Seasonal influences on the efficacy of anti-programmed cell death (ligand) 1 inhibitors in lung cancer.

BACKGROUND: Seasonal variations in systemic immunity have been reported. This study aimed to evaluate whether seasonality affects the efficacy of anticancer immunotherapy. METHODS: A total of 604 patients with lung cancer receiving single anti-programmed cell death (ligand) 1 (anti-PD-[L]1) inhibitors from two prospective observational cohorts were screened. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Patients were classified into two groups according to the season when the treatment started: winter (November-February) and other seasons (March-October). Kaplan-Meier analysis and Cox proportional hazards models were fitted to evaluate the impact of seasonality on survival. For validation, propensity score matching was performed. RESULTS: A total of 484 patients with advanced non-small cell lung cancer were included. In an unmatched population, multivariable analysis demonstrated that the winter group (n = 173) had a significantly lower risk of progression or death from immunotherapy than the other group (n = 311) (PFS: hazard ratio [HR], 0.77 [95% confidence interval (CI), 0.62-0.96]; p = .018; OS: HR, 0.77 [95% CI, 0.1-0.98]; p = .032). In a propensity score-matched population, the winter group (n = 162) showed significantly longer median PFS (2.8 months [95% CI, 1.9-4.1 months] vs. 2.0 months [95% CI, 1.4-2.7 months]; p = .009) than the other group (n = 162). The winter group's median OS was also significantly longer than that of the other group (13.4 months [95% CI, 10.2-18.0 months] vs. 8.0 months [95% CI, 3.6-8.7 months]; p = .012). The trend toward longer survival in the winter group continued in subgroup analyses. CONCLUSIONS: Starting an anti-PD-(L)1 inhibitor in winter was associated with better treatment outcomes in patients with lung cancer compared to other seasons.

Percutaneous Cementoplasty for the Pelvis in Bone Metastasis: 12-Year Experience.

BACKGROUND: In advanced cancer patients, pelvic bone metastasis often causes pain and gait disturbance. The use of percutaneous bone cement [polymethylmethacrylate (PMMA)] injection for pain management and strengthening in pelvic bone metastasis has rarely been reported. To evaluate this method, we aimed to determine surgical outcomes and complications over a long-term follow-up period using a large patient group. PATIENTS AND METHODS: We retrospectively collected data from 178 patients who underwent percutaneous cementoplasty for pelvic metastatic lesions, 201 in total. Surgical outcomes evaluated included pain reduction and improvement of ambulation. Mortality within 1 month after procedure and pulmonary embolism caused by thrombus, fat, tumor emboli, or bone cement were investigated as surgical complications. For long-term survivors, pain relapse and mechanical failure were analyzed. The mean follow-up period was 12.6 months, and there were 159 fatalities at last follow-up. RESULTS: The mean regional pain numerical rating scale scores decreased from 6.1 preoperatively to 2.4 1 month after procedure (p < 0.01). Gait function was maintained, worsened, and uncheckable in 68%, 24%, and 8% of patients, respectively, 1 month after procedure. Of long-term survivors followed up for > 12 months (n = 53), there were no significant changes in serial plain radiographs, and regional pain aggravation was observed in 9%. Pulmonary cement embolism and bone cement implantation syndrome was observed in 11% and 10%, respectively. However, all patients with these complications were asymptomatic. CONCLUSIONS: Percutaneous cement injection into the pelvis is a feasible and safe palliative surgical option for patients with advanced malignancy in terms of pain reduction and maintenance of ambulatory function under regional anesthesia.

Initial M Staging of Rectal Cancer: FDG PET/MRI with a Hepatocyte-specific Contrast Agent versus Contrast-enhanced CT.

