Background: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. Methods: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. Results: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events. Conclusion The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

Purpose: There are few reports on outcomes following surgical repair of recurrent rectal prolapse. The purpose of this study was to examine surgical outcomes for recurrent rectal prolapse. Methods: We conducted a multicenter retrospective study of patients who underwent surgery for recurrent rectal prolapse. This study used data collected by the Korean Anorectal Physiology and Pelvic Floor Disorder Study Group. Results: A total of 166 patients who underwent surgery for recurrent rectal prolapse were registered retrospectively between 2011 and 2016 in 8 referral hospitals. Among them, 153 patients were finally enrolled, excluding 13 patients who were not followed up postoperatively. Median follow-up duration was 40 months (range, 0.2–129.3 months). Methods of surgical repair for recurrent rectal prolapse included perineal approach (n = 96) and abdominal approach (n = 57). Postoperative complications occurred in 16 patients (10.5%). There was no significant difference in complication rate between perineal and abdominal approach groups. While patients who underwent the perineal approach were older and more fragile, patients who underwent the abdominal approach had longer operation time and admission days (P < 0.05). Overall, 29 patients (19.0%) showed re-recurrence after surgery. Among variables, none affected the re-recurrence. Conclusion For the recurrent rectal prolapse, the perineal approach is used for the old and fragile patients. The postoperative complications and re-recurrence rate between perineal and abdominal approach were not different significantly. No factor including surgical method affected re-recurrence for recurrent rectal prolapse.

Currently, antimicrobial resistance (AMR) is a major threat to global public health. The antimicrobial stewardship program (ASP) has been proposed as an important approach to overcome this crisis. ASP supports the optimal use of antimicrobials, including appropriate dosing decisions, administration duration, and administration routes. In Korea, efforts are being made to overcome AMR using ASPs as a national policy. The current study aimed to develop core elements of ASP that could be introduced in domestic medical facilities. A Delphi survey was conducted twice to select the core elements through expert consensus.The core elements for implementing the ASP included (1) leadership commitment, (2) operating system, (3) action, (4) tracking, (5) reporting, and (6) education. To ensure these core elements are present at medical facilities, multiple departments must collaborate as teams for ASP operations. Establishing a reimbursement system and a workforce for ASPs are prerequisites for implementing ASPs. To ensure that ASP core elements are actively implemented in medical facilities, it is necessary to provide financial support for ASPs in medical facilities, nurture the healthcare workforce in performing ASPs, apply the core elements to healthcare accreditation, and provide incentives to medical facilities by quality evaluation criteria.

Objectives: . Facial nerve monitoring (FNM) can be used to identify the facial nerve, to obtain information regarding its course, and to evaluate its status during parotidectomy. However, there has been disagreement regarding the efficacy of FNM in reducing the incidence of facial nerve palsy during parotid surgery. Therefore, instead of using electromyography (EMG) to identify the location and state of the facial nerve, we applied an intraoperative neuromonitoring (IONM) system using a surface pressure sensor to detect facial muscle twitching. The objective of this study was to investigate the feasibility of using the IONM system with a surface pressure sensor to detect facial muscle twitching during parotidectomy. Methods: . We evaluated the stimulus thresholds for the detection of muscle twitching in the orbicularis oris and orbicularis oculi, as well as the amplitude and latency of EMG and the surface pressure sensor in 13 facial nerves of seven rabbits, using the same stimulus intensity. Results: . The surface pressure sensor detected muscle twitching in the orbicularis oris and orbicularis oculi in response to a stimulation of 0.1 mA in all 13 facial nerves. The stimulus threshold did not differ between the surface pressure sensor and EMG. Conclusion . The application of IONM using a surface pressure sensor during parotidectomy is noninvasive, reliable, and feasible. Therefore, the IONM system with a surface pressure sensor to measure facial muscle twitching may be an alternative to EMG for verifying the status of the facial nerve.

Alzheimer’s disease (AD) is a progressive and most frequently diagnosed neurodegenerative disorder. However, there is still no drug preventing the progress of this disorder. β-Amyrin, an ingredient of the surface wax of tomato fruit and dandelion coffee, is previously reported to ameliorate memory impairment induced by cholinergic dysfunction. Therefore, we tested whether β-amyrin can prevent AD-like pathology. β-Amyrin blocked amyloid β (Aβ)-induced long-term potentiation (LTP) impairment in the hippocampal slices. Moreover, β-amyrin improved Aβ-induced suppression of phosphatidylinositol-3-kinase (PI3K)/Akt signaling.LY294002, a PI3K inhibitor, blocked the effect of β-amyrin on Aβ-induced LTP impairment. In in vivo experiments, we observed that β-amyrin ameliorated object recognition memory deficit in Aβ-injected AD mice model. Moreover, neurogenesis impairments induced by Aβ was improved by β-amyrin treatment. Taken together, β-amyrin might be a good candidate of treatment or supplement for AD patients.

