The oxytocin analogue carbetocin prevents emotional impairment and stress-induced reinstatement of opioid-seeking in morphine-abstinent mice.

The main challenge in treating opioid addicts is to maintain abstinence due to the affective consequences associated with withdrawal which may trigger relapse. Emerging evidence suggests a role of the neurohypophysial peptide oxytocin (OT) in the modulation of mood disorders as well as drug addiction. However, its involvement in the emotional consequences of drug abstinence remains unclear. We investigated the effect of 7-day opioid abstinence on the oxytocinergic system and assessed the effect of the OT analogue carbetocin (CBT) on the emotional consequences of opioid abstinence, as well as relapse. Male C57BL/6J mice were treated with a chronic escalating-dose morphine regimen (20-100 mg/kg/day, i.p.). Seven days withdrawal from this administration paradigm induced a decrease of hypothalamic OT levels and a concomitant increase of oxytocin receptor (OTR) binding in the lateral septum and amygdala. Although no physical withdrawal symptoms or alterations in the plasma corticosterone levels were observed after 7 days of abstinence, mice exhibited increased anxiety-like and depressive-like behaviors and impaired sociability. CBT (6.4 mg/kg, i.p.) attenuated the observed negative emotional consequences of opioid withdrawal. Furthermore, in the conditioned place preference paradigm with 10 mg/kg morphine conditioning, CBT (6.4 mg/kg, i.p.) was able to prevent the stress-induced reinstatement to morphine-seeking following extinction. Overall, our results suggest that alterations of the oxytocinergic system contribute to the mechanisms underlying anxiety, depression, and social deficits observed during opioid abstinence. This study also highlights the oxytocinergic system as a target for developing pharmacotherapy for the treatment of emotional impairment associated with abstinence and thereby prevention of relapse

4Pipe4-A 454 data analysis pipeline for SNP detection in datasets with no reference sequence or strain information

This work was fully supported by projects SOBREIRO/0036/2009 (under the framework of the Cork Oak ESTs Consortium), PTDC/BIA-BEC/098783/2008 and PTDC/AGR-GPL/119943/2010 from Fundação para a Ciência e Tecnologia (FCT) – Portugal. F. Pina-Martins was funded by FCT grant SFRH/BD/51411/2011, under the PhD program “Biology and Ecology of Global Changes”, Univ. Aveiro & Univ. Lisbon, Portugal. D. Batista was funded by FCT grant SFRH/BPD/104629/2014

FACTORS AFFECTING FARMERS' DESIRE TO CHANGE THE CULTIVATION PATTERN (MEDICINAL PLANTS CULTIVATION)

Achieving sustainable development is one of the most important agricultural resources. Therefore, the overall purpose of this study is to investigate the factors affecting farmers' desire to change the cultivation pattern to cultivation of medicinal plants. The research method is allowed as a field-library. After determining the variables through questionnaires and software SPSS. The statistical population of this study is rural producers in Targabah district in Khorasan Razavi Province in Iran. The statistical sample for this study was 204 rural households. The sample was calculated using random sampling based on Cochran formula. The results show that the farmers' desire to change the cultivation pattern to cultivation of medicinal plants has a significant positive correlation with its level of economic, social, technical and environmental awareness. Also, it has a significant and positive relationship with his understanding of the production of medicinal plants which can enhance the protection of the environment. The results of the diagnostic analysis showed that the level of economic awareness and awareness of processing plants and product packaging can affect the farmers' desire to change the cultivation pattern to cultivation of medicinal plants

Could One-Hand Compression for a Small Child Cause Intra-abdominal Injuries?

Purpose: We examined the question of whether one-hand chest compression for a small child could compress intraabdominal organs. Methods: We retrospectively examined medical charts and multidirectional computed tomography (MDCT) images obtained from children aged 1 to 18 years who presented to the hospital from March 2002 to March 2012. We measured the length of the sternum (Stotal) and the length of the lower half of the sternum (Stotal/2~X). We also measured the distance from the diaphragm to the midpoint of the sternum (Stotal/2~D) and half the width of an adult hand (Wtotal/2). Finally, we counted the number of instances at each age in which Stotal/2~X and Stotal/2~D were less than Wtotal/2. Results: This study included records and MDCT images for 301 children with a mean age of 12.05±5.59 years. We also enrolled 47 adult rescuers (25 men, 53.2%) with a mean age of 23.20±2.13 years. The mean Wtotal/2 was 4.62 ±0.46 cm. All 1-year-old children had Stotal/2~X and Stotal/2~D less than Wtotal/2. Among children aged 2 years, six (60.0%) had Stotal/2~X and Stotal/2~D less than Wtotal/2. Among children aged 3 years, four (26.7%) had Stotal/2~X and Stotal/2~D less than Wtotal/2, and among those aged 4 years, two (13.3%) had Stotal/2~X and Stotal/2~D less than Wtotal/2. However, Stotal/2~X and Stotal/2~D were greater than Wtotal/2 in children aged 5 years or more. Conclusion: Our measurements indicate that one-hand chest compression for a small child could cause intraabdominal organ injury

