Preclinical evaluation of an 18F-labeled Tenascin-C aptamer for PET imaging of atherosclerotic plaque in mouse models of atherosclerosis.

Tenascin-C is an extracellular matrix glycoprotein strongly expressed in coronary atherosclerotic plaque. Aptamers are single-stranded oligonucleotides that bind to specific target molecules with high affinity. This study hypothesized that tenascin-C expression at atherosclerotic plaque in vivo could be detected by tenascin-C specific aptamers using positron emission tomography (PET). This paper reports the radiosynthesis of a fluorine-18 (18F)-labeled tenascin-C aptamer for the biodistribution and PET imaging of the tenascin-C expression in apolipoprotein E-deficient (ApoE-/-) mice. The aortas ApoE-/- mice showed significantly increased positive areas of Oil red O staining than control C57BL/6 mice, and tenascin-C expression was detected in foam cells accumulated in the subendothelial lesions of ApoE-/- mice. The ex vivo biodistribution of the 18F-labeled tenascin-C aptamer showed significantly increased uptake at the aorta of ApoE-/- mice, and ex vivo autoradiography of aorta revealed the high accumulation of the 18F-labeled tenascin-C aptamer in the atherosclerotic lesions of ApoE-/- mice, which was consistent with the location of the atherosclerotic plaques detected by Oil red O staining. PET imaging of the 18F-labeled tenascin-C aptamer revealed a significantly higher mean standardized uptake in the aorta of the ApoE-/- mice than the control C57BL/6 mice. These data highlight the potential use of tenascin-C aptamer to diagnose atherosclerotic lesions in vivo.

Combination of [18F]FDG and [18F]PSMA-1007 PET/CT predicts tumour aggressiveness at staging and biochemical failure postoperatively in patients with prostate cancer.

PURPOSE: [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) has limitations in prostate cancer (PCa) detection owing to low glycolysis in the primary tumour. Recently, prostate-specific membrane antigen (PSMA) PET/CT has been useful for biochemical failure detection and radioligand therapy (RLT) guidance. However, few studies have evaluated its use in primary prostate tumours using PSMA and [18F]FDG PET/CT. This study aimed to evaluate [18F]PSMA-1007 and [18F]FDG PET/CT for primary tumour detection and understand the association of metabolic heterogeneity with clinicopathological characteristics at staging and postoperatively. METHOD: This prospective study included 42 index tumours (27 acinar and 15 ductal-dominant) in 42 patients who underwent [18F]PSMA-1007 and [18F]FDG PET/CT and subsequent radical prostatectomy. All patients were followed for a median of 26 mo, and serum prostate-specific antigen levels were measured every 3 mo to evaluate biochemical failure. One-way analysis of variance, Tukey's multiple comparison test, and Fisher's exact test were performed. RESULTS: All 42 index tumours were detected on [18F]PSMA-1007 PET/CT, whereas only 15 were detected on [18F]FDG PET/CT (62.3% vs. 37.7%, p < 0.0001). A high SUVmax for [18F]PSMA-1007 was observed in tumours with high Gleason scores (GS 6-7 vs. GS 8-10; 12.1 vs. 20.1, p < 0.05). Tumours with [18F]FDG uptake were mostly ductal dominant (acinar-dominant 4/27; ductal-dominant; 11/15, p < 0.001), with lower [18F]PSMA-1007 uptake than tumours without [18F]FDG uptake (SUVmax 16.58 vs. 11.19, p < 0.001). There were 16.6% (7/42) of patients with pStage IV in whom the primary tumours were [18F]FDG positive. Biochemical failure was observed in 14.8% (4/27) of patients with [18F]FDG negative tumours but in 53.3% (8/15) of patients with [18F]FDG positive tumours (p = 0.013). CONCLUSIONS: [18F]PSMA-1007 PET/CT was superior to [18F]FDG PET/CT in detecting primary PCa. In contrast, tumours with [18F]FDG uptake are associated with larger size, a ductal-dominant type, and likely to undergo metastasis at staging and biochemical failure postoperatively.

The collateral map: prediction of lesion growth and penumbra after acute anterior circulation ischemic stroke.