Tryptamines are monoamine alkaloids with hallucinogenic properties and are widely abused worldwide. To hasten the regulations of novel substances and predict their abuse potential, we designed and synthesized four novel synthetic tryptamine analogs: Pyrrolidino tryptamine hydrochloride (PYT HCl), Piperidino tryptamine hydrochloride (PIT HCl), N,N-dibutyl tryptamine hydrochloride (DBT HCl), and 2-Methyl tryptamine hydrochloride (2-MT HCl). Then, we evaluated their rewarding and reinforcing effects using the conditioned place preference (CPP) and self-administration (SA) paradigms. We conducted an open field test (OFT) to deter-mine the effects of the novel compounds on locomotor activity. A head-twitch response (HTR) was also performed to characterize their hallucinogenic properties. Lastly, we examined the effects of the compounds on 5-HTR1a and 5-HTR2a in the prefrontal cortex using a quantitative real-time polymerase chain reaction (qRT-PCR) assay. None of the compounds induced CPP in mice or initiated SA in rats. PYT HCl and PIT HCl reduced the locomotor activity and elevated the 5-HTR1a mRNA levels in mice. Acute and repeated treatment with the novel tryptamines elicited HTR in mice. Furthermore, a drug challenge involving a 7-day abstinence from drug use produced higher HTR than acute and repeated treatments. Both the acute treatment and drug challenge increased the 5-HTR2a mRNA levels. Ketanserin blocked the induced HTR. Taken together, the findings suggest that PYT HCl, PIT HCl, DBT HCl, and 2-MT HCl produce hallucinogenic effects via 5-HTR2a stimulation, but may have low abuse potential.

Objectives: . The loss of signal during intraoperative neuromonitoring (IONM) using electromyography (EMG) in thyroidectomy is one of the biggest problems. We have developed a novel IONM system with an endotracheal tube (ETT) with an attached pressure sensor instead of EMG to detect laryngeal twitching. The aim of the present study was to investigate the feasibility and reliability of this novel IONM system using an ETT with pressure sensor during thyroidectomy in a porcine model. Methods: . We developed an ETT-attached pressure sensor that uses the piezoelectric effect to measure laryngeal muscle twitching. Stimulus thresholds, amplitude, and latency of laryngeal twitching evaluated using the pressure sensor were compared to those measured using transcartilage needle EMG. The measured amplitude changes by EMG and the pressure sensor during recurrent laryngeal nerve (RLN) traction injury were compared. Results: . No significant differences in stimulus threshold intensity between EMG and the pressure sensor were observed. The EMG amplitude detected at 0.3 mA, increased with increasing stimulus intensity. When the stimulus was more than 1.0 mA, the amplitude showed a plateau. In a RLN traction injury experiment, the EMG amplitude did not recover even 20 minutes after stopping RLN traction. However, the pressure sensor showed a mostly recovery. Conclusion . The change in amplitude due to stimulation of the pressure sensor showed a pattern similar to EMG. Pressure sensors can be feasibly and reliably used for RLN traction injury prediction, RLN identification, and preservation through the detection of laryngeal muscle twitching. Our novel IONM system that uses an ETT with an attached pressure sensor to measure the change of surface pressure can be an alternative to EMG in the future.

PURPOSE: Survival after liver transplantation (LT) has improved over the years, but infection is still a major complication. We aimed to identify the characteristics of bacterial infections in pediatric LT recipients. METHODS: This study is a retrospective review of 189 consecutive children undergoing LT between 2000 and 2015 at a single center. In this study, the incidence of infection was determined for the following periods: within 1 month, between 1–5 months, and between 6–12 months. Patients who underwent liver transplants more than once or multiple organ transplants were excluded. RESULTS: All patients had received postoperative antibiotic for 3 days. Only the maintenance immunosuppression with oral tacrolimus and steroids were performed. As a result, 132 bacterial infections developed in 87 (46.0%) patients (0.70 events per person-year). Bacterial infections occurred most frequently within the first month (n=84, 63.6%) after LT. In the pathogens, Staphylococcus aureus (15.2%), Enterococcus species (15.2%), and Klebsiella species (13.6%) were most common. Regarding the organ infected, bloodstream was most common (n=39, 29.5%), followed by peritoneum (n=28, 21.2%), urinary tract (n=25, 18.9%), and lungs (n=20, 15.2%). We changed prophylactic antibiotics from ampicillin-sulbactam to piperacillin-tazobactam at 2011, October, there were no significant effects in the prevalence of antibiotics resistant bacterial infections. The 1-year mortality was 9.0% (n=17), in which 41.2% (n=7) was attributable to bacterial infection; septicemia (n=4), pneumonia (n=2), and peritonitis (n=1). CONCLUSIONS: The incidence and type of bacterial infectious complications after LT in pediatric patients were similar to those of previous studies. Bacterial complications affecting mortality occur within 6 months after transplantation, so proper prophylaxis and treatment in this period may improve the prognosis of LT.
Anti-Bacterial Agents ; Bacterial Infections ; Child ; Enterococcus ; Humans ; Immunosuppression ; Incidence ; Klebsiella ; Korea ; Liver Transplantation ; Liver ; Lung ; Mortality ; Peritoneum ; Peritonitis ; Pneumonia ; Prevalence ; Prognosis ; Retrospective Studies ; Sepsis ; Staphylococcus aureus ; Steroids ; Tacrolimus ; Transplants ; Urinary Tract

