Role of p53 in transcriptional repression of SVCT2.

SVCT2, Sodium-dependent Vitamin C Transporter 2, uniquely transports ascorbic acid (also known as vitamin C and ascorbate) into all types of cells. Vitamin C is an essential nutrient that must be obtained through the diet and plasma levels are tightly regulated by transporter activity. Vitamin C plays an important role in antioxidant defenses and is a cofactor for many enzymes that enable hormone synthesis, oxygen sensing, collagen synthesis and epigenetic pathways. Although SVCT2 has various functions, regulation of its expression/activity remains poorly understood. We found a p53-binding site, within the SVCT2 promoter, using a transcription factor binding-site prediction tool. In this study, we show that p53 can directly repress SVCT2 transcription by binding a proximal- (~-185 to -171 bp) and a distal- (~-1800 to -1787 bp) p53-responsive element (PRE), Chromatin immunoprecipitation assays showed that PRE-bound p53 interacts with the corepressor-histone deacetylase 3 (HDAC3), resulting in deacetylation of histones Ac-H4, at the proximal promoter, resulting in transcriptional silencing of SVCT2. Overall, our data suggests that p53 is a potent transcriptional repressor of SVCT2, a critical transporter of diet-derived ascorbic acid, across the plasma membranes of numerous essential tissue cell types.

Patient-family communication mediates the relation between family hardiness and caregiver positivity: Exploring the moderating role of caregiver depression and anxiety.

Purpose: Despite the theoretical and empirical significance of positive aspects of caregiving in caregiver well-being, relatively little is known regarding family-related predictors of caregiver positivity. This study examines whether patient-family communication (p-f communication) mediates the relation between family hardiness and caregiver positivity and whether the mediating effects of p-f communication are moderated by the levels of caregiver depression and anxiety. Design/Sample: This study used secondary data obtained from a large-scale cross-sectional national survey conducted in South Korea. Participants were 544 spousal cancer patient-caregiver dyads recruited from the National Cancer Center and nine government-designated regional cancer centers in South Korea. Methods: To test the hypotheses, a simple mediation model and two moderated mediation tests were conducted using the PROCESS macro for SPSS. Findings: Higher family hardiness was related to higher p-f positive communication and higher caregiver positivity. The effects of family hardiness were partially mediated by p-f communication, controlling for caregiver sex, education, health status, depression and anxiety, time spent caregiving, and patient depression and anxiety, cancer stage, and time since diagnosis. The mediating effects of p-f communication were not significantly moderated by caregiver depression and anxiety. Conclusions/Implications: Health care professionals could consider p-f communication as a reasonable target of intervention to increase caregiver positivity, even for caregivers with heightened depression and anxiety.

Fundamental Characteristics of Deep-UV Light-Emitting Diodes and Their Application To Control Foodborne Pathogens.

Low-pressure mercury UV (LP-UV) lamps have long been used for bacterial inactivation, but due to certain disadvantages, such as the possibility of mercury leakage, deep-UV-C light-emitting diodes (DUV-LEDs) for disinfection have recently been of great interest as an alternative. Therefore, in this study, we examined the basic spectral properties of DUV-LEDs and the effects of UV-C irradiation for inactivating foodborne pathogens, including Escherichia coli O157:H7, Salmonella enterica serovar Typhimurium, and Listeria monocytogenes, on solid media, as well as in water. As the temperature increased, DUV-LED light intensity decreased slightly, whereas LP-UV lamps showed increasing intensity until they reached a peak at around 30°C. As the irradiation dosage and temperature increased, E. coli O157:H7 and S. Typhimurium experienced 5- to 6-log-unit reductions. L. monocytogenes was reduced by over 5 log units at a dose of 1.67 mJ/cm(2). At 90% relative humidity (RH), only E. coli O157:H7 experienced inactivation significantly greater than at 30 and 60% RH. In a water treatment study involving a continuous system, 6.38-, 5.81-, and 3.47-log-unit reductions were achieved in E. coli O157:H7, S. Typhimurium, and L. monocytogenes, respectively, at 0.5 liter per minute (LPM) and 200 mW output power. The results of this study suggest that the use of DUV-LEDs may compensate for the drawbacks of using LP-UV lamps to inactivate foodborne pathogens.

The effects on caregivers of cancer patients' needs and family hardiness.

OBJECTIVES: Family caregivers of cancer patients are anticipated to serve multiple roles but the factors that influence their reaction to caregiving have not gotten much attention. The current study aimed to investigate the effects of cancer patient's needs level and the family hardiness on the caregivers' reaction. METHODS: A national survey was conducted through regional branches of the National Cancer Center of South Korea, yielding 990 patient-caregiver dyads. Patients and caregivers provided self-report questionnaires. Patient's medical records complemented the self-report survey data. RESULTS: On all five domains of caregiver reaction, which were schedule, esteem, support, health, and finance, family hardiness was a significant predictor. Male, older, low-income caregivers reported more burden in caregiving with some. The interaction effect of patient's needs and family hardiness was found only on esteem. CONCLUSIONS: The implications based on the findings are discussed in terms of the psycho-oncological and psycho-social interventions for the cancer patients and their family caregivers.

