COVID-19 Pandemic-Related Job Loss Impacts on Mental Health in South Korea.

OBJECTIVE: The economic hardship brought by the coronavirus disease-2019 (COVID-2019) pandemic has caused mental health problems among people of different socioeconomic status (SES). As social support helps to buffer these problems, we investigated the association between job loss related to COVID-19 and depression, anxiety, and suicidal thoughts; the differences in the effects according to SES; and the mediating effects of social support. METHODS: The effects of COVID-19-related job loss on depression, anxiety, and suicidal thoughts among 1,364 people were investigated through semi-structured and self-administered questionnaires: Patient Health Questionnaire-9, General Anxiety Disorder-7, and the Functional Social Support Questionnaire. Logistic regression and subgroup analyses were performed to assess the association between job loss and mental health status, and the moderating effects of income and educational levels. Moreover, the mediating effects of perceived social support on the association between job loss and depression, anxiety, and suicidal thoughts were analyzed. RESULTS: COVID-19-related job loss increased the risk of depression and suicidal thoughts. Adults with lower income and education level were at higher risk of depression, anxiety, and suicidal thoughts; perceived social support level had significant mediating effects on the association between job loss and depression/anxiety; and income level had significant moderating effects on this mediating pathway. CONCLUSION: COVID-19-related job loss were likely to be significantly associated with negative mental health outcomes, especially among individuals with low income and education levels. As social support had buffering effects on such outcomes, related government policies in cooperation with the governance of communities and stakeholders must be prepared.

Exploring Fear of Cancer Recurrence (FCR) in cancer survivors from a medical social work perspective: A qualitative study of medical social workers in South Korea.

BACKGROUND: Fear of Cancer Recurrence (FCR) in cancer survivors has been insufficiently addressed despite its imperativeness in cancer journey. Although several studies have investigated healthcare professionals' experience with FCR in cancer survivors, a medical social work perspective has rarely been reflected. This study aimed to explore Korean medical social workers' experience with intervening FCR in cancer survivors. METHODS: Snowball sampling recruited 12 experienced medical social workers intervening with cancer survivors at tertiary or university cancer hospitals in South Korea. Individual and focus-group interviews (FGI) were conducted with the medical social workers. The interviews were recorded, transcribed, and analyzed by using an inductive qualitative content analysis. RESULTS: Content analysis of the interviews extracted the following major themes regarding FCR in cancer survivors. First, when and how FCR among cancer survivors emerged at the early stage of medical social work interventions was identified. Second, how medical social workers dealt with FCR in cancer survivors was illustrated. Third, the responses of cancer survivors to medical social work interventions for FCR were assessed. Finally, the internal and external issues underlying the medical social work interventions for FCR among cancer survivors were revealed and discussed. CONCLUSION: Based on the results, this study suggested the implications on dealing with FCR in cancer survivors in the realm of medial social work profession. Furthermore, it expanded the discussion about FCR in cancer survivors from cancer hospitals to community.

Time-Series Trends of Depressive Levels of Korean Adults During the 2020 COVID-19 Pandemic in South Korea.

OBJECTIVE: This study aimed to observe the changes in people's depressive levels over 9 months since the coronavirus disease of 2019 (COVID-19) outbreak as well as to identify the predictors of people's depressive levels including COVID-19 infection fear in the context of South Korea in 2020. METHODS: For these purposes, four cross-sectional surveys were periodically implemented from March to December 2020. We randomly recruited 6,142 Korean adults (aged 19 to 70) by using a quota survey. Along with descriptive analysis, which included a one-way analysis of variance and correlations, multiple regression models were built to identify the predictors of people's depressive levels during the pandemic. RESULTS: Overall, people's depressive levels and fear of COVID-19 infection gradually increased since the COVID-19 outbreak. In addition to demographic variables (i.e., being a female, young age, unemployed, and living alone) and the duration of the pandemic, people's COVID-19 infection fear was associated with their depressive levels. CONCLUSION: To ameliorate these rising mental health issues, access to mental health services should be secured and expanded, particularly for individuals who present greater vulnerabilities due to socioeconomic characteristics that may affect their mental health.