BackgroundThe performance of PET/MRI in the determination of distant metastases (M stage) in rectal cancer relative to the current practice with contrast material-enhanced CT is largely unknown.PurposeTo compare the staging of clinical M stage rectal cancer with fluorine 18 fluorodeoxyglucose (FDG) PET/MRI (including dedicated liver and rectal MRI) to that of chest and abdominopelvic CT and dedicated rectal MRI.Materials and MethodsFrom January 2016 to August 2017, patients with newly diagnosed advanced mid to low rectal cancers were recruited for this prospective study (clinicaltrials.gov identifier: NCT0265170). Participants underwent both FDG PET/MRI with dedicated liver and rectal MRI and chest and abdominopelvic CT (the standard-of-care protocol) within 3 weeks of each other. Thereafter, M stage assessment performance was determined by using findings from 6-month clinical follow-up or biopsy as the reference standard. Performance was compared between protocols. Agreement in M stage classification was also assessed. Nonparametric statistical analyses were performed, and P < .05 indicated a significance difference.ResultsSeventy-one participants (28 women; mean age ± standard deviation, 61 years ± 9; age range, 39-79 years) were enrolled. The M stage could not be determined with the standard-of-care protocol in 22 of the 71 participants (31%; 95% confidence interval [CI]: 20.5%, 43.1%) because of indeterminate lesions. However, among these participants, PET/MRI correctly helped identify all 14 (100%; 95% CI: 76.8%, 100%) without metastases and seven of eight (88%; 95% CI: 47.4%, 99.7%) who were later confirmed to have metastases. PET/MRI showed high specificity for ruling out metastatic disease compared with the standard-of-care protocol (98% [54 of 55 participants] vs 72% [40 of 55 participants], respectively; P < .001), without increasing the number of participants with missed metastasis (6% [one of 16 participants] vs 6% [one of 16 participants]; P > .99).ConclusionPET/MRI with dedicated rectal and liver MRI can facilitate the staging work-up of newly diagnosed advanced rectal cancers by helping assess indeterminate lesions, metastases, and incidental findings better than contrast-enhanced CT, obviating for additional imaging work-up.© RSNA, 2019Online supplemental material is available for this article.Clinical trial registration no. NCT02651701.

Effect of miR-155 as a molecular adjuvant of DNA vaccine against VHSV in olive flounder (Paralichthys olivaceus).

Rhabdoviral G protein-based DNA vaccines have been recognized as a useful way to protect cultured fish from rhabdoviral diseases. In Korea, viral hemorrhagic septicemia virus (VHSV) genotype IVa has been the primary culprit of high mortalities of cultured olive flounder (Paralichthys olivaceus). In this study, we inserted a miR-155-expressing cassette into the VHSV's G protein-based DNA vaccine, and analyzed the effects of miR-155 on the antiviral activity and on the vaccine efficacy in olive flounder. Olive flounder fingerlings were intramuscularly (i.m.) immunized with 10 µg/fish (1st experiment) or 1 µg/fish (2nd experiment) of DNA vaccine plasmids. However, there were no significant differences in mortalities and serum neutralization titers between fish immunized with 1 µg and 10 µg plasmids/fish, suggesting that i.m. injection with 1 µg plasmids/fish would be enough to induce effective adaptive immune responses in olive flounder fingerlings. In survival rates, as fish immunized with just G protein expressing plasmids showed no or too low mortalities, the adjuvant effect of miR-155 was not discernible. Also, in the serum neutralization activities, although G gene or G gene plus miR-155 expressing DNA vaccines induced significantly higher activities than control vaccines (PBS and vacant vector), no significant differences were found between G gene alone and G gene plus miR-155 expressing DNA vaccines. In the serum virucidal activity, fish immunized with G gene plus miR-155 expressing DNA vaccine showed significantly higher activity against hirame rhabdovirus (HIRRV) at 3 days post-immunization (d.p.i.) compared to other groups, suggesting that miR-155 produced from the vector can enhance innate immune responses in olive flounder. The significantly enhanced serum virucidal activities against VHSV especially at 28 d.p.i. in the groups immunized with G gene alone and G gene plus miR-155 expressing DNA vaccines reflect the increased antibodies against G protein, which could activate the classical complement pathway and subsequent viral inactivation. As the available information on the DNA vaccines in olive flounder is not sufficient, more diverse researches on the protective efficacy of DNA vaccines are needed to make more practical use of DNA vaccines in olive flounder farms.

Risk factors for haemoptysis after percutaneous transthoracic needle biopsies in 4,172 cases: Focusing on the effects of enlarged main pulmonary artery diameter.

