Study of the soothing effects of troxerutin in alleviating skin sensitivity.

BACKGROUND: Transient receptor potential vanilloid 1 (TRPV1) is associated with skin sensitivity and mainly activated by capsaicin and heat. Interestingly, troxerutin can inhibit TRPV1 activation. However, its efficacy in reducing skin sensitivity remains undetermined. AIMS: We evaluated the efficacy of troxerutin in alleviating skin sensitivity using clinical tests and in vitro experiments. METHODS: For the in vitro experiment, HaCaT keratinocytes were pretreated with different concentrations of troxerutin, followed by incubation with 50 µM capsaicin for 1, 24, or 48 h. The gene and protein expressions of four inflammatory cytokines involved in skin irritation were determined. Among 35 Korean women with sensitive skin recruited for the clinical trial, 13 were involved in assessing the immediate soothing effects of 0.1% and 0.0095% troxerutin following capsaicin irritation, whereas 22 participated in evaluating the preventive soothing effect of 10% and 1% troxerutin over 4 weeks against capsaicin- and heat-induced irritation. We evaluated the soothing rate using skin redness, visual analog scale, and high temperature sensitive index as evaluation indices. RESULTS: Troxerutin inhibited the mRNA and protein expressions of cytokines in capsaicin-treated keratinocytes. In the clinical study, 0.1% and 0.0095% troxerutin promptly alleviated capsaicin-induced skin redness, whereas 10% troxerutin notably decreased both the visual analog scale and high temperature sensitive index for capsaicin- and heat-related irritation. However, 1% troxerutin was only effective in reducing the visual analog scale in response to capsaicin irritation. CONCLUSIONS: Troxerutin can inhibit TRPV1 activation in clinical and in vitro tests.

A Simple Nomogram for Predicting Stroke-Associated Pneumonia in Patients with Acute Ischemic Stroke.

The purpose of this study was to develop a prediction model for stroke-associated pneumonia (SAP) based on risk factors for SAP and to suggest nursing interventions to prevent SAP. In addition, a nomogram was developed to enhance its utility in nursing practice. The retrospective cohort study included 551 patients hospitalized for acute ischemic stroke at a university hospital in South Korea. Data were collected through a structured questionnaire and a review of the electronic medical record (EMR). In the development of a predictive model for SAP, multivariate logistic regression analysis showed that independent risk factors for SAP were age ≥ 65 years, National Institute of Health Stroke Scale (NIHSS) score ≥ 7, nasogastric tube feeding, and C-reactive protein (CRP) ≥ 5.0 mg/dL. The logit model was used to construct the SAP prediction nomogram, and the area under the curve (AUC) of the nomogram was 0.94. Furthermore, the slope of the calibration plot was close to the 45-degree line, indicating that the developed nomogram may be useful for predicting SAP. It is necessary to monitor the age, NIHSS score, nasogastric tube feeding status, and CRP level of stroke patients and identify high-risk groups using the developed nomogram to provide active nursing interventions to prevent SAP.

Role of α-Defensin and the Microbiome in Prosthetic Joint Infection: A Prospective Cohort Study in Korea.

The utility of α-defensin (AD), leukocyte esterase (LE) levels, and metagenomics sequencing as diagnostic tools for prosthetic joint infection (PJI) has been suggested, but there are few studies among the Asian population. This study aimed to evaluate the diagnostic performance of various biomarkers for PJI and the role of the microbiome in the synovial fluid of patients with prostheses. Patients with suspected knee PJI were enrolled, and their blood and synovial fluid were collected. The cases were classified into the PJI and non-PJI groups. Significant differences between the two groups were observed in the levels of AD (4698 µg/L vs. 296 µg/L, p < 0.001) and positivity for LE (62.5% vs. 21.1%, p = 0.01). AD had 94.4% sensitivity and 89.5% specificity for diagnosing PJI, whereas LE had 37.5% sensitivity and 100% specificity. Microbiome taxonomic profiling showed high sensitivity. The number of operational taxonomic units and the richness of the microbiome in the synovial fluid were higher in the non-PJI than in the PJI group. AD has shown encouraging results in the Asian population as a diagnostic biomarker for PJI, and LE can be used as a diagnostic adjunct. The bacterial richness of the synovial fluid is likely associated with infections.