Factors Related to Anxiety and Depression Among Adolescents During COVID-19: A Web-Based Cross-Sectional Survey.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak and subsequent disease-containment measures (such as school closures) significantly affected the lives of adolescents. We evaluated the mental-health status and factors associated with anxiety and depression among South Korean adolescents. METHODS: A nationwide online survey was conducted to evaluate the mental-health status of South Korean adolescents during the COVID-19 pandemic. In total, 570 adolescents aged 13-18 years were surveyed between May 27 and June 11, 2021. The participants completed the Generalized Anxiety Disorder Scale (GAD-7) and Patient Health Questionnaire (PHQ-9) to determine anxiety and depression symptoms, respectively. Stepwise logistic regression models were constructed to determine factors related to anxiety and depression. RESULTS: Among the study participants, 11.2% and 14.2% had anxiety and depression, respectively. The results suggested that several factors, such as the experience of COVID-19 infection and quarantine of oneself, a family member or an acquaintance, physical and mental health problems, and fear of one's local community being discriminated against as a COVID-19 area were related to anxiety and depression. CONCLUSION: The present study identified COVID-19-related factors associated with anxiety and depression among adolescents, and provides insights regarding potential interventions to improve the mental health of adolescents. To promote the mental health of adolescents during the COVID-19 pandemic, special attention should be paid to individuals with physical or mental-health problems, and efforts should be made to reduce the negative social and emotional impacts of infection-control measures.

Platelet-Mediated NET Release Amplifies Coagulopathy and Drives Lung Pathology During Severe Influenza Infection.

The influenza A virus (IAV) causes a respiratory tract infection with approximately 10% of the population infected by the virus each year. Severe IAV infection is characterized by excessive inflammation and tissue pathology in the lungs. Platelet and neutrophil recruitment to the lung are involved in the pathogenesis of IAV, but the specific mechanisms involved have not been clarified. Using confocal intravital microscopy in a mouse model of IAV infection, we observed profound neutrophil recruitment, platelet aggregation, neutrophil extracellular trap (NET) production and thrombin activation within the lung microvasculature in vivo. Importantly, deficiency or antagonism of the protease-activated receptor 4 (PAR4) reduced platelet aggregation, NET production, and neutrophil recruitment. Critically, inhibition of thrombin or PAR4 protected mice from virus-induced lung tissue damage and edema. Together, these data imply thrombin-stimulated platelets play a critical role in the activation/recruitment of neutrophils, NET release and directly contribute to IAV pathogenesis in the lung.

COVID-19 and Risk Factors of Anxiety and Depression in South Korea.

OBJECTIVE: The aims of this study were to explore the prevalence of and identify predictors of anxiety and depression related to coronavirus disease of 2019 (COVID-19) in South Korea. METHODS: The analysis is based on a quota survey design and a sampling frame that permitted recruitment of a national sample of 1,014 individuals between March 17-31, 2020. Several standardized measurements were used, including GAD-7, PHQ-9, COVID-19 related fear, restrictions in deaily life, as well as sociodemographic information and physical and psychosocial needs during the pandemic. Multiple logistic regression was conducted to analyze the influence of sociodemographic factors, fear, and physical/psychosocial needs on anxiety and depression. RESULTS: Significant numbers of the respondents were identifiable anxiety (19.0%) and depression group (17.5%), respectively. This indicates that the depression and anxiety prevalence rate after the COVID-19 is substantially high compared to the depression rate of 2.6% in 2020 and 2.8% in 2018 both reported in the Korea Community Health Survey and the anxiety rate of 5.7% reported in 2016 Survey of Mental Disorders in Korea. Multiple logistic regression results showed age, COVID-19 related fear, and the level of restrictions in daily as significant factors in understanding and predicting the anxiety group. Likfewise, the COVID-19 related fear, restrictions in daily life, and need for economic support were important predictors in predicting the depression group. CONCLUSION: Findings on predictors for greater vulnerability to anxiety and depression has important implications for public mental health in the context of the COVID-19 pandemic.