PURPOSE: The purpose of this study was to describe the long-term effects of stenting in patients with hepatic venous outflow obstruction (HVOO), who underwent living donor liver transplantation (LDLT). METHODS: Between January 2000 and December 2009, 622 adult patients underwent LDLT at our hospital, and of these patients, 21 (3.3%) were diagnosed with HVOO; among these patients, 17 underwent stenting. The patients were divided into early or late groups according to the time of their HVOO diagnoses (cutoff: 60 days after liver transplantation). RESULTS: The median follow-up period was 54.2 months (range, 0.5–192.4 months). Stent insertion was successful in 8 of 10 patients in the early group and 6 of 7 in the late group. The 5-year primary patency rates were 46% and 20%, respectively. In both groups, patients with recurrent HVOO at the beginning showed kinking confirmed by venography. Patients who carried their stents for more than 3 years maintained long-term patency. There was no significant difference in spleen size between groups; however, when the groups were compared according to whether they maintained patency, spleens tended to be smaller in the patency-maintained group. CONCLUSION: Unlike stenosis, if kinking is confirmed on venography, stenting is not feasible in the long term for patients with LDLT.
Adult ; Budd-Chiari Syndrome ; Constriction, Pathologic ; Diagnosis ; Follow-Up Studies ; Hepatic Veins* ; Humans ; Liver Transplantation* ; Liver* ; Living Donors* ; Phlebography ; Spleen ; Stents*

Artemisia capillaris Thunberg is a medicinal plant used as a traditional medicine in many cultures. It is an effective remedy for liver problems including hepatitis. Recent pharmacological reports have indicated that Artemisia species can exert various neurological effects. Previously, we reported a memory-enhancing effect of Artemisia species. However, the mechanisms underlying the neuroprotective effect of A. capillaris (AC) are still unknown. In the present study, we investigated the effect of an ethanol extract of AC on ischemic brain injury in a mouse model of transient forebrain ischemia. The mice were treated with AC for seven days, beginning one day before induction of transient forebrain ischemia. Behavioral deficits were investigated using the Y-maze. Nissl and Fluoro-jade B staining were used to indicate the site of injury. To determine the underlying mechanisms for the drug, we measured acetylcholinesterase activity. AC (200 mg·kg) treatment reduced transient forebrain ischemia-induced neuronal cell death in the hippocampal CA1 region. The AC-treated group also showed significant amelioration in the spontaneous alternation of the Y-maze test performance, compared to that in the untreated transient forebrain ischemia group. Moreover, AC treatment showed a concentration-dependent inhibitory effect on acetylcholinesterase activity in vitro. Finally, the effect of AC on forebrain ischemia was blocked by mecamylamine, a nonselective nicotinic acetylcholine receptor antagonist. Our results suggested that in a model of forebrain ischemia, AC protected against neuronal death through the activation of nicotinic acetylcholine receptors.
Acetylcholinesterase ; metabolism ; Animals ; Artemisia ; Cell Death ; drug effects ; Cholinergic Antagonists ; pharmacology ; Disease Models, Animal ; Ethanol ; chemistry ; Hippocampus ; pathology ; physiopathology ; Ischemic Attack, Transient ; drug therapy ; pathology ; physiopathology ; Male ; Mecamylamine ; pharmacology ; Memory ; drug effects ; Mice ; Mice, Inbred C57BL ; Models, Neurological ; Neuroprotective Agents ; administration & dosage ; pharmacology ; Phytotherapy ; Plant Components, Aerial ; chemistry ; Plant Extracts ; administration & dosage ; pharmacology ; Receptors, Cholinergic ; metabolism