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Angiogenesis is mainly regulated by the delivery of VEGF-dependent signaling to cells. However, the angiogenesis mechanism regulated by VEGF-induced miRNA is still not understood. After VEGF treatment in HUVECs, we screened the changed miRNAs through small-RNA sequencing and found VEGF-induced miR-4701-3p. Furthermore, the GFP reporter gene was used to reveal that TOB2 expression was regulated by miR-4701-3p, and it was found that TOB2 and miR-4701-3p modulation could cause angiogenesis in an in-vitro angiogenic assay. Through the luciferase assay, it was confirmed that the activation of the angiogenic transcription factor MEF2 was regulated by the suppression and overexpression of TOB2 and miR-4701-3p. As a result, MEF2 downstream gene mRNAs that induce angiogenic function were regulated. We used the NCBI GEO datasets to reveal that the expression of TOB2 and MEF2 was significantly changed in cardiovascular disease. Finally, it was confirmed that the expression of circulating miR-4701-3p in the blood of myocardial infarction patients was remarkably increased. In patients with myocardial infarction, circulating miR-4701-3p was increased regardless of age, BMI, and sex, and showed high AUC levels in specificity and sensitivity analysis (AUROC) (AUC = 0.8451, 95 % CI 0.78-0.90). Our data showed TOB2-mediated modulation of MEF2 and its angiogenesis by VEGF-induced miR-4701-3p in vascular endothelial cells. In addition, through bioinformatics analysis using GEO data, changes in TOB2 and MEF2 were revealed in cardiovascular disease. We suggest that circulating miR-4701-3p has high potential as a biomarker for myocardial infarction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: We conducted a one-year, retrospective, mirror-image study to investigate the clinical effectiveness and safety of aripiprazole once monthly (AOM) in patients with bipolar disorder (BD). We compared pre-treatment conditions with outcomes after 12 months of AOM treatment., Methods: Seventy-five bipolar patients were recruited from 12 hospitals in Korea. We included 75 patients with BD who had received at least three AOM treatments from September 2019 to September 2022 and had accessible electronic medical record (EMRs) for the year before and after the baseline visit., Results: The overall number of mood episodes significantly decreased from a mean of 1.5 ± 1.2 episodes pre-AOM to 0.5 ± 1.2 episodes post-AOM. Manic episodes significantly decreased from 0.8 ± 0.8 episodes pre-AOM to 0.2 ± 0.5 episodes post-AOM, and depressive episodes significantly decreased from 0.5 ± 0.8 episodes pre-AOM to 0.2 ± 0.6 episodes post-AOM (p = 0.017). Moreover, the number of psychiatric medications and pills and the proportion of patients treated with complex polypharmacy were significantly decreased post-AOM., Limitations: The small sample size was insufficient to fully represent the entire population of individuals with BD, and potential selection bias was introduced due to only including subjects who received AOM three or more times., Conclusion: The results of this study suggest that AOM can reduce mood episode relapse and may be clinically beneficial in the treatment of BD patients, potentially reducing issues associated with polypharmacy in some individuals., Competing Interests: Declaration of competing interest The authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Clinical chorioamnionitis, the most common infection-related diagnosis in labor and delivery units, is an antecedent of puerperal infection and neonatal sepsis. The condition is suspected when intrapartum fever is associated with two other maternal and fetal signs of local or systemic inflammation (eg, maternal tachycardia, uterine tenderness, maternal leukocytosis, malodorous vaginal discharge or amniotic fluid, and fetal tachycardia). Clinical chorioamnionitis is a syndrome caused by intraamniotic infection, sterile intraamniotic inflammation (inflammation without bacteria), or systemic maternal inflammation induced by epidural analgesia. In cases of uncertainty, a definitive diagnosis can be made by analyzing amniotic fluid with methods to detect bacteria (Gram stain, culture, or microbial nucleic acid) and inflammation (white blood cell count, glucose concentration, interleukin-6, interleukin-8, matrix metalloproteinase-8). The most common microorganisms are Ureaplasma species, and polymicrobial infections occur in 70% of cases. The fetal attack rate is low, and the rate of positive neonatal blood cultures ranges between 0.2% and 4%. Intrapartum antibiotic administration is the standard treatment to reduce neonatal sepsis. Treatment with ampicillin and gentamicin have been recommended by professional societies, although other antibiotic regimens, eg, cephalosporins, have been used. Given the importance of Ureaplasma species as a cause of intraamniotic infection, consideration needs to be given to the administration of antimicrobial agents effective against these microorganisms such as azithromycin or clarithromycin. We have used the combination of ceftriaxone, clarithromycin, and metronidazole, which has been shown to eradicate intraamniotic infection with microbiologic studies. Routine testing of neonates born to affected mothers for genital mycoplasmas could improve the detection of neonatal sepsis. Clinical chorioamnionitis is associated with decreased uterine activity, failure to progress in labor, and postpartum hemorrhage; however, clinical chorioamnionitis by itself is not an indication for cesarean delivery. Oxytocin is often administered for labor augmentation, and it is prudent to have uterotonic agents at hand to manage postpartum hemorrhage. Infants born to mothers with clinical chorioamnionitis near term are at risk for early-onset neonatal sepsis and for long-term disability such as cerebral palsy. A frontier is the noninvasive assessment of amniotic fluid to diagnose intraamniotic inflammation with a transcervical amniotic fluid collector and a rapid bedside test for IL-8 for patients with ruptured membranes. This approach promises to improve diagnostic accuracy and to provide a basis for antimicrobial administration., (Published by Elsevier Inc.)

Objective: We aimed to identify the expectations and preferences for medication and medical decision-making in patients with major psychiatric disorders., Methods: A survey was conducted among patients with major psychiatric disorders who visited psychiatric outpatient clinics at 15 hospitals between 2016 and 2018 in Korea. The survey consisted of 12 questions about demographic variables and opinions on their expectations for medication, important medical decision-makers, and preferred drug type. The most preferred value in each category in the total population was identified, and differences in the preference ratio of each item among the disease groups were compared., Results: A total of 707 participants were surveyed. In the total population, patients reported high efficacy (44.01%±21.44%) as the main wish for medication, themselves (37.39%±22.57%) and a doctor (35.27%±22.88%) as the main decision makers, and tablet/capsule (36.16%±30.69%) as the preferred type of drug. In the depressive disorders group, the preference ratio of high efficacy was significantly lower, and the preference ratio of a small amount was significantly higher than that of the psychotic disorder and bipolar disorder groups. The preference ratio of a doctor as an important decision maker in the bipolar disorder group was higher compared to the other groups., Conclusion: This study revealed the preference for medications and showed differences among patients with psychiatric disorders. Providing personalized medicine that considers a patient's preference for the drug may contribute to the improvement of drug compliance and outcomes.

Objective: : Attention-deficit/hyperactivity disorder (ADHD) is prevalent in adults, and psychiatric comorbidities are common in adults with ADHD. We aimed to examine the prevalence of adult ADHD with several common psychiatric conditions in a community sample in Korea and the association between adult ADHD and risk of psychiatric comorbidities., Methods: : This study used a cross-sectional survey design. We provided supplementary and optional self-report questionnaires, including the Korean version of the World Health Organization Adult ADHD Self-Report Scale (ASRS) short screening scale, Patient Health Questionnaire-9 for screening for depression, Alcohol Use Disorders Identification Test alcohol consumption questions, and the Korean version of the Mood Disorders Questionnaire, to Korean adults who visited one of six centers of a large private healthcare company for the National General Health Examination., Results: : A total of 17,799 subjects included in this study, and 430 (2.4%) were positive on the ASRS screen. ADHD was significantly associated with the 19-30-year-old age group (odds ratio [OR] = 3.938), lower income (OR = 1.298), depression (OR = 11.563), and bipolar disorder (OR = 3.162)., Conclusion: : Adult ADHD was highly associated with depression and bipolar disorder, suggesting that clinicians should carefully evaluate and treat such psychiatric disorders in adults with ADHD symptoms.

Due to the short storage period, large quantities of platelet concentrate (PC) are expiring. The expired PC cannot be injected into a blood vessel, but the activity of bioactive molecules, especially growth factors, is still preserved. In this paper, we organized a process to obtain a growth factor-rich bioproduct for use as a supplement in human cell culture by optimizing freezing, thawing, and sterilization conditions. Each unit of PC displayed visual differences, diverse biochemical values, and growth factor concentrations. To minimize lot-to-lot variation, we pooled a minimum of 10 PC units. The concentrations of growth factors were maximized through five freeze-thaw cycles for 12 h at -80 °C for freezing and for 5 min at 36 °C for thawing. We used a cell strainer with 40 µm pores, followed by a 0.45 μm filter and a 0.22 μm filter sequentially to sterilize the bioproduct with minimizing loss. The obtained growth factors remained stable for 4-6 h at room temperature (23 °C), 24 h at 4 °C, and 12 months at -80 °C. Cellular responses to the growth factor-rich bioproduct were tested with primary human renal proximal tubule epithelial cells. The cells exhibited a significantly increased growth rate, compared to the fetal bovine serum (FBS)-treated control group. The cells maintained their characteristic cuboidal shape, and stem cells and renal progenitor cells also preserved their genetic characteristics during culture. Therefore, the growth factor-rich bioproduct isolated from expired PC through our process can be used as a medium supplement to replace FBS in human cell culture for clinical application.

