Chimeric Singleton Placenta Comprising Placental Mesenchymal Dysplasia and Complete Hydatidiform Mole with Live Birth and Postpartum Diagnosis of Gestational Trophoblastic Neoplasia.

INTRODUCTION: Placental mesenchymal dysplasia (PMD) is a benign lesion that is often misdiagnosed as complete (CHM) or partial hydatidiform mole. PMD usually results in live birth but can be associated with several fetal defects. Herein, we report PMD with CHM in a singleton placenta with live birth. CASE PRESENTATION: A 34-year-old gravida 2, para 1, living 1 (G2P1L1) woman was referred on suspicion of a molar pregnancy in the first trimester. Maternal serum human chorionic gonadotrophin levels were increased during early pregnancy, with multicystic lesions and placentomegaly observed on ultrasonography. Levels decreased to normal with no fetal structural abnormalities observed. A healthy male infant was delivered at 34 gestational weeks. Placental p57KIP2 immunostaining and short tandem repeat analysis revealed three distinct histologies and genetic features: normal infant and placenta, PMD, and CHM. Gestational trophoblastic neoplasia was diagnosed and up to fourth-line chemotherapy administered. CONCLUSION: Distinguishing PMD from hydatidiform moles is critical for avoiding unnecessary termination of pregnancy. CHM coexisting with a live fetus rarely occurs. This case is unique in that a healthy male infant was born from a singleton placenta with PMD and CHM.

DOSAGE AND DURATION OF ETANERCEPT THERAPY FOR ANKYLOSING SPONDYLITIS: A META-ANALYSIS.

OBJECTIVES: We conducted a meta-analysis of recently published randomized controlled trials (RCTs) to identify the most effective and safe etanercept dosing regimen and duration of therapy for the treatment of patients with ankylosing spondylitis (AS). METHODS: We systematically reviewed PubMed, Embase, Cochrane Library, and Web of Science databases for RCTs. The proportion of patients attaining 20 percent improvement (according to the Spondyloarthritis International Society response criteria [ASAS 20]) was evaluated as a primary outcome. Secondary outcomes included 50 percent increase in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI 50) used for evaluating efficacy, as well as the BASDAI/Bath Ankylosing Spondylitis Functional Index (BASFI) scores and adverse events. RESULTS: ASAS 20 indicated that the efficacy of etanercept did not differ amongst dosing regimens (25 mg twice-weekly versus 50 mg once-weekly: relative risk [RR], 2.18, 95 percent confidence interval [CI], 1.78-2.67 versus RR, 2.00, 95 percent CI, 1.70-2.37). The ASAS 20 reported subgroup differences among treatment durations of less than 12 weeks (RR, 2.70; 95 percent CI, 2.09-3.49); 12 weeks (RR, 1.74; 95 percent CI, 1.37-2.22); and more than 12 weeks (RR, 2.56; 95 percent CI, 1.88-3.48). Other outcomes included BASDAI, BASDAI 50, and BASFI. Drug safety differed according to the treatment regimen and duration. CONCLUSION: Our meta-analysis found that there was no significant efficacy difference between 50 mg once-weekly and 25 mg twice-weekly dosing for the treatment of AS, and a dosing duration of less than 12 weeks was more effective for treating AS patients.

Gut microbial and clinical characteristics of individuals with autism spectrum disorder differ depending on the ecological structure of the gut microbiome.

Understanding the relationship between the gut microbiome and autism spectrum disorder (ASD) is challenging due to the heterogeneous nature of ASD. Here, we analyzed the microbial and clinical characteristics of individuals with ASD using enterotypes. A total of 456 individuals participated in the study, including 249 participants with ASD, 106 typically developing siblings, and 101 controls. The alpha and beta diversities of the ASD, sibling, and control groups did not show significant differences. Analysis revealed a negative association between the Bifidobacterium longum group and the Childhood Autism Rating Scale, as well as a negative association between the Streptococcus salivarus group and the Social Responsiveness Scale (SRS) within the ASD group. When clustered based on microbial composition, participants with ASD exhibited two distinct enterotypes, E1 and E2. In the E2 group, the SRS score was significantly higher, and the Vineland Adaptive Behavior Scale score was significantly lower compared to the E1 group. Machine learning results indicated that the microbial species predicting SRS scores were distinct between the two enterotypes. Our study suggests that the microbial composition in individuals with ASD exhibits considerable variability, and the patterns of associations between the gut microbiome and clinical symptoms may vary depending on the enterotype.

Advanced Therapy medicinal products for autologous chondrocytes and comparison of regulatory systems in target countries.

