Quantitative Analysis and Molecular Docking Simulation of Flavonols from Eruca sativa Mill. and Their Effect on Skin Barrier Function.

Eruca sativa is a commonly used edible plant in Italian cuisine. E. sativa 70% ethanol extract (ES) was fractionated with five organic solvents, including n-hexane (EHex), chloroform (ECHCl3), ethyl acetate (EEA), n-butyl alcohol (EBuOH), and water (EDW). Ethyl acetate fraction (EEA) had the highest antioxidant activity, which was correlated with the total polyphenol and flavonoid content. ES and EEA acted as PPAR-α ligands by PPAR-α competitive binding assay. EEA significantly increased cornified envelope formation as a keratinocyte terminal differentiation marker in HaCaT cells. Further, it significantly reduced nitric oxide and pro-inflammatory cytokines (IL-6 and TNF-α) in lipopolysaccharide-stimulated RAW 264.7 cells. The main flavonol forms detected in high amounts from EEA are mono-and di-glycoside of each aglycone. The main flavonol form of EEA is the mono-glycoside of each aglycone detected, and the most abundant flavonol mono-glycoside is kaempferol 3-glucoside 7.4%, followed by quercetin-3-glucoside 2.3% and isorhamnetin 3-glucoside 1.4%. Flavonol mono-glycosides were shown to be a potent PPAR-α ligand using molecular docking simulation and showed the inhibition of nitric oxide. These results suggest that the flavonol composition of E. sativa is suitable for use in improving skin barrier function and inflammation in skin disorders, such as atopic dermatitis.

Evaluating a shared care pathway intervention for people receiving chemotherapy to reduce post-treatment unplanned hospital presentations: a randomised controlled trial.

PURPOSE: The aim of this randomised controlled trial (RCT) was to explore whether a community nursing intervention for outpatients receiving systemic therapy reduced unplanned hospital presentations and improved physical and psychosocial health outcomes over the first three cycles of treatment compared to a control group receiving standard care. METHODS: The number of and reasons for unplanned presentations were obtained for 170 intervention and 176 control group adult patients with solid tumours starting outpatient chemotherapy. Poisson regression was used to compare the number of presentations between the intervention and control groups. Patients self-completed the Hospital Anxiety and Depression Scale, the Cancer Behavior Inventory and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30 (EORTC QLQ-C30) at the start of the first four cycles. Linear regression techniques were used to compare quality of life outcomes. RESULTS: The reduction in unplanned presentations in the intervention group relative to the control group was 12% (95% CI, - 25%, 37%; P = 0.48). At the start of cycle 4, there was no difference in anxiety (difference = 0.47 (95% CI, - 0.28, 1.22; P = 0.22)), depression (difference = 0.57 (95% CI, - 0.18, 1.31; P = 0.13)) or EORTC QLQ-C30 summary score (difference = 0.16 (95% CI, - 2.67, 3.00; P = 0.91)). Scores for self-efficacy as measured by the Cancer Behavior Inventory were higher in the intervention group (difference = 4.3 (95% CI, 0.7, 7.9; P = 0.02)). CONCLUSION: This RCT did not demonstrate a benefit in reducing unplanned presentations to hospital. The trial identified improved cancer-based self-efficacy in patients receiving the intervention. TRIAL REGISTRATION: Registered at Australian and New Zealand Clinical Trials Registry: ACTRN12614001113640, registered 21/10/2014.

Alkalimarinus alittae sp. nov., isolated from gut of marine sandworm (Alitta virens) and emended description of the genus Alkalimarinus.