Objective: This study aimed to investigate COVID-19 vaccine acceptance and related factors in individuals with mental disorders in Korea., Methods: We surveyed 572 individuals with mental disorders about their attitudes toward COVID-19 vaccination using a 7-item self-rating questionnaire on vaccine acceptance and hesitancy. We categorized the respondents into groups based on their level of vaccine acceptance using hierarchical clustering. In addition, we evaluated the respondents' vaccination status and trust in sources of information regarding COVID-19 vaccines, and assessed their psychological characteristics using the Patient Health Questionnaire-9, Gratitude Questionnaire-6, and Big Five Inventory-10., Results: Clustering revealed three groups according to vaccine acceptance: 'totally accepting' ( n = 246, 43.0%), 'somewhat accepting' ( n = 184, 32.2%), and 'hesitant' ( n = 142, 24.8%) groups. Three quarters of all participants, who belonged to the 'totally accepting' or 'somewhat accepting' groups, were willing to receive a COVID-19 vaccine despite concerns about its side effects. Individuals in the high vaccine acceptance group were older ( F = 12.52, p < 0.001), more likely to receive the influenza vaccine regularly, and more likely to trust formal information sources. Additionally, they had higher levels of gratitude ( F = 21.00, p < 0.001) and agreeableness ( F = 4.50, p = 0.011), and lower levels of depression ( χ 2 = 11.81, p = 0.003) and neuroticism ( F = 3.71, p = 0.025)., Conclusion: The present study demonstrated that individuals with mental disorders were generally willing to receive COVID-19 vaccination. However, they weighed its need and effectiveness against potential side effects before coming to a decision. It is important to understand the behavioral and psychological characteristics associated with vaccine acceptance, to effectively communicate its importance to individuals with mental disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ryu, Kang, Jung, Yun, Kang, Kim, Choi, Kim, Lee, Kim, Jung, Yoon and Kim.)

Green-stained amniotic fluid, often referred to as meconium-stained amniotic fluid, is present in 5% to 20% of patients in labor and is considered an obstetric hazard. The condition has been attributed to the passage of fetal colonic content (meconium), intraamniotic bleeding with the presence of heme catabolic products, or both. The frequency of green-stained amniotic fluid increases as a function of gestational age, reaching approximately 27% in post-term gestation. Green-stained amniotic fluid during labor has been associated with fetal acidemia (umbilical artery pH <7.00), neonatal respiratory distress, and seizures as well as cerebral palsy. Hypoxia is widely considered a mechanism responsible for fetal defecation and meconium-stained amniotic fluid; however, most fetuses with meconium-stained amniotic fluid do not have fetal acidemia. Intraamniotic infection/inflammation has emerged as an important factor in meconium-stained amniotic fluid in term and preterm gestations, as patients with these conditions have a higher rate of clinical chorioamnionitis and neonatal sepsis. The precise mechanisms linking intraamniotic inflammation to green-stained amniotic fluid have not been determined, but the effects of oxidative stress in heme catabolism have been implicated. Two randomized clinical trials suggest that antibiotic administration decreases the rate of clinical chorioamnionitis in patients with meconium-stained amniotic fluid. A serious complication of meconium-stained amniotic fluid is meconium aspiration syndrome. This condition develops in 5% of cases presenting with meconium-stained amniotic fluid and is a severe complication typical of term newborns. Meconium aspiration syndrome is attributed to the mechanical and chemical effects of aspirated meconium coupled with local and systemic fetal inflammation. Routine naso/oropharyngeal suctioning and tracheal intubation in cases of meconium-stained amniotic fluid have not been shown to be beneficial and are no longer recommended in obstetrical practice. A systematic review of randomized controlled trials suggested that amnioinfusion may decrease the rate of meconium aspiration syndrome. Histologic examination of the fetal membranes for meconium has been invoked in medical legal litigation to time the occurrence of fetal injury. However, inferences have been largely based on the results of in vitro experiments, and extrapolation of such findings to the clinical setting warrants caution. Fetal defecation throughout gestation appears to be a physiologic phenomenon based on ultrasound as well as in observations in animals., (Published by Elsevier Inc.)

Background: Interstitial cystitis (IC) is a chronic and intractable disease that can severely deteriorate patients' quality of life. Recently, stem cell therapy has been introduced as a promising alternative treatment for IC in animal models. We aimed to verify the efficacy and safety of the human perirenal adipose tissue-derived stromal vascular fraction (SVF) in an IC rat model., Methods: From eight-week-old female rats, an IC rat model was established by subcutaneous injection of 200 μg of uroplakin3A. The SVF was injected into the bladder submucosal layer of IC rats, and pain scale analysis, awakening cytometry, and histological and gene analyses of the bladder were performed. For the in vivo safety analysis, genomic DNA purification and histological analysis were also performed to check tumorigenicity and thrombus formation., Results: The mean pain scores in the SVF 20 μl group were significantly lower on days 7 and 14 than those in the control group, and bladder intercontraction intervals were significantly improved in the SVF groups in a dose-dependent manner. Regeneration of the bladder epithelium, basement membrane, and lamina propria was observed in the SVF group. In the SVF groups, however, bladder fibrosis and the expression of inflammatory markers were not significantly improved compared to those in the control group., Conclusion: This study demonstrated that a perirenal adipose tissue-derived SVF is a promising alternative for the management of IC in terms of improving bladder pain and overactivity., (© 2023. The Author(s).)

The objective of this study was to compare recommendations of the Korean Medication Algorithm Project for Bipolar Disorder 2022 (KMAP-BP 2022) with other recently published guidelines for treating bipolar disorder. We reviewed a total of six recently published global treatment guidelines and compared treatment recommendation of the KMAP-BP 2022 with those of other guidelines. For initial treatment of mania, there were no significant differences across treatment guidelines. All guidelines recommended mood stabilizer (MS) or atypical antipsychotic (AAP) monotherapy or a combination of an MS with an AAP as a first-line treatment strategy in a same degree for mania. However, the KMAP-BP 2022 recommended MS + AAP combination therapy for psychotic mania, mixed mania and psychotic depression as treatment of choice. Aripiprazole, quetiapine and olanzapine were the first-line AAPs for nearly all phases of bipolar disorder across guidelines. Some guideline suggested olanzapine is a second-line options during maintenance treatment, related to concern about long-term tolerability. Most guidelines advocated newer AAPs (asenapine, cariprazine, long-acting injectable risperidone, and aripiprazole once monthly) as first-line treatment options for all phases while lamotrigine was recommended for depressive and maintenance phases. Lithium and valproic acid were commonly used as MSs in all phases of bipolar disorder. KMAP-BP 2022 guidelines were similar to other guidelines, reflecting current changes in prescription patterns for bipolar disorder based on accumulated research data. Strong preference for combination therapy was characteristic of KMAP-BP 2022, predominantly in the treatment of psychotic mania, mixed mania and psychotic depression.

Objective: The Functioning Assessment Short Test (FAST) is a relatively specific test for bipolar disorders designed to assess the main functioning problems experienced by patients. This brief instrument includes 24 items assessing impairment or disability in 6 domains of functioning: autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships, and leisure time. It has already been translated into standardized versions in several languages. The aim of this study is to measure the validity and reliability of the Korean version of FAST (K-FAST)., Methods: A total of 209 bipolar disorder patients were recruited from 14 centers in Korea. K-FAST, Young Mania Rating Scale (YMRS), Bipolar Depression Rating Scale (BDRS), Global Assessment of Functioning (GAF) and the World Health Organization Quality of Life Assessment Instrument Brief Form (WHOQOL-BREF) were administered, and psychometric analysis of the K-FAST was conducted., Results: The internal consistency (Cronbach's alpha) of the K-FAST was 0.95. Test-retest reliability analysis showed a strong correlation between the two measures assessed at a 1-week interval (ICC = 0.97; p < 0.001). The K-FAST exhibited significant correlations with GAF (r = -0.771), WHOQOL-BREF (r = -0.326), YMRS (r = 0.509) and BDRS (r = 0.598). A strong negative correlation with GAF pointed to a reasonable degree of concurrent validity. Although the exploratory factor analysis showed four factors, the confirmatory factor analysis of questionnaires had a good fit for a six factors model (CFI = 0.925; TLI = 0.912; RMSEA = 0.078)., Conclusion: The K-FAST has good psychometric properties, good internal consistency, and can be applicable and acceptable to the Korean context.

Elastin is very rarely repaired extracellular matrix (ECM) in physiological condition. The commercial human elastin for exogenous medical treatment is very expensive, and has a potential for disease transmission. Animal-origin elastin is relatively low price, but has concerns for xenogeneic immune responses. Considering cost and safety, we focused on the perirenal adipose tissue, donated from healthy young people via donor nephrectomy. Until now, all of the perirenal adipose tissues are discarded as a medical waste after kidney transplantation. In the present study, we applied perirenal adipose tissues as the source of human elastin, and optimized the extraction process to get high purified and quantified elastin. Through pre-processing step, the delipidated and decellularized ECM was prepared. Next, with four different elastin extraction process (acidic solvents, neutral salt, organic solvents or hot alkali method), elastin was extracted, and the concentration of amino acid between each product was compared, and bright-field/electron microscopy, Fourier transform infrared (FT-IR) spectroscopy and cytotoxicity analysis were also performed. As controls, bovine neck ligament-derived and human skin-derived elastin were used. Among the elastin extraction methods, the hot alkali insoluble product showed (1) relatively high positive area of Verhoeff's and low Masson's trichrome stain, (2) 64.24% purity, 159.29 mg/g quantity, and ∼6.37% yield in amino acid analysis, (3) β-sheet second structure, and (4) thin fiber composed mesh-like sheet structure in SEM image. These values were higher than those of the commercial human skin elastin. When comparing hydrolyzed forms, α-elastin from hot alkali insoluble product showed enhanced cell proliferation and maintained cell properties compared to the κ-elastin. Therefore, we confirmed that the perirenal adipose tissue is an ideal source of human elastin with safety assurance, and the hot alkali process combined with pre-process seems to be the optimal method for elastin extraction with high purity and quantity.