Immunogenicity and Safety of Vaccines against Coronavirus Disease in Actively Treated Patients with Solid Tumors: A Prospective Cohort Study.

PURPOSE: We aimed to assess the humoral response to and reactogenicity of coronavirus disease 2019 (COVID-19) vaccination according to the vaccine type and to analyze factors associated with immunogenicity in actively treated solid cancer patients (CPs). Materials and Methods: Prospective cohorts of CPs, undergoing anticancer treatment, and healthcare workers (HCWs) were established. The participants had no history of previous COVID-19 and received either mRNA-based or adenovirus vector-based (AdV) vaccines as the primary series. Blood samples were collected before the first vaccination and after 2 weeks for each dose vaccination. Spike-specific binding antibodies (bAbs) in all participants and neutralizing antibodies (nAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type, Delta, and Omicron variants in CPs were analyzed and presented as the geometric mean titer. RESULTS: Age-matched 20 HCWs and 118 CPs were included in the analysis. The bAb seroconversion rate and antibody concentrations after the first vaccination were significantly lower in CPs than in HCWs. After the third vaccination, antibody levels in CPs with a primary series of AdV were comparable to those in HCWs, but nAb titers against the Omicron variant did not quantitatively increase in CPs with AdV vaccine as the primary series. The incidence and severity of adverse reactions post-vaccination were similar between CPs and HCWs. CONCLUSION: CPs displayed delayed humoral immune response after SARS-CoV-2 vaccination. The booster dose elicited comparable bAb concentrations between CPs and HCWs, regardless of the primary vaccine type. Neutralization against the Omicron variant was not robustly elicited following the booster dose in some CPs, implying the need for additional interventions to protect them from COVID-19.

A heterologous AZD1222 priming and BNT162b2 boosting regimen more efficiently elicits neutralizing antibodies, but not memory T cells, than the homologous BNT162b2 regimen.

BACKGROUND: Comparative analyses of SARS-CoV-2-specific immune responses elicited by diverse prime-boost regimens are required to establish efficient regimens for the control of COVID-19. METHOD: In this prospective observational cohort study, spike-specific immunoglobulin G (IgG) and neutralizing antibodies (nAbs) alongside spike-specific T-cell responses in age-matched groups of homologous BNT162b2/BNT162b2 or AZD1222/AZD1222 vaccination, heterologous AZD1222/BNT162b2 vaccination, and prior wild-type SARS-CoV-2 infection/vaccination were evaluated. RESULTS: Peak immune responses were achieved after the second vaccine dose in the naïve vaccinated groups and after the first dose in the prior infection/vaccination group. Peak titers of anti-spike IgG and nAb were significantly higher in the AZD1222/BNT162b2 vaccination and prior infection/vaccination groups than in the BNT162b2/BNT162b2 or AZD1222/AZD1222 groups. However, the frequency of interferon-γ-producing CD4+ T cells was highest in the BNT162b2/BNT162b2 vaccination group. Similar results were observed in the analysis of polyfunctional T cells. When nAb and CD4+T-cell responses against the Delta variant were analyzed, the prior infection/vaccination group exhibited higher responses than the groups of other homologous or heterologous vaccination regimens. CONCLUSION: nAbs are efficiently elicited by heterologous AZD1222/BNT162b2 vaccination, as well as prior infection/vaccination, whereas spike-specific CD4+T-cell responses are efficiently elicited by homologous BNT162b2 vaccination. Variant-recognizing immunity is more efficiently generated by prior infection/vaccination than the other homologous or heterologous vaccination regimens.

In Vitro Replication Inhibitory Activity of Xanthorrhizol against Severe Acute Respiratory Syndrome Coronavirus 2.