A novel, Gram-stain-negative, aerobic, motile, catalase- and oxidase-negative bacterial strain, designated A2M4T, was isolated from the gut contents of a marine sandworm Alitta virens, collected from the eastern coast of the Republic of Korea. Strain A2M4T formed translucent circular colonies and showed rod-shaped cells with peritrichous flagella. Optimal growth of strain A2M4T occurred at 25 °C, pH 7.0 and in the presence of 2 % (w/v) NaCl. Phylogenetic analysis based on the 16S rRNA gene sequences showed that strain A2M4T was closely related to Alkalimarinus sediminis FA028T, with the highest sequence similarity of 98.9 %. The complete genome sequence of strain A2M4T was 4.25 Mbp in size and the genomic G+C content, calculated from the genome sequence, was 43.2 mol%. A comparison between the genome sequence of strain A2M4T and that of its closest relative, A. sediminis FA028T, showed an average nucleotide identity value of 76.63 % and a digital DNA-DNA hybridization value of 22.2 %. Strain A2M4T contained Q-9 as the sole respiratory isoprenoid quinone and the major polar lipids were phosphatidylglycerol, diphosphatidylglycerol and phosphatidylethanolamine. The major cellular fatty acids of strain A2M4T were C14 : 0, C16 : 0 and summed feature 3 (comprising C16 : 1 ω7c and/or C16 : 1 ω6c). Based on its phenotypic, chemotaxonomic and genomic characteristics, strain A2M4T represents a novel species of the genus Alkalimarinus, for which the name Alkalimarinus alittae sp. nov. is proposed. The type is strain A2M4T (=KCTC 92030T=JCM 35924T). The description of the genus Alkalimarinus has also been emended.

Synthesis of Tricyclic Tetrazoles by Cascade Diazotization/Intramolecular Radical C-H Heteroarylation of Arenes.

A cascade diazotization/intramolecular radical C-H heteroarylation of 1-benzyloxy-5-aminotetrazoles and 1-phenethyl-5-aminotetrazoles as substrates using sodium nitrite and acetic acid without any heating, catalysis, irradiation, or electrolysis is reported. This one-pot reaction afforded the desired tricyclic tetrazole products in good yields (up to 94%) without isolation of the diazonium salt intermediate under mild reaction conditions.

How consequences of colorectal cancer treatment are managed: a qualitative study of stakeholder experiences about supportive care and current practices.

PURPOSE: Colorectal cancer (CRC) survivors experience treatment-effects such as symptoms and functional impairments. There is limited evidence about how these are managed and what services or supports are available in the community. We aimed to identify current practice and available supports for managing consequences of treatment from clinician and CRC survivor perspectives. METHODS: This qualitative study, informed by an interpretivist constructionist paradigm, included semi-structured interviews. Clinicians with experience of treating CRC patients and adult CRC survivors were recruited across Australia. Interviews explored experiences about problems experienced after CRC treatment and how these were managed. Data collection and analysis, using thematic analysis, was iterative whereby emergent themes during analysis were incorporated into subsequent interviews. RESULTS: We interviewed 16 clinicians and 18 survivors. Survivors experienced a range of consequences of treatment amendable to support including allied health, information, and self-management. Barriers to support access included clinicians' worry about patient out-of-pocket expenses, long waitlists, lack of awareness about existing supports, and perception no therapeutic options were available. Healthcare professionals with expertise in CRC were often difficult to identify outside of cancer settings. Survivorship care could be improved with individualised timely information and identification of pathways to access healthcare providers with expertise in managing consequences of CRC treatment within primary care. CONCLUSIONS: To improve CRC survivor lives posttreatment, routine assessment of consequences of treatment, individualised care planning involving relevant healthcare professionals, access to supportive care when needed, and improved information provision and engagement of a range of health professionals in follow-up care are needed.

Eight-Month Follow-up After the Third Dose of BNT162b2 Vaccine in Healthcare Workers: The Question of a Fourth Dose.

BACKGROUND: A fourth dose of vaccination is known to help reduce the severity and mortality rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The South Korean vaccination guidelines for the fourth dose do not include healthcare workers (HCWs) as priority candidates. We investigated the necessity of the fourth dose in South Korean HCWs based on an 8-month follow-up period after the third vaccination. METHODS: Changes in the surrogate virus neutralization test (sVNT) inhibition (%) score were measured at one month, four months and eight months after the third vaccination. The sVNT values were analyzed between infected and uninfected groups, and their trajectories were compared. RESULTS: A total of 43 HCWs were enrolled in this study. In total, 28 cases (65.1%) were confirmed to be infected with SARS-CoV-2 (presumed omicron variant), and all had mild symptoms. Meanwhile, 22 cases (78.6%) were infected within four months of the third dose (median, 97.5 days). Eight months after the third dose, the SARS-CoV-2 (presumed omicron variant)-infected group showed significantly higher sVNT inhibition than that in the uninfected group (91.3% vs. 30.7%; P < 0.001). The antibody response due to hybrid immunity, provided by a combination of infection and vaccination, was maintained at sufficient levels for more than four months. CONCLUSION: For HCWs who had coronavirus disease 2019 infection after completing a third vaccination, a sufficient antibody response was maintained until eight months after the third dose. The recommendation of the fourth dose may not be prioritized in subjects with hybrid immunity.

