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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. Methamphetamine abstinence persistently enhances the psychiatric risk gene miR-137 in the dorsal striatum, which then suppresses the expression of SYNCRIP to aberrantly diminish circulating miR-137 and promote egocentric spatial learning. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: The number of young patients with hematological disease requiring total hip arthroplasty (THA) is expected to increase. We aimed to investigate the long-term THA outcomes in patients with osteonecrosis of the femoral head (ONFH) following allogeneic bone marrow transplantation (BMT) for hematological disease.Methods: All patients who underwent THA for osteonecrosis after BMT from 1997 to 2012 were identified at 2 institutions. Using propensity scores, 75 THAs in 45 patients were matched for age, gender, body mass index, American Society of Anesthesiologists score, and year of surgery with 75 THAs in 58 patients with idiopathic ONFH without a history of hematological disease (1:1 ratio). The mean age at surgery was 36.7 years and 52% were men. Clinical and radiographic evaluations were performed and clinical scores were obtained at last follow-up. Kaplan-Meier analyses were used to compare survivorship.Results: At a mean follow-up of 10.6 ± 3.5 years, clinical, radiographic, and survivorship outcomes, and the Harris hip scores were similar between both groups. The 13-year survivorship for all-cause revision was 93.4% for the BMT group and 95% for the control group (P = .928). No significant differences were observed between groups in the rates of reoperation (4% vs 5.3%, P = 1.000), 90-day readmission (all 5.3%), or overall mortality (4.4% vs 1.7%, P = .681). No hips had periprosthetic joint infection or septic loosening in either group. Osteolysis occurred in none of the BMT patients and in 2 hips (2.7%) of the control patients (P = .497).Conclusion: This large cohort multicenter survey at 11-year follow-up shows that contemporary cementless THA in young hematological disease patients after allogeneic BMT is not associated with a higher risk for surgical complications, revision, reoperation, readmission, and mortality compared to a matched cohort of idiopathic ONFH. [ABSTRACT FROM AUTHOR]

Highlights • Propose a new low-cost Hexapod (or Stewart platform) design for the performance evaluation of industrial robots. • Suggest simple calibration process utilizing magnetic-ball-and-socket joints. • Create a corresponding software for the hexapod kinematics and its visualization. • The experiments show the average root mean square (RMS) position accuracy error of the proposed device is less than 0.186 mm and the average of angular accuracy error is less than 0.160°. Abstract This paper presents a six degree-of-freedom (DOF) real-time motion tracking system of measuring the position and the orientation for industrial robots in three-dimensional (3D) space. The proposed system is based on a typical Stewart platform design and utilizes six low-cost displacement sensors to monitor the motion of the Stewart platform. The advantage of the proposed system is its simple calibration and easy accessibility; the magnetic ball-and-socket joints used for rotational joints. With special measurement tools, the center of rotation of all twelve joints can be measured in 3D space at a glance. Following more than fifty measurements, the average root mean square (RMS) position accuracy error of the proposed device is less than 0.186 mm and the average of angular accuracy error is less than 0.160 °, making it suitable for monitoring the performance of industrial robot. A commercial robot is also tested by the proposed system to verify its usefulness. [ABSTRACT FROM AUTHOR]

Background: A contralateral normal hip joint has been often used as a reference standard in preoperative planning and intraoperative assessment of hip arthroplasty, with the assumption that bilateral hip joint geometries have no significant differences. However, one previous study using analog measurements on hardcopy films reported significant bilateral variation in hip joint geometry. We therefore investigated the level of agreement between the right and left hips for each measurement and determined index values and the range of normal bilateral variations.Methods: We assessed 100 standard anteroposterior radiographs of the pelvis in this study. Two independent observers measured the actual value of femoral head diameter, location of the femoral head center, acetabular offset, femoral offset, hip offset, greater trochanteric height, neck-shaft angle, medullary canal diameter, and proximal femoral diameter. Intraclass correlation coefficients (ICCs) and values of mean difference were calculated for each measurement.Results: The results demonstrated perfect agreement (ICC >0.8) between the right and left hips for most parameters and substantial agreement for greater trochanteric height (ICC = 0.735) and femoral offset (ICC = 0.773). The mean difference and standard deviation in the measurement between the right and left hips for the location of the femoral head center and the acetabular offset were 0.60 ± 0.48 mm and 0.42 ± 0.30 mm, respectively.Conclusion: Hip joint geometry is not influenced by side. In hip arthroplasty, a contralateral normal hip can be reliably used as a guide for preoperative planning using measurement tools on a picture archiving and communication system. [ABSTRACT FROM AUTHOR]