A comparative study of postoperative outcomes between minimally invasive living donor hepatectomy and open living donor hepatectomy: The Korean organ transplantation registry

Background: This study evaluated the safety and effectiveness of minimally invasive living donor hepatectomy in comparison with the open procedure, using Korean Organ Transplantation Registry data. Methods: We reviewed the prospectively collected data of all 1,694 living liver donors (1,071 men, 623 women) who underwent donor hepatectomy between April 2014 and December 2017. The donors were grouped on the basis of procedure type to the minimally invasive procedure group (n = 304) or to the open procedure group (n = 1,390) and analyzed the relationships between clinical data and complications. Results: No donors died after the procedure. The overall complication rates after operation in the minimally invasive procedure group and the open procedure group were 6.2% and 3.5%, respectively. Biliary complications were the most frequent events in both groups (minimally invasive procedure group, 2.4%; open procedure group, 1.6%). The majority of complications occurred within 7 days after surgery in both groups. The duration of hospitalization was shorter in the minimally invasive procedure group than in the open procedure group (9.04 ± 3.78 days versus 10.29 ± 4.01 days; P < .05). Conclusion: Based on its similar outcomes in our study, minimally invasive donor hepatectomy cannot be an alternative option compared with the open procedure method. To overcome this, we need to ensure better surgical safety, such as lower complication rate and shorter duration of hospitalization

Differential transcriptomic profiles effected by oil palm phenolics indicate novel health outcomes

Abstract Background Plant phenolics are important nutritional antioxidants which could aid in overcoming chronic diseases such as cardiovascular disease and cancer, two leading causes of death in the world. The oil palm (Elaeis guineensis) is a rich source of water-soluble phenolics which have high antioxidant activities. This study aimed to identify the in vivo effects and molecular mechanisms involved in the biological activities of oil palm phenolics (OPP) during healthy states via microarray gene expression profiling, using mice supplemented with a normal diet as biological models. Results Having confirmed via histology, haematology and clinical biochemistry analyses that OPP is not toxic to mice, we further explored the gene expression changes caused by OPP through statistical and functional analyses using Illumina microarrays. OPP showed numerous biological activities in three major organs of mice, the liver, spleen and heart. In livers of mice given OPP, four lipid catabolism genes were up-regulated while five cholesterol biosynthesis genes were down-regulated, suggesting that OPP may play a role in reducing cardiovascular disease. OPP also up-regulated eighteen blood coagulation genes in spleens of mice. OPP elicited gene expression changes similar to the effects of caloric restriction in the hearts of mice supplemented with OPP. Microarray gene expression fold changes for six target genes in the three major organs tested were validated with real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and the correlation of fold changes obtained with these two techniques was high (R2 = 0.9653). Conclusions OPP showed non-toxicity and various pleiotropic effects in mice. This study implies the potential application of OPP as a valuable source of wellness nutraceuticals, and further suggests the molecular mechanisms as to how dietary phenolics work in vivo.</p

New-onset diabetes after adult liver transplantation in the Korean Organ Transplantation Registry (KOTRY) study

BACKGROUND: New-onset diabetes after transplantation (NODAT) is a serious complication following liver transplantation (LT). The present study aimed to investigate the incidence of and risk factors for NODAT using the Korean Organ Transplantation Registry (KOTRY) database. METHODS: Patients with history of pediatric transplantation (ag

ENU Mutagenesis Identifies Mice with Morbid Obesity and Severe Hyperinsulinemia Caused by a Novel Mutation in Leptin

