible osteoporotic conditions may affect PTBE development after linear accelerator-based radiation treatment for intracranial meningioma. However, due to the study’s small number of patients, these findings need to be validated in future studies with larger cohorts, before firm recommendations can be made. Graphic abstract

Cancer immunotherapy, or the utilization of a patient's own immune system to treat cancer, has shifted the paradigm of cancer treatment. Despite meaningful responses being observed in multiple studies, currently available immunotherapy platforms have only proven effective to a small subset of patients. To address this, nanoparticles have been utilized as a novel carrier for immunotherapeutic drugs, achieving robust anti-tumor effects with increased adaptive and durable responses. Specifically, dendrimer nanoparticles have attracted a great deal of scientific interest due to their versatility in various therapeutic applications, resulting from their unique physicochemical properties and chemically well-defined architecture. This review offers a comprehensive overview of dendrimer-based immunotherapy technologies, including their formulations, biological functionalities, and therapeutic applications. Common formulations include: (1) modulators of cytokine secretion of immune cells (adjuvants); (2) facilitators of the recognition of tumorous antigens (vaccines); (3) stimulators of immune effectors to selectively attack cells expressing specific antigens (antibodies); and (4) inhibitors of immune-suppressive responses (immune checkpoint inhibitors). On-going works and prospects of dendrimer-based immunotherapies are also discussed. Overall, this review provides a critical overview on rapidly growing dendrimer-based immunotherapy technologies and serves as a guideline for researchers and clinicians who are interested in this field. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.

We investigated whether the development of delayed graft function (DGF) in pre-sensitized patients affects the clinical outcomes after deceased-donor kidney transplantation (DDKT).The study included 709 kidney transplant recipients (KTRs) from three transplant centers. We divided KTRs into four subgroups (highly sensitized DGF, highly sensitized non-DGF, low-sensitized DGF, and low-sensitized non-DGF) according to panel reactive antibody level of 50%, or DGF development. We compared post-transplant clinical outcomes among the four subgroups.Incidence of biopsy-proven acute rejection (BPAR) was higher in two highly sensitized subgroups than in low-sensitized subgroups. It tended to be higher in highly sensitized DGF subgroups than in the highly sensitized non-DGF subgroups. In addition, the highly sensitized DGF subgroup showed the highest risk for BPAR (hazard ratio, 3.051; P=0.005) and independently predicted BPAR. Allograft function was lower in the two DGF subgroups than in the non-DGF subgroup until one month after transplantation, but thereafter it was similar. Death-censored graft loss rates and patient mortality tended to be low when DGF developed, but it did not reach statistical significance.DGF development in highly sensitized patients increases the risk for BPAR in DDKT compared with patients without DGF, suggesting the need for strict monitoring and management of such cases.

Apium graveolens (celery) of the family Apiaceae contains bioactive compounds including luteolin and apigenin. The purpose of this study was to increase the extraction yield of apigenin and luteolin in celery extract using green technology and to evaluate their biological activities. The results showed that CA and β-glucosidase-assisted celery extraction transformed apiin in the celery to apigenin with an increase in luteolin concentration. The CA and β-glucosidase-treated celery extract (CAGE) improved the anti-inflammatory properties of celery extract by inhibiting the expression and production of inflammatory cytokines (IL-6, IL-8, IL-31, and TNF-α) in IL-33-stimulated mast cells (HMC-1.2 cells). Their mechanism of action was tied to the inhibition of ERK, JNK, IKKα, IκBα, and NF-κB activation by CAGE in the stimulated cells. In conclusion, CA and enzyme treatment can be considered as a useful biotechnology tool for the improvement of bioactive compounds in celery and hence improve on their bioactivity. PRACTICAL APPLICATIONS: Apium graveolens commonly called celery is an edible agricultural product cultivated throughout the world and known as a "superfood." Celery contains bioactive compounds including apigenin and luteolin that contribute to their described biological activities. However, extracting celery using normal extraction procedures such as hot water and ethanol methods yields only a small amount of apigenin and luteolin. In the present study, we introduced an eco-friendly method using citric and β-glucosidase to obtain apigenin and luteolin-rich celery extract with improved anti-inflammatory activities. The present work will spark studies on the conversion of less biologically active compounds in functional food materials to more active compounds using CA and β-glucosidase, and the development of functional food with specifically enriched bioactive substances at the industrial levels.

In order to design composites that mimic the remarkable balance of properties such as strength, toughness, and stiffness of staggered platelet structures in nature, it is crucial to understand their load transfer and failure mechanisms. Recently, we proposed an analytical model to predict the stress distribution within staggered platelet structures for a wide range of constituent materials’ moduli and geometric parameters in the elastic response regime. Here, based on the model, a fracture pattern diagram featuring three distinct mechanisms categorized according to the failure sequences of soft tip, soft shear zone, and hard platelet is constructed. The proposed fracture map is capable of capturing the transition of failure mechanisms observed in crack phase field simulations and draws parallels to mechanisms seen in experiments. Our study sheds light on the origin of failure mechanism transitions and enables rational designs of future staggered platelet composites with unprecedented properties.