OBJECTIVES: This study evaluated the collateral map's ability to predict lesion growth and penumbra after acute anterior circulation ischemic strokes. METHODS: This was a retrospective analysis of selected data from a prospectively collected database. The lesion growth ratio was the ratio of the follow-up lesion volume to the baseline lesion volume on diffusion-weighted imaging (DWI). The time-to-maximum (Tmax)/DWI ratio was the ratio of the baseline Tmax > 6 s volume to the baseline lesion volume. The collateral ratio was the ratio of the hypoperfused lesion volume of the phase_FU (phase with the hypoperfused lesions most approximate to the follow-up DWI lesion) to the hypoperfused lesion volume of the phase_baseline of the collateral map. Multiple logistic regression analyses were conducted to identify independent predictors of lesion growth. The concordance correlation coefficients of Tmax/DWI ratio and collateral ratio for lesion growth ratio were analyzed. RESULTS: Fifty-two patients, including twenty-six males (mean age, 74 years), were included. Intermediate (OR, 1234.5; p < 0.001) and poor collateral perfusion grades (OR, 664.7; p = 0.006) were independently associated with lesion growth. Phase_FUs were immediately preceded phases of the phase_baselines in intermediate or poor collateral perfusion grades. The concordance correlation coefficients of the Tmax/DWI ratio and collateral ratio for the lesion growth ratio were 0.28 (95% CI, 0.17-0.38) and 0.88 (95% CI, 0.82-0.92), respectively. CONCLUSION: Precise prediction of lesion growth and penumbra can be possible using collateral maps, allowing for personalized application of recanalization treatments. Further studies are needed to generalize the findings of this study. CLINICAL RELEVANCE STATEMENT: Precise prediction of lesion growth and penumbra can be possible using collateral maps, allowing for personalized application of recanalization treatments. KEY POINTS: • Cell viability in cerebral ischemia due to proximal arterial steno-occlusion mainly depends on the collateral circulation. • The collateral map shows salvageable brain extent, which can survive by recanalization treatments after acute anterior circulation ischemic stroke. • Precise estimation of salvageable brain makes it possible to make patient-specific treatment decision.

Clinical relevance of the living kidney donor profile index in Korean kidney transplant recipients.

BACKGROUND: The Living Kidney Donor Profile Index (LKDPI) was developed in the United States to predict graft outcomes based on donor characteristics. However, there are significant differences in donor demographics, access to transplantation, proportion of ABO incompatibility, and posttransplant mortality in Asian countries compared with the United States. METHODS: We evaluated the clinical relevance of the LKDPI score in a Korean kidney transplant cohort by analyzing 1860 patients who underwent kidney transplantation between 2000 and 2019. Patients were divided into three groups according to LKDPI score: <0, 1-19.9, and ≥20. RESULTS: During a median follow-up of 119 months, 232 recipients (12.5%) experienced death-censored graft loss, and 98 recipients (5.3%) died. High LKDPI scores were significantly associated with increased risk of death-censored graft loss independent of recipient characteristics (LKDPI 1-19.9: HR 1.389, 95% CI 1.036-1.863; LKDPI ≥20: HR 2.121, 95% CI 1.50-2.998). High LKDPI score was also significantly associated with increased risk of biopsy-proven acute rejection and impaired graft renal function. By contrast, overall patient survival rates were comparable among the LKDPI groups. CONCLUSION: High LKDPI scores were associated with an increased risk of death-censored graft loss, biopsy-proven acute rejection, and impaired graft renal function among a Korean kidney transplant cohort.

Particulate matter (PM10) exacerbates on MK-801-induced schizophrenia-like behaviors through the inhibition of ERK-CREB-BDNF signaling pathway.