BACKGROUND: Obesity is a multifactorial disease that arises from complex interactions between genetic predisposition and environmental factors. Leptin is central to the regulation of energy metabolism and control of body weight in mammals. METHODOLOGY/PRINCIPAL FINDINGS: To better recapitulate the complexity of human obesity syndrome, we applied N-ethyl-N-nitrosourea (ENU) mutagenesis in combination with a set of metabolic assays in screening mice for obesity. Mapping revealed linkage to the chromosome 6 within a region containing mouse Leptin gene. Sequencing on the candidate genes identified a novel T-to-A mutation in the third exon of Leptin gene, which translates to a V145E amino acid exchange in the leptin propeptide. Homozygous Leptin(145E/145E) mutant mice exhibited morbid obesity, accompanied by adipose hypertrophy, energy imbalance, and liver steatosis. This was further associated with severe insulin resistance, hyperinsulinemia, dyslipidemia, and hyperleptinemia, characteristics of human obesity syndrome. Hypothalamic leptin actions in inhibition of orexigenic peptides NPY and AgRP and induction of SOCS1 and SOCS3 were attenuated in Leptin(145E/145E) mice. Administration of exogenous wild-type leptin attenuated hyperphagia and body weight increase in Leptin(145E/145E) mice. However, mutant V145E leptin coimmunoprecipitated with leptin receptor, suggesting that the V145E mutation does not affect the binding of leptin to its receptor. Molecular modeling predicted that the mutated residue would form hydrogen bond with the adjacent residues, potentially affecting the structure and formation of an active complex with leptin receptor within that region. CONCLUSIONS/SIGNIFICANCE: Thus, our evolutionary, structural, and in vivo metabolic information suggests the residue 145 as of special function significance. The mouse model harboring leptin V145E mutation will provide new information on the current understanding of leptin biology and novel mouse model for the study of human obesity syndrome

Inhibition of Autoimmune Diabetes in NOD Mice by miRNA Therapy.

Autoimmune destruction of the pancreatic islets in Type 1 diabetes is mediated by both increased proinflammatory (Teff) and decreased regulatory (Treg) T lymphocytes resulting in a significant decrease in the Treg:Teff ratio. The non-obese diabetic (NOD) mouse is an excellent in vivo model for testing potential therapeutics for attenuating the decrease in the Treg:Teff ratio and inhibiting disease pathogenesis. Here we show for the first time that a bioreactor manufactured therapeutic consisting of a complex of miRNA species (denoted as TA1) can effectively reset the NOD immune system from a proinflammatory to a tolerogenic state thus preventing or delaying autoimmune diabetes. Treatment of NOD mice with TA1 resulted in a systemic broad-spectrum upregulation of tolerogenic T cell subsets with a parallel downregulation of Teff subsets yielding a dramatic increase in the Treg:Teff ratio. Moreover, the murine-derived TA1 was highly effective in the inhibition of allorecognition of HLA-disparate human PBMC. TA1 demonstrated dose-responsiveness and exhibited equivalent or better inhibition of allorecognition driven proliferation than etanercept (a soluble TNF receptor). These findings demonstrate that miRNA-based therapeutics can effectively attenuate or arrest autoimmune disease processes and may be of significant utility in a broad range of autoimmune diseases including Type 1 diabetes

Exploring Takfir, Its Origins and Contemporary Use: The Case of Takfiri Approach in Daesh’s Media

Muslims have been the primary targets of Daesh’s attacks since 2014 in different countries such as Afghanistan, Iraq, and Syria. These attacks were based on its takfiri ideology. As Daesh official media and documents indicate, kufr (unbelief, infidelity) in Daesh’s approach is not limited to non-Muslims (original disbelievers), but Muslims are the most significant parts of kuffar (unbelievers) in its view and defined as incidental disbelievers. Through studying Daesh’s official documents and various Arabic, English, and Persian media productions, in an explanatory research, this article attempts to display Daesh’s takfiri approach toward Muslims and explains its historical and ideological roots, difference with Al-Qaeda’s takfiri approach, different approaches to takfir inside Daesh, main targets of Daesh’s takfir, and the reasons behinds its takfiri view. This article displays that for Daesh, the Muslims are limited only to Sunni Muslims who are accepting and following its approach. Other Sunni and non-Sunni Muslims are thus kuffar. This study also shows that the assertion of takfir has become a method for Daesh to discredit its opponents, such as Shi’a Muslims and other Muslim groups