SYNCRIP controls miR-137 and striatal learning in animal models of methamphetamine abstinence

Abstinence from prolonged psychostimulant use prompts stimulant withdrawal syndrome. Molecular adaptations within the dorsal striatum have been considered the main hallmark of stimulant abstinence. Here we explored striatal miRNA–target interaction and its impact on circulating miRNA marker as well as behavioral dysfunctions in methamphetamine (MA) abstinence. We conducted miRNA sequencing and profiling in the nonhuman primate model of MA abstinence, followed by miRNA qPCR, LC–MS/MS proteomics, immunoassays, and behavior tests in mice. In nonhuman primates, MA abstinence triggered a lasting upregulation of miR-137 in the dorsal striatum but a simultaneous downregulation of circulating miR-137. In mice, aberrant increase in striatal miR-137-dependent inhibition of SYNCRIP essentially mediated the MA abstinence-induced reduction of circulating miR-137. Pathway modeling through experimental deduction illustrated that the MA abstinence-mediated downregulation of circulating miR-137 was caused by reduction of SYNCRIP-dependent miRNA sorting into the exosomes in the dorsal striatum. Furthermore, diminished SYNCRIP in the dorsal striatum was necessary for MA abstinence-induced behavioral bias towards egocentric spatial learning. Taken together, our data revealed circulating miR-137 as a potential blood-based marker that could reflect MA abstinence-dependent changes in striatal miR-137/SYNCRIP axis, and striatal SYNCRIP as a potential therapeutic target for striatum-associated cognitive dysfunction by MA withdrawal syndrome.     

Role of adjuvant chemoradiotherapy and chemotherapy in patients with resected gallbladder carcinoma: a multi-institutional analysis (KROG 19-04)

Objective:The effectiveness of adjuvant treatments for resected gallbladder carcinoma (GBC) has remained unclear due to lack of randomized controlled trials; thus, the aim of present study was to evaluate the role of adjuvant treatments, including chemoradiotherapy (CRT) and/or chemotherapy (CTx), in patients with resected GBC.Methods:A total of 733 GBC patients who received curative-intent surgical resection were identified in a multi-institutional database. Of 733 patients, 372 (50.8%) did not receive adjuvant treatment, whereas 215 (29.3%) and 146 (19.9%) received adjuvant CTx and CRT, respectively. The locoregional recurrence-free survival (LRFS), recurrence-free survival (RFS), and overall survival (OS) of the adjuvant treatment groups were compared according to tumor stage (stage II vs. stage III–IV).Results:In stage II disease (n = 381), the 5-year LRFS, RFS, and OS were not significantly different among the no-adjuvant therapy, CTx, and CRT groups, and positive resection margin, presence of perineural invasion, and Nx classification were consistently associated with worse LRFS, RFS, and OS in the multivariate analysis (P < 0.05). For stage III–IV (n = 352), the CRT group had significantly higher 5-year LRFS, RFS, and OS than the no-adjuvant therapy and CTx groups (67.8%, 45.2%, and 56.9%; 37.9%, 28.8%, and 35.4%; and 45.0%, 30.0%, and 45.7%, respectively) (P < 0.05).Conclusions:CRT has value as adjuvant treatment for resected GBC with stage III–IV disease. Further study is needed for stage II disease with high-risk features.     

Children in the Blind Spot of Social Medical Concerns: Supporting Children with Mentally Ill Parents in Korea

Community Mental Health Journal - Children whose parents have mental disorders are more likely to be vulnerable and exposed to an environment where they may not be cared for by parents or guardians...     

Study of cobalt doping control via various routes in thoroughbred horses

Cobalt is a substance that has been abused for athletic performance enhancement and has thus been prohibited by human and animal sports doping control authorities. However, because cobalt is present in humans and animals as a trace element, a certain level of cobalt is naturally present in their excretions. In the racing industry, cobalt is a controlled substance with a threshold concentration specified by the International Agreement on Breeding, Racing and Wagering (IABRW) for international harmonization. Due to environmental and feed consumption differences among countries, regional cobalt concentration trends should be evaluated before cobalt testing is introduced. In this study, we conducted a preliminary evaluation of the urinary concentration of cobalt among a population of racehorses in Korea using inductively coupled plasma mass spectrometry (ICP-MS) analysis, followed by analysis of the urinary release of cobalt after the administration of cobalt chloride in various situations. The normal distribution for the Korea-based racehorses was used to determine a urine concentration limit (96.5 ng/ml, risk factor of 1 in 10,000). After the intravenous (IV) administration of CoCl₂, the initial elimination of cobalt was rapid. A high concentration (over 2,000 ng/ml) and a slow excretion pattern were observed during the final 2 weeks of the 3-week observation period. When CoCl₂ was administered orally, maximum concentration (C_max, 92–992 ng/ml) was observed at 6–8 h.     

Intracardiac Eustachian Valve Cyst in an Adult Detected with Other Cardiac Anomalies: Usefulness of Multidetector CT in Diagnosis

We present an unusual case of an intracardiac Eustachian valve cyst observed concurrently with atresia of the coronary sinus ostium, a persistent left superior vena cava (LSVC) and a bicuspid aortic valve. There have been several echocardiographic reports of Eustachian valve cysts; however, there is no report of multidetector computed tomography (MDCT) findings related to a Eustachian valve cyst. Recently, we observed a Eustachian valve cyst diagnosed on MDCT showing a hypodense cyst at the characteristic location of the Eustachian valve (the junction of the right atrium and inferior vena cava). MDCT also demonstrated additional cardiovascular anomalies including atresia of the coronary sinus ostium and a persistent LSVC and bicuspid aortic valve.