Objective Endovascular treatment for unruptured intracranial aneurysms (UIAs) has been regarded as second to none management nowadays as the result of its proven efficacy and need for less-invasive treatment. Most researchers have focused on the anatomical outcome after endovascular treatment, so in this study we estimated the real incidence of untoward effect and degree of patients' satisfaction based on s survey. Methods This retrospective study was approved by the institutional review board, and 112 patients treated for saccular UIAs were evaluated among a total of 135 patients. After informed consent was obtained, these patients were sent a questionnaire regarding treatment effectiveness, complications, and patient satisfaction. These data were collected and compared with angiographic and clinical outcome. Results The response rate was 87.5% (98/112). Intracranial complications occurred in 10 aneurysms (10.2%): 7 ischemic and 3 hemorrhagic strokes. Other complications occurred in 30 patients (30.6%): 17 alopecia, 15 bleeding tendency, and 3 puncture-site complications. Overall, 89 (90.8%) patients reported being satisfied with their treatment. Patient satisfaction was closely correlated with clinically successful outcome of treatment. Conclusions Ninety percent of patients were satisfied with the results after endovascular treatment of UIAs. Endovascular coil embolization was effective and safe procedure, with high clinical success rate and degree of satisfaction.

Dementia is used as a general term to describe chronic disorders of mental processes caused by the deterioration of cognitive functions to the extent that one's ability to perform daily activities is impaired. Currently, age is known to be the main risk factor for dementia, suggesting that the risk of being diagnosed with dementia significantly increases later in one's life. Therefore, there are two approaches one can take when confronting dementia: to cure it when it occurs in late adulthood or to prevent the onset of symptoms beforehand. Recently, the latter strategy of delaying and preventing Alzheimer's disease, the most prevalent form and most studied type of dementia, through both pharmaceutical and nonpharmaceutical interventions is becoming increasingly recognized. In this review, we discuss studies conducted in various fields that addresses nonpharmaceutical lifestyle interventions, including diet, physical activity, cognitive stimulation, and social engagement, and their effects in preventing and inhibiting dementia.

Composites are ubiquitous throughout nature and often display both high strength and toughness, despite the use of simple base constituents. In the hopes of recreating the high-performance of natural composites, numerical methods such as finite element method (FEM) are often used to calculate the mechanical properties of composites. However, the vast design space of composites and computational cost of numerical methods limit the application of high-throughput computing for optimizing composite design, especially when considering the entire failure path. In this work, the authors leverage deep learning (DL) to predict material properties (stiffness, strength, and toughness) calculated by FEM, motivated by DL’s significantly faster inference speed. Results of this study demonstrate potential for DL to accelerate composite design optimization.

Recent reports have suggested an association between rotavirus infection and a distinctive pattern of white matter injury (WMI) in neonates with seizures; however, the connection between the two is not fully understood. To evaluate the underlying mechanism, we profiled and compared eight cytokines (IL [interleukin]-1β, IL-6, IL-8, IL-10, IFN-γ [interferon-γ ], MCP-1 [monocyte chemoattractant protein-1], MIP-1β [macrophage inflammatory protein-1β], and TNF-α [tumor necrosis factor-α]) in the cerebrospinal fluid (CSF) of 33 neonates with seizures who had no other well-known causes of seizures and 13 control patients (rotavirus-induced gastroenteritis but without seizures). Among the 33 neonates with seizures, 9 showed WMI and all were infected with rotavirus (R + W + ). Among the 24 patients without WMI, 11 were infected with rotavirus (R + W − ) and 13 were not (R − W − ).Only MCP-1 and MIP-1β were different between the groups. MCP-1 was increased in R+ W+ compared with R + W− (p

OBJECTIVE There is no scale for rating the severity of autoimmune encephalitis (AE). In this study, we aimed to develop a novel scale for rating severity in patients with diverse AE syndromes and to verify the reliability and validity of the developed scale. METHODS The key items were generated by a panel of experts and selected according to content validity ratios. The developed scale was initially applied to 50 patients with AE (development cohort) to evaluate its acceptability, reproducibility, internal consistency, and construct validity. Then, the scale was applied to another independent cohort (validation cohort, n = 38). RESULTS A new scale consisting of 9 items (seizure, memory dysfunction, psychiatric symptoms, consciousness, language problems, dyskinesia/dystonia, gait instability and ataxia, brainstem dysfunction, and weakness) was developed. Each item was assigned a value of up to 3 points. The total score could therefore range from 0 to 27. We named the scale the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). The new scale showed excellent interobserver (intraclass correlation coefficient [ICC] = 0.97) and intraobserver (ICC = 0.96) reliability for total scores, was highly correlated with modified Rankin scale (r = 0.86, p