OBJECTIVES: To evaluate the risk factors for haemoptysis after cone-beam computed tomography (CBCT)-guided percutaneous transthoracic needle biopsy (PTNB), particularly on whether the enlargement of main pulmonary artery diameter (mPAD) is a risk factor for PTNB-related haemoptysis. METHODS: 4,172 cases of CBCT-guided PTNBs in 3,840 patients were retrospectively included in this study. Various data including mPAD measured on preprocedural CT images were evaluated using logistic regression analyses to determine significant risk factors for both haemoptysis and severe haemoptysis, designated as when blood transfusion, vascular embolisation or cardiopulmonary resuscitation were required to manage patients with haemoptysis. RESULTS: Haemoptysis occurred in 5.78 % (241/4172) of all PTNB procedures, while severe haemoptysis occurred in 0.18 % (7/4172). Female sex, history of antiplatelet or anticoagulative drugs, prolonged activated partial thromboplastin time, subsolid nodules, cavitary nodules and long pleura-to-target distance were revealed to be independent risk factors for haemoptysis, while mPAD enlargement (> 29.5 mm) was not. Regarding severe haemoptysis, however, mPAD enlargement was demonstrated to be an independent risk factor along with the presence of subsolid and cavitary target nodules. CONCLUSION: mPAD enlargement was not a significant risk factor for PTNB-related haemoptysis; however, it was a significant risk factor for severe haemoptysis. KEY POINTS: • mPAD enlargement was a significant risk factor for severe PTNB-related haemoptysis. • mPAD can be useful in screening high-risk patients for severe haemoptysis. • Subsolid or cavitary nodule was another significant risk factor for severe haemoptysis.

Time-dependent analysis of incidence, risk factors and clinical significance of pneumothorax after percutaneous lung biopsy.

OBJECTIVES: To evaluate the time-dependent incidence, risk factors and clinical significance of percutaneous lung biopsy (PLB)-related pneumothorax. METHODS: From January 2012-November 2015, 3,251 patients underwent 3,354 cone-beam CT-guided PLBs for lung lesions. Cox, logistic and linear regression analyses were performed to identify time-dependent risk factors of PLB-related pneumothorax, risk factors of drainage catheter insertion and those of prolonged catheter placement, respectively. RESULTS: Pneumothorax occurred in 915/3,354 PLBs (27.3 %), with 230/915 (25.1 %) occurring during follow-ups. Risk factors for earlier occurrence of PLB-related pneumothorax include emphysema (HR=1.624), smaller target (HR=0.922), deeper location (HR=1.175) and longer puncture time (HR=1.036), while haemoptysis (HR=0.503) showed a protective effect against earlier development of pneumothorax. Seventy-five cases (8.2 %) underwent chest catheter placement. Mean duration of catheter placement was 3.2±2.0 days. Emphysema (odds ratio [OR]=2.400) and longer puncture time (OR=1.053) were assessed as significant risk factors for catheter insertion, and older age (parameter estimate=1.014) was a predictive factor for prolonged catheter placement. CONCLUSION: PLB-related pneumothorax occurred in 27.3 %, of which 25.1 % developed during follow-ups. Smaller target size, emphysema, deeply-located lesions were significant risk factors of PLB-related pneumothorax. Emphysema and older age were related to drainage catheter insertion and prolonged catheter placement, respectively. KEY POINTS: • One-fourth of percutaneous lung biopsy (PLB)-related pneumothorax occurs during follow-up. • Smaller, deeply-located target and emphysema lead to early occurrence of pneumothorax. • Emphysema is related to drainage catheter insertion for PLB-related pneumothorax. • Older age may lead to prolonged catheter placement for PLB-related pneumothorax. • Tailored management can be possible with time-dependent information of PLB-related pneumothorax.

Predictors of clinical outcome in emphysema patients with atelectasis following endoscopic valve therapy: A retrospective study.