Effects of Omicron Infection and Changes in Serum Antibody Response to Wild-Type, Delta, and Omicron After a Booster Dose With BNT163b2 Vaccine in Korean Healthcare Workers.

BACKGROUND: Although the primary vaccine coverage rate for coronavirus disease 2019 (COVID-19) in South Korea has exceeded 80%, the coronavirus continues to spread, with reports of a rapid decline in vaccine effectiveness. South Korea is administering booster shots despite concerns about the effectiveness of the existing vaccine. METHODS: Neutralizing antibody inhibition scores were evaluated in two cohorts after the booster dose. For the first cohort, neutralizing activity against the wild-type, delta, and omicron variants after the booster dose was evaluated. For the second cohort, we assessed the difference in neutralizing activity between the omicron infected and uninfected groups after booster vaccination. We also compared the effectiveness and adverse events (AEs) between homologous and heterologous booster doses for BNT162b2 or ChAdOx1 vaccines. RESULTS: A total of 105 healthcare workers (HCWs) that were additionally vaccinated with BNT162b2 at Soonchunhyang University Bucheon Hospital were enrolled in this study. Significantly higher surrogate virus neutralization test (sVNT) inhibition (%) was observed for the wild-type and delta variants compared to sVNT (%) for the omicron after the booster dose (97%, 98% vs. 75%; P < 0.001). No significant difference in the neutralizing antibody inhibition score was found between variants in the BNT/BNT/BNT group (n = 48) and the ChA/ChA/BNT group (n = 57). Total AEs were not significantly different between the ChA/ChA/BNT group (85.96%) and the BNT/BNT group (95.83%; P = 0.11). In the second cohort with 58 HCWs, markedly higher sVNT inhibition to omicron was observed in the omicron-infected group (95.13%) compared to the uninfected group (mean of 48.44%; P < 0.001) after four months of the booster dose. In 41 HCWs (39.0%) infected with the omicron variant, no difference in immunogenicity, AEs, or effectiveness between homogeneous and heterogeneous boosters was observed. CONCLUSION: Booster vaccination with BNT162b2 was significantly less effective for the neutralizing antibody responses to omicron variant compared to the wild-type or delta variant in healthy population. Humoral immunogenicity was sustained significantly high after 4 months of booster vaccine in the infected population after booster vaccination. Further studies are needed to understand the characteristics of immunogenicity in these populations.

Expression of Immune-Related and Inflammatory Markers and Their Prognostic Impact in Colorectal Cancer Patients.

The tumor microenvironment of colorectal cancer (CRC) is heterogenous; thus, it is likely that multiple immune-related and inflammatory markers are simultaneously expressed in the tumor. The aim of this study was to identify immune-related and inflammatory markers expressed in freshly frozen CRC tissues and to investigate whether they are related to the clinicopathological features and prognosis of CRC. Seventy patients with CRC who underwent curative surgical resection between December 2014 and January 2017 were included in this study. Tissue samples were obtained from tumor and non-tumor areas in the patients' colons. The concentrations of immune-related markers (APRIL/TNFSF13, BAFF, LAG-3, PD-1, PD-L1, and CTLA-4) and inflammatory markers (CHIT, MMP-3, osteocalcin, pentraxin-3, sTNF-R1, and sTNF-R2) in the samples were measured using the Bio-plex Multiplex Immunoassay system. The concentrations of APRIL/TNFSF13, BAFF, and MMP-3 in the samples were significantly high; thus, we conducted analyses based on the cut-off values for these three markers. The high-APRIL/TNFSH13-expression group showed a significantly higher rate of metastatic lesions than the low-expression group, whereas the high-MMP-3-expression group had higher CEA levels, more lymph node metastases, and more advanced disease stages than the low-expression group. The five-year disease-free survival of the high-MMP-3-expression group was significantly shorter than that of the low-expression group (65.1% vs. 90.2%, p = 0.033). This study provides evidence that the APRIL/TNFSF13, BAFF, and MMP-3 pathway is overexpressed in CRC tissues and is associated with unfavorable clinicopathological features and poor prognosis in CRC patients. These markers could serve as diagnostic or prognostic biomarkers for CRC.