Particulate matter (PM), released into the air by a variety of natural and human activities, is a key indicator of air pollution. Although PM is known as the extensive health hazard to affect a variety of illness, few studies have specifically investigated the effects of PM10 exposure on schizophrenic development. In the present study, we aimed to investigate the impact of PM10 on MK-801, N-methyl-D-aspartate (NMDA) receptor antagonist, induced schizophrenia-like behaviors in C57BL/6 mouse. Preadolescent mice were exposed PM10 to 3.2 mg/m3 concentration for 4 h/day for 2 weeks through a compartmentalized whole-body inhalation chamber. After PM10 exposure, we conducted behavioral tests during adolescence and adulthood to investigate longitudinal development of schizophrenia. We found that PM10 exacerbated schizophrenia-like behavior, such as psychomotor agitation, social interaction deficits and cognitive deficits at adulthood in MK-801-induced schizophrenia animal model. Furthermore, the reduced expression levels of brain-derived neurotrophic factor (BDNF) and the phosphorylation of BDNF related signaling molecules, extracellular signal-regulated kinase (ERK) and cAMP response element-binding protein (CREB), were exacerbated by PM10 exposure in the adult hippocampus of MK-801-treated mice. Thus, our present study demonstrates that exposure to PM10 in preadolescence exacerbates the cognitive impairment in animal model of schizophrenia, which are considered to be facilitated by the decreased level of BDNF through reduced ERK-CREB expression.

Development of a model to predict vancomycin serum concentration during continuous infusion of vancomycin in critically ill pediatric patients.

Vancomycin is a frequently used antibiotic in intensive care units, and the patient's renal clearance affects the pharmacokinetic characteristics of vancomycin. Several advantages have been reported for vancomycin continuous intravenous infusion, but studies on continuous dosing regimens based on patients' renal clearance are insufficient. The aim of this study was to develop a vancomycin serum concentration prediction model by factoring in a patient's renal clearance. Children admitted to our institution between July 1, 2021, and July 31, 2022 with records of continuous infusion of vancomycin were included in the study. Sex, age, height, weight, vancomycin dose by weight, interval from the start of vancomycin administration to the time of therapeutic drug monitoring sampling, and vancomycin serum concentrations were analyzed with the linear regression analysis of the mixed effect model. Univariable regression analysis was performed using the vancomycin serum concentration as a dependent variable. It showed that vancomycin dose (p < 0.001) and serum creatinine (p = 0.007) were factors that had the most impact on vancomycin serum concentration. Vancomycin serum concentration was affected by vancomycin dose (p < 0.001) and serum creatinine (p = 0.001) with statistical significance, and a multivariable regression model was obtained as follows: Vancomycin serum concentration (mg/l) = -1.296 + 0.281 × vancomycin dose (mg/kg) + 20.458 × serum creatinine (mg/dl) (adjusted coefficient of determination, R2 = 0.66). This prediction model is expected to contribute to establishing an optimal continuous infusion regimen for vancomycin.

Low skeletal muscle mass is associated with mortality in kidney transplant recipients.

Muscle wasting in chronic kidney disease is associated with increased cardiovascular events, morbidity, and mortality. However, whether pretransplantation skeletal muscle mass affects kidney transplantation (KT) outcomes has not been established. We analyzed 623 patients who underwent KT between 2004 and 2019. We measured the cross-sectional area of total skeletal muscle at the third lumbar vertebra level on pretransplantation computed tomography scan. The patients were grouped into low and normal skeletal muscle mass groups based on the sex-specific skeletal muscle mass index lowest quartile. During the entire follow-up period, 45 patients (7.2%) died and 56 patients (9.0%) experienced death-censored graft loss. Pretransplantation low skeletal muscle mass was independently associated with all-cause mortality (adjusted hazard ratio, 2.269; 95% confidence interval, 1.232-4.182). Low muscle mass was also associated with an increased risk of hospital readmission within 1 year after transplantation. Death-censored graft survival rates were comparable between the 2 groups. The low muscle group showed higher creatinine-based estimated glomerular filtration rates (eGFRs) than the normal muscle group. Although cystatin C-based eGFRs were measured in only one-third of patients, cystatin C-based eGFRs were comparable between the 2 groups. Pretransplantation low skeletal muscle mass index is associated with an increased risk of mortality and hospital readmission after KT.

Perfusion Maps Acquired From Dynamic Angiography MRI Using Deep Learning Approaches.