BACKGROUND AND OBJECTIVE: The aim of endoscopic valve therapy in patients with emphysema is complete lobar atelectasis of the most emphysematous lobe. However, even after the radiological advent of atelectasis, great variability in clinical outcomes can be observed. METHODS: The baseline clinical measures (vital capacity (VC), forced expiratory flow in 1 s (FEV1 ), residual volume (RV) and 6-min walk test (6-MWT)) and computed tomography variables (low attenuation volume (LAV) of the target lobe, LAV% of the target and the ipsilateral untreated lobe and LAV of the target lobe to LAV of the target lung and to LAV of the total lung) of 77 patients with complete atelectasis following valve therapy were retrospectively examined to determine their impact on patient´s outcome (changes in VC, FEV1 , RV and 6-MWT from baseline to the time of atelectasis). RESULTS: Low attenuation volume of the target lobe to LAV of the target lung predicts a significant FEV1 improvement in patients with complete lobar atelectasis following valve therapy. A 10% difference in that computed tomography predictor was associated with a 82-mL improvement in FEV1 (P = 0.006). Lower 6-MWT scores, low VC and high RV at baseline were significantly associated with greater improvement in the respective parameter (all P < 0.001). CONCLUSION: Low attenuation volume of the target lobe to LAV of the target lung and baseline clinical measures seem to significantly predict clinical outcomes in patients with complete lobar atelectasis following valve treatment.

Ossification of the Medial Clavicular Epiphysis on Chest Radiographs: Utility and Diagnostic Accuracy in Identifying Korean Adolescents and Young Adults under the Age of Majority.

The aim of our study was to evaluate the utility and diagnostic accuracy of the ossification grade of medial clavicular epiphysis on chest radiographs for identifying Korean adolescents and young adults under the age of majority. Overall, 1,151 patients (age, 16-30) without any systemic disease and who underwent chest radiography were included for ossification grading. Two radiologists independently classified the ossification of the medial clavicular epiphysis from chest radiographs into five grades. The age distribution and inter-observer agreement on the ossification grade were assessed. The diagnostic accuracy of the averaged ossification grades for determining whether the patient is under the age of majority was analyzed by using receiver operating characteristic (ROC) curves. Two separate inexperienced radiologists assessed the ossification grade in a subgroup of the patients after reviewing the detailed descriptions and image atlases developed for ossification grading. The median value of the ossification grades increased with increasing age (from 16 to 30 years), and the trend was best fitted by a quadratic function (R-square, 0.978). The inter-observer agreements on the ossification grade were 0.420 (right) and 0.404 (left). The area under the ROC curve (AUC) was 0.922 (95% CI, 0.902-0.942). The averaged ossification scores of 2.62 and 4.37 provided 95% specificity for a person < 19 years of age and a person ≥ 19 years of age, respectively. A preliminary assessment by inexperienced radiologists resulted in an AUC of 0.860 (95% CI, 0.740-0.981). The age of majority in Korean adolescents and young adults can be estimated using chest radiographs.

Expression Patterns of HIF-1α Under Hypoxia in Vascular Smooth Muscle Cells of Venous Malformations.

PURPOSE: The molecular pathophysiology of venous malformations (VMs), which are a type of vascular malformation, is poorly understood. Until now, it is known that VM lesions are related to the process of angiogenesis. Because angiogenesis is induced under hypoxic conditions, hypoxia is thought to be important in VM lesion formation. Therefore, we examined the implications of hypoxia on the biological behavior of VM vascular smooth muscle cells (VSMCs). In doing so, we investigated the expression patterns of hypoxia-inducible factor-1α (HIF-1α), which plays a key role in hypoxia-induced angiogenesis, to provide a further understanding of the molecular mechanisms involved in VM. METHODS: Vascular smooth muscle cells from 5 normal veins and 5 VM lesions were cultured under moderate hypoxic conditions (3% O2, 5% CO2). The effects of hypoxia on HIF-1α expression were measured by immunocytochemical staining, reverse transcription-polymerase chain reaction, and real-time reverse transcription-polymerase chain reaction. RESULTS: Overall, the expression of HIF-1α in cells was high after exposure to hypoxia for 6 or 12 hours, but decreased after 24 hours of hypoxia. HIF-1α expression in VM VSMCs was 2 times higher than that in normal VSMCs. Immunocytochemically, HIF-1α was mainly located in the nucleus and the intensity in VM VSMCs was stronger after 6 and 12 hours of hypoxia when compared to the expression pattern of HIF-1α in VSMCs from normal tissue. This suggested that VM tissue is more susceptible to the effects of hypoxia than normal tissue. CONCLUSIONS: These results indicate that the high expression of HIF-1α in VM VSMCs under hypoxic conditions could be an important factor for stimulating downstream angiogenesis in VM. Furthermore, the results of this investigation could provide the basis for future studies of VM pathophysiology, and ultimately lead to the development of new therapeutic approaches.