Modulation of the liver immune microenvironment by the adeno-associated virus serotype 8 gene therapy vector.

Adeno-associated viruses (AAVs) are emerging as one of the vehicles of choice for gene therapy. However, the potential immunogenicity of these vectors is a major limitation of their use, leading to the necessity of a better understanding of how viral vectors engage the innate immune system. In this study, we demonstrate the immune response mediated by an AAV vector in a mouse model. Mice were infected intravenously with 4 × 1012 copies (cp)/kg of AAV8, and the ensuing immune response was analyzed using intravital microscopy during a period of weeks. Administration of AAV8 resulted in the infection of hepatocytes, and this infection led to a moderate, but significant, activation of the immune system in the liver. This host immune response involved platelet aggregation, neutrophil extracellular trap (NET) formation, and the recruitment of monocytes, B cells, and T cells. The resident liver macrophage population, Kupffer cells, was necessary to initiate this immune response, as its depletion abrogated platelet aggregation and NET formation and delayed the recruitment of immune cells. Moreover, the death of liver cells produced by this AAV was moderate and failed to result in a robust, sustained inflammatory response. Altogether, these data suggest that AAV8 is a suitable vector for gene therapy approaches.

Visualizing Oncolytic Virus-Host Interactions in Live Mice Using Intravital Microscopy.

Oncolytic virus (OV) therapy is an emerging cancer treatment that uses replicating viruses to infect and kill tumor cells and incite anticancer immunity. While the approach shows promise, it currently fails most patients, indicating strategies to improve OV activity are needed. Developing these will require greater understanding of OV biology, particularly in the context of OV delivery and clearance, the infection process within a complex tumor microenvironment, and the modulation of anticancer immunity. To help achieve this, we have established a technique for high-resolution 4D imaging of OV-host interactions within intact tissues of live mice using intravital microscopy (IVM). We show that oncolytic vesicular stomatitis virus (VSV) directly labeled with Alexa Fluor dyes is easily visualized by single- or multiphoton microscopy while retaining bioactivity in vivo. The addition of fluorophore-tagged antibodies and genetically encoded reporter proteins to image target cells and the virus infection enables real-time imaging of dynamic interactions between VSV and host cells in blood, tumor, and visceral organs of live mice. The method has sufficient in vivo resolution to observe leukocytes in blood binding to and transporting VSV particles, foci of VSV infection spreading through a tumor, and antigen-presenting cells in the spleen interacting with and being infected by VSV. Visualizing OV-host interactions by IVM represents a powerful new tool for studying OV therapy.

Neutrophils in viral infection.

Neutrophils are the first wave of recruited immune cells to sites of injury or infection and are crucial players in controlling bacterial and fungal infections. Although the role of neutrophils during bacterial or fungal infections is well understood, their impact on antiviral immunity is much less studied. Furthermore, neutrophil function in tumor pathogenesis and cancer treatment has recently received much attention, particularly within the context of oncolytic virus infection where neutrophils produce antitumor cytokines and enhance oncolysis. In this review, multiple functions of neutrophils in viral infections and immunity are discussed. Understanding the role of neutrophils during viral infection may provide insight into the pathogenesis of virus infections and the outcome of virus-based therapies.

Platelets as Modulators of Inflammation.

Platelets have classically been considered crucial effector cells in hemostasis, but now are increasingly recognized as players during inflammatory responses in innate and adaptive immunity. Platelets can recognize and kill invading pathogens, and, upon stimulation, also release a wide array of mediators that modify immune and endothelial cell responses. Increased platelet activity can protect the host against infectious insults; however, the excessive activity can lead to inflammation-mediated tissue damage. These critical roles highlight the necessity of balancing the platelet response at the intersection of hemostasis and inflammation. In this review, the authors present the current understanding of the inflammatory role of platelets. They also highlight recent findings on a modulator that links inflammation and deleterious tissue damage in disease pathogenesis.