BACKGROUND: A typical stroke MRI protocol includes perfusion-weighted imaging (PWI) and MR angiography (MRA), requiring a second dose of contrast agent. A deep learning method to acquire both PWI and MRA with single dose can resolve this issue. PURPOSE: To acquire both PWI and MRA simultaneously using deep learning approaches. STUDY TYPE: Retrospective. SUBJECTS: A total of 60 patients (30-73 years old, 31 females) with ischemic symptoms due to occlusion or ≥50% stenosis (measured relative to proximal artery diameter) of the internal carotid artery, middle cerebral artery, or anterior cerebral artery. The 51/1/8 patient data were used as training/validation/test. FIELD STRENGTH/SEQUENCE: A 3 T, time-resolved angiography with stochastic trajectory (contrast-enhanced MRA) and echo planar imaging (dynamic susceptibility contrast MRI, DSC-MRI). ASSESSMENT: We investigated eight different U-Net architectures with different encoder/decoder sizes and with/without an adversarial network to generate perfusion maps from contrast-enhanced MRA. Relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), mean transit time (MTT), and time-to-max (Tmax ) were mapped from DSC-MRI and used as ground truth to train the networks and to generate the perfusion maps from the contrast-enhanced MRA input. STATISTICAL TESTS: Normalized root mean square error, structural similarity (SSIM), peak signal-to-noise ratio (pSNR), DICE, and FID scores were calculated between the perfusion maps from DSC-MRI and contrast-enhanced MRA. One-tailed t-test was performed to check the significance of the improvements between networks. P values < 0.05 were considered significant. RESULTS: The four perfusion maps were successfully extracted using the deep learning networks. U-net with multiple decoders and enhanced encoders showed the best performance (pSNR 24.7 ± 3.2 and SSIM 0.89 ± 0.08 for rCBV). DICE score in hypo-perfused area showed strong agreement between the generated perfusion maps and the ground truth (highest DICE: 0.95 ± 0.04). DATA CONCLUSION: With the proposed approach, dynamic angiography MRI may provide vessel architecture and perfusion-relevant parameters simultaneously from a single scan. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 5.

Prognostic value of collateral perfusion estimation by arterial spin labeling for acute anterior circulation ischemic stroke.

PURPOSE: This study aimed to verify the value of arterial spin labeling (ASL) collateral perfusion estimation for predicting functional outcomes in acute anterior circulation ischemic stroke. METHODS: This secondary analysis of an ongoing prospective observational study included data from participants with acute ischemic stroke due to steno-occlusion of the internal carotid artery and/or the middle cerebral artery within 8 h of symptom onset. We compared the collateral map, which is a 5-phase collateral imaging derived from dynamic contrast-enhanced magnetic resonance angiography, and ASL to validate the ASL collateral perfusion estimation. Multiple logistic regression analyses were conducted to identify independent predictors of favorable functional outcomes. RESULTS: One hundred forty-eight participants (68 ± 13 years, 96 men) were evaluated. The ASL collateral perfusion grade was positively correlated with the collateral perfusion grade of the collateral map (P < .001). Younger age (OR = 0.53, 95% CI = 0.36-0.78, P = .002), lower baseline NIHSS score (OR = 0.85, 95% CI = 0.78-0.92, P < .001), intermediate ASL collateral perfusion grade (OR = 4.02, 95% CI = 1.43-11.26, P = .008), good ASL collateral perfusion grade (OR = 26.37, 95% CI = 1.06-655.01, P = .046), and successful reperfusion (OR = 5.84, 95% CI = 2.08-16.42, P < .001) were independently associated with favorable functional outcomes. CONCLUSION: ASL collateral perfusion estimation provides prognostic information, which can be helpful in guiding management decisions.

A collaborative study to establish the second national standard for hepatitis B immunoglobulin in Korea.