Impact of customer incivility on restaurant employee stress spread and turnover: COVID-19 vaccination mandate.

In response to the unprecedented pandemic in recent history, COVID-19 vaccination mandates in the U.S. caused significant changes and disruption in hospitality operations and customer experiences. The primary goal of this study is to examine whether and how customer incivility induced by the COVID-19 vaccine mandate in the U.S. affects employees' behavioral outcomes (i.e., stress spread between employees and turnover intention) via psychological mechanisms (i.e., stress and negative emotion) and when the relationship is moderated by personal (employee prosocial motivation) and organizational (supervisor support) characteristics. Findings show that customer incivility increases employee turnover intention as well as interpersonal conflicts at work via increased stress and negative emotions. These relationships are weakened when prosocial motivation of employees and the level of supervisor support is high. Findings expand the occupational stress model by specifically incorporating the context of the COVID-19 vaccine mandate and further provide implications for restaurant managers and policy makers.

The effect of vaccination during the COVID-19 for the restaurant industry.

The purpose of the study is to determine whether vaccination rates and the use of franchising have an impact on the volatility of stock returns in the restaurant industry. Based on the agency and resource scarcity theories, this study first examines the effect of vaccinations against COVID-19 on a restaurant firm's stock return volatilities caused by uncertainty during a crisis. The study further investigates whether firm-specific vaccination rates more greatly reduce stock return volatilities as the degree of franchising increases. With a two-way fixed-effects model, the study finds that the firm-specific vaccination rate reduces volatilities of the firm's stock returns. However, the study also finds an opposite direction to the moderating effect of franchising in that the more a restaurant firm franchises, the further the risk-reduction effect of its vaccination rate diminishes. Theoretical and practical implications along with limitations are discussed.

The effects of orthodontic treatment on personal dental expenditures in South Korea: a follow-up study using Korean health panel survey.

BACKGROUND: This study aimed to investigate the effects of orthodontic treatment on cumulative out-of-pocket (OOP) expenditures for up to 8 years and the factors contributing to changes in individual OOP dental expenses. METHODS: The data of adults aged ≥19 years, 218 with experience of orthodontic treatment (OT group) and 654 without experience of orthodontic treatment (non-OT group) were extracted from the Korea Health Panel Survey between 2009 and 2017 using the propensity score matching method. The total personal OOP expenditure for dental care incurred after orthodontic treatment in the OT group and that incurred in the matched non-OT group were calculated. Since dependent variables, cumulative dental expenditures, were continuous with excess zeros, Tweedie compound Poisson linear models were used to explore the influence of orthodontic treatment experience and demographic and socioeconomic factors, including private insurance, on per capita OOP dental expenditures. RESULTS: The OT group had socioeconomic characteristics distinct from those of general dental patients. The Box-Cox transformed per capita OOP expenditures for dental care in the OT group were lower than those in the non-OT group (P < 0.05). When all covariates were held constant, the non-OT group spent 1.4-times more on OOP dental expenditures, but this was not statistically significant (P > 0.1). The data from those with higher incomes revealed the opposite trend (P < 0.05), while the other covariates were not statistically significant. CONCLUSIONS: Orthodontic treatment had no positive or negative effect on future oral care use. This finding is similar to the inconsistent results of previous clinical studies on oral health and orthodontic treatment.

Reshaping wound care: Evaluation of an artificial intelligence app to improve wound assessment and management amid the COVID-19 pandemic.