Background: The assessment and management of patients with threatened midtrimester miscarriage is a clinical challenge because the etiology of this condition is poorly understood., Objective: This study aimed to examine the frequency of intraamniotic infection or inflammation and the effect of antibiotics in patients presenting with regular uterine contractions and intact membranes before 20 weeks of gestation., Study Design: This retrospective study comprised patients who met the following criteria: (1) singleton gestation, (2) gestational age before 20 weeks, (3) the presence of regular uterine contractions confirmed by a tocodynamometer (8 or more contractions in 60 minutes), (4) intact amniotic membranes, and (5) transabdominal amniocentesis performed for the evaluation of the microbiologic and inflammatory status of the amniotic cavity. Samples of amniotic fluid were cultured for aerobic and anaerobic bacteria and genital mycoplasmas, and polymerase chain reaction was performed to detect Ureaplasma species. Amniotic fluid was tested for white blood cell counts and matrix metalloproteinase-8 concentrations to diagnose intraamniotic inflammation. Patients with intraamniotic inflammation, or intraamniotic infection, were treated with antibiotics (a combination of ceftriaxone, clarithromycin, and metronidazole). Treatment success was defined as the resolution of intraamniotic infection/inflammation at the follow-up amniocentesis or delivery after 34 weeks of gestation., Results: 1) Intraamniotic inflammation was present in 88% (15/17) of patients, whereas infection was detectable in only 2 cases; 2) objective evidence of resolution of intraamniotic inflammation after antibiotic treatment was demonstrated in 100% (4/4) of patients who underwent a follow-up amniocentesis; 3) 30% (5/15) of women receiving antibiotics delivered after 34 weeks of gestation (3 of the 5 patients had a negative follow-up amniocentesis, and 2 of the women were without a follow-up amniocentesis); 4) the overall treatment success of antibiotics was 40% (6/15; 4 cases of objective evidence of resolution of intra-amniotic inflammation and 5 cases of delivery after 34 weeks of gestation)., Conclusion: The prevalence of intraamniotic inflammation in patients who presented with a threatened midtrimester miscarriage was 88% (15/17), and, in most cases, microorganisms could not be detected. Antibiotic treatment, administered to patients with intraamniotic inflammation, was associated with either objective resolution of intraamniotic inflammation or delivery after 34 weeks of gestation in 40% (6/15) of the cases., (Copyright © 2022. Published by Elsevier Inc.)

Cervical insufficiency generally refers to a condition in which there is mid-trimester cervical dilatation or protruding chorioamniotic membranes in the absence of uterine contractions. Such condition is a risk factor for spontaneous mid-trimester abortion or early preterm birth, and is associated with adverse neonatal outcomes. Both intra-amniotic infection and inflammation ascertained by amniocentesis have been identified in patients with cervical insufficiency, and are poor prognostic factors. A subset of patients with intra-amniotic inflammation will have no demonstrable microorganisms detected via cultivation or molecular methods, and therefore represent cases of sterile intra-amniotic inflammation. Amniotic fluid sludge (free-floating hyperechogenic material within the amniotic fluid in close proximity to the uterine cervix) identified on sonography is a biomarker for intra-amniotic infection and inflammation. Recent evidence suggests that intra-amniotic infection, as well as sterile intra-amniotic inflammation can be treated successfully using antimicrobial agents. We report a unique case in which administration of antibiotics in the presence of mid-trimester cervical insufficiency, sterile intra-amniotic inflammation, and amniotic fluid sludge was associated with resolution of the cervical findings, as demonstrated on both sonographic and speculum examination. The patient successfully underwent elective cesarean delivery at 36-2/7 weeks of gestation. This case illustrates that antibiotic therapy may be effective despite the presence of several high-risk pregnancy conditions, and that successful outcome is possible.

Objective: To develop a noninvasive scoring system to identify patients at high risk for intra-amniotic infection and/or inflammation, which would reduce the need for amniocentesis., Methods: This prospective cohort study comprised patients admitted with preterm labor and intact membranes (20-34 weeks of gestation) who underwent a transabdominal amniocentesis and for whom concentrations of quantitative cervical fetal fibronectin and of maternal serum C-reactive protein (CRP) were determined. Intra-amniotic infection was defined as a positive amniotic fluid culture for microorganisms. Intra-amniotic inflammation was defined as an amniotic fluid matrix metalloproteinase-8 concentration >23 ng/mL. Multivariate logistic regression analysis was performed to identify intra-amniotic infection/inflammtion with noninvasive parameters that had a significant relationship with univariate analysis. With four parameters identified by multivariate analysis, we generated a noninvasive risk scoring system., Results: Of the study population consisting of 138 singleton pregnant women, (1) the overall rate of intra-amniotic infection/inflammation was 28.3% (39/138); (2) four parameters were used to develop a noninvasive risk scoring system [i.e. cervical fetal fibronectin concentration (score 0-2), maternal serum CRP concentration (score 0-2), cervical dilatation (score 0-2), and gestational age at presentation (score 0-1)]; the total score ranges from 0 to 7; 3) the area under the curve of the risk score was 0.96 (95% confidence interval (CI), 0.92-0.99), significantly higher than that of each predictor in the identification of intra-amniotic infection/inflammation ( p  < .001, for all); 4) the risk score with a cutoff of 4 had a sensitivity of 94.9% (37/39), a specificity of 90.9% (90/99), a positive predictive value of 80.4% (37/46), a negative predictive value of 97.8% (90/92), a positive likelihood ratio of 10.4 (95% CI, 5.6-19.5), and a negative likelihood ratio of 0.06 (95% CI, 0.15-0.22) in the identification of intra-amniotic infection/inflammation., Conclusions: (1) The combination of four parameters (concentrations of cervical fetal fibronectin and maternal serum CRP, cervical dilatation, and gestational age) was independently associated with intra-amniotic infection and/or inflammation; and (2) the risk scoring system comprised of the combination of 4 noninvasive parameters was sensitive and specific to identify the patients at risk for intra-amniotic infection and/or inflammation.

Objective: We revised the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP), first published in 2002 and revised in 2006, 2010, 2014, and 2018, to reflect recent progress in the treatment of bipolar disorder., Methods: The questionnaires consisted of 56 items for adult patients and 7 items for child/adolescent patients, and were used to obtain the consensus of experts regarding pharmacological treatment strategies for various phases of bipolar disorder. The review committee included 87 Korean psychiatrists and 40 child and adolescent psychiatry experts., Results: For treatment of manic episodes, a combination of a mood stabilizer (MS) and atypical antipsychotics (AAP), or monotherapy with MS or AAP were recommended as first-line treatments. Combinations of MS and AAP, or AAP and lamotrigine (LMT) were recommended as first-line treatments for depressive episodes regardless of the severity. Monotherapy with MS, AAP, or LMT were also first-line treatments for mild to moderate depressive episodes. For mixed features, a combination of MS and AAP, or monotherapy with AAP or MS were recommended as first-line treatments, and a combination of AAP and LMT, or MS and LMT were the first-line treatments for depressive mixed state., Conclusion: The recommendations of the KMAP-BP 2022 have changed from the previous version, to reflect the evolution of the social culture and healthcare system in Korea and recent evidence regarding pharmacotherapy of bipolar disorder. The KMAP-BP 2022 provides clinicians with a wealth of information regarding appropriate strategies to treat patients with bipolar disorder.

Bladder cancer is a common global cancer with a high percentage of metastases and high mortality rate. Thus, it is necessary to identify new biomarkers that can be helpful in diagnosis. Pyruvate dehydrogenase kinase 4 (PDK4) belongs to the PDK family and plays an important role in glucose utilization in living organisms. In the present study, we evaluated the role of PDK4 in bladder cancer and its related protein changes. First, we observed elevated PDK4 expression in high-grade bladder cancers. To screen for changes in PDK4-related proteins in bladder cancer, we performed a comparative proteomic analysis using PDK4 knockdown cells. In bladder cancer cell lines, PDK4 silencing resulted in a lower rate of cell migration and invasion. In addition, a PDK4 knockdown xenograft model showed reduced bladder cancer growth in nude mice. Based on our results, PDK4 plays a critical role in the metastasis and growth of bladder cancer cells through changes in ERK, SRC, and JNK.

Background: The major challenge for obstetrics is the prediction and prevention of the great obstetrical syndromes. We propose that defining obstetrical diseases by the combination of clinical presentation and disease mechanisms as inferred by placental pathology will aid in the discovery of biomarkers and add specificity to those already known., Objective: To describe the longitudinal profile of placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and the PlGF/sFlt-1 ratio throughout gestation, and to determine whether the association between abnormal biomarker profiles and obstetrical syndromes is strengthened by information derived from placental examination, eg, the presence or absence of placental lesions of maternal vascular malperfusion., Study Design: This retrospective case cohort study was based on a parent cohort of 4006 pregnant women enrolled prospectively. The case cohort of 1499 pregnant women included 1000 randomly selected patients from the parent cohort and all additional patients with obstetrical syndromes from the parent cohort. Pregnant women were classified into six groups: 1) term delivery without pregnancy complications (n=540; control); 2) preterm labor and delivery (n=203); 3) preterm premature rupture of the membranes (n=112); 4) preeclampsia (n=230); 5) small-for-gestational-age neonate (n=334); and 6) other pregnancy complications (n=182). Maternal plasma concentrations of PlGF and sFlt-1 were determined by enzyme-linked immunosorbent assays in 7560 longitudinal samples. Placental pathologists, masked to clinical outcomes, diagnosed the presence or absence of placental lesions of maternal vascular malperfusion. Comparisons between mean biomarker concentrations in cases and controls were performed by utilizing longitudinal generalized additive models. Comparisons were made between controls and each obstetrical syndrome with and without subclassifying cases according to the presence or absence of placental lesions of maternal vascular malperfusion., Results: 1) When obstetrical syndromes are classified based on the presence or absence of placental lesions of maternal vascular malperfusion, significant differences in the mean plasma concentrations of PlGF, sFlt-1, and the PlGF/sFlt-1 ratio between cases and controls emerge earlier in gestation; 2) the strength of association between an abnormal PlGF/sFlt-1 ratio and the occurrence of obstetrical syndromes increases when placental lesions of maternal vascular malperfusion are present (adjusted odds ratio [aOR], 13.6 vs 6.7 for preeclampsia; aOR, 8.1 vs 4.4 for small-for-gestational-age neonates; aOR, 5.5 vs 2.1 for preterm premature rupture of the membranes; and aOR, 3.3 vs 2.1 for preterm labor (all P<0.05); and 3) the PlGF/sFlt-1 ratio at 28 to 32 weeks of gestation is abnormal in patients who subsequently delivered due to preterm labor with intact membranes and in those with preterm premature rupture of the membranes if both groups have placental lesions of maternal vascular malperfusion. Such association is not significant in patients with these obstetrical syndromes who do not have placental lesions., Conclusion: Classification of obstetrical syndromes according to the presence or absence of placental lesions of maternal vascular malperfusion allows biomarkers to be informative earlier in gestation and enhances the strength of association between biomarkers and clinical outcomes. We propose that a new taxonomy of obstetrical disorders informed by placental pathology will facilitate the discovery and implementation of biomarkers as well as the prediction and prevention of such disorders., (Published by Elsevier Inc.)