In spite of the large number of repositioned drugs and direct-acting antivirals in clinical trials for the management of the ongoing COVID-19 pandemic, there are few cost-effective therapeutic options for severe acute respiratory syndrome (SARS) coronavirus 2 (SCoV2) infection. In this paper, we show that xanthorrhizol (XNT), a bisabolane-type sesquiterpenoid compound isolated from the Curcuma xanthorrhizza Roxb., a ginger-line plant of the family Zingiberaceae, displays a potent antiviral efficacy in vitro against SCoV2 and other related coronaviruses, including SARS-CoV-1 (SCoV1) and a common cold-causing human coronavirus. XNT reduced infectious SCoV2 titer by ~3-log10 at 20 µM and interfered with the replication of the SCoV1 subgenomic replicon, while it had no significant antiviral effects against hepatitis C virus and noroviruses. Further, XNT exerted similar antiviral functions against SCoV2 variants, such as a GH clade strain and a delta strain currently predominant worldwide. Neither SCoV2 entry into cells nor the enzymatic activity of viral RNA polymerase (Nsp12), RNA helicase (Nsp13), or the 3CL main protease (Nsp5) was inhibited by XNT. While its CoV replication inhibitory mechanism remains elusive, our results demonstrate that the traditional folk medicine XNT could be a promising antiviral candidate that inhibits a broad range of SCoV2 variants of concern and other related CoVs.

Association Between Suicide and Drinking Habits in Adolescents.

OBJECTIVES: Adolescent suicide is a serious social problem. Adolescent alcohol use is one of the most important risk factors for adolescent suicide. This study aimed to identify the relationship between drinking habits and suicide among Korean adolescents. METHODS: Data from the 14th and 15th Korean Youth Risk Behavior Web-based Survey, conducted in 2018 and 2019, were used for analysis. Multiple logistic regression analysis was used to identify the relationship between drinking habits-including the age of drinking initiation, frequency of drinking, average drinking amount, frequency of drunkenness-and suicidal ideation, plans, and attempts. RESULTS: Even after adjusting for age, sex, school grade, academic achievement, socioeconomic status, depression, stress, and drinking habits, the frequencies of drinking and drunkenness increased the risk of suicide attempts. Suicide attempts were associated with the frequency of drinking in girls and middle school students, and with the frequency of drunkenness in boys and high school students. CONCLUSION: This study identified associations between drinking habits (the age of drinking initiation, frequency of drinking, average amount of drinking, frequency of drunkenness) and suicidal behavior in adolescents. Our findings suggest that to prevent adolescent suicide, it might be necessary to investigate drinking habits, including the frequencies of drinking and drunkenness. Moreover, considering the differences in sex and school grade, it is important to include the individual group characteristics when evaluating drinking habits.

Additional Reduction of Residual Symptoms with Aripiprazole Augmentation in the Patients with Partially Remitted Major Depressive Disorder.

OBJECTIVE: Many patients with major depressive disorder (MDD) suffer from residual symptoms without achieving remission. However, pharmacologic options for residual symptoms of MDD have been limited. This study aimed to investigate benefit of aripiprazole augmentation in the treatment of residual symptoms in the patients with partially remitted MDD. METHODS: We retrospectively analyzed the 8-week medical records of the patients. The enrolled patients did respond to treatment of antidepressant but were not remitted. The range of 17-item Hamilton Depression Rating Scale (HAMD) total score of the subjects were 8 to 15 points. All patients were currently taking antidepressants when they started aripiprazole. The primary endpoint was the mean change of Clinically Useful Depression Outcome Scale (CUDOS). Secondary endpoint measures were HAMD, Clinical Global Impression-severity (CGI-S) scores, Patient Health Questionnaire-15 (PHQ-15), Beck Anxiety Inventory (BAI), Perceived Deficit Questionnaire-depression (PDQ-D), Sheehan Disability Scale (SDS) and General Health Questionnaire/Quality of Life-12 (GHQ/QL-12). RESULTS: A total of 134 medical records were analyzed. The changes of CUDOS, HAMD, CGI-S, BAI, PHQ-15, PDQ-D, SDS and GHQ/QL-12 from baseline to the endpoint were -7.93, -3.29, -0.80, -4.02, -2.05, -4.35, -4.77 and -2.82, respectively (all p < 0.001). At the endpoint, the newly remitted subjects rate by HAMD score criteria were approximately 46%. CONCLUSION: Our preliminary findings have presented the effectiveness of aripiprazole augmentation for residual symptoms of partially remitted MDD patients in routine practice. This study assures subsequent well-controlled studies of the possibility of generalizing the above promising outcome in the future.