Background: Cryptotanshinone (CT), a major tanshinone found in Salvia miltiorrhiza Bunge (Lamiaceae), has various pharmacological effects such as antitumor, anti-inflammatory, and antioxidant properties. Despite its well-documented benefits in a wide range of diseases, the effect of CT on adipocyte differentiation has not been well characterized.Purpose: The present study was designed to determine the in vitro anti-adipogenic effect and underlying molecular mechanisms of CT using 3T3-L1 murine pre-adipocytes.Methods: We measured the levels of intracellular triglyceride accumulation and mRNA and protein expression of key adipogenic transcription factors and their target genes.Results: Treatment with CT drastically reduced lipid accumulation in a dose- and time-dependent manner. Molecular assays showed that CT effectively suppressed the expression of C/EBPβ, C/EBPα, and PPARγ and of their target adipocyte-specific genes aP2, adiponectin, and GLUT4 but activated the expression of anti-adipogenic genes such as GATA2, CHOP10, and TNF-α. CT treatment also inhibited the phosphorylation of STAT3 in the early phase of adipogenesis. A small-interfering-RNA-mediated knock-down of STAT3 potentiated the anti-adipogenic effect of CT.Conclusion: Taken together, the results suggest that CT may be a good anti-adipogenic candidate because it regulates STAT3 during early adipogenesis. [ABSTRACT FROM AUTHOR]

Abstract: We determined whether a PACS-based method (head-lesser trochanter distance [HLD]) better equalized leg length discrepancy (LLD) after primary THA than a conventional method. We retrospectively reviewed 312 patients (379 hips) with osteonecrosis or primary osteoarthritis who underwent primary cementless THA: 198 patients (240 hips) underwent THA using the HLD method, while the conventional group consisted of 114 patients (139 hips) in whom we measured with the method of McGee and Scott. We then compared the LLDs in the two groups. We observed no difference in the mean postoperative LLD. A higher percentage of patients in the HLD group had an LLD less than 6mm: 81% vs 68% hips, respectively. HLD method decreases the possibility of an LLD over 6mm after THA. [Copyright &y& Elsevier]

Abstract: Methicillin-resistant Staphylococcus aureus (MRSA) are spread among infected patients, with infection rates increasing at an alarming rate. Furthermore, increased resistance to antibiotics has resulted in serious challenges in the treatment of infectious diseases worldwide. Under the selection pressure of exposure to antibiotics, microorganisms evolve to survive against the new conditions imposed by therapy. Therefore, there exists a need to develop alternative natural or combination drug therapies. Curcumin (CCM), a natural polyphenolic flavonoid isolated from the rhizome of a plant, Curcuma longa Linné., has been found to possess many beneficial biological activities. The aim of this study was to investigate the synergistic effect of curcumin and antibiotics as well as to determine the antibacterial activity of CCM against specific MRSA strains. The antibacterial activity of CCM was assessed by the broth microdilution method (by calculating the minimal inhibitory concentration [MIC]), checkerboard dilution test, and time-kill assay. Antimicrobial activity of CCM was observed against all tested strains. The MICs of CCM against 10 strains of S. aureus ranged from 125 to 250μg/ml. In the checkerboard test, CCM markedly reduced the MICs of the antibiotics oxacillin (OXI), ampicillin (AMP), ciprofloxacin (CIP), and norfloxacin (NOR) used against MRSA. The time-kill curves showed that a combined CCM and OXI treatment reduced the bacterial counts below the lowest detectable limit after 24h. This study suggested that CCM reduced the MICs of several antibiotics tested, notably of OXI, AMP, CIP, and NOR, and that CCM in combination with antibiotics could lead to the development of new combination of antibiotics against MRSA infection. [Copyright &y& Elsevier]