A 635-nm light-emitting diode (LED) therapy inhibits bone resorptive osteoclast formation by regulating the actin cytoskeleton.

Bone diseases such as osteoporosis are mainly caused by upregulated activity of osteoclasts. The present study was designed to examine the effects of light-emitting diode (LED) irradiation on the formation and activity of multinucleated osteoclasts, specifically "round-shaped" osteoclast cells (ROC) in different cell types derived from mouse. After 635-nm LED irradiation, the cell viability was evaluated by MTT assay. The amount of total tartrate-resistant acid phosphatase (TRAP) + osteoclast and the number of ROC cells were also estimated by TRAP solution assay and TRAP staining, respectively. Actin rings were stained with rhodamine-conjugated phalloidin, and resorption assay was performed by dentin slices. In addition, gene expression levels between the control and irradiation groups were evaluated by RT-PCR. In a morphological analysis, the formation of ROC was significantly inhibited by 635-nm LED irradiation in the different cell types. Actin rings were seen at cell peripheries in most ROC cells of the control group, but patches containing disorganized actin were found in the irradiation group. Both the number of ROCs and bone resorption activity were much lower in the irradiation group than in the control group. Also, the gene expression levels involved in actin ring formation such as integrin ß3 and c-Src decreased in RT-PCR analysis. Overall, 635-nm LED therapy may play a pivotal role in regulating bone remodeling, and it may prove to be a valuable tool to prevent bone loss in osteoporosis and other resorptive bone diseases.

The Dropout Rates and Associated Factors in Patients with Mood Disorders in Long-term Naturalistic Treatment.

Objective: Although maintenance treatment for mood disorders is important, the treatment discontinuation rate is reported to be high. This study aimed to investigate the dropout rates and associated factors in mood disorders. Methods: The patients in a mood disorder clinic (n = 535) were examined. Demographic and clinical factors, scores of psychometric scales, time to dropout from initial treatment in patients with bipolar disorder (BP) (n = 288) and depressive disorder (DD) (n = 143) were evaluated based on database of the mood disorder clinic. Results: Among the studied patients with BP and DD, 50% showed dropout in 4.05 and 2.17 years, respectively. The mean survival times were 8.90 years in bipolar disorder I (BP-I), 5.19 years in bipolar II disorder, 3.22 years in bipolar disorder not otherwise specified, 4.24 years in major depressive disorder, and 4.03 years in other depressive disorders. In the multivariate Cox proportional hazards regression model in the BP group, diagnosis BP-I was found to be significantly related to the decrease in dropout rate (hazard ratio [HR] = 0.22, p = 0.001); however, increased past suicide attempt number was significantly related to the increase in dropout rate (HR = 1.13, p = 0.017). In the DD group, none of anxiety disorders as comorbidity, increased scores of openness, and extraversion personality were related to the increase in dropout rate. Conclusion: Patients with BP, especially BP-I, showed a lower dropout rate as compared to patients with other mood disorders.

Infection-related Hospitalizations During Immune Checkpoint Inhibitor Treatment Without Immunosuppressants.

Immunosuppressants are increasingly being used in the clinic to manage immune-related adverse effects. Consequently, the incidence of secondary infections associated with immunosuppression is increasing. However, little is known about primary infections during immune checkpoint inhibitor (ICI) treatment without immunosuppressants. We aimed to evaluate primary infectious diseases during antiprogrammed death ligand-1 immunotherapy without immunosuppressants. We retrospectively screened medical records of 233 patients who underwent ICI treatment for advanced non-small cell lung cancer between January 2014 and May 2018 at National Cancer Center, Republic of Korea. Subsequently, we evaluated the clinical characteristics and treatment outcomes of selected patients hospitalized for potential infectious disease without immunosuppressive treatment (n=80). Eight cases (3.4%) were identified as bacterial pneumonia (n=5) and cellulitis, inflamed epidermoid cyst, and wound infection (n=1 each). The bacterial pathogens Streptococcus pneumoniae and Haemophilus influenzae were identified in 4 patients with pneumonia. The period between the start of ICI treatment and infection varied between 3 and 189 days (median, 24.5 days). Five (62.5%) patients were infected within a month after ICI treatment initiation. All patients were treated with empirical antibiotics and discharged without complications. The median progression-free and overall survival for ICI treatment was 11.5 and 25.5 months, respectively. Six patients experienced ICI-associated adverse effects postinfection: Herpes zoster infection (n=4) and pneumonitis (n=2). Infectious disease independent of immunosuppression is a rare, but possible event in patients with lung cancer receiving ICI treatment. Clinical awareness would enable prompt diagnosis of primary infection during immunotherapy.