Objective: The purpose of this study was to compare the efficacy and tolerability of continued olanzapine (OLA) versus amisulpride (AMI) augmentation in schizophrenic patients with poor response to OLA monotherapy., Methods: The present 4-week, randomized, rater-blinded study included 25 patients with schizophrenia who were partially or completely unresponsive to treatment with OLA monotherapy. Eligible subjects were randomly assigned at a 1:1 ratio to continuation of OLA monotherapy (OLA group) or OLA with AMI augmentation (AMI group). Efficacy was primarily evaluated using the Positive and Negative Syndrome Scale (PANSS) at baseline and at 1, 2, and 4 weeks., Results: The changes in PANSS total score and PANSS-positive subscale score were significantly different ( p < 0.05) between the OLA and AMI groups. The differences between the two groups in PANSS-negative subscale, PANSS-general subscale, Brief Psychiatric Rating Scale, and Clinical Global Impression-Severity (CGI-S) scale scores were not statistically significant., Conclusion: AMI augmentation could be an effective strategy for patients with schizophrenia who show inadequate early response to OLA monotherapy.

Early diagnosis is critical for treating bladder cancer, as this cancer is very aggressive and lethal if detected too late. To address this important clinical issue, a photoacoustic tomography (PAT)-based transabdominal imaging approach was suggested in previous reports, in which its in vivo feasibility was also demonstrated based on a small animal model. However, successful translation of this approach to real clinical settings would be challenging because the human bladder is located at a depth that far exceeds the typical penetration depth of PAT (∼3 cm for in vivo cases). In this study, we developed a tapered catheter-based, transurethral photoacoustic and ultrasonic endoscopic probe with a 2.8 mm outer diameter to investigate whether the well-known benefits of PAT can be harnessed to resolve unmet urological issues, including early diagnosis of bladder cancer. To demonstrate the in vivo imaging capability of the proposed imaging probe, we performed a rabbit model-based urinary system imaging experiment and acquired a 3D microvasculature map distributed in the wall of the urinary system, which is a first in PAT, to the best of our knowledge. We believe that the results strongly support the use of this transurethral imaging approach as a feasible strategy for addressing urological diagnosis issues.

The objective of this study was to select the optimal delipidation solvent for preparation of human perirenal adipose tissue-derived extracellular matrix (ECM). Human perirenal adipose tissue can be obtained in large amounts during surgery, and it can be an alternative source of human ECM. Delipidation is an essential procedure for the ECM preparation, because lipid strongly inhibits regeneration of target tissue. Isopropanol has been widely used as a delipidation solvent for adipose tissue. However, because adipose tissue is mostly composed of nonpolar lipid, a nonpolar solvent might be more effective for delipidation. We evaluated the delipidation efficiency of acetone, chloroform, methanol, ether, ethanol, isopropanol, water, chloroform/methanol, ethanol/heptane, ether/methanol, hexane/ethanol, and butanol/methanol solvents for ECM extraction from human perirenal adipose tissue. Among them, acetone-treated adipose tissue showed the greatest delipidation efficiency (93.05%), significantly lower residual DNA content, and the greatest residual collagen concentration (42.49 ± 0.05 μg/g). In addition, acetone-treated tissue also had well-preserved ultrastructure with high porosity and significantly low in vitro cytotoxicity. These results suggested that acetone may be an optimal delipidation solvent for extraction of ECM from human perirenal adipose tissue., (© 2021 Wiley Periodicals LLC.)

There is growing interest in human adipose tissue-derived collagen as a replacement for animal origin or synthetic materials. Large amounts of adipose tissues around the kidney are being discarded after kidney surgery; thus, we planned to use this tissue as a potentially ideal source of human collagen. Optimization of the collagen extraction process can contribute to the quality, quantity, supply, and cost of collagen production. To extract highly purified and concentrated collagen from human perirenal adipose tissue, we developed a novel extraction process that is superior to the conventional methods in terms of extraction yield, in vitro cytocompatibility, and physicochemical aspects. The sequence of the process and optimized conditions are as follows: (1) destaining with 0.5% H 2 O 2 for 1 h at 4°C, (2) noncollagenous proteins elimination with 1.5 M NaOH for 24 h at 4°C, (3) atelocollagen preparation with 1.0% pepsin for 48 h at 25°C, and (4) collagen hydrolysis with 1.0 M NaOH for 10 min at 60°C. The final product showed significantly increased hydroxyproline (355.26 ± 18.71 pg/mL) and glycine (22.752  μ g/mL) content than the conventional acetic acid hydrolyzed collagen (164.13 ± 1.11 pg/mL and 0.947  μ g/mL, respectively). The lyophilized collagen showed more specific peaks for amides A, B, I, II, and III on FT-IR analysis and showed a further native architecture of collagen fibrils in scanning electron microscope images. Therefore, the optimized process can be an effective protocol for extracting collagen from human perirenal adipose tissue., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2022 Eun Hye Lee et al.)

The Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) first was published in 2002, and has been revised four times, in 2006, 2012, 2017, and 2021. In this review, we compared recommendations from the recently revised KMAP-DD 2021 to four global clinical practice guidelines (CPGs) for depression published after 2010. The recommendations from the KMAP-DD 2021 were similar to those from other CPGs, although there were some differences. The KMAP-DD 2021 reflected social culture and the healthcare system in Korea and recent evidence about pharmacotherapy for depression, as did other recently published evidence-based guidelines. Despite some intrinsic limitations as an expert consensus-based guideline, the KMAP-DD 2021 can be helpful for Korean psychiatrists making decisions in clinical settings by complementing previously published evidence-based guidelines, especially for some clinical situations lacking evidence from rigorously designed clinical trials.

Despite the strong influence of the gut microbiota on atherosclerosis, a causal relationship between atherosclerosis pathophysiology and gut microbiota is still unverified. This study was performed to determine the impact of the gut microbiota on the pathogenesis of atherosclerosis caused by genetic deficiency. To elucidate the influence of the gut microbiota on atherosclerosis pathogenesis, an atherosclerosis-prone mouse model (C1q/TNF-related protein 9-knockout (CTRP9-KO) mice) was generated. The gut microbial compositions of CTRP9-KO and WT control mice were compared. Fecal microbiota transplantation (FMT) was performed to confirm the association between gut microbial composition and the progression of atherosclerosis. FMT largely affected the gut microbiota in both CTRP9-KO and WT mice, and all transplanted mice acquired the gut microbiotas of the donor mice. Atherosclerotic lesions in the carotid arteries were decreased in transplanted CTRP9-KO mice compared to CTRP9-KO mice prior to transplantation. Conversely, WT mice transplanted with the gut microbiotas of CTRP9-KO mice showed the opposite effect as that of CTRP9-KO mice transplanted with the gut microbiotas of WT mice. Here, we show that CTRP9 gene deficiency is related to the distribution of the gut microbiota in subjects with atherosclerosis. Transplantation of WT microbiotas into CTRP9-KO mice protected against the progression of atherosclerosis. Conversely, the transplantation of CTRP9-KO microbiotas into WT mice promoted the progression of atherosclerosis. Treating atherosclerosis by restoring gut microbial homeostasis may be an effective therapeutic strategy., (© 2022. The Author(s).)

Background: Human renal proximal tubular epithelial (RPTE) cell is a very useful tool for kidney-related experiments in vitro/ex vivo. However, only a few primary RPTE cells can be obtained through kidney biopsy, the proliferation rate of primary cell is very low, and the cultured cell properties are easily altered in artificial conditions. Thus, RPTE cell usage is very tricky; we applied porcine kidney-derived extracellular matrix (renal ECM) as coating, hydrogel, and scaffold material to increase cell proliferation and maintain cellular properties providing three-dimensional (3D) niche, which can be a valuable cell delivery vehicle., Methods: Porcine renal ECM was prepared by decellularization using 1% Triton X-100, solubilized with 0.5 M acetic acid. The final protein concentration was adjusted to 10  μ g/ μ L (pH 7.0). The efficacies as coating, hydrogel, and scaffold materials were analyzed through cell morphology, proliferation rate, renal-associated gene expressions, chemical composition, and microstructure evaluation. The efficacies as a coating material were compared with Matrigel, collagen type 1 (col1), gelatin, fibrinogen, and thrombin. After confirmation of coating effects, the effective concentration range was decided. The efficacies as hydrogel and scaffold materials were compared with hyaluronic acid (HA) and col1, respectively., Results: As the coating material, renal ECM showed a higher cell proliferation rate compared to other materials, except for Matrigel. Renal-associated gene expressions were significantly enhanced in the renal ECM than other materials. Coating effect on cell proliferation was dependent on the renal ECM concentration, and the effective concentration ranged from 30 to 100  μ g. As the hydrogel material, renal ECM showed a distinct inner cell network morphology and significantly increased renal-associated gene expressions, compared to HA hydrogel. As the scaffold material, renal ECM showed specific amide peaks, enhanced internal porosity, cell proliferation rate, and renal-associated gene expression compared to the col1 scaffold., Conclusions: We concluded that renal ECM can be a suitable material for RPTE cell culture and usage. More practically, the coated renal ECM stimulates RPTE cell proliferation, and the hydrogel and scaffold of renal ECM provide useful 3D culture niche and cell delivery vehicles maintaining renal cell properties., Competing Interests: There are no conflicts of interest., (Copyright © 2022 Eun Hye Lee et al.)