Wound documentation is integral to effective wound care, health data coding and facilitating continuity of care. This study evaluated the usability and effectiveness of an artificial intelligence application for wound assessment and management from a clinician-and-patient user perspective. A quasi-experimental design was conducted in four settings in an Australian health service. Data were collected from patients in the standard group (n = 166, 243 wounds) and intervention group (n = 124, 184 wounds), at baseline and post-intervention. Clinicians participated in a survey (n = 10) and focus group interviews (n = 13) and patients were interviewed (n = 4). Wound documentation data were analysed descriptively, and bivariate statistics were used to determine between-group differences. Thematic analysis of interviews was conducted. Compared with the standard group, wound documentation in the intervention group improved significantly (more than two items documented 24% vs 70%, P < .001). During the intervention, 101 out of 132 wounds improved (mean wound size reduction = 53.99%). Positive evaluations identified improvements such as instantaneous objective wound assessment, shared wound plans, increased patient adherence and enhanced efficiency in providing virtual care. The use of the application facilitated remote patient monitoring and reduced patient travel time while maintaining optimal wound care.

Information and communication technology for physical activity in persons living with dementia: A systematic review with implications for evidence-based practice.

BACKGROUND: Persons living with dementia often encounter many difficulties in their community due to functional limitations. Information and Communication Technology (ICT) could be useful to monitor changes in their physical function. However, there is a lack of systematic reviews about using ICT for physical activity. AIM: This review aimed to synthesize the literature regarding the use of ICT to monitor the physical activity of persons living with dementia. METHODS: A systematic search was conducted in five electronic databases using search terms derived from the Patient, Intervention, Comparison, Outcome (PICO) framework. We included articles published in English from 2011 to 2021. Quality of the included studies was evaluated by two independent authors using the Mixed Methods Appraisal Tool (MMAT). RESULTS: Thirty-three quantitative studies were included for review. Included studies showed fairly good quality in the MMAT evaluation. Wearable devices were mainly employed (88%). The ICTs were used to objectively measure physical activity, activity status, gait, and circadian rhythm. ICTs have been utilized for four purposes: (1) comparing physical activity within the dementia subgroups or with the normal group, (2) exploring the relationship with other variables, 3) examining the experimental study's outcomes, and (4) checking the sensors' feasibility. The results demonstrated that ICT devices were feasible to use in persons living with dementia in the community, helpful for monitoring the physical activity of persons living with dementia, and useful for improving physical activity when properly incorporated in care planning. LINKING EVIDENCE TO ACTION: ICTs can help gather objective data regarding the type, intensity, and level of physical activity in persons living with dementia without time constraints. Also, ICTs use in persons living with dementia in the community was acceptable. We suggest future studies to activate and use ICTs in dementia research.

Male size and reproductive performance in three species of livebearing fishes (Gambusia spp.): A systematic review and meta-analysis.

The genus Gambusia represents approximately 45 species of polyandrous livebearing fishes with reversed sexual size dimorphism (i.e. males smaller than females) and with copulation predominantly via male coercion. Male body size has been suggested as an important sexually selected trait, but despite abundant research, evidence for sexual selection on male body size in this genus is mixed. Studies have found that large males have an advantage in both male-male competition and female choice, but that small males perform sneaky copulations better and at higher frequency and thus may sire more offspring in this coercive mating system. Here, we synthesized this inconsistent body of evidence using pre-registered methods and hypotheses. We performed a systematic review and meta-analysis of summary and primary (raw) data combining both published (n = 19 studies, k = 106 effect sizes) and unpublished effect sizes (n = 17, k = 242) to test whether there is overall selection on male body size across studies in Gambusia. We also tested several specific hypotheses to understand the sources of heterogeneity across effects. Meta-analysis revealed an overall positive correlation between male size and reproductive performance (r = 0.23, 95% confidence interval: 0.10-0.35, n = 36, k = 348, 4,514 males, three Gambusia species). Despite high heterogeneity, the large-male advantage appeared robust across all measures studied (i.e. female choice, mating success, paternity, sperm quantity and quality), and was considerably larger for female choice (r = 0.43, 95% confidence interval: 0.28-0.59, n = 14, k = 43). Meta-regressions found several important factors explaining heterogeneity across effects, including type of sperm characteristic, male-to-female ratio, female reproductive status and environmental conditions. We found evidence of publication bias; however, its influence on our estimates was attenuated by including a substantial amount of unpublished effects, highlighting the importance of open primary data for more accurate meta-analytic estimates. In addition to positive selection on male size, our study suggests that we need to rethink the role and form of sexual selection in Gambusia and, more broadly, to consider the ecological factors that affect reproductive behaviour in livebearing fishes.