Necrostatin-1 Protects Against D-Galactosamine and Lipopolysaccharide-Induced Hepatic Injury by Preventing TLR4 and RAGE Signaling.

Fulminant hepatic failure (FHF) is a life-threatening clinical syndrome results in massive inflammation and hepatocyte death. Necroptosis is a regulated form of necrotic cell death that is emerging as a crucial control point for inflammatory diseases. The kinases receptor interacting protein (RIP) 1 and RIP3 are known as key modulators of necroptosis. In this study, we investigated the impact of necroptosis in the pathogenesis of FHF and molecular mechanisms, particularly its linkage to damage-associated molecular pattern (DAMP)-mediated pattern recognition receptor (PRR) signaling pathways. Male C57BL/6 mice were given an intraperitoneal injection of necrostatin-1 (Nec-1, RIP1 inhibitor; 1.8 mg/kg; dissolved in 2% dimethyl sulfoxide in phosphate-buffered saline) 1 h before receiving D-galactosamine (GalN; 800 mg/kg)/lipopolysaccharide (LPS; 40 µg/kg). Hepatic RIP1, RIP3 protein expression, their phosphorylation, and RIP1/RIP3 complex formation upregulated in the GalN/LPS group were attenuated by Nec-1. Nec-1 markedly reduced the increases in mortality and serum alanine aminotransferase activity induced by GalN/LPS. Increased serum high mobility group box 1 (HMGB1) and interleukin (IL)-33 release, HMGB1-toll-like receptor 4 and HMGB1-receptor for advanced glycation end products (RAGE) interaction, and nuclear protein expressions of NF-κB and early growth response protein-1 (egr-1) were attenuated by Nec-1. Our finding suggests that necroptosis is responsible for GalN/LPS-induced liver injury through DAMP-activated PRR signaling.

Genipin protects d-galactosamine and lipopolysaccharide-induced hepatic injury through suppression of the necroptosis-mediated inflammasome signaling.

Acute liver failure (ALF) is a life-threatening syndrome resulting from massive inflammation and hepatocyte death. Necroptosis, a programmed cell death controlled by receptor-interacting protein kinase (RIP) 1 and RIP3, has been shown to play an important role in regulating inflammation via crosstalk between other intracellular signaling. The inflammasome is a major intracellular multiprotein that induces inflammatory responses by mediating immune cell infiltration, thus potentiating injury. Genipin, a major active compound of the gardenia fruit, exhibits anti-inflammatory, antioxidant, and anti-apoptotic properties. This study investigated the hepatoprotective mechanisms of genipin on d-galactosamine (GalN) and lipopolysaccharide (LPS)-induced ALF, particularly focusing on interaction between necroptosis and inflammasome. Mice were given an intraperitoneal injection of genipin (25, 50, and 100mg/kg) or necrostatin-1 (Nec-1, a necroptosis inhibitor; 1.8mg/kg) 1h prior to GalN (800mg/kg)/LPS (40µg/kg) injection and were killed 3h after GalN/LPS injection. Genipin improved the survival rate and attenuated increases in serum aminotransferase activities and inflammatory cytokines after GalN/LPS injection. Genipin reduced GalN/LPS-induced increases in RIP3, phosphorylated RIP1 and RIP3 protein expression, and RIP1/RIP3 necrosome complex, similar to the effects of Nec-1. GalN/LPS significantly increased serum levels of high-mobility group box 1 and interleukin (IL)-33, which were attenuated by genipin and Nec-1. Moreover, similar to Nec-1, genipin attenuated GalN/LPS-induced increases in the protein expression levels of NLRP3, ASC, and caspase-1, inflammasome components, and levels of liver and serum IL-1ß. Taken together, our findings suggest that genipin ameliorates GalN/LPS-induced hepatocellular damage by suppressing necroptosis-mediated inflammasome signaling.

Platelets and neutrophil extracellular traps collaborate to promote intravascular coagulation during sepsis in mice.