The Relationship between Plasma Erythropoietin Levels and Symptoms of Attention Deficit Hyperactivity Disorder.

OBJECTIVE: There are animal models associating dopamine dysfunction with behavioral impairments that model attention deficit hyperactivity disorder (ADHD). Erythropoietin (EPO) has trophic effects on dopaminergic neurons. The aim of this study was to examine the EPO plasma levels and determine whether there was any correlation between plasma EPO levels and clinical characteristics of ADHD. METHODS: Plasma EPO levels were measured in 78 drug-naïve children with ADHD and in 81 healthy children. The severity of ADHD symptoms was determined by scores on the Korean ADHD Rating Scale (K-ARS) in ADHD children and healthy controls. RESULTS: The difference between median plasma EPO levels in ADHD children and in healthy controls was not statistically significant. Adjusting for age and sex, a linear regression analysis showed that inattention score was significantly higher in the second highest tertile of plasma EPO compared to those in the lowest tertile. Hyperactivity-impulsivity score was significantly higher in the highest tertile of plasma EPO compared to those in the lowest tertile. Moreover, total K-ARS scores were significantly higher in the second highest tertile of plasma EPO compared to those in the lowest tertile. CONCLUSION: These findings suggest that plasma EPO levels were related to some ADHD symptoms, which could be used in the monitoring of the disorder.

Association between Early Spermarche and Suicide Attempts in Boys: the Korea Youth Risk Behavior Web-based Survey.

BACKGROUND: Puberty is a biologically and psychologically unstable period, and pubertal changes differ by sex. However, most previous studies on pubertal timing and suicide have focused on girls. This study investigated the association between early spermarche and suicide attempts in boys. METHODS: We analyzed a nationally representative sample of Korean adolescents (The Korea Youth Risk Behavior Web-Based Survey, KYRBS) that included approximately 35,000 boys annually from 2011 to 2015. Pubertal timing in boys was defined by spermarche. Complex sampling logistic regression analyses were performed to evaluate the odds ratios (ORs) for suicide attempts between the early and average spermarche groups. RESULTS: The ORs for suicide attempts in boys with early spermarche were significantly higher than those in boys with average spermarche after adjustment for age, perceived stress, depressive symptoms, and suicidal ideation. The ORs from 2011 to 2015 were as follows: 1.782 (P < 0.001), 1.490 (P = 0.002), 1.693 (P < 0.001), 1.541 (P = 0.001), and 1.393 (1.024-1.895; P = 0.035), respectively. CONCLUSION: These findings suggest that early pubertal timing is a risk factor for suicide attempts in Korean boys after adjustment for depressive symptoms, perceived stress, and suicidal ideation, which have been previously reported as risk factors for suicide attempts. Therefore, careful attention should be paid to the prevention of suicide in boys who experience early spermarche in Korea.

Genome Sequences of Two GH Clade SARS-CoV-2 Strains Isolated from Patients with COVID-19 in South Korea.

We report the genome sequences of two GH clade severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains isolated from nasopharyngeal swabs from patients with coronavirus disease 2019 (COVID-19) in South Korea. These strains had two mutations in the untranslated regions and seven nonsynonymous substitutions in open reading frames, compared with Wuhan/Hu-1/2019, showing 99.96% sequence identity.

Effect of a multidisciplinary program to improve organ donation in the emergency department.