The influence of poverty attribution on attitudes toward suicide and suicidal thought: A cross-national comparison between South Korean, Japanese, and American populations.

BACKGROUND: Previous studies report that income inequality is an important risk factor for depression and suicide, and an increasing income gap appears inevitable. However, little study to date has investigated associations between the attribution of poverty and suicide. Though we previously reported associations between socio-cultural factors, including income, and suicide, we tried to explore more focused associations between income, attribution of poverty (individualistic, societal), permissive attitude toward suicide, and suicidal thought using a structural equation model. METHODS: A total of 2213 participants from each of three nations (South Korea, Japan, and the United States) completed an online survey. Participants without a history of psychological disorders or suicide attempts completed scales measuring attributions of poverty, attitudes toward suicide, and severity of suicidal thoughts. RESULTS: We established a structural equation model, which exhibited a good fit for all nations, and compared significant path coefficients by country. South Korea had the highest severity of suicidal thought and societal attribution of poverty, followed by Japan and America. In all nations, a permissive attitude was positively related to the severity of suicidal thought and individualistic attribution of poverty was positively related to a permissive attitude toward suicide. Societal attribution of poverty was positively associated with a permissive attitude in Japan and the United States. Income was negatively associated with the severity of suicide in South Korea and the United States. CONCLUSION: Through an established structural equation model, we found the influence of poverty on suicide and identify the common and distinctive factors associated with suicide in each country.

Plasmopara viticola causing downy mildew on Vitis davidii in Korea.

Vitis davidii (Rom.Caill.) Foëx, commonly known as spine grape, is a deciduous climber native to China. Its fruits are consumed fresh or used to make wine in South and Central China. In recent years, spine grape has been cultivated in Korea. In July 2020, downy mildew was detected on spine grape vines in Jeongeup (35°42'17″N, 126°54'02″E), Korea, with a disease incidence of 70%. The symptoms appeared as yellowish, brownish, or reddish, vein-limited, poly-angular adaxial leaf spots, correspond to dense, white downy growth abaxially. A representative specimen was deposited in the Kunsan National University Herbarium (KSNUH679). Sporangiophores were tree-like, hyaline, mostly straight, and monopodially branched in orders of three to six; they measured (219.4-)273.2 to 435.1(-546.6) × (4.8-)6.7 to 9.0(-10.0) µm (n = 50). Ultimate branchlets were bi or trifurcate, straight to slightly curved, with truncate or, rarely, a swollen tip and measured 2.9 to 9.7 µm long and 0.8 to 2.5 µm wide at the base (n = 50). Sporangia were hyaline, ovoidal or lemon-shaped; they measured (16.8-)20.0 to 28.8(-34.2) × (11.4-)13.1 to 17.0(-20.1) µm with a length to width ratio of (1.28-)1.46 to 1.78(-2.07) (n = 50). This morphology was as described for Plasmopara viticola (Berk. & M. A. Curtis) Berl. & De Toni (Hall, 1989). Genomic DNA was extracted directly from infected V. davidii leaves. Three regions were PCR-amplified and sequenced: cox2 mtDNA with primers cox2F and cox2-RC4 (Choi et al., 2015), actin with primers pve04815-F and pve04815-R, and beta-tubulin with primers pvc389-F3 and pvc389-R4 (Rouxel et al., 2013). The resulting sequences were deposited in GenBank (accession nos. MT834527 for cox2, MT834525 for actin, and MT834526 for beta-tubulin). A BLASTn search revealed that the Korean sample was identical to P. viticola clade aestivalis originating from Vitis species: MK215072 for cox2 sequence, KY933800 for actin, and MK358393 for beta-tubulin. In all phylogenetic analyses of the three genes (cox2, actin, and beta-tubulin), KSNUH679 came out as phylogenetically place within P. viticola clade aestivalis, which has recently been reported on V. coignetiae and V. ficifolia var. sinuata in Korea (Kim et al., 2019). A pathogenicity test was performed twice by inoculating the leaves of 10 healthy spine grape plants with a sporangial suspension (~1 × 106 sporangia·mL-1) and incubating them in a growth chamber at 25 °C, 12-h day/night cycle, and 90% relative humidity; five non-inoculated plants served as controls. After two weeks, all inoculated plants developed typical downy mildew symptoms could be observed, whereas the controls remained symptomless. Morphology and molecular features confirmed the identity of the pathogen of spine grape to be P. viticola. To the best of our knowledge, this is the first report of downy mildew caused by P. viticola on V. davidii in Korea. Recently, downy mildew outbreaks caused by P. viticola have been recorded in spine grape plantations in southern China (Yi et al., 2019). Considering the potential of spine grape as a novel crop for Korea, P. viticola appears to represent a significant threat to this industry.