Objective: In the 19 years since the Korean College of Neuropsychopharmacology and the Korean Society for Affective Disorders developed the Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) in 2002, four revisions have been conducted., Methods: To increase survey efficiency in this revision, to cover the general clinical practice, and to compare the results with previous KMAP-DD series, the overall structure of the questionnaire was maintained. The six sections of the questionnaire were as follows: 1) pharmacological treatment strategies for major depressive disorder (MDD) with/without psychotic features; 2) pharmacological treatment strategies for persistent depressive disorder and other depressive disorder subtypes; 3) consensus for treatment-resistant depression; 4) the choice of an antidepressant in the context of safety, adverse effects, and comorbid physical illnesses; 5) treatment strategies for special populations (children/adolescents, elderly, and women); and 6) non-pharmacological biological therapies. Recommended first-, second-, and third-line strategies were derived statistically., Results: There has been little change in the four years since KMAP-DD 2017 due to the lack of newly introduced drug or treatment strategies. However, shortened waiting time between the initial and subsequent treatments, increased preference for atypical antipsychotics (AAPs), especially aripiprazole, and combination strategies with AAPs yield an active and somewhat aggressive treatment trend in Korea., Conclusion: We expect KMAP-DD to provide clinicians with useful information about the specific strategies and medications appropriate for treating patients with MDD by bridging the gap between clinical real practice and the evidence-based world.

Perirenal adipose tissue, one of the fat masses surrounding the kidneys, can be obtained from healthy donors during a kidney transplant. Perirenal adipose tissue has only ever been known as a connective tissue to protect the kidneys and renal blood vessels from external physical stimulation. Yet, recently, as adipose tissue has begun to be considered an endocrine organ, and perirenal adipose tissue is now regarded to have a direct effect on metabolic diseases. The characteristics of perirenal adipose tissue from a healthy donor are that: (1) There are a large number of brown adipose cells (70-80% of the total), (2) Most of the brown adipose cells are inactive in the resting cell cycle, (3) Activating factors are constant low-temperature exposure, hormones, metastasis factors, and environmental factors, (4) Anatomically, a large number of brown adipose cells are distributed close to the adrenal glands, (5) Beige cells, produced by converting white adipocytes to brown-like adipocytes, are highly active, (6) Activated cells secrete BATokines, and (7) Energy consumption efficiency is high. Despite these advantages, all of the perirenal adipose tissue from a healthy donor is incinerated as medical waste. With a view to its use, this review discusses the brown adipocytes and beige cells in perirenal adipose tissue from a healthy donor, and proposes opportunities for their clinical application.

Objectives: Intra-amniotic infection, defined by the presence of microorganisms in the amniotic cavity, is often accompanied by intra-amniotic inflammation. Occasionally, laboratories report the growth of bacteria or the presence of microbial nucleic acids in amniotic fluid in the absence of intra-amniotic inflammation. This study was conducted to determine the clinical significance of the presence of bacteria in amniotic fluid samples in the absence of intra-amniotic inflammation., Methods: A retrospective cross-sectional study included 360 patients with preterm labor and intact membranes who underwent transabdominal amniocentesis for evaluation of the microbial state of the amniotic cavity as well as intra-amniotic inflammation. Cultivation techniques were used to isolate microorganisms, and broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry (PCR/ESI-MS) was utilized to detect the nucleic acids of bacteria, viruses, and fungi., Results: Patients whose amniotic fluid samples evinced microorganisms but did not indicate inflammation had a similar perinatal outcome to those without microorganisms or inflammation [amniocentesis-to-delivery interval (p=0.31), spontaneous preterm birth before 34 weeks (p=0.83), acute placental inflammatory lesions (p=1), and composite neonatal morbidity (p=0.8)]., Conclusions: The isolation of microorganisms from a sample of amniotic fluid in the absence of intra-amniotic inflammation is indicative of a benign condition, which most likely represents contamination of the specimen during the collection procedure or laboratory processing rather than early colonization or infection., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Human adipose tissue includes useful substrates for regenerative medicine such as the extracellular matrix (ECM), but most perirenal fat tissue is wasted after kidney surgery. Since a lot of adipose tissue can be procured after a kidney, we extracted ECM from human perirenal adipose tissue and optimized the extraction process. To verify the efficacy for ECM extraction, we compared the products in several steps. Perirenal adipose tissue was either finely homogenized or underwent crude manual dissection. The amount of extracted ECM was quantified with ELISA for verification of the initial tissue downsizing effect. To validate the drying effect for fast and complete delipidation, tissues were prepared in a dry or wet phase, and residual lipids were visualized with Oil-Red-O staining. The extracted lipid was assayed at each time point to quantify the appropriate delipidation time. To select the optimal decellularization method, tissues were treated with physical, chemical, or enzymatic method, and the residual cell debris were identified with histological staining. The biochemical properties of the ECM extracted by the above methods were analyzed. The ECM extracted by fine homogenization showed a significantly enhanced amount of collagen, laminin and fibronectin compared to the crude dissection method. The dried tissue showed fast and complete lipid elimination compared to the wet tissue. Complete delipidation was achieved at 45 min after acetone treatment. Additionally, 1% triton X-100 chemical treatment showed complete decellularization with well-preserved collagen fibers. Biochemical analysis revealed preserved ECM proteins, a high cell proliferation rate and normal cell morphology without cell debris or lipids. The established process of homogenization, drying, delipidation with acetone, and decellularization with Triton X-100 treatment can be an optimal method for ECM extraction from human perirenal adipose tissue. Using this technique, human perirenal adipose tissue may be a valuable source for tissue engineering and regenerative medicine.

Competing Interests: Declaration of competing interest The authors declare no conflicts of interest.

Objectives: Clinical chorioamnionitis at term is considered the most common infection-related diagnosis in labor and delivery units worldwide. The syndrome affects 5-12% of all term pregnancies and is a leading cause of maternal morbidity and mortality as well as neonatal death and sepsis. The objectives of this study were to determine the (1) amniotic fluid microbiology using cultivation and molecular microbiologic techniques; (2) diagnostic accuracy of the clinical criteria used to identify patients with intra-amniotic infection; (3) relationship between acute inflammatory lesions of the placenta (maternal and fetal inflammatory responses) and amniotic fluid microbiology and inflammatory markers; and (4) frequency of neonatal bacteremia., Methods: This retrospective cross-sectional study included 43 women with the diagnosis of clinical chorioamnionitis at term. The presence of microorganisms in the amniotic cavity was determined through the analysis of amniotic fluid samples by cultivation for aerobes, anaerobes, and genital mycoplasmas. A broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry was also used to detect bacteria, select viruses, and fungi. Intra-amniotic inflammation was defined as an elevated amniotic fluid interleukin-6 (IL-6) concentration ≥2.6 ng/mL., Results: (1) Intra-amniotic infection (defined as the combination of microorganisms detected in amniotic fluid and an elevated IL-6 concentration) was present in 63% (27/43) of cases; (2) the most common microorganisms found in the amniotic fluid samples were Ureaplasma species, followed by Gardnerella vaginalis ; (3) sterile intra-amniotic inflammation (elevated IL-6 in amniotic fluid but without detectable microorganisms) was present in 5% (2/43) of cases; (4) 26% of patients with the diagnosis of clinical chorioamnionitis had no evidence of intra-amniotic infection or intra-amniotic inflammation; (5) intra-amniotic infection was more common when the membranes were ruptured than when they were intact (78% [21/27] vs. 38% [6/16]; p=0.01); (6) the traditional criteria for the diagnosis of clinical chorioamnionitis had poor diagnostic performance in identifying proven intra-amniotic infection (overall accuracy, 40-58%); (7) neonatal bacteremia was diagnosed in 4.9% (2/41) of cases; and (8) a fetal inflammatory response defined as the presence of severe acute funisitis was observed in 33% (9/27) of cases., Conclusions: Clinical chorioamnionitis at term, a syndrome that can result from intra-amniotic infection, was diagnosed in approximately 63% of cases and sterile intra-amniotic inflammation in 5% of cases. However, a substantial number of patients had no evidence of intra-amniotic infection or intra-amniotic inflammation. Evidence of the fetal inflammatory response syndrome was frequently present, but microorganisms were detected in only 4.9% of cases based on cultures of aerobic and anaerobic bacteria in neonatal blood., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Bladder cancer (BC) is one of the most common malignancies of the urinary tract. The role of transient receptor potential melastatin 7 (TRPM7) in BC remains unclear. The aim of this study was to investigate the function and signal transduction pathway of TRPM7 in BC., Methods: T24 and UMUC3 cells were used to evaluate the molecular mechanism of TRPM7 by immunoblot analysis. Small interfering RNA was used to knockdown TRPM7, and the effect of silencing TRPM7 was studied by wound healing, migration, and invasion assays in T24 and UMUC3 cells. Xenograft model study was obtained to analyze the effect of TRPM7 inhibition in vivo., Results: Silencing of TRPM7 decreased the migration and invasion ability of T24 and UMUC3 cells. The phosphorylation of Src, Akt, and JNK (c-Jun N-terminal kinase) was also suppressed by TRPM7 silencing. Src, Akt, and JNK inhibitors effectively inhibited the migration and invasion of T24 and UMUC3 cells. In addition, the TRPM7 inhibitor, carvacrol, limited the tumor size in a xenograft model., Conclusion: Our data reveal that TRPM7 regulates the migration and invasion of T24 and UMUC3 cells via the Src, Akt, and JNK signaling pathway. Therefore, TRPM7 suppression could be a potential treatment for BC patients.