Subjective Experience on Virtual Reality-Assisted Mental Health Promotion Program.

OBJECTIVE: Mental health promotion programs using virtual reality (VR) technology have been developed in various forms. This study aimed to investigate the subjective experience of a VR-assisted mental health promotion program for the community population, which was provided in the form of VR experience on a bus to increase accessibility. METHODS: Ninety-six people participated in this study. The relationship between the subjective experience and mental health states such as depression, anxiety, perceived stress, and quality of life was explored. The subjective experience on depression and stress before and after VR program treatment was compared using the Wilcoxon signed-rank test. The satisfaction with the VR-assisted mental health promotion program was examined after using the VR program. RESULTS: The VR-assisted mental health promotion program on a bus significantly improved subjective symptoms such as depression (p=0.036) and perceived stress (p=0.010) among all the participants. Among the high-risk group, this VR program significantly relieved subjective depressive feeling score (p=0.033), and subjective stressful feeling score (p=0.035). In contrast, there were no significant changes in subjective depressive feelings (p=0.182) and subjective stressful feelings (p=0.058) among the healthy group. Seventy-two percent of the participants reported a high level of satisfaction, scoring 80 points or more. CONCLUSION: The findings of this study suggest that the VR-assisted mental health promotion program may effectively improve the subjective depressive and stressful feelings. The use of VR programs on buses to increase of accessibility for the community could be a useful approach for promoting mental health among the population.

Influence of Optimism, Social Support, and Spirituality on COVID-19 Stress in Christian Church Community.

OBJECTIVE: Optimism, social support, and spirituality can be important factors related to coronavirus disease-2019 (COVID-19) stress. However, studies investigating the influence and interplay of optimism, social support, and spirituality on COVID-19 simultaneously are still few. This study is aimed to explore the influence of optimism, social support, and spirituality on COVID-19 stress in the Christian church community. METHODS: A total 350 participants were included in this study. This study was cross-sectionally conducted by using an online survey on optimism, social support, spirituality, and COVID-19 stress that were measured by the Life Orientation Test-Revised (LOT-R), Multidimensional Scale of Perceived Social Support Scale (MSPSS), Spiritual Well-Being Scale (SWBS), and COVID-19 Stress Scale for Korean People (CSSK). The prediction models for COVID-19 stress were analyzed by using univariate and multiple linear regression. RESULTS: Based on the results of univariate linear regression, subjective feelings on income (p<0.001) and health status (p<0.001), LOTR (p<0.001), MSPSS (p=0.025), and SWBS (p<0.001) scores were significantly associated with COVID-19 stress. The multiple linear regression model with subjective feelings on income and health status and SWSB score was significant (p<0.001) and explained 17.7% of the variance (R2=0.177). CONCLUSION: This study showed that subjective feeling on low income, those who had poor health status, lower optimism, lower perceived social support, and lower spirituality were significantly affected with COVID-19 stress. Especially, the model with subjective feelings on income and health status, and spirituality showed highly significant effects, despite the interaction with associated factors. To cope with unpredictable stressful situations like the COVID-19 pandemic, integrated interventions on psycho-socio-spiritual aspect are warranted.

Changes of Locomotor Activity by Dopamine D2, D3 Agonist Quinpirole in Mice Using Home-cage Monitoring System.