Abstract: Objective: Epigastric pain management following endoscopic submucosal dissection is an important consideration. This study aimed to investigate the utility and safety of fentanyl patches for pain relief after the procedure. Methods: Patients who were scheduled to undergo endoscopic submucosal dissection were prospectively randomised to either a transdermal fentanyl patch group or a placebo control group. An additional pethidine was intravenously administered when pain developed and a numerical rating scale was used to evaluate both pre- and post-procedural pain. Results: One hundred and ten patients were randomly assigned to receive either a 12mcg/h fentanyl patch or a control patch on the night before the procedure. The fentanyl patch group had significantly lower pain scores immediately following the procedure (mean, 5.17 vs. 4.26, p =0.030). Maximal pain scores during the first 24h (5.43 vs. 4.46, p =0.038) and pain scores on the day after the procedure (2.98 vs. 1.20, p <0.001) were also lower in the fentanyl patch group. In addition, the fentanyl patch group required a significantly lower dose of pethidine for pain management (24.54 vs. 11.25, p =0.004). Conclusions: The application of a transdermal fentanyl patch is an effective, convenient, and safe method to control epigastric pain after endoscopic submucosal dissection. [Copyright &y& Elsevier]

Abstract: Paraquat (PQ) is not only widely used as a potent herbicide but also causes severe fatality to humans around the world due to accidental or intentional ingestion. Silymarin is a well-known phytochemical whose multi-functional effects in humans include anti-oxidant, anti-inflammatory and anti-cancer activities. The efficacy of silymarin in protecting against PQ-induced cytotoxicity is unknown. This study investigated the potential role of silymarin against PQ-induced oxidative stress on human A549 adenocarcinoma cell line. Colorimetric-based viability assay, determination of reactive oxygen species, cell damage assay based on lactate dehydrogense retention, anti-oxidant enzyme assay, Western blot and quantitative reverse transcription-polymerase chain reaction analyses were done. Our data revealed that silymarin could dramatically prevent cell toxicity, and reduce the LDH retention induced by PQ on A549 cell line. Silymarin acted as a potent cytoprotective effector through the effective induction of anti-oxidant related genes, including Nrf2, NQO1 and HO-1, in the presence of PQ. The induction of the Nrf2, HO-1 and NQO1 genes was first evident after 3h. The data indicate the potential of silymarin in alleviating PQ intoxication. [Copyright &y& Elsevier]

The Krüppel-like zinc finger transcription factor, Glis3, has been associated with neonatal diabetes in humans and mice, and implicated in the regulation of pancreatic β-cell generation. However, its precise function in the development of pancreatic β-cells has not yet been elucidated. In this study, we provide evidence that Glis3 regulates Neurogenin 3 (Ngn3) through its distal promoter region. Previous studies showed that the distal region and proximal region of Ngn3 promoter contains various transcription binding sites, including binding sites for pancreatic and duodenal homeobox 1 (Pdx1), Hnf1β and Hnf6. Interestingly, putative Glis3 binding sites (Glis3BS) were found in the distal region of Ngn3 promoter close to the Hnf6 binding sites. This suggested that along with Hnf6, Glis3 may also be involved in the regulation of Ngn3 expression. This hypothesis is supported by data showing that Glis3 can bind to the Ngn3 promoter directly and activate Ngn3 transcriptional activity. Additionally, Glis3 can interact directly with Hnf6 in vitro and in vivo. The amino-terminus in Glis3 and the homeodomain of Hnf6 are critical for this interaction. These data suggest that crosstalk between Glis3 and Hnf6 may play an important role in the regulation of Ngn3 during pancreatic endocrine progenitor cell specification and development. [ABSTRACT FROM AUTHOR]

Abstract: A significant overlap between childhood mood disorders and many aspects of attention deficit hyperactivity disorder (ADHD) has been established. High rates of co-occurrence, familial aggregation, and more severe clinical manifestations of the illnesses when they are comorbid suggest that common genetic and environmental factors may contribute to the development of both disorders. Research on the co-occurrence of childhood ADHD and mood disorders in childhood has been conducted. We retrospectively investigated childhood ADHD features in adults with mood disorders. Childhood ADHD features were measured with the Korean version of the Wender Utah Rating Scale (WURS). The sample consisted of 1305 subjects: 108 subjects were diagnosed with bipolar disorder type I, 41 with bipolar disorder type II, 101 with major depressive disorder, and 1055 served as normal controls. We compared total WURS scores as well as scores on 3 factors (impulsivity, inattention, and mood instability and anxiety) among the 4 different diagnostic groups. The 4 groups differed significantly from one another on all scores. The group with bipolar disorder type II obtained the highest total scores on the WURS. The impulsivity and inattention associated with childhood ADHD were more significantly related to bipolar disorder type II than with bipolar disorder type I. The mood instability and anxiety associated with childhood ADHD seem to be significantly related to major depressive disorder in adulthood. In conclusion, multifactorial childhood ADHD features were associated with mood disorders of adulthood. [Copyright &y& Elsevier]