This study aimed to establish a second national standard for hepatitis B immunoglobulin (HBIG) that can be used for potency assays of hepatitis B and normal immunoglobulin. The candidate material was manufactured using a process approved as Good Manufacturing Practice. The freeze-dried candidate preparation was tested for physicochemical and biological properties, including pH, residual moisture, molecular size distribution, and potency. A collaborative study was performed involving four laboratories, including the National Institute of Food and Drug Safety Evaluation, as an official national control laboratory in Korea and manufacturers. The potency was calibrated against the second international standard for HBIG using two enzyme immunoassays: enzyme-linked immunosorbent assay and electrochemiluminescence immunoassay. Results from 240 assays were obtained from four laboratories, and combined potency estimates were obtained by calculating the geometric means. Intra- and inter-laboratory variability showed acceptable geometric coefficients of variation of 1.3-6.0 and 3.2-3.6%, respectively. The candidate preparation showed satisfactory stability in accelerated thermal degradation and real-time stability tests. Based on these results, the potency value of 105 IU/vial was assigned (95% confidence intervals: 100.0-109.2 IU/vial), and it was deemed suitable to serve as the Korean national standard for HBIG.

A Novel Screening, Brief Intervention, and Referral to Treatment (SBIRT) Based Model for Mental Health in Occupational Health Implemented on Smartphone and Web-Based Platforms: Development Study With Results From an Epidemiologic Survey.

BACKGROUND: While the importance of mental health is well-recognized in the field of occupational health, implementation of effective strategies in the workplace has been limited by gaps in infrastructure, program comprehensiveness, coverage, and adherence. The authors developed a Screening, Brief Intervention, and Referral to Treatment (SBIRT) model based occupational mental health intervention, and implemented in a web-based format with a smartphone application. METHODS: The SBIRT-based intervention was developed by a multidisciplinary team, including occupational health physicians, nurses, psychiatrists, and software developers. The following mental health areas were included, based on outcomes of an epidemiological survey conducted: insomnia, depression, anxiety, problematic alcohol use, and suicidal risk. The viability of the two-step evaluation process utilizing a combination of the brief version and the full-length version of the questionnaire was examined using responses from the survey. The intervention was adjusted according to the survey results and expert opinions. RESULTS: The epidemiological survey included 346 employees who completed the long-form version of mental health scales. These data were the used to confirm the diagnostic value of using a combination of short-form and long-form version of the scales for screening in the SBIRT model. The model uses a smartphone application for screening, provision of psychoeducation, and for surveillance. The universal methods of the model ensure it can be implemented by all occupational managers, regardless of their specialization in mental health. In addition to the two-step screening procedure to identify employees at-risk for mental health problems, the model includes a stepped care approach, based on risk stratification, to promote mental health education, management, and follow-up for continuous care. CONCLUSION: The SBIRT model-based intervention provides an easy-to-implement approach for the management of mental health in the workplace. Further studies are required to examine the effectiveness and feasibility of the model.

The impact of physical activity changes on exercise capacity and health-related quality of life in young patients with CHD: a 3-year follow-up study.

OBJECTIVE: This study examined the relationship between changes in physical activity and their impact on exercise capacity and health-related quality of life over a 3-year span in patients with CHD. METHODS: We evaluated 99 young patients with CHD, aged 13-18 years at the outset. Physical activity, health-related quality of life, and exercise capacity were assessed via questionnaires and peak oxygen uptake measurements at baseline and after 3 years; changes in measures were estimated between the two time points and categorised into quartiles. Participants were stratified according to achieved (active) or not-achieved (inactive) recommended levels of physical activity (≥150 minutes/week) at both time points. RESULTS: Despite increases in physical activity, exercise capacity, and health-related quality of life over 3 years, the changes were not statistically significant (all p > 0.05). However, a positive association was found between physical activity changes and exercise capacity (ß = 0.250, p = 0.040) and health-related quality of life improvements (ß = 0.380, p < 0.001). Those with the most pronounced physical activity increase showed notable exercise capacity (p < 0.001) and health-related quality of life increases (p < 0.001) compared with patients with the largest decline in physical activity. The active-inactive category demonstrated a notable decline in exercise capacity compared to the active-active group, while the inactive-active group showed health-related quality of life improvements. CONCLUSIONS: Over 3 years, increased physical activity was consistently linked to increases in exercise capacity and health-related quality of life in patients with CHD, highlighting the potential of physical activity augmentation as an intervention strategy.

The Anti-Atopic Dermatitis Effects of Mentha arvensis Essential Oil Are Involved in the Inhibition of the NLRP3 Inflammasome in DNCB-Challenged Atopic Dermatitis BALB/c Mice.