Background: Microbial invasion of the amniotic cavity, a clinical condition present in approximately 50% of patients with preterm prelabor rupture of membranes, is often associated with intraamniotic inflammation, a risk factor for a short admission-to-delivery interval, early preterm delivery, and neonatal complications. We previously developed a transcervical amniotic fluid collector, the device that allows the collection of fluid noninvasively from the cervical canal when membrane rupture occurs., Objective: This study was designed to determine whether rapid analysis of an interleukin-8 concentration in fluid obtained noninvasively by the transcervical amniotic fluid collector can be used to assess the risk of intraamniotic inflammation. We also compared the diagnostic performance of this point-of-care test for interleukin-8 in transcervically obtained fluid to that of a white blood cell count determined in amniotic fluid retrieved by transabdominal amniocentesis., Study Design: This prospective cohort study was conducted between October 2011 and April 2017. Fluid was retrieved through both transabdominal amniocentesis and the use of a transcervical amniotic fluid collector within 24 hours of amniocentesis in patients with a singleton pregnancy and preterm prelabor rupture of the membranes (16-35 weeks of gestation). Amniotic fluid obtained via amniocentesis was cultured for aerobic and anaerobic bacteria and genital mycoplasmas; a white blood cell count was also measured in amniotic fluid. Intraamniotic infection was diagnosed when microorganisms were identified by the cultivation of amniotic fluid. Intraamniotic inflammation was defined as an elevated amniotic fluid matrix metalloproteinase-8 concentration (>23 ng/mL) assayed by enzyme-linked immunosorbent assay. Interleukin-8 in cervical fluid obtained by the collector was measured by the point-of-care test that used a test strip and scanner based on the fluorescence immunochromatographic analysis in 2019. The diagnostic indices, predictive values, and likelihood ratios of the 2 different tests were calculated., Results: First, interleukin-8 concentration ≥9.5 ng/mL in cervical fluid, determined by the point-of-care test, was at the knee of the receiver operating characteristic curve analysis and had a sensitivity of 98% (56/57; 95% confidence interval, 91-99.96%), specificity of 74% (40/54; 95% confidence interval, 60-85%), positive predictive value of 80% (56/70; 95% confidence interval, 72-86%), negative predictive value of 98% (40/41; 95% confidence interval, 85-99.6%), positive likelihood ratio of 3.79 (95% confidence interval, 2.41-5.96), and negative likelihood ratio of 0.02 (95% confidence interval, 0.003-0.17) in the identification of intraamniotic inflammation; a concentration of matrix metalloproteinase-8 >23 ng/mL by enzyme-linked immunosorbent assay had a prevalence of 51% (57/111). Second, a cervical fluid interleukin-8 concentration ≥9.5 ng/mL had significantly higher sensitivity than a transabdominally obtained amniotic fluid white blood cell count (≥19 cells/mm 3 ) in the identification of intraamniotic inflammation (sensitivity: 98% [95% confidence interval, 91-99.96%] vs 84% [95% confidence interval, 72-93%]; P<.05; specificity: 74% [95% confidence interval, 60-85%] vs 76% [95% confidence interval, 62-87%); positive and negative predictive values: 80% [95% confidence interval, 72-86%] and 98% [95% confidence interval, 85-99.6%] vs 79% [95% confidence interval, 69-86%] and 82% [95% confidence interval, 71-89%]) and in the identification of intraamniotic inflammation/infection (gold standard: positive culture for bacteria or a matrix metalloproteinase-8 >23 ng/mL; sensitivity: 91% [95% confidence interval, 82-97%] vs 75% [95% confidence interval, 63-85%]; P<.05)., Conclusion: The point-of-care test was predictive of intraamniotic inflammation, based on the determination of interleukin-8 in fluid retrieved by a transcervical amniotic fluid collector. Therefore, the analysis of cervically obtained fluid by such point-of-care test may be used to noninvasively monitor intraamniotic inflammation in patients with preterm prelabor rupture of membranes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: The Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) is based on expert consensus and has been revised five times since 2002. This study evaluated the changes in treatment strategies advocated by the KMAP-BP over time., Methods: The five editions of the KMAP-BP were reviewed, and the recommendations of the KMAP-BP were compared with those of other bipolar disorder (BP) treatment guidelines., Results: The most preferred option for the initial treatment of mania was a combination of a mood stabilizer (MS) and an atypical antipsychotic (AAP). Either MS or AAP monotherapy was also considered a first-line strategy for mania, but not for all types of episodes, including mixed/psychotic mania. In general, although lithium and valproic acid were commonly recommended, valproic acid has been increasingly preferred for all phases of BP. The most notable changes over time included the increasing preference for AAPs for all phases of BP, and lamotrigine for the depressive and maintenance phases. The use of antidepressants for BP has gradually decreased, but still represents a first-line option for severe and psychotic depression., Conclusions: In general, the recommended strategies of the KMAP-BP were similar to those of other guidelines, but differed in terms of the emphasis on rapid effectiveness, which is often desirable in actual clinical situations. The major limitation of the KMAP-BP is that it is a consensus-based rather than an evidence-based tool. Nevertheless, it may confer advantages in actual clinical practice., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The fetus can deploy a local or systemic inflammatory response when exposed to microorganisms or, alternatively, to non-infection-related stimuli (e.g., danger signals or alarmins). The term "Fetal Inflammatory Response Syndrome" (FIRS) was coined to describe a condition characterized by evidence of a systemic inflammatory response, frequently a result of the activation of the innate limb of the immune response. FIRS can be diagnosed by an increased concentration of umbilical cord plasma or serum acute phase reactants such as C-reactive protein or cytokines (e.g., interleukin-6). Pathologic evidence of a systemic fetal inflammatory response indicates the presence of funisitis or chorionic vasculitis. FIRS was first described in patients at risk for intraamniotic infection who presented preterm labor with intact membranes or preterm prelabor rupture of the membranes. However, FIRS can also be observed in patients with sterile intra-amniotic inflammation, alloimmunization (e.g., Rh disease), and active autoimmune disorders. Neonates born with FIRS have a higher rate of complications, such as early-onset neonatal sepsis, intraventricular hemorrhage, periventricular leukomalacia, and death, than those born without FIRS. Survivors are at risk for long-term sequelae that may include bronchopulmonary dysplasia, neurodevelopmental disorders, such as cerebral palsy, retinopathy of prematurity, and sensorineuronal hearing loss. Experimental FIRS can be induced by intra-amniotic administration of bacteria, microbial products (such as endotoxin), or inflammatory cytokines (such as interleukin-1), and animal models have provided important insights about the mechanisms responsible for multiple organ involvement and dysfunction. A systemic fetal inflammatory response is thought to be adaptive, but, on occasion, may become dysregulated whereby a fetal cytokine storm ensues and can lead to multiple organ dysfunction and even fetal death if delivery does not occur ("rescued by birth"). Thus, the onset of preterm labor in this context can be considered to have survival value. The evidence so far suggests that FIRS may compound the effects of immaturity and neonatal inflammation, thus increasing the risk of neonatal complications and long-term morbidity. Modulation of a dysregulated fetal inflammatory response by the administration of antimicrobial agents, anti-inflammatory agents, or cell-based therapy holds promise to reduce infant morbidity and mortality., (Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

Objective: In this study we investigated whether current mood states of patients with bipolar disorder have an influence on the screening accuracy of the Mood Disorder Questionnaire (MDQ)., Methods: A total of 452 patients with mood disorder (including 192 with major depressive disorder and 260 with bipolar disorder completed the Korean version of the MDQ. Patients with bipolar disorder were subdivided into three groups (bipolar depressed only, bipolar euthymic only, bipolar manic/hypomanic only) according to current mood states. The screening accuracy of the MDQ including sensitivity, specificity and area under the curve (AUC) of receiver operating characteristic (ROC) curves were evaluated according to current mood states., Results: The optimal cutoff of MDQ was 5 in this study sample. Sensitivity and specificity were not significantly different according to current mood states. Significant differences in AUCs of four independent ROC curves were not found (ROC 1st curve included all bipolar patients; ROC 2nd curve included only bipolar depressed patients; ROC 3rd curve included only bipolar manic/hypomanic patients; ROC 4th curve included only bipolar euthymic patients)., Conclusion: The study results showed that current mood states (either euthymic state, depressed or manic/hypomanic) did not significantly influence the screening accuracy of the MDQ suggesting that the MDQ could be a useful screening instrument for detecting bipolar disorder in clinical practice regardless of the current mood symptoms of subjects.

Background: Although mood stabilizers such as lithium (LIT), valproate (VAL), and lamotrigine (LMT) appear to be efficacious treatments for bipolar disorder (BD) in research settings, the long-term response to these mood stabilizers in clinical practice is highly variable among individuals. Thus, the present study examined the characteristics associated with good or insufficient responses to long-term treatment with LIT, VAL, or LMT for BD., Methods: This study retrospectively analyzed the medical records of patients who visited an outpatient clinic with a diagnosis of BD I or II. Data from patients who were treated with one of three mood stabilizing medications (LIT, VAL, or LMT) for more than 6 months were selected, and the long-term treatment responses were evaluated using the Alda scale. For the purposes of this study, two response categories were formed: insufficient response (ISR), including non-response or poor response (Alda total score ≤ 6), and good response (GR; Alda total score ≥ 7)., Results: Of the 645 patients included in the present study, 172 were prescribed LIT, 320 were prescribed VAL, and 153 were prescribed LMT for at least 6 months. A binary logistic regression analysis revealed that a diagnosis of BD II (odds ratio [OR], 8.868; 95% confidence interval [CI], 1.123-70.046; p = 0.038), comorbid alcohol/substance use disorder (OR, 4.238; 95% CI, 1.154-15.566; p = 0.030), and a history of mixed episodes (OR, 4.363; 95% CI, 1.191-15.985; p = 0.026) were significant predictors of LIT-ISR. Additionally, a depressive-predominant polarity significantly predicted LMT-GR (OR, 8.586; 95% CI, 2.767-26.644; p < 0.001)., Conclusion: The present findings demonstrated that patients with a diagnosis of BD II, a comorbid alcohol/substance problem, or a history of mixed episodes were not likely to respond to LIT treatment. Additionally, LMT might be a better treatment choice for patients with a depressive-predominant polarity., Competing Interests: The authors have declared that no competing interests exist.