Abstract: Paraquat (PQ) is the third most extensively used herbicide in the world, causing thousands of deaths due to accidental or intentional self-poisoning in developing countries. Although many therapeutic treatments for PQ-induced poisonings have been proposed and developed, the efficacy of these treatments is still poor and requires further investigation. Methylprednisolone (trade name Solumedrol, hereinafter MP) is a widely used steroid for the treatment of various diseases but the function of MP has not yet been studied in the context of PQ-induced intoxication. The aim of this study was to determine if MP can ameliorate PQ-induced toxicity in an alveolar A549 cell line by inducing ATP-dependent transporter P-glycoprotein (P-gp) expression. P-gp expression and activity in the PQ-treated A549 cell line were enhanced by MP treatment and cytotoxicity by PQ was dramatically decreased. We also found that MP per se or together with PQ induced P-gp expression by both Western blot and qRT-PCR analyses. In addition, induced P-gp transporter was shown to improve the efflux effect on PQ-treated A549 cell lines as was demonstrated using the Calcein-AM fluorescence accumulation assay. In summary, MP induces the transmembrane ATP-dependent transporter P-gp expression, which greatly improves PQ-treated A549 cell viability, reduces accumulation of intracellular PQ and prevents PQ induced cytotoxicity but it should be further evaluated in in vivo studies. [Copyright &y& Elsevier]

Background: Increased visceral adiposity is a key feature of obesity and metabolic syndrome. Previous studies have generated controversial results regarding visceral fat (VF) removal as a therapy for obesity and metabolic syndrome. Objective: To study the effect of surgical VF removal on metabolic profiles in a mouse model of diet-induced obesity and metabolic syndrome and to evaluate for the first time the feasibility of endoscopic omentectomy using natural orifice transluminal endoscopic surgery (NOTES) technique as treatment for obesity and metabolic syndrome in a feline model. Setting: The Johns Hopkins Hospital. Design: Sham-controlled study in a mouse model of metabolic syndrome and then pilot endoscopic sham-controlled study in cats. Interventions: Partial or total surgical VF removal was performed in a high-fat diet-induced mouse model of obesity and metabolic syndrome, followed by measurements of metabolic profiles, and endoscopic omentectomy was performed in a feline model using the NOTES approach. Main Outcome Measurements: Weight loss and metabolic profiles. Results: In a mouse model of obesity, total but not partial VF removal significantly improved obesity and metabolic syndrome, including insulin resistance and hepatic steatosis (all P < .05 vs sham surgery). The improved metabolic syndrome was associated with significantly decreased inflammatory cytokines. In a feline model, endoscopic omentectomy was feasible and safe and resulted in a net weight loss compared with sham surgery (−387 ± 437 g vs 233 ± 351 g, P = .1, respectively). Limitations: Animal experiments. Conclusions: Endoscopic omentectomy is safe and feasible and has the potential to treat obesity and metabolic syndrome. Near-total VF removal is required to achieve net weight loss and improvement of metabolic syndrome. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study was to determine the mortality rate and factors related to mortality in elderly patients with acute and monotraumatic femoral neck fractures. This study included 241 patients with femoral neck fractures after bipolar hemiarthroplasty. We analyzed the mortality rate and the relationship between postoperative mortality and risk factors, such as age, sex, body mass index, the time to surgery, and the Society of Anesthesiologists'' score. The postoperative mortality rate 1 and 3 years after surgery was 11.2% and 19.5%, respectively. There proved to be a relationship between postoperative mortality and age, the time to surgery, and the Society of Anesthesiologists score. We recommend that surgery should not be delayed, and caution should be exercised for the high-risk group patients. [Copyright &y& Elsevier]