The NLRP3 inflammasome is upregulated by various agents, such as nuclear factor-kappa B (NF-κB), lipopolysaccharide (LPS), and adenosine triphosphate (ATP). The NLRP3 inflammasome facilitations the maturation of interleukin (IL)-1ß, a proinflammatory cytokine that is critically involved in the pathogenesis of atopic dermatitis (AD). Although the NLRP3 inflammasome clearly exacerbates AD symptoms such as erythema and pruritus, drugs for AD patients targeting the NLRP3 inflammasome are still lacking. Based on the previous findings that Mentha arvensis essential oil (MAEO) possesses strong anti-inflammatory and anti-AD properties through its inhibition of the ERK/NF-κB signaling pathway, we postulated that MAEO might be capable of modulating the NLRP3 inflammasome in AD. The aim of this research was to investigate whether MAEO affects the inhibition of NLRP3 inflammasome activation in murine bone marrow-derived macrophages (BMDMs) stimulated with LPS + ATP in vitro and in a murine model displaying AD-like symptoms induced by 2,4-dinitrochlorobenzene (DNCB) in vivo. We found that MAEO inhibited the expression of NLRP3 and caspase-1, leading to the suppression of NLRP3 inflammasome activation and IL-1ß production in BMDMs stimulated with LPS + ATP. In addition, MAEO exhibited efficacy in ameliorating AD symptoms in a murine model induced by DNCB, as indicated by the reduction in dermatitis score, ear thickness, transepidermal water loss (TEWL), epidermal thickness, and immunoglobulin E (IgE) levels. Furthermore, MAEO attenuated the recruitment of NLRP3-expressing macrophages and NLRP3 inflammasome activation in murine dorsal skin lesions induced by DNCB. Overall, we provide evidence for the anti-AD effects of MAEO via inhibition of NLRP3 inflammasome activation.

Association between nuclear factor of activated T cells C2 polymorphisms and treatment response in rheumatoid arthritis patients receiving tumor necrosis factor-alpha inhibitors.

OBJECTIVES: Nuclear factor of activated T cells C2 (NFATC2) is known as a member of the transcription family and enhances tumor necrosis factor-alpha (TNF-α) synthesis in human T cells at the gene transcription level. Although NFATC2 has a potential role in rheumatoid arthritis (RA) progression and treatment, no study has investigated the association between NFATC2 gene polymorphisms and response status in RA patients receiving TNF-α inhibitors. This study aimed to examine the effects of polymorphisms in NFATC2, a TNF-α transcription factor, on response to TNF-α inhibitors. METHODS: This prospective observational study was performed in two centers. Seven single nucleotide polymorphisms (SNPs) were investigated. Good responders were defined as patients with disease activity score (DAS)28 ≤3.2 after 6 months of treatment. Logistic regression analyses were used to investigate the association between genetic polymorphisms and response to the treatment. To test the model's goodness of fit, a Hosmer-Lemeshow test was performed. RESULTS: This study included 98 patients, among whom 46 showed favorable responses to the treatment. Patients with hypertension revealed an approximately three-fold lower response to TNF-α inhibitors compared to those without hypertension (23.5 vs. 76.5%; P = 0.049). After adjusting for covariates, C allele carriers of NFATC2 rs3787186 exhibited approximately three-fold lower rates of treatment response compared to those with TT genotype (P = 0.037). The Hosmer-Lemeshow test showed that the fitness of the multivariable analysis model was satisfactory (χ2 = 9.745; 8 degrees of freedom; P = 0.283). CONCLUSION: This study suggested an association between the C allele of rs3787186 and treatment response in RA patients receiving TNF-α inhibitors.

Frontline nurses' burnout and its associated factors during the COVID-19 pandemic in South Korea.