Background: Blonanserin is a second-generation antipsychotic used for the treatment of schizophrenia. This study determined the efficacy, safety and pharmacokinetics of a blonanserin transdermal patch in patients with acutely exacerbated schizophrenia., Methods: This double-blind, multicenter, phase 3 study consisted of a 1-week observation period during which patients were treated with two patches of placebo, followed by a 6-week double-blind period where patients were randomized (1:1:1) to receive once-daily blonanserin 40 mg, blonanserin 80 mg, or placebo patches. The primary endpoint was the change from baseline in the total Positive and Negative Symptom Scale (PANSS) score. Safety assessments included treatment-emergent adverse events (TEAEs)., Results: Between December 2014 and October 2018, patients were recruited and randomly assigned to blonanserin 40 mg (n = 196), blonanserin 80 mg (n = 194), or placebo (n = 190); of these, 77.2% completed the study. Compared with placebo, blonanserin significantly improved PANSS total scores at 6 weeks (least square mean [LSM] difference vs placebo: -5.6 with blonanserin 40 mg; 95% confidence interval [CI] -9.6, -1.6; adjusted p = 0.007, and - 10.4 with blonanserin 80 mg; 95% CI -14.4, -6.4; adjusted p < 0.001). Blonanserin was well tolerated; the most common TEAEs reported were application-site erythema and pruritus, akathisia, tremor, and insomnia., Conclusions: Blonanserin transdermal patch improved the symptoms of acute schizophrenia with acceptable tolerability., Competing Interests: Declaration of Competing Interest NI reports personal fees from Otsuka, Sumitomo Dainippon, Janssen, Eli Lilly, and Pfizer, grants from Otsuka, Daiichi-Sankyo, outside the submitted work. JI reports grants from Sumitomo Dainippon during the conduct of the study, personal fees from Meiji Seika Pharma, MSD, Astellas, Novartis, Pfizer, Otsuka, Eli Lilly, Takeda, and Eisai, outside the submitted work. WHK reports grants from Sumitomo Dainippon, during the conduct of the study. TH reports personal fees from Meiji Seika Pharma, MSD, Allergan, Eisai, Pfizer, Janssen, Lundbeck, Shionogi, Yoshitomi, Kyowa Hakko Kirin, Mochida, Otsuka, Sumitomo Dainippon, Mitsubishi Tanabe, Eli Lilly, and Takeda, outside the submitted work. CUC reports personal fees from Alkermes, Allergan, Angelini, Boehringer-Ingelheim, Gerson Lehrman Group, Indivior, IntraCellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, MedAvante-ProPhase, Medscape, Merck, Neurocrine, Noven, Otsuka, Pfizer, Rovi, Servier, Sumitomo Dainippon, Sunovion, Supernus, Takeda, Teva, Bristol-Myers Squibb, and UpToDate, grants from Janssen and Takeda, other from Boehringer-Ingelheim, Lundbeck, Rovi, Supernus, Teva, and LB Pharma, outside the submitted work. JMK reports personal fees from Alkermes, Sumitomo Dainippon, Eli Lilly, EnVivo Pharmaceuticals (Forum), Forest (Allergan), Genentech, H. Lundbeck, Intracellular Therapies, Janssen, Johnson and Johnson, LB Pharmaceuticals, Merck, Minerva, Neurocrine, Otsuka, Pierre Fabre, Reviva, Roche, Sunovion, Takeda and Teva, grants from Otsuka, Lundbeck and Janssen, participated in advisory boards for Alkermes, Sumitomo Dainippon, Intracellular Therapies, Lundbeck, Neurocrine, Otsuka, Pierre Fabre, Takeda and Teva, outside the submitted work. JMK is a shareholder in Vanguard Research Group and LB Pharmaceuticals. All other authors declare no competing interests., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Mannoproteins (MPs) are a major component of yeast cell walls and consist of high levels of mannose in covalent complexes with proteins. MPs complexly enhance the immune system. We previously isolated a mutant yeast, K48L3, with a higher yield of MP from its cell wall than wild-type Saccharomyces cerevisiae, YPH499. We determined that K48L3 induces the release of nitric oxide in macrophage cells. The present study reports nitric-oxide-mediated angiogenesis by MP from K48L3 and the induction of the Akt/eNOS signal pathway. Western blotting and RT-PCR were used to demonstrate that MP treatment resulted in the upregulation of p-Akt, p-eNOS, and angiogenesis-mediated gene expression. Moreover, the angiogenesis activity of the MPs was demonstrated using three angiogenesis assays, namely, a cell migration assay, a tube-forming assay, and an ex vivo aorta ring assay. Thus, this study demonstrates for the first time that MPs from S. cerevisiae K48L3 induce angiogenesis in HUVECs via the Akt-eNOS-dependent signaling pathway., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to evaluate the prevalence of mixed features using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and to examine how patients with mixed states would be classified using the DSM-5., Methods: In total, 12 hospitals participated in this study, and data on the demographic characteristics and clinical diagnoses of patients treated between October 2013 and September 2016 were obtained. We reviewed the data for opposite-polarity symptoms according to the DSM-5 criteria and the research-based diagnostic criteria., Results: Of the 859 patients included in the final analysis, the prevalence of mixed features in patients with major depressive episodes based on the DSM-5 remained low. Patients with major depressive disorder were more likely to be classified as experiencing anxious distress and/or a cluster-B personality disorder in mixed state patients not diagnosed with DSM-5 mixed features, whereas more mixed state patients with bipolar disorder were diagnosed with mixed features using the DSM-5., Conclusions: The prevalence of mixed features did not increase significantly when the DSM-5 was used, and patients with mixed states were more likely to be classified as having anxious distress and/or a cluster-B personality disorder in addition to mixed features., (© 2019 John Wiley & Sons, Ltd.)

Objective: This study was performed to investigate the efficacy and tolerability of blonanserin in schizophrenic patients who were previously treated with other antipsychotics but, due to insufficient response, were switched to blonanserin., Methods: A total of 52 patients with schizophrenia who were unresponsive to treatment with antipsychotic monotherapy or combination therapy were recruited into this 12-week, open-label, prospective, multicenter study. Patients were switched to blonanserin from their existing antipsychotics over a maximum 2-week tapering-off period. Efficacy was primarily evaluated using the 18-item Brief Psychiatric Rating Scale (BPRS). Assessments were performed at baseline, and at weeks 1, 2, 4, 8, and 12., Results: Switching to blonanserin resulted in a significant decrease in the mean total score on the BPRS from baseline (56.8 ± 9.4) to week 12 (42.1 ± 13.8, p > 0.001). The most common adverse events were extrapyramidal symptoms (n = 12, 23.1%), insomnia (n = 10, 19.2%), and emotional arousal (n = 6, 11.5%). Overweight or obese patients (body mass index ≥ 23 kg/m 2 , n = 33) who switched to blonanserin exhibited significant weight loss from 75.2 ± 9.3 kg at baseline to 73.5 ± 9.2 kg at week 12 ( p = 0.006). The total cholesterol (baseline, 236.1 ± 47.6 mg/dl; endpoint [week 12], 209.9 ± 28.0 mg/dl; p = 0.005) and prolactin levels (baseline, 80.0 ± 85.2 ng/ml; endpoint [week 12], 63.2 ± 88.9 ng/ml; p = 0.003) were also significantly improved in patients with hypercholesterolemia or hyperprolactinemia., Conclusion: The results of the present study suggest that switching to blonanserin may be an effective strategy for schizophrenic patients unresponsive to other antipsychotic treatments.

Objective: The Depression in Old Age Scale (DIA-S) is a new screening tool for assessing depression in the elderly. The primary aims of this study were to describe the validation of the Korean version of the DIA-S (K-DIA-S) and to compare its validity with that of other depression screening questionnaires used in elderly outpatients in medical settings., Methods: A total of 385 elderly outpatients completed the K-DIA-S and underwent the Mini International Neuropsychiatric Interview to diagnose depressive disorders. Other measures included the 15-item short form of the Geriatric Depression Scale (SGDS), the 9-item depression module of the Patient Health Questionnaire (PHQ-9), and the Montgomery-Asberg Depression Rating Scale (MADRS). Reliability and validity tests, an optimal cutoff point estimate, and receiver operating characteristic curve analysis were performed to investigate the diagnostic validity of the K-DIA-S. Areas under the curves (AUCs) for the K-DIA-S, SGDS, and PHQ-9 were compared statistically., Results: The K-DIA-S showed good internal consistency and strong correlations with the SGDS ( r = 0.853), PHQ-9 ( r = 0.739), and MADRS ( r = 0.772). The cut-off point of the K-DIA-S that can be recommended for screening depressive symptoms was a score of 4. For "any depressive disorder", the AUC (standard error) for the K-DIA-S was 0.896 (0.015), which was significantly larger than that for the PHQ-9 ( p = 0.033)., Conclusion: The present findings suggest that the K-DIA-S has good psychometric properties and is a valid and reliable tool for assessing depressive symptoms in elderly populations and medically ill patients.