Objective: : As dopamine is closely linked to locomotor activities, animal studies on locomotor activities using dopaminergic agents were widely done. However, most of animal studies were performed for a short period that there is a lack of longitudinal study on the effects of dopaminergic agents on locomotor activities. This study aimed to examine the longterm effect of a dopamine D2, D3 agonist quinpirole on locomotor activities in mice using a home-cage monitoring system. Methods: : The locomotor activities of Institute Cancer Research mice were measured by infrared motion detectors in home-cages under the 12-hour dark and 12-hour light condition for three days after the quinpirole injection. Quinpirole was injected at a concentration of 0.5 mg/kg intraperitoneally in the beginning of the dark phase. The locomotor activities before and after the quinpirole administration were compared by the Wilcoxon signed-rank test and one-way repeated measures ANOVA. Results: : After the quinpirole administration, the 24-hour total locomotor activity did not change (p = 0.169), but activities were significantly increased in the 12-hour dark phase sum (p = 0.013) and decreased in the 12-hour light phase sum (p = 0.009). Significant increases in the activities were observed in the dark-light difference (p = 0.005) and dark-light ratio (p = 0.005) as well. Conclusion: : This study suggests that quinpirole injection entrains the circadian rest-activity rhythm of locomotor activities. Therefore, quinpirole can be a drug that mediates locomotor activity as a dopamine agonist as well as a modulator of the circadian rhythms.

Cluster Analysis on the Mental Health States in a Community Sample of Young Women During Pre-Pregnancy, Pregnancy, or the Postpartum Period.

OBJECTIVE: It is necessary to identify the mental health types of young women considering the importance of the mental health during the peripartum period. This study aimed to classify the mental health types in a community sample of young women with pre-pregnancy, pregnancy, or the postpartum period. METHODS: A total of 293 young women during pre-pregnancy, pregnancy, or the postpartum period were included in this study. The clinical characteristics of depression, anxiety, perceived stress, and quality of life were assessed. The clinical characteristics of the subject were classified by cluster analysis and compared by analysis of variance. RESULTS: From the cluster analysis, the subjects were classified into three groups. Cluster 1 showed significantly lower depression and anxiety and higher quality of life than those of cluster 2 and 3. Cluster 2 demonstrated significantly higher depression and anxiety and lower quality of life than those of cluster 3 and 1. Cluster 3 represented the intermediate levels between cluster 2 and 1. CONCLUSION: This study suggested that young women during pre-pregnancy, pregnancy, or the postpartum period might be in a good mental health group, a high-risk group requiring active monitoring, or a group in need of treatment. By monitoring mental health, the groups with high risk or requiring treatment could be discovered and proper management for prevention or improvement of mental health and quality of life can be provided.

A Validation Study of Mental Health Monitoring Through a Mobile Application.

OBJECTIVE: Face-to-face evaluation is the most important in psychiatric evaluation, but smart healthcare, including non-face-to-face evaluation, can be beneficial considering the situation in which face-to-face evaluation is limited or the preventive aspect of mental illness. In this paper, we aimed to check whether mental health screening tests have the same significance as paper-based tests even when collected through mobile applications. METHODS: A smart mental healthcare screening test was conducted on the 1,327 community subjects. We measured two indicators of depression (Patient Health Questionnaire 9-item scale, PHQ-9) and anxiety (Generalized Anxiety Disorder 7-item scale, GAD-7) to check mental health conditions. RESULTS: The average Cronbach's alpha value of the PHQ-9 questionnaire was good at 0.870. As a result of PHQ-9's principal component analysis, one component with an eigenvalue of 1 or more was identified, which is suitable to be described as a single factor. The average Cronbach's alpha value of the GAD-7 was 0.919. The structural validity of the GAD-7 was confirmed through principal component analysis. CONCLUSION: Our results show that PHQ-9 and GAD-7 scales performed through mobile applications can have the same meaning as paper-based tests. Surveys using a tablet PC, or smartphone application can monitor residents' mental health and accumulate data. Based on these data, smart mental health management can check the mental health of residents and treat mental illness in connection with medical services.

Human amniotic fluid stem cell injection therapy for urethral sphincter regeneration in an animal model.