Ischemia-Reperfusion under Hyperthermia Increases Heme Oxygenase-1 in Pyramidal Neurons and Astrocytes with Accelerating Neuronal Loss in Gerbil Hippocampus.

It has been studied that the damage or death of neurons in the hippocampus is different according to hippocampal subregions, cornu ammonis 1-3 (CA1-3), after transient ischemia in the forebrain, showing that pyramidal neurons located in the subfield CA1 (CA1) are most vulnerable to this ischemia. Hyperthermia is a proven risk factor for brain ischemia and can develop more severe and extensive brain damage related with mortality rate. It is well known that heme oxygenase-1 (HO-1) activity and expression is increased by various stimuli in the brain, including hyperthermia. HO-1 can be either protective or deleterious in the central nervous system, and its roles depend on the expression levels of enzymes. In this study, we investigated the effects of hyperthermia during ischemia on HO-1 expression and neuronal damage/death in the hippocampus to examine the relationship between HO-1 and neuronal damage/death following 5-min transient ischemia in the forebrain using gerbils. Gerbils were assigned to four groups: (1) sham-operated gerbils with normothermia (Normo + sham group); (2) ischemia-operated gerbils with normothermia (Normo + ischemia group); (3) sham-operated gerbils with hyperthermia (39.5 ± 0.2 °C) during ischemia (Hyper + sham group); and (4) ischemia-operated gerbils with hyperthermia during ischemia (Hyper + ischemia group). HO-1 expression levels in CA1-3 of the Hyper + ischemia group were significantly higher than those in the Normo + ischemia group. HO-1 immunoreactivity in the Hyper + ischemia group was significantly increased in pyramidal neurons and astrocytes with time after ischemia, and the immunoreactivity was significantly higher than that in the Normo + ischemia group. In the Normo + Ischemia group, neuronal death was shown in pyramidal neurons located only in CA1 at 5 days after ischemia. However, in the Hyper + ischemia group, pyramidal neuronal death occurred in CA1-3 at 2 days after ischemia. Taken together, our findings showed that brain ischemic insult during hyperthermic condition brings up earlier and severer neuronal damage/death in the hippocampus, showing that HO-1 expression in neurons and astrocytes is different according to brain subregions and temperature condition. Based on these findings, we suggest that hyperthermia in patients with ischemic stroke must be taken into the consideration in the therapy.

CD200 Change Is Involved in Neuronal Death in Gerbil Hippocampal CA1 Field Following Transient Forebrain Ischemia and Postischemic Treatment with Risperidone Displays Neuroprotection without CD200 Change.

It has been reported that CD200 (Cluster of Differentiation 200), expressed in neurons, regulates microglial activation in the central nervous system, and a decrease in CD200 expression causes an increase in microglial activation and neuronal loss. The aim of this study was to investigate time-dependent changes in CD200 expression in the hippocampus proper (CA1, 2, and 3 fields) after transient forebrain ischemia for 5 min in gerbils. In this study, 5-min ischemia evoked neuronal death (loss) of pyramidal neurons in the CA1 field, but not in the CA2/3 fields, at 5 days postischemia. In the sham group, CD200 expression was found in pyramidal neurons of the CA1 field, and the immunoreactivity in the group with ischemia was decreased at 6 h postischemia, dramatically increased at 12 h postischemia, decreased (to level found at 6 h postischemia) at 1 and 2 days postischemia, and significantly increased again at 5 days postischemia. At 5 days postischemia, CD200 immunoreactivity was strongly expressed in microglia and GABAergic neurons. However, in the CA3 field, the change in CD200 immunoreactivity in pyramidal neurons was markedly weaker than that in the CA1 field, showing there was no expression of CD 200 in microglia and GABAergic neurons. In addition, treatment of 10 mg/kg risperidone (an atypical antipsychotic drug) after the ischemia hardly changed CD200 immunoreactivity in the CA1 field, showing that CA1 pyramidal neurons were protected from the ischemic injury. These results indicate that the transient ischemia-induced change in CD200 expression may be associated with specific and selective neuronal death in the hippocampal CA1 field following transient forebrain ischemia.