Background The problem of organ shortage is an important issue in kidney transplantation, but the effect of kidney donation on AKI is unclear. The aim of this study was to investigate the impact of acute kidney injury (AKI) on post-transplant clinical outcomes for deceased donor kidney transplantation (DDKT) using standard criteria donors (SCDs) versus expanded criteria donors (ECDs). Methods Five-hundred nine KT recipients receiving kidneys from 386 deceased donors (DDs) were included from three transplant centers. Recipients were classified into the SCD-KT or ECD-KT group according to corresponding DDs and both groups were divided into the AKI-KT or non-AKI-KT subgroups according to AKI in donor. We compared the clinical outcomes among those four groups and investigated the interaction between AKI in donors and ECD on allograft outcome. Results The incidence of delayed allograft function was higher when the donors had AKI within SCD-KT and ECD-KT groups. In allograft biopsies within 3 months, chronic change was more significant in the AKI-ECD-KT subgroup than in the non-AKI-ECD-KT subgroup, but it did not differ between AKI-SCD-KT and non-AKI-SCD-KT group. AKI-ECD-KT showed higher risk for death-censored allograft failure than the other three groups and a significant interaction was observed between AKI in donors and ECD on the allograft outcome. Conclusions The presence of AKI in ECDs significantly impacted the long-term allograft outcomes of kidney transplant recipients, but it did not in SCDs. Electronic supplementary material The online version of this article (10.1186/s12882-019-1225-1) contains supplementary material, which is available to authorized users.

Background At most centers, general anesthesia (GA) has been preferred for endovascular treatment (EVT) of ruptured intracranial aneurysms (RIAs). In this study, we analyzed procedural results, clinical outcomes, and follow-up angiographic findings for patients undergoing EVT for RIA under local anesthesia (LA) with conscious sedation (CS). Methods We retrospectively evaluated 308 consecutive patients who underwent EVT for RIAs at a single institution between June 2009 and February 2017. EVT under LA with CS was considered for all patients with aneurysmal subarachnoid hemorrhage, regardless of Hunt and Hess (HH) scale score. Results EVT was performed for 320 aneurysms in 308 patients with subarachnoid hemorrhages. The mean patient age was 55.5±12.6 years. Moderate (III) and poor (IV, V) HH grades were observed in 75 (24.4%) and 77 patients (25%), respectively. Complete occlusion immediately after EVT was achieved for 270 (84.4%) of 320 aneurysms. Thromboembolic complications and intraprocedural ruptures occurred in 25 (7.8%) and 14 cases (4.3%), respectively. The morbidity rate at discharge (as defined by a modified Rankin scale score of 3 or greater) was 27.3% (84/308), while the mortality rate was 11.7% (36/308). Follow-up angiographic results were available for 210 (68.1%) of 308 patients. Recanalization was observed in 64 (29.3%) of 218 aneurysms in 210 patients. Conclusion Based on our experience, EVT for RIAs under LA with CS was feasible, regardless of the clinical grade of the subarachnoid hemorrhage. Complication rates and follow-up angiographic results were also comparable to those observed when GA was used to perform the procedure.

Background New-onset refractory status epilepticus (NORSE) occurs in people without a history of seizures. In these cases, the seizure causes are unclear, and the seizures are not controlled by standard treatment. Autoimmune encephalitis (AIE) can be a cause of NORSE. Cryptogenic NORSE may be associated with AIE, but antibodies associated with the condition have not yet been identified. Primary immunotherapy may not be effective for AIE. Rituximab has improved the prognosis in some cases. Case Report We treated a cryptogenic NORSE patient with a combination of antiepileptic drugs and immunotherapy. On the 13th hospital day, the seizures were controlled, but the patient remained in a coma. The patient rapidly recovered after administration of rituximab started on the 26th hospital day. Conclusion Rituximab may be helpful for cryptogenic NORSE patients in whom primary immunotherapy controls seizures, but fails to improve consciousness.

Background:. The temporoparietal fascia (TPF) flap has been successfully used in the treatment of microtia with primary or secondary cases. The literature contains numerous studies about its structure and vascular anatomy in adults. However, it is rare to study its vasculature and characteristics in children. Methods:. From September of 2013 to May of 2020, 188 patients with average age of 9.8 years (range, 5–14 years) underwent total ear reconstruction with costal cartilage in 67 patients (68 ears) or porous polyethylene framework in 121 patients (128 ears) using 196 TPF flaps. The TPF flap was most commonly used in second-stage operations to elevate the reconstructed auricle in the costal cartilage group. Contrastingly, the TPF flap was routinely used in the porous polyethylene framework group. The vascular pattern and characteristics of the TPF flap were evaluated during flap elevation. Results:. Only 140/196 cases (71.4%) showed a typical pattern with the superficial temporal artery and the superficial temporal vein in this study; others (28.6%) were supplied by combinations of the posterior auricular artery or vein, occipital vein, diploic vein, and superficial artery or vein. Meanwhile, there are variants of the STA and posterior origin-superficial temporal artery, which originates posterior to the lobule beneath the cartilage remnant (3/196, 1.5%). Conclusion:. Surgeons should inspect the pattern of the TPF flap thoroughly before elevation in children, because of the variety of the vessels and anatomic patterns of TPF.