Caregiver burden, patients' self-perceived burden, and preference for palliative care among cancer patients and caregivers.

OBJECTIVE: Recently, caregiver burden (CB) has emerged as an important issue in the area of palliative medicine. However, patients' feelings related to being a burden to their families (i.e., self-perceived burden [SPB]) is also a significant issue. We evaluated the relation of CB and SPB as preference for palliative care. METHODS: A national, multicenter, cross-sectional survey of 326 patient-caregiver dyads was performed. A set of paired questionnaires evaluating CB and SPB (five domain items assessed on a four-point Likert scale) were independently administered to patients and their caregivers. Among the respondents, only the patients with distant stage cancer and their caregivers were included. Multivariate analyses were conducted to identify the associations between CB and SPB and preference for palliative care. RESULTS: Caregivers and patients who preferred palliative care to life sustaining treatment reported higher CB and SPB scores, respectively. Caregivers who felt more of a burden were more likely to prefer palliative care over life sustaining treatment for their patients (adjusted odds ratio [aOR] = 1.67, 95% CI: 1.21-2.31). In addition, patients who perceived their caregivers' burden as large tended to prefer palliative care (aOR = 1.61, 95% CI: 1.16-2.22). CONCLUSIONS: Both CB and SPB increased preference for palliative care. This could be interpreted that high CB can lead to preference for palliative care in both patients and their caregivers, potentially threatening patient autonomy. Efforts to relieve CB and SPB are needed.

Interventions to reduce repetitive ordering of low-value inpatient laboratory tests: a systematic review.

BACKGROUND: Over-ordering of daily laboratory tests adversely affects patient care through hospital-acquired anaemia, patient discomfort, burden on front-line staff and unnecessary downstream testing. This remains a prevalent issue despite the 2013 Choosing Wisely recommendation to minimise unnecessary daily labs. We conducted a systematic review of the literature to identify interventions targeting unnecessary laboratory testing. METHODS: We systematically searched MEDLINE, EMBASE, Cochrane Central and SCOPUS databases to identify interventions focused on reducing daily complete blood count, complete metabolic panel and basic metabolic panel labs. We defined interventions as 'effective' if a statistically significant reduction was attained and 'highly effective' if a reduction of ≥25% was attained. RESULTS: The search yielded 5646 studies with 41 articles that met inclusion criteria. We grouped interventions into one or more categories: audit and feedback, cost display, education, electronic medical record (EMR) change, and policy change. Most interventions lasted less than a year and used a multipronged approach. All five strategies were effective in most studies with EMR change being the most commonly used independent strategy. EMR change and policy change were the strategies most frequently reported as effective. EMR change was the strategy most frequently reported as highly effective. CONCLUSION: Our analysis identified five categories of interventions targeting daily laboratory testing. All categories were effective in most studies, with EMR change being most frequently highly effective. PROSPERO REGISTRATION NUMBER: CRD42021254076.

Assessing quality of life among elementary school students: Validation of the Korean version of the Meaning in Life in Children Questionnaire.

Meaning in life (MIL) has been widely recognized as a hallmark of psychological well-being and positive youth development. The goal of this study was to validate the Korean version of the Meaning in Life in Children Questionnaire (K-MIL-CQ) utilizing the framework suggested by the Standards for Educational and Psychological Testing. Data were obtained from 277 fifth graders aged 10-11 in three elementary schools in Seoul and Gyeonggi through a paper-and-pencil survey (55.2% boys). We translated the MIL-CQ, a 21-item self-report measure developed based on Frankl's "meaning triangle," into Korean. Psychological well-being measures were also assessed. Validity and reliability data were collected. (1) The content of domains and items was appropriate for measuring MIL among children. (2) A three-factor model consisting of attitude, creativity, and experience pathways was extracted via exploratory factor analysis, and a three-factor hierarchical model including attitude, creativity, and experience as first-order factors and MIL as a second-order factor was confirmed via confirmatory factor analysis. (3) Higher levels of MIL were related to higher levels of satisfaction with life, self-esteem, positive affectivity, and lower levels of negative affectivity. (4) All item fit statistics were acceptable based on the Rasch model. (5) The analysis of the measurement invariance of each item showed that the responses to one item varied by gender, suggesting that additional items might facilitate better measurement of MIL in children. This study provides validity and reliability evidence that K-MIL-CQ is appropriate for measuring MIL among South Korean elementary school students.

Mutation SVCT2 promotes cell proliferation, invasion and migration in colorectal cancer.