BACKGROUND AND IMPORTANCE: As the emergency department (ED) is an important source of potential organ donors, it may play an important role in the organ donation process. OBJECTIVE: To assess the effectiveness of the multidisciplinary organ donation improvement program (ODIP) on identifying potential donors and improving organ donation in South Korean EDs. DESIGN, SETTINGS, AND PARTICIPANTS: This study was a retrospective, observational study of the ED-inclusive ODIP implemented in 55 tertiary teaching hospitals contracted with the Korea Organ Donation Agency (KODA) since 2014. The inclusion criteria were: patients in the ED with a serious brain injury and futile prognosis or expected death of the patient within a few days, no contraindications for organ donation, and no objections registered in the donor registry. INTERVENTION: The ED-inclusive multidisciplinary approach was implemented to improve organ donation. It included regular meetings of the ODIP committee, hospital visits and staff education, improvement of notifications, and support of a coordination team. OUTCOMES MEASURE AND ANALYSIS: We assessed the changes in the number of deceased organ donors per year and notifications of potential brain-dead donors by medical staff after the implementation of the new ED-inclusive ODIP. The entire organ donation process was monitored and measured. RESULTS: There was a significant increase in deceased organ donors per million population after the implementation of the ED-inclusive multidisciplinary ODIP of KODA compared to the pre-intervention period: 5.21 vs. 9.72, difference 4.51 (95% confidence interval 2.11-6.91). During the study period, the proportion of deceased organ donors occurred from KODA-contracted hospitals increased from 25.3 to 50.3% in South Korea's total deceased organ donors. Emergency physicians of KODA-contracted hospitals notified increasingly more potential brain-dead donors each year throughout the study period (36 in 2014 vs. 135 in 2018). The longer the period contracted with KODA, the higher the potential brain-death identification rates (P < 0.001). CONCLUSION: In this retrospective study, the implementation of multidisciplinary ODIP in the ED led to significantly higher deceased organ donors per million population and awareness of potential brain-dead donors in South Korea.

Association between genetic variants of the norepinephrine transporter gene (SLC6A2) and bipolar I disorder.

We aimed to investigate the associations between genetic variants of the norepinephrine transporter gene (NET, also known as SLC6A2) and diagnosis of bipolar I disorder. In addition, we examined the relationship between the genetic variants and manic and psychotic symptoms in patients with bipolar I disorder. The three SNPs rs28386840, rs2242446, and rs5569 were genotyped in 326 patients: patients with bipolar I disorder (n = 160) and a control group (n = 166). Subsequently, multivariate logistic regression analysis adjusting for age and sex was conducted to identify independent influences of the SNPs on diagnosis of bipolar I disorder. A possible association between manic and psychotic symptoms and variants of SLC6A2 was also investigated in patients with bipolar I disorder. The rs28836840 SNP in the 5'-UTR of SLC6A2 was significantly associated with bipolar I disorder and with severity of manic and psychotic symptoms in this disorder. Individuals carrying a T allele in the rs28836840 SNP were likely to have a lower risk of bipolar I disorder or lower severity of manic and psychotic symptoms in patients with bipolar I disorder (bipolar I disorder diagnosis: OR = 0.643, 95% Cl = 0.468-0.883, p = 0.006; manic symptoms: ß = -2.457, 95% Cl = -4.674 ~ -0.239, p = 0.031; psychotic symptoms: ß = -2.501, 95% Cl = -4.700 ~ -0.301, p = 0.027). For the rs2242446 and rs5569 SNPs, there were no significant differences between patients with bipolar I disorder and those without. Our results revealed associations of the rs28386840 SNP with bipolar I disorder diagnosis and with severity of manic and psychotic symptoms. However, the findings reported here require replication in larger samples and various ethnic groups.

Social participation and depressive symptoms in community-dwelling older adults: Emotional social support as a mediator.

Previous studies have documented the protective effects of social participation on depression in older adults. In this study, we investigated the association between social participation and depressive symptoms and the associated gender difference in older adults. In addition, we explored the mediating role of emotional social support in the association between social participation and depressive symptoms. We collected data from 4751 community-dwelling adults aged 60 and above from the Korean Retirement and Income Study (KReIS) conducted in 2017 and 2018. The relationship between social participation (participation in different types of activities, frequency of participation, and the number of activities participated) and the risk for depressive symptoms was examined. Older adults who participated in social activity, volunteer work, and donation had decreased risk of depressive symptoms. More frequent and more diverse participation in activities further reduced the risk. Overall, women benefited more from social participation than men. Importantly, emotional social support significantly mediated the relationship between social participation and depressive symptoms. Social participation was associated lower odds for depression in older adults, particularly in older women. Our findings provided one of very few pieces of evidence that documents the mediating role of emotional social support in the relationship between social participation and depression among the elderly.