Neutrophil extracellular traps (NETs; webs of DNA coated in antimicrobial proteins) are released into the vasculature during sepsis where they contribute to host defense, but also cause tissue damage and organ dysfunction. Various components of NETs have also been implicated as activators of coagulation. Using multicolor confocal intravital microscopy in mouse models of sepsis, we observed profound platelet aggregation, thrombin activation, and fibrin clot formation within (and downstream of) NETs in vivo. NETs were critical for the development of sepsis-induced intravascular coagulation regardless of the inciting bacterial stimulus (gram-negative, gram-positive, or bacterial products). Removal of NETs via DNase infusion, or in peptidylarginine deiminase-4-deficient mice (which have impaired NET production), resulted in significantly lower quantities of intravascular thrombin activity, reduced platelet aggregation, and improved microvascular perfusion. NET-induced intravascular coagulation was dependent on a collaborative interaction between histone H4 in NETs, platelets, and the release of inorganic polyphosphate. Real-time perfusion imaging revealed markedly improved microvascular perfusion in response to the blockade of NET-induced coagulation, which correlated with reduced markers of systemic intravascular coagulation and end-organ damage in septic mice. Together, these data demonstrate, for the first time in an in vivo model of infection, a dynamic NET-platelet-thrombin axis that promotes intravascular coagulation and microvascular dysfunction in sepsis.

Role of platelets in neutrophil extracellular trap (NET) production and tissue injury.

In addition to their well-known role as the cellular mediator of thrombosis, numerous studies have identified key roles for platelets during various disease processes. Importantly, platelets play a critical role in the host immune response, directly interacting with, and eliminating pathogens, from the blood stream. In addition to pathogen clearance, platelets also contribute to leukocyte recruitment at sites of infection and inflammation, and modulate leukocyte activity. Platelet interaction with activated neutrophils is a potent inducer of neutrophil extracellular trap (NET). NETs consist of a diffuse, sticky web of extracellular DNA, nuclear and granular proteins, and serve to ensnare and kill pathogens. In addition to catching pathogens, the cytotoxic molecules and proteases on NETs have the potential to inflict significant tissue damage. Additionally, NET components have been suggested to be key activators of infection-induced coagulopathy. These critical roles, at the interface between hemostasis and immunity, highlight the need for balance in the platelet response; too little platelet activity results in bleeding and immune deficit, too much leads to tissue pathogenesis. In this review, we highlight recent advances in our understanding of the role platelets play in inflammation, the link between platelets and NETs and the role platelets play in disease pathogenesis.

Role of necroptosis in autophagy signaling during hepatic ischemia and reperfusion.

Ischemia and reperfusion (I/R) is a complex phenomenon involving massive inflammation and cell death. Necroptosis refers to a newly described cell death as "programmed necrosis" that is controlled by receptor-interacting protein kinase (RIP) 1 and RIP3, which is involved in the pathogenesis of several inflammatory diseases. Autophagy is an essential cytoprotective system that is rapidly activated in response to various stimuli and involves crosstalk between different modes of cell death and inflammation. In this study, we investigated pattern changes in necroptosis and its role in autophagy signaling during hepatic I/R. Male C57BL/6 mice were subjected to 60min of ischemia followed by 3h reperfusion. Necrostatin-1 (Nec-1, a necroptosis inhibitor; 1.65mg/kg) was administered intraperitoneally 5min before reperfusion. Hepatic I/R significantly increased the level of RIP3, phosphorylated RIP1 and RIP3 protein expression, and RIP1/RIP3 necrosome formation, which were attenuated by Nec-1. I/R also significantly increased serum levels of alanine aminotransferase, tumor necrosis factor-α, and interleukin-6, which were attenuated by Nec-1. Meanwhile, hepatic I/R activated autophagy and mitophagy, as evidenced by increased LC3-II, PINK1, and Parkin, and decreased sequestosome 1/p62 protein expression. Nec-1 attenuated these changes and attenuated the increased levels of autophagy-related protein (ATG) 3, ATG7, Rab7, and cathepsin B protein expression during hepatic I/R. Moreover, hepatic I/R activated the extracellular signal-regulated kinase (ERK) pathway, and Nec-1 attenuated this increase. Taken together, our findings suggest that necroptosis contributes to hepatic damage during I/R, which induces autophagy via ERK activation.