The sodium-dependent vitamin C transporter 2 (SVCT2) surface glycoprotein regulates ascorbate accumulation in the plasma, often resulting in the induction of cancer cell death. Therefore, high expression of this gene associates with increased overall survival in several cancers. However, in colorectal cancer (CRC), high (likely mutated) SVCT2 expression relates to poor overall survival, and its functional significance has not been studied. Thus, we hypothesize that mutant SVCT2 expression could affect CRC patient survival. According to biological databases, SVCT2 has been found to be mutated frequently, and SVCT2 E264K has a particularly high pathogenic score (0.98), compared to other SVCT2 mutant sites, in CRC patients. Interestingly, our results reveal expression of SVCT2 E264K in many CRC tissues and cells. Also, we found wild-type SVCT2 expression to be largely localized to the cytoplasm and membrane, while SVCT2 E264K was restricted to the cytoplasm. We further found that SVCT2 E264K overexpression increases cell growth. By contrast, SVCT2 E264K knockdown significantly reduced cell proliferation and promoted cell apoptosis, resulting in inhibition of cell invasion and migration. Taken together, SVCT2 E264K plays a critical role in proliferation in CRC. Our results suggest that SVCT2 E264K could be a promising novel therapeutic target in CRC.

Cross-cultural application of the Korean version of the EORTC QLQ-ELD14 questionnaire for elderly patients with cancer.

OBJECTIVES: The European Organization for Research and Treatment of Cancer (EORTC) QLQ-ELD14 is a validated tool that measures Health-related Quality-of-life (HRQOL) for elderly patients with cancer. This study was conducted to evaluate the psychometric properties of the Korean version of the EORTC QLQ-ELD14 to determine if this tool can be used to evaluate HRQOL for older Korean patients with cancer. MATERIALS AND METHODS: We recruited 439 elderly patients with cancer aged ≥60years from 11 cancer centers and completed the EORTC QLQ-ELD14 questionnaires. The reliability and validity of the EORTC QLQ-ELD14 questionnaire were assessed via Cronbach alpha, multitrait scaling analyses, correlation analyses with the EORTC QLQ-C30, and known-group comparisons. Known-group comparisons were conducted by dividing the patients into groups based on the cancer stage, depression level, and loss of mobility. RESULTS: The scale structure of the Korean version of the EORTC QLQ-ELD14 was consistent with the originally hypothesized scale structure. Cronbach alpha coefficients ranged 0.65-0.88. Multitrait scaling analysis showed good item convergent and discriminant validity. Low scaling errors (3.1%) were observed. Divergent validity was demonstrated by no strong correlation with the EORTC QLQ C30. The clinical validity of the Korean version of the EORTC QLQ-ELD14 was demonstrated by its ability to discriminate among patient subgroups categorized by AJCC stage, depression level, and loss of mobility. CONCLUSION: Our findings indicate that the Korean version of the EORTC QLQ-ELD14 questionnaire is reliable and valid for measuring QOL of older Korean patients with cancer.

Preclinical evidence of rapid-onset antidepressant-like effect in Radix Polygalae extract.

Radix Polygalae (the root of Polygala tenuifolia) is a herb widely used in traditional Asian medicine that is thought to exert a variety of neuropsychiatric effects. Radix Polygalae extract can protect against N-methyl D-aspartate (NMDA) neurotoxicity and induce brain-derived neurotrophic factor (BDNF) expression, suggesting modulatory roles at glutamatergic synapses and possible antidepressant action. In accordance with this hypothesis, Radix Polygalae extract demonstrated antidepressant-like effects in 8-week-old male C57Bl/6 mice by decreasing behavioral despair in the forced swim and tail suspension tasks and increasing hedonic-like behavior in the female urine sniffing test 30 minutes after a single oral administration of 0.1 mg/kg. Reduced latency to acquire a food pellet in the novely suppressed feeding paradigm, without change in anxiety-like behaviors suggested a rapid-onset nature of the antidepressant-like effect. In addition, it decreased the number of failed escapes in the learned helplessness paradigm after two oral administrations 24 hours and 30 minutes before the first test. Finally, it reversed anhedonia as measured by saccharin preference in mice exposed to the chronic stress model after two administrations of 0.1 mg/kg, in contrast to the repeated administration generally needed for similar effect by monoamergic antidepressants. Immobility reduction in tail suspension task was blocked by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist NBQX, a pattern previously demonstrated by ketamine and other ketamine-like rapid-onset antidepressants. Also similarly to ketamine, Radix Polygalae appeared to acutely decrease phosphorylation of GluR1 serine-845 in the hippocampus while leaving the phosphorylation of hippocampal mTOR serine 2448 unchanged. These findings serve as preclinical evidence that Radix Polygalae extract exerts rapid-onset antidepressant effects by modulating glutamatergic synapses in critical brain circuits of depression and may be worthy of further evaluation as a safe substitute to other rapid-onset antidepressants known to have unacceptable side effects.