Association between the IL10 rs1800896 Polymorphism and Tardive Dyskinesia in Schizophrenia.

OBJECTIVE: Interleukin-10 (IL-10) is a major immunoregulatory cytokine and its gene plays a fundamental role in anti-inflammatory and immunosuppressive activity. This study aimed to examine the association between the IL10 gene promoter -1082G/A polymorphism (rs1800896) and tardive dyskinesia (TD) in schizophrenia. METHODS: Two hundred and eighty unrelated Korean schizophrenic patients participated in this study (105 TD and 175 non-TD patients). TD was diagnosed using the Research Diagnostic Criteria for TD and Abnormal Involuntary Movement Scale (AIMS). Genotyping was performed by RT-PCR and high-resolution melting curve analysis. RESULTS: The distributions of genotypic frequencies did not differ between patients with and without TD (χ2=4.33, p=0.115). However, allelic frequencies of the two groups were different (χ2=4.45, p=0.035); the A allele frequency was higher in TD. The total AIMS scores of the three genotypes were not different (F=1.33, p=0.266). However, the total AIMS scores of the A allele carrier and the A allele non-carrier were significantly different (t=5.79, p<0.001). Logistic regression analaysis showed that IL10 -1082G/A genotype significantly predicts presence of TD (p=0.045) after adjusting for covariates such as age and treatment duration. CONCLUSION: This finding suggests that the A allele of rs1800896 may be associated with TD development following a low IL-10 function.

Identification of Fungal Species and Detection of Azole-Resistance Mutations in the Aspergillus fumigatus cyp51A Gene at a South Korean Hospital.

PURPOSE: With changing fungal epidemiology and azole resistance in Aspergillus species, identifying fungal species and susceptibility patterns is crucial to the management of aspergillosis and mucormycosis. The objectives of this study were to evaluate performance of panfungal polymerase chain reaction (PCR) assays on formalin-fixed paraffin embedded (FFPE) samples in the identification of fungal species and in the detection of azole-resistance mutations in the Aspergillus fumigatus cyp51A gene at a South Korean hospital. MATERIALS AND METHODS: A total of 75 FFPE specimens with a histopathological diagnosis of aspergillosis or mucormycosis were identified during the 10-year study period (2006-2015). After deparaffinization and DNA extraction, panfungal PCR assays were conducted on FFPE samples for fungal species identification. The identified fungal species were compared with histopathological diagnosis. On samples identified as A. fumigatus, sequencing to identify frequent mutations in the cyp51A gene [tandem repeat 46 (TR46), L98H, and M220 alterations] that confer azole resistance was performed. RESULTS: Specific fungal DNA was identified in 31 (41.3%) FFPE samples, and of these, 16 samples of specific fungal DNA were in accord with a histopathological diagnosis of aspergillosis or mucormycosis; 15 samples had discordant histopathology and PCR results. No azole-mediating cyp51A gene mutation was noted among nine cases of aspergillosis. Moreover, no cyp51A mutations were identified among three cases with history of prior azole use. CONCLUSION: Panfungal PCR assay with FFPE samples may provide additional information of use to fungal species identification. No azole-resistance mediating mutations in the A. fumigatus cyp51A gene were identified among FFPE samples during study period.

Electron Beam Irradiated Al Doped ZnO Thin Films as Efficient Tunnel Recombination Junction for Hydrogenated Amorphous Silicon/Cu(In,Ga)Se2 Tandem Solar Cells.

A tunnel recombination junction (TRJ) layer for hydrogenated amorphous silicon (a-Si:H)/ Cu(In,Ga)Se2 (CIGS) tandem solar cells is investigated. An Al-doped zinc oxide (AZO) thin film is applied to the TRJ, and the influence of electron beam (e-beam) irradiation on defects along the TRJ is investigated. The AZO thin films are prepared using radio frequency (RF) sputtering and the e-beam is irradiated at 200 W RF power and 2 keV DC power for 5 min. In the e-beam irradiated AZO thin film, the number of oxygen vacancies and Zn interstitials increases, which in turn strengthens the effect of defect-enhanced tunnel recombination.