BACKGROUND: Stem cell injection therapies have been proposed to overcome the limited efficacy and adverse reactions of bulking agents. However, most have significant limitations, including painful procurement, requirement for anesthesia, donor site infection and a frequently low cell yield. Recently, human amniotic fluid stem cells (hAFSCs) have been proposed as an ideal cell therapy source. In this study, we investigated whether periurethral injection of hAFSCs can restore urethral sphincter competency in a mouse model. METHODS: Amniotic fluids were collected and harvested cells were analyzed for stem cell characteristics and in vitro myogenic differentiation potency. Mice underwent bilateral pudendal nerve transection to generate a stress urinary incontinence (SUI) model and received either periurethral injection of hAFSCs, periurethral injection of Plasma-Lyte (control group), or underwent a sham (normal control group).For in vivo cell tracking, cells were labeled with silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate (MNPs@SiO2 (RITC)) and were injected into the urethral sphincter region (n = 9). Signals were detected by optical imaging. Leak point pressure and closing pressure were recorded serially after injection.Tumorigenicity of hAFSCs was evaluated by implanting hAFSCs into the subcapsular space of the kidney, followed two weeks later by retrieval and histologic analysis. RESULTS: Flow activated cell sorting showed that hAFSCs expressed mesenchymal stem cell (MSC) markers, but no hematopoietic stem cell markers. Induction of myogenic differentiation in the hAFSCs resulted in expression of PAX7 and MYOD at Day 3, and DYSTROPHIN at Day 7. The nanoparticle-labeled hAFSCs could be tracked in vivo with optical imaging for up to 10 days after injection. Four weeks after injection, the mean LPP and CP were significantly increased in the hAFSC-injected group compared with the control group. Nerve regeneration and neuromuscular junction formation of injected hAFSCs in vivo was confirmed with expression of neuronal markers and acetylcholine receptor. Injection of hAFSCs caused no in vivo host CD8 lymphocyte aggregation or tumor formation. CONCLUSIONS: hAFSCs displayed MSC characteristics and could differentiate into cells of myogenic lineage. Periurethral injection of hAFSCs into an SUI animal model restored the urethral sphincter to apparently normal histology and function, in absence of immunogenicity and tumorigenicity.

Human amniotic fluid stem cell-derived muscle progenitor cell therapy for stress urinary incontinence.

The most promising treatment for stress urinary incontinence can be a cell therapy. We suggest human amniotic fluid stem cells (hAFSCs) as an alternative cell source. We established the optimum in vitro protocol for the differentiation from hAFSCs into muscle progenitors. These progenitors were transplanted into the injured urethral sphincter and their therapeutic effect was analyzed. For the development of an efficient differentiation system in vitro, we examined a commercial medium, co-culture and conditioned medium (CM) systems. After being treated with CM, hAFSCs were effectively developed into a muscle lineage. The progenitors were integrated into the host urethral sphincter and the host cell differentiation was stimulated in vivo. Urodynamic analysis showed significant increase of leak point pressure and closing pressure. Immunohistochemistry revealed the regeneration of circular muscle mass with normal appearance. Molecular analysis observed the expression of a larger number of target markers. In the immunogenicity analysis, the progenitor group had a scant CD8 lymphocyte. In tumorigenicity, the progenitors showed no teratoma formation. These results suggest that hAFSCs can effectively be differentiated into muscle progenitors in CM and that the hAFSC-derived muscle progenitors are an accessible cell source for the regeneration of injured urethral sphincter.

Relationship of Circadian Rhythm in Behavioral Characteristics and Lipid Peroxidation of Brain Tissues in Mice.

Objective: This study aimed to explore the relationship among several indices of circadian rhythms and lipid peroxidation of brain tissue in mice. Methods: After entrainment of 4-week-old mice, one group was disrupted their circadian rhythms for three days and the other group for seven days (n = 10, respectively). After a recovery period, the Y-maze test, the elevated plus maze test, the tail suspension test, and the forced swimming test were conducted. To assess lipid peroxidation in brain tissue, thiobarbituric acid reactive substances were measured in the cortex, hippocampus, and cerebellum. Results: When circadian rhythms were disrupted and adapted back to their original rhythm, the recovery time of the 7-day disruption group (median 3.35 days) was significiantly faster than one of the 3-day disruption group (median 4.87 days). In the group with a 7-day disruption, mice that had recovered their rhythms early had higher malondialdehyde levels in their hippocampus compared to those with delayed recovery. The entrainment of circadian rhythms was negatively correlated with the malondialdehyde level of brain tissue. The behavioral test results showed no differences depending on the disruption durations or recovery patterns of circadian rhythms. Conclusion: These results suggest that disruption types, recovery patterns, and the entrainment of circadian rhythms are likely to affect oxidative stress in adolescents or young adult mice. Future study is needed to confirm and specify these results on the effects of circadian rhythms on oxidative stress and age-dependent effects.