Activation of NLRP3 and AIM2 inflammasomes in Kupffer cells in hepatic ischemia/reperfusion.

Inflammasome activation by danger signals in ischemia/reperfusion (I/R) injury is responsible for the sterile inflammatory response. Signals triggering formation and activation of the inflammasome involve the generation of oxidative stress. The aim of this study was to examine the molecular mechanisms of inflammasome activation and the involvement of reactive oxygen species in hepatic I/R. I/R induced the formation of nucleotide-binding domain leucine-rich repeat containing family pyrin domain containing 3 (NLRP3) and absent in melanoma 2 (AIM2) inflammasomes and the subsequent serum release of interleukin 1ß. Pannexin-1 inhibitor and anti-cathepsin B antibody attenuated I/R-induced inflammasome activation and hepatic injury. The expression of the thioredoxin-interacting protein gene and the interaction between NLRP3 and the thioredoxin-interacting protein increased after I/R. Treatment with the antioxidant N-acetylcysteine significantly attenuated protein conversion of interleukin 1ß after hepatic I/R. Moreover, pannexin-1 protein expression and cathepsin B release were strongly attenuated by N-acetylcysteine. The depletion of Kupffer cells with gadolinium chloride markedly decreased NLRP3 and AIM2 inflammasome expression and activation of their signaling pathways, and also reduced the level of caspase-1 protein in F4/80-positive cells. Our findings suggest that reactive-oxygen-species-mediated activation of NLRP3 and AIM2 inflammasomes leads to I/R-induced inflammatory responses in which Kupffer cells play a crucial role.

Protective effect of wild ginseng cambial meristematic cells on d-galactosamine-induced hepatotoxicity in rats.

BACKGROUND: Panax ginseng has a wide range of biological activities including anti-inflammatory, antioxidant, and immunomodulatory functions. Wild ginseng cambial meristematic cells (CMCs) were obtained from P. ginseng cambium. This study examined the protective mechanism of wild ginseng CMCs against d-galactosamine (GalN)-induced liver injury. GalN, a well-known hepatotoxicant, causes severe hepatocellular inflammatory damage and clinical features similar to those of human viral hepatitis in experimental animals. METHODS: Hepatotoxicity was induced in rats using GalN (700 mg/kg, i.p.). Wild ginseng CMCs was administered orally once a day for 2 wks, and then 2 h prior to and 6 h after GalN injection. RESULTS: Wild ginseng CMCs attenuated the increase in serum aminotransferase activity that occurs 24 h after GalN injection. Wild ginseng CMCs also attenuated the GalN-induced increase in serum tumor necrosis factor-α, interleukin-6 level, and hepatic cyclooxygenase-2 protein and mRNA expression. Wild ginseng CMCs augmented the increase in serum interleukin -10 and hepatic heme oxygenase-1 protein and mRNA expression that was induced by GalN, inhibited the increase in the nuclear level of nuclear factor-kappa B, and enhanced the increase in NF-E2-related factor 2. CONCLUSION: Our findings suggest that wild ginseng CMCs protects liver against GalN-induced inflammation by suppressing proinflammatory mediators and enhancing production of anti-inflammatory mediators.

Protective effects of lupeol against D-galactosamine and lipopolysaccharide-induced fulminant hepatic failure in mice.