Background: Cervical insufficiency is a risk factor for spontaneous midtrimester abortion or early preterm birth. Intra-amniotic infection has been reported in 8-52% of such patients and intra-amniotic inflammation in 81%. Some professional organizations have recommended perioperative antibiotic treatment when emergency cervical cerclage is performed. The use of prophylactic antibiotics is predicated largely on the basis that they reduce the rate of complications during the course of vaginal surgery. However, it is possible that antibiotic administration can also eradicate intra-amniotic infection/inflammation and improve pregnancy outcome., Objective: To describe the outcome of antibiotic treatment in patients with cervical insufficiency and intra-amniotic infection/inflammation., Study Design: The study population consisted of 22 women who met the following criteria: (1) singleton pregnancy; (2) painless cervical dilatation of >1 cm between 16.0 and 27.9 weeks of gestation; (3) intact membranes and absence of uterine contractions; (4) transabdominal amniocentesis performed for the evaluation of the microbiologic and inflammatory status of the amniotic cavity; (5) presence of intra-amniotic infection/inflammation; and (6) antibiotic treatment (regimen consisted of ceftriaxone, clarithromycin, and metronidazole). Amniotic fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas, and polymerase chain reaction for Ureaplasma spp. was performed. Intra-amniotic infection was defined as a positive amniotic fluid culture for microorganisms or a positive polymerase chain reaction for Ureaplasma spp., and intra-amniotic inflammation was suspected when there was an elevated amniotic fluid white blood cell count (≥19 cells/mm 3 ) or a positive rapid test for metalloproteinase-8 (sensitivity 10 ng/mL). For the purpose of this study, the "gold standard" for diagnosis of intra-amniotic inflammation was an elevated interleukin-6 concentration (>2.6 ng/mL) using an enzyme-linked immunosorbent assay. The results of amniotic fluid interleukin-6 were not available to managing clinicians. Follow-up amniocentesis was routinely offered to monitor the microbiologic and inflammatory status of the amniotic cavity and fetal lung maturity. Treatment success was defined as resolution of intra-amniotic infection/inflammation or delivery ≥34 weeks of gestation., Results: Of 22 patients with cervical insufficiency and intra-amniotic infection/inflammation, 3 (14%) had microorganisms in the amniotic fluid. Of the 22 patients, 6 (27%) delivered within 1 week of amniocentesis and the remaining 16 (73%) delivered more than 1 week after the diagnostic procedure. Among these, 12 had a repeat amniocentesis to assess the microbial and inflammatory status of the amniotic cavity; in 75% (9/12), there was objective evidence of resolution of intra-amniotic inflammation or intra-amniotic infection demonstrated by analysis of amniotic fluid at the time of the repeat amniocentesis. Of the 4 patients who did not have a follow-up amniocentesis, all delivered ≥34 weeks, 2 of them at term; thus, treatment success occurred in 59% (13/22) of cases., Conclusion: In patients with cervical insufficiency and intra-amniotic infection/inflammation, administration of antibiotics (ceftriaxone, clarithromycin, and metronidazole) was followed by resolution of the intra-amniotic inflammatory process or intra-amniotic infection in 75% of patients and was associated with treatment success in about 60% of cases., (Published by Elsevier Inc.)

Background: Intra-amniotic infection is present in 10% of patients with an episode of preterm labor, and is a risk factor for impending preterm delivery and neonatal morbidity/mortality. Intra-amniotic inflammation is often associated with intra-amniotic infection, but is sometimes present in the absence of detectable microorganisms. Antibiotic treatment of intra-amniotic infection has traditionally been considered to be ineffective. Intra-amniotic inflammation without microorganisms has a prognosis similar to that of intra-amniotic infection., Objective: To determine whether antibiotics can eradicate intra-amniotic infection or intra-amniotic inflammation in a subset of patients with preterm labor and intact membranes., Materials and Methods: The study population consisted of women who met the following criteria: 1) singleton gestation between 20 and 34 weeks; 2) preterm labor and intact membranes; 3) transabdominal amniocentesis performed for the evaluation of the microbiologic/inflammatory status of the amniotic cavity; 4) intra-amniotic infection and/or intra-amniotic inflammation; and 5) received antibiotic treatment that consisted of ceftriaxone, clarithromycin, and metronidazole. Follow-up amniocentesis was performed in a subset of patients. Amniotic fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas, and polymerase chain reaction was performed for Ureaplasma spp. Intra-amniotic infection was defined as a positive amniotic fluid culture or positive polymerase chain reaction, and intra-amniotic inflammation was suspected when there was an elevated amniotic fluid white blood cell count or a positive result of a rapid test for matrix metalloproteinase-8. For this study, the final diagnosis of intra-amniotic inflammation was made by measuring the interleukin-6 concentration in stored amniotic fluid (>2.6 ng/mL). These results were not available to managing clinicians. Treatment success was defined as eradication of intra-amniotic infection and/or intra-amniotic inflammation or delivery ≥37 weeks., Results: Of 62 patients with intra-amniotic infection and/or intra-amniotic inflammation, 50 received the antibiotic regimen. Of those patients, 29 were undelivered for ≥7 days and 19 underwent a follow-up amniocentesis. Microorganisms were identified by culture or polymerase chain reaction of amniotic fluid obtained at admission in 21% of patients (4/19) who had a follow-up amniocentesis, and were eradicated in 3 of the 4 patients. Resolution of intra-amniotic infection/inflammation was confirmed in 79% of patients (15/19), and 1 other patient delivered at term, although resolution of intra-amniotic inflammation could not be confirmed after a follow-up amniocentesis. Thus, resolution of intra-amniotic inflammation/infection or term delivery (treatment success) occurred in 84% of patients (16/19) who had a follow-up amniocentesis. Treatment success occurred in 32% of patients (16/50) with intra-amniotic infection/inflammation who received antibiotics. The median amniocentesis-to-delivery interval was significantly longer among women who received the combination of antibiotics than among those who did not (11.4 days vs 3.1 days: P = .04)., Conclusion: Eradication of intra-amniotic infection/inflammation after treatment with antibiotics was confirmed in 79% of patients with preterm labor, intact membranes, and intra-amniotic infection/inflammation who had a follow-up amniocentesis. Treatment success occurred in 84% of patients who underwent a follow-up amniocentesis and in 32% of women who received the antibiotic regimen., (Published by Elsevier Inc.)

Objectives To determine the relationship between the intensity of the intra-amniotic inflammatory response and the gestational age at the time of diagnosis in cases with preterm premature rupture of membranes (PROM) and intra-amniotic infection caused by Ureaplasma spp. Methods A retrospective cohort study was conducted which included 71 women with preterm PROM and a positive amniotic fluid culture with Ureaplasma spp. Women with mixed intra-amniotic infections were excluded. The study population was classified into three groups according to gestational age: group 1, <26 weeks (extreme preterm PROM, n = 17); group 2, 26.0-33.9 weeks (moderate preterm PROM, n = 39); group 3, 34.0-36.9 weeks (late preterm PROM, n = 15). The intensity of the intra-amniotic and maternal inflammatory response was compared among the three groups. The intensity of the intra-amniotic inflammatory response was assessed by the concentration of amniotic fluid matrix metalloproteinase-8 (MMP-8) and white blood cell (WBC) count. The maternal inflammatory response was assessed by the concentration of C-reactive protein (CRP) and WBC count in maternal blood at the time of amniocentesis. Results (1) The median values of amniotic fluid MMP-8 concentration and WBC count were the highest in the extreme preterm PROM group and the lowest in the late preterm PROM group (P < 0.001 and P = 0.01, respectively); (2) the intensity of the maternal inflammatory response measured by maternal blood WBC count and CRP concentration was not significantly associated with gestational age at the time of diagnosis. Conclusion The earlier the gestational age at the time of PROM, the higher the intensity of the intra-amniotic inflammatory response in women with preterm PROM and intra-amniotic infection caused by Ureaplasma spp.

Introduction: To evaluate efficacy and safety of lurasidone for the treatment of Asian patients with schizophrenia., Methods: Patients with schizophrenia from Japan, South Korea, Malaysia, and Taiwan were randomly assigned to 6 weeks of double-blind treatment with 40 or 80 mg/d of lurasidone or placebo. The primary efficacy measure was change from baseline to week 6 on the Positive and Negative Syndrome Scale (PANSS) total score. Efficacy was evaluated using a mixed-model repeated-measures (MMRM) analysis in the modified intention-to-treat (mITT) population., Results: On the basis of the analysis for the mITT population, the estimated difference score for lurasidone 40 and 80 mg/d vs placebo was -4.8 (P = 0.050) and -4.2 (P = 0.080). For the full intention-to-treat (ITT) population, the difference score for lurasidone 40 and 80 mg/d vs placebo was -5.8 (P = 0.017) and -4.2 (P = 0.043). The most frequent adverse events in the lurasidone 40 and 80 mg/d and placebo groups, respectively, were akathisia (7.3%, 10.4%, 3.3%), somnolence (6.0%, 2.6%, 0.7%), and vomiting (6.0%, 5.8%, 2.0%). The proportion of patients experiencing clinically significant weight gain (≥7%) was 5.3% for lurasidone 40 mg/d, 1.3% for 80 mg/d, and 1.4% for placebo. End point changes in metabolic parameters and prolactin were comparable for both lurasidone groups and placebo., Conclusions: In the ITT (but not the mITT) population, treatment with lurasidone was associated with significant improvement in the PANSS total score in patients with schizophrenia. Lurasidone was generally well tolerated with minimal impact on weight and metabolic parameters., (© 2019 John Wiley & Sons Australia, Ltd.)

The objective of this study was to compare recommendations of the Korean Medication Algorithm Project for Bipolar Disorder 2018 (KMAP-BP 2018) with other recently published guidelines for treating bipolar disorder. We reviewed a total of five recently published global treatment guidelines and compared treatment recommendation of the KMAP-BP 2018 with those of other guidelines. For initial treatment of mania, there were no significant differences across treatment guidelines. All guidelines recommended mood stabilizer (MS) or atypical antipsychotic (AAP) monotherapy or a combination of an MS with an AAP as a first-line treatment strategy for mania. However, the KMAP-BP 2018 did not prefer monotherapy with MS or AAP for psychotic mania. Quetiapine, olanzapine and aripiprazole were the first-line AAPs for nearly all phases of bipolar disorder across guidelines. Most guidelines advocated newer AAPs as first-line treatment options for all phases while lamotrigine was recommended for depressive and maintenance phases. Lithium and valproic acid were commonly used as MSs in all phases of bipolar disorder. As research evidence accumulated over time, recommendations of newer AAPs (such as asenapine, cariprazine, paliperidone, lurasidine, long-acting injectable risperidone and aripiprazole once monthly) became prominent. KMAP-BP 2018 guidelines were similar to other guidelines, reflecting current changes in prescription patterns for bipolar disorder based on accumulated research data. Strong preference for combination therapy was characteristic of KMAP-BP 2018, predominantly in the treatment of psychotic mania and severe depression. Further studies were needed to address several issues identified in our review.