BACKGROUND: The Coronavirus disease pandemic is a global health crisis with psychological consequences for healthcare workers. PURPOSE: To identify the prevalence and potential factors influencing burnout among frontline nurses in South Korea. METHODS: This cross-sectional study comprised 161 nurses who voluntarily participated in the survey through advertisements at a general hospital. Data on sociodemographic and professional characteristics, insomnia, depression, anxiety, stress, and burnout were collected via an online questionnaire in 2021. RESULTS: Among the participants, 90 had a high level of burnout. Overall, 59.6 %, 23.0 %, 36.0 %, and 17.4 % of nurses experienced insomnia, depression, anxiety, and stress, respectively. The results showed that the assigned number of patients, insomnia, and depression were the major factors affecting burnout levels of nursing staff. CONCLUSIONS: Frontline nurses were the main force in the fight against public health emergencies. The government and medical institutions must consider professional and psychological factors in ameliorating burnout and safety for nurses.

Active Aging In Long-Term Care Facilities In Korea : Beyond The Lexical Meaning.

The discourse of active aging, as introduced by the WHO, aims at optimizing older adults' opportunities for health, participation, and security that could eventually enhance their social integration and quality of life. Considering that even those with frailty could strive for active aging in the given circumstances, we examined the meaning of active aging in long-term care settings and care strategies to promote it based on the WHO's framework. We conducted interviews with a total of 35 participants. The interpretative analyses revealed that the activities taken place in LTCFs have various scopes depending on older adults' physical and cognitive functional ability, and it captures the forms of activities that go beyond its lexical meaning. By defining being "active," the present findings could contribute to an understanding of how the three elements of active aging can be carried out in LTCFs.

Cancer-associated fibroblasts induce an aggressive phenotypic shift in non-malignant breast epithelial cells via interleukin-8 and S100A8.

Cancer-associated fibroblasts (CAFs) in the tumor microenvironment have been associated with tumor progression in breast cancer. Although crosstalk between breast cancer cells and CAFs has been studied, the effect of CAFs on non-neoplastic breast epithelial cells is not fully understood to date. Here, we investigated the effect of CAFs on aggressive phenotypes in non-neoplastic MCF10A breast epithelial cells. CAFs induced epithelial-to-mesenchymal transition (EMT) and invasive phenotype in MCF10A cells. S100A8, a potential prognostic marker in several cancers, was markedly increased in MCF10A cells by CAFs. S100A8 was crucial for CAFs-induced invasive phenotype of MCF10A cells. Among cytokines increased by CAFs, interleukin (IL)-8 induced S100A8 through transcription factors p65 NF-κB and C/EBPß. In a xenograft mouse model with MCF10A cells and CAFs, tumor was not developed, suggesting that coinjection with CAFs may not be sufficient for in vivo tumorigenicity of MCF10A cells. Xenograft mouse tumor models with MDA-MB-231 breast carcinoma cells provided an in vivo evidence for the effect of CAFs on breast cancer progression as well as a crucial role of IL-8 in tumor growth and S100A8 expression in vivo. Using a tissue microarray of human breast cancer, we showed that S100A8 expression was correlated with poor outcomes. S100A8 expression was more frequently detected in cancer-adjacent normal human breast tissues than in normal breast tissues. Together, this study elucidated a novel mechanism for the acquisition of invasive phenotype of non-neoplastic breast cells induced by CAFs, suggesting that targeting IL-8 and S100A8 may be an effective strategy against breast cancer.

LRP1 regulates food intake and energy balance in GABAergic neurons independently of leptin action.

Low-density lipoprotein receptor-related protein 1 (LRP1) is a member of LDL receptor family that plays a key role in systemic glucose and lipid homeostasis. LRP1 also regulates energy balance in the hypothalamus by mediating leptin's anorexigenic action, although the underlying neurocircuitry involved is still unclear. Because GABAergic neurons are a major mediator of hypothalamic leptin action, we studied the role of GABAergic LRP1 in energy balance and leptin action using mice lacking LRP1 in Vgat- or AgRP-expressing neurons (Vgat-Cre; LRP1loxP/loxP or AgRP-Cre; LRP1loxP/loxP). Here, we show that LRP1 deficiency in GABAergic neurons results in severe obesity in male and female mice fed a normal-chow diet. This effect is most likely due to increased food intake and decreased energy expenditure and locomotor activity. Increased adiposity in GABAergic neuron-specific LRP1-deficient mice is accompanied by hyperleptinemia and hyperinsulinemia. Insulin resistance and glucose intolerance in these mice are occurred without change in body weight. Importantly, LRP1 in GABAergic neurons is not required for leptin action, as evidenced by normal leptin's anorexigenic action and leptin-induced hypothalamic Stat3 phosphorylation. In contrast, LRP1 deficiency in AgRP neurons has no effect on adiposity and caloric intake. In conclusion, our data identify GABAergic neurons as a key neurocircuitry that underpins LRP1-dependent regulation of systemic energy balance and body-weight homeostasis. We further find that the GABAergic LRP1 signaling pathway modulates food intake and energy expenditure independently of leptin signaling and AgRP neurons.