This study examined the hepatoprotective effects of lupeol (1, a major active triterpenoid isolated from Adenophora triphylla var. japonica) against d-galactosamine (GalN) and lipopolysaccharide (LPS)-induced fulminant hepatic failure. Mice were orally administered 1 (25, 50, and 100 mg/kg; dissolved in olive oil) 1 h before GalN (800 mg/kg)/LPS (40 µg/kg) treatment. Treatment with GalN/LPS resulted in increased levels of serum alanine aminotransferase, tumor necrosis factor (TNF)-α, and interleukin (IL)-6, as well as increased mortality, all of which were attenuated by treatment with 1. In addition, levels of toll-like receptor (TLR)4, myeloid differentiation primary response gene 88, TIR-domain-containing adapter-inducing interferon-ß (TRIF), IL-1 receptor-associated kinase (IRAK)-1, and TNF receptor associated factor 6 protein expression were increased by GalN/LPS. These increases, except TRIF, were attenuated by 1. Interestingly, 1 augmented GalN/LPS-mediated increases in the protein expression of IRAK-M, a negative regulator of TLR signaling. Following GalN/LPS treatment, nuclear translocation of nuclear factor-κB and the levels of TNF-α and IL-6 mRNA expression increased, which were attenuated by 1. Together, the present findings suggest that lupeol (1) ameliorates GalN/LPS-induced liver injury, which may be due to inhibition of IRAK-mediated TLR inflammatory signaling.

Protective effect of linarin against D-galactosamine and lipopolysaccharide-induced fulminant hepatic failure.

Linarin was isolated from Chrysanthemum indicum L. Fulminant hepatic failure is a serious clinical syndrome that results in massive inflammation and hepatocyte death. Apoptosis is an important cellular pathological process in d-galactosamine (GalN)/lipopolysaccharide (LPS)-induced liver injury, and regulation of liver apoptosis might be an effective therapeutic method for fulminant hepatic failure. This study examined the cytoprotective mechanisms of linarin against GalN/LPS-induced hepatic failure. Mice were given an oral administration of linarin (12.5, 25 and 50mg/kg) 1h before receiving GalN (800 mg/kg)/LPS (40 µg/kg). Linarin treatment reversed the lethality induced by GalN/LPS. After 6h of GalN/LPS injection, the serum levels of alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor (TNF)-α, interleukin-6 and interferon-γ were significantly elevated. GalN/LPS increased toll-like receptor 4 and interleukin-1 receptor-associated kinase protein expression. These increases were attenuated by linarin. Linarin attenuated the increased expression of Fas-associated death domain and caspase-8 induced by GalN/LPS, reduced the cytosolic release of cytochrome c and caspase-3 cleavage induced by GalN/LPS, and reduced the pro-apoptotic Bim phosphorylation induced by GalN/LPS. However, linarin increased the level of anti-apoptotic Bcl-xL and phosphorylation of STAT3. Our results suggest that linarin alleviates GalN/LPS-induced liver injury by suppressing TNF-α-mediated apoptotic pathways.

Community factors predicting dental care utilization among older adults.

BACKGROUND: Few investigators have studied the influence of community factors on dental care utilization among older adults. The authors' objective in this study was to investigate the effect of community factors on dental care utilization after adjustment for individual factors. METHODS: Using data from a cross-sectional survey of Ohio residents, the authors assessed dental care utilization in a sample of 2,166 adults 65 years or older. They linked individual-level dental care utilization, predisposing factors (age, sex, race or ethnicity, marital status, education), enabling factors (poverty, dental insurance) and need-related factors (physical and mental health problems) with county-level data (socioeconomic environment and health resource environment) from the 2010 Area Health Resource Files (from the U.S. Department of Health and Human Services) and the American Community Survey (from the 2006-2010 U.S. census). By using multilevel logistic regression models, the authors evaluated the association between dental care utilization and community factors after adjustment for individual factors. RESULTS: The results indicated that individual factors such as being female, married and nonpoor and having a higher educational level and private dental insurance were associated with higher odds of having utilized dental care. Furthermore, older adults living in a county with a higher dentist-to-population ratio were more likely to use dental services even after the authors adjusted the results for the individual-level factors (odds ratio = 1.10; P = .03). CONCLUSIONS: County-level dentist-to-population ratio has independent effects on older adults' dental care utilization even after adjustment for individual-level characteristics. Practical Implications. A comprehensive policy plan is required to intervene at both the individual and community levels to improve dental care utilization among older adults. By understanding the factors influencing dental care utilization among older adults, U.S. dentists will be better positioned to meet the dental needs of this population.