Increased Calbindin D28k Expression via Long-Term Alternate-Day Fasting Does Not Protect against Ischemia-Reperfusion Injury: A Focus on Delayed Neuronal Death, Gliosis and Immunoglobulin G Leakage.

Calbindin-D28k (CB), a calcium-binding protein, mediates diverse neuronal functions. In this study, adult gerbils were fed a normal diet (ND) or exposed to intermittent fasting (IF) for three months, and were randomly assigned to sham or ischemia operated groups. Ischemic injury was induced by transient forebrain ischemia for 5 min. Short-term memory was examined via passive avoidance test. CB expression was investigated in the Cornu Ammonis 1 (CA1) region of the hippocampus via western blot analysis and immunohistochemistry. Finally, histological analysis was used to assess neuroprotection and gliosis (microgliosis and astrogliosis) in the CA1 region. Short-term memory did not vary significantly between ischemic gerbils with IF and those exposed to ND. CB expression was increased significantly in the CA1 pyramidal neurons of ischemic gerbils with IF compared with that of gerbils fed ND. However, the CB expression was significantly decreased in ischemic gerbils with IF, similarly to that of ischemic gerbils exposed to ND. The CA1 pyramidal neurons were not protected from ischemic injury in both groups, and gliosis (astrogliosis and microgliosis) was gradually increased with time after ischemia. In addition, immunoglobulin G was leaked into the CA1 parenchyma from blood vessels and gradually increased with time after ischemic insult in both groups. Taken together, our study suggests that IF for three months increases CB expression in hippocampal CA1 pyramidal neurons; however, the CA1 pyramidal neurons are not protected from transient forebrain ischemia. This failure in neuroprotection may be attributed to disruption of the blood-brain barrier, which triggers gliosis after ischemic insults.

Neuroprotective and Anti-Inflammatory Effects of Pinus densiflora Bark Extract in Gerbil Hippocampus Following Transient Forebrain Ischemia.

Korean red pine (Pinus densiflora) belongs to the Genus Pinus, and its bark contains a great amount of naturally occurring phenolic compounds. Until now, few studies have been conducted to assess the neuroprotective effects of Pinus densiflora bark extract against brain ischemic injury. The aim of this study was to investigate the neuroprotective effects of pre-treatment with the extract in the hippocampus following 5-min transient forebrain ischemia in gerbils. Furthermore, this study examined the anti-inflammatory effect as a neuroprotective mechanism of the extract. Pinus densiflora bark was extracted by pure water (100 °C), and this extract was quantitatively analyzed and contained abundant polyphenols, flavonoids, and proanthocyanidins. The extract (25, 50, and 100 mg/kg) was orally administered once a day for seven days before the ischemia. In the gerbil hippocampus, death of the pyramidal neurons was found in the subfield cornu ammonis 1 (CA1) five days after the ischemia. This death was significantly attenuated by pre-treatment with 100 mg/kg, not 25 or 50 mg/kg, of the extract. The treatment with 100 mg/kg of the extract markedly inhibited the activation of microglia (microgliosis) and significantly decreased the expression of pro-inflammatory cytokines (interleukin 1ß and tumor necrosis factor α). In addition, the treatment significantly increased anti-inflammatory cytokines (interleukin 4 and interleukin 13). Taken together, this study clearly indicates that pre-treatment with 100 mg/kg of Pinus densiflora bark extract in gerbils can exert neuroprotection against brain ischemic injury by the attenuation of neuroinflammatory responses.