Introduction: Autologous chondrocytes (ACs) are Human cell/tissue-based products used for the treatment of joint cartilage defects. Regulatory agencies have established regulations related to ACs to ensure their safety and efficacy. This study investigated the status and characteristics of ACs approved worldwide. Furthermore, the AC-related regulations were compared by country to provide reference materials for the development of product approval procedures. Methods: This study reviewed the current status of global AC products over the past 20 years by referring to the AC approval list provided on the International Society for Cell & Gene Therapy (ISCT) website. Based on the review report provided by the regulatory agencies that approved the products, major nonclinical/clinical data and product characteristics were reviewed; and the classification and definition of ACs and the approval review procedures were compared through the regulatory agencies' websites. The development status of ACs was also analyzed using a clinical trial registration site. Results: Eight ACs were approved during the study period in Europe, the US, Japan, Australia, and Korea. Two products were withdrawn owing to marketability problems. Human cell/tissue-based products in each country are classified and defined distinguished from biopharmaceuticals, but the approval process for both products is the same. The approval period differs by country, with an average of 282.4 days and the shortest being in Korea (115 days). On Clinical Trials.gov, we screened 46 clinical trials related to ACs, which were conducted in Europe (41%), Korea (20%), and the US (17%). The knee accounted for the largest portion of the indication (37/46, 80%), followed by the ankle or hip joints. Measurements of improvements in function and pain were the main endpoints used to evaluate the efficacy of ACs. Observational studies were conducted to confirm the long-term safety of these products. Conclusions: This is the first study comparing the current status and characteristics of globally approved AC products, as well as their classification and definition by country. In the past two decades, clinical trials have been conducted on the application of ACs in tissue engineering to treat joint cartilage defects. ACs are expected to be used for the treatment of cartilage defect diseases.

Protein Stability of Pyruvate Kinase Isozyme M2 Is Mediated by HAUSP.

The ubiquitin-proteasome system (UPS) is responsible for proteasomal degradation, regulating the half-life of the protein. Deubiquitinating enzymes (DUBs) are components of the UPS and inhibit degradation by removing ubiquitins from protein substrates. Herpesvirus-associated ubiquitin-specific protease (HAUSP) is one such deubiquitinating enzyme and has been closely associated with tumor development. In a previous study, we isolated putative HAUSP binding substrates by two-dimensional electrophoresis (2-DE) and identified them by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF/MS) analysis. The analysis showed that pyruvate kinase isoenzyme M2 (PKM2) was likely to be one of the substrates for HAUSP. Further study revealed that PKM2 binds to HAUSP, confirming the interaction between these proteins, and that PKM2 possesses the putative HAUSP binding motif, E or P/AXXS. Therefore, we generated mutant forms of PKM2 S57A, S97A, and S346A, and found that S57A had less binding affinity. In a previous study, we demonstrated that PKM2 is regulated by the UPS, and that HAUSP- as a DUB-acted on PKM2, thus siRNA for HAUSP increases PKM2 ubiquitination. Our present study newly highlights the direct interaction between HAUSP and PKM2.

Is gender still a predisposing factor in contrast-media associated adverse drug reactions? A systematic review and meta-analysis of randomized trials and observational studies.

OBJECTIVE: To evaluate the role of gender as a risk factor for developing contrast media-associated adverse drug reactions (CM-ADRs) by comparing the incidence of CM-ADR between male and female patients according to study design, ADR type, and computed tomography (CT) examination. MATERIAL AND METHODS: We systematically searched three electronic databases for eligible studies. In the studies included (n=18), we assessed effect estimates of the relative incidence of CM-ADR, analysed by experimental design, ADR type and CT examination. This was calculated by using a random effects model if clinical conditions showed heterogeneity; otherwise, a fixed effects model was used. RESULTS: We identified 10,776 patients administered CM. According to the designs, studies were classified into randomised controlled trials (RCTs) and observational studies. Results were as follows: risk ratio (RR)=1.07 (95% confidence interval (CI): 0.79-1.46, P=0.66) for RCTs, and RR=0.77 (95% CI: 0.58-1.04, P=0.09) for observational studies. The results of analysis according to ADR type and for undergoing CT demonstrated that the incidence of CM-ADR did not differ between males and females. CONCLUSIONS: We found no significant difference in the incidence of CM-ADRs between male and female patients according to study design, ADR type, or CT examination. Future studies to determine why gender has shown different roles as a risk factor between CM-ADRs and non-CM ADRs are needed.

Addressing the academic gap between 4- and 6-year pharmacy programs in South Korea.

OBJECTIVE: To address the academic gap (or lack of adequate training and programs) between 4- and 6-year pharmacy programs and suggest methods for reducing this gap and to evaluate pharmacists' perceptions of preceptorship. METHODS: We surveyed a convenience sample of 200 community pharmacists who graduated from a 4-year program who were participating in a continuing education program for clinical pharmacy as organized by the Daejeon branch of the Korea Pharmaceutical Association in 2011. Twenty-one questions were asked about the academic gap, needs for an education program, preceptorship, and medication therapy management services. International precedents were examined through a literature review to glean ideas of how to bridge the academic gap between the 4- and 6-year programs. RESULTS: In total, 132 pharmacists answered the survey (return rate=66.0%). The survey findings included problems caused by the academic gap, high need for an adequate education program, low acceptability of preceptorship, and the possibility of medication therapy management services. US-based, non-traditional PharmD programs and new curriculum-support training in Japan provided examples of how the academic gap has been successfully bridged. CONCLUSION: Nationwide efforts and government support are urgently required to close the academic gap, and experiential education should be included in transitional programs for 4-year pharmacy program pharmacists.