Collateral and permeability imaging derived from dynamic contrast material-enhanced MR angiography in prediction of PH 2 hemorrhagic transformation after acute ischemic stroke: a pilot study.

PURPOSE: To evaluate the role of collateral and permeability imaging derived from dynamic contrast material-enhanced magnetic resonance angiography to predict PH 2 hemorrhagic transformation in acute ischemic stroke. METHODS: The secondary analysis of a published data from participants with acute ischemic stroke. The multiphase collateral map and permeability imaging were generated by using dynamic signals from dynamic contrast material-enhanced magnetic resonance angiography obtained at admission. To identify independent predictors of PH 2 hemorrhagic transformation, age, sex, risk factors, baseline National Institutes of Health Stoke Scale (NIHSS) score, baseline DWI lesion volume, collateral-perfusion status, mode of treatment, and successful early reperfusion were evaluated with multiple logistic regression analyses and the significance of permeability imaging in prediction of PH 2 hemorrhagic transformation was evaluated by subgroup analysis. RESULTS: In 115 participants, including 70 males (mean (SD) age, 69 (12) years), PH 2 hemorrhagic transformation occurred in 6 participants with very poor collateral-perfusion status (MAC 0). MAC 0 (OR, 0.06; 95% CI, 0.01, 0.74; P = .03) was independently associated with PH 2 hemorrhagic transformation. In 22 participants with MAC 0, the permeable signal on Kep permeability imaging was the only significant characteristic associated with PH 2 hemorrhagic transformation (P = .009). The specificity of Kep permeability imaging was 93.8% (95% confidence interval: 69.8, 99.8) in predicting PH 2 hemorrhagic transformation. CONCLUSION: Individual-based prediction of PH 2 hemorrhagic transformation in patients with acute ischemic stroke may be possible with multiphase collateral map and permeability imaging derived from dynamic contrast material-enhanced magnetic resonance angiography.

A Mixed-Methods Study of Early Childhood Education and Care in South Korea: Policies and Practices During COVID-19.

This study of South Korea's response to COVID-19 has three purposes. First, it uses document analysis to examine policies, strategies, and resources offered by the South Korean government and public organizations to support young children and families during the first 6 months of the pandemic. Next, it uses open-ended surveys with 30 directors of early childhood institutions to explore institutional-level supports and needs during the pandemic. Finally, it looks at the discrepancies between stated policies outlining the South Korea's response to COVID-19 and the lived experiences of early childhood educators as a route to arriving at recommendations for education policymakers and other stakeholders. To that end, we reviewed government documents (n = 84) containing early childhood education-related responses to Covid-19 established by the Ministry of Education, the Ministry of Health and Welfare, and other relevant government sectors. An online survey with 17 kindergarten and 13 child care center directors was also analyzed. Using content analysis, the findings revealed that the government's policies and guidance for Early Childhood Education and Care (ECEC) as well as the institutional supports for children and families were overall comprehensive in its scope. The analysis, based on the five tenets of the Whole Child approach, also indicated that the government's policy responses and services for ECEC focused mainly on the 'Safe' and 'Supported' tenets, while 'Challenged' was given the least amount of consideration. The survey responses demonstrated different measures taken by kindergartens and child care centers highlighting the separate nature of 'education' and 'care' in South Korea, while also indicating limited resources for supporting children's psychological well-being and for children and families in need. This overview provides a foundation for further discussion and research on the impact of Covid-19 on ECEC in South Korea and beyond.