Ameliorative potential of Lavandula stoechas in metabolic syndrome via multitarget interactions

Ethnopharmacological importance: Decoction and infusion prepared from aerial parts of Lavandula stoechas L. (L. stoechas) have been traditionally used as remedy against several components of metabolic syndrome (MetS) and associated disorders including type II diabetes and cardiovascular diseases by Anatolian people. Aim of the study: The aim is to elucidate the potential ameliorative effects of L. stoechas aqueous extracts on insulin resistance and inflammation models through multitarget in vitro approaches and also to elucidate mechanism of action by analyzing transcriptional and metabolic responses. Materials and methods: An aqueous extract was prepared and fractionated to give rise to ethyl acetate (EE) and butanol (BE) extracts. The anti-insulin resistance effects of BE and EE were evaluated on palmitate induced insulin resistance model of H4IIE, C2C12 and 3T3L1 cells by using several metabolic parameters. Specifically, whole genome transcriptome analysis was performed by using microarray over 55.000 genes in control, insulin resistant and EE (25 µg/mL) treated insulin resistant H4IIE cells. Anti-inflammatory effects of both extracts were analyzed in LPS-stimulated RAW264.7 macrophages. Results: Both EE and BE at low doses (25–50 µg/mL) significantly decreased hepatic gluconeogenesis in H4IIE cell line by suppressing the expression of PEPCK and G6Pase. In C2C12 myotubes, both extracts increased the insulin stimulated glucose uptake more effectively than metformin. Both extracts decreased the isoproterenol induced lipolysis in 3T3L1 cell line. Moreover, they also effectively increased the expression of lipoprotein lipase protein level in insulin resistant myotubes at low doses. EE increased the protein level of PPARγ and stimulated the activation AKT in insulin resistant H4IIE and C2C12 cell lines. The results obtained from biochemical assays, mRNA/protein studies and whole genome transcriptome analyses were found to be complementary and provided support for the hypothesis that EE might be biologically active against insulin resistance and act through the inhibition of liver gluconeogenesis and AKT activation. Besides, LPS induced inflammation in RAW264.7 macrophages was mainly inhibited by EE through suppression of iNOS/NO signaling, IL1β and COX-2 genes. HPLC-TOF/MS analysis of EE of L. stoechas mainly resulted in caffeic acid, apigenin, luteolin, rosmarinic acid and its methyl ester, 4-hydroxybenzoic acid, vanillic acid, ferrulic acid and salicylic acid. Conclusion: Data suggest that EE of L. stoechas contains phytochemicals that can be effective in the treatment/prevention of insulin resistance and inflammation. These results validate the traditional use of L. stoechas in Anatolia against several metabolic disorders including metabolic syndrome. © 201

Structures and physical properties of new ??-BEDT-TTF tris-oxalatometallate (III) salts containing chlorobenzene and halomethane guest molecules

We report the structures and physical properties of new ??-(BEDT-TTF)4[Fe(oxalate)3]·G salts where A = H3O+, G = PhCl; A = Rb+ G = Pyridine. The structure of the PhCl salt is isomorphous with ??-(BEDT-TTF)4[(H3O)M(oxalate)3] with other guest molecules. PhCl is ordered in die hexagonal pockets formed by the [(H3O)Fe(oxalate)3] layer. The electrical conductivity is metallic down to 100 K, below which the resistivity increases with decreasing temperature. The specific conductivity at room temperature is about 10 S/cm. We also report the salt ??-(BEDT-TTF)4[RbFe(oxalate)3]·Pyridine where Rb+ replaces H3O. The electrical resistivity shows metallic behavior down to 100 K. and turns up gradually to a maximum at 65 K below which the system re-enters the metallic state down to liquid helium temperature. Neither salt shows superconductivity down to 2 K. In addition, other new ??-(BEDT-TTF)4[(H3O)M(oxalate)3]·salts with M = Cr, Ga, Fe; G = CH2Cl2, CH2ClBr, CH2Br2 are also reported

Genome-wide Association Study points to novel locus for Gilles de la Tourette Syndrome.

Tourette Syndrome (TS) is a childhood-onset neurodevelopmental disorder of complex genetic architecture, characterized by multiple motor tics and at least one vocal tic persisting for more than one year. We performed a genome-wide meta-analysis integrating a novel TS cohort with previously published data, resulting in a sample size of 6,133 TS individuals and 13,565 ancestry-matched controls. We identified a genome-wide significant locus on chromosome 5q15. Integration of eQTL, Hi-C and GWAS data implicated the NR2F1 gene and associated lncRNAs within the 5q15 locus. Heritability partitioning identified statistically significant enrichment in brain tissue histone marks, while polygenic risk scoring on brain volume data identified statistically significant associations with right and left thalamus volumes and right putamen volume. Our work presents novel insights in the neurobiology of TS opening up new directions for future studies

Safety of hospital discharge before return of bowel function after elective colorectal surgery

Background: Ileus is common after colorectal surgery and is associated with an increased risk of postoperative complications. Identifying features of normal bowel recovery and the appropriateness for hospital discharge is challenging. This study explored the safety of hospital discharge before the return of bowel function. Methods: A prospective, multicentre cohort study was undertaken across an international collaborative network. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The main outcome of interest was readmission to hospital within 30 days of surgery. The impact of discharge timing according to the return of bowel function was explored using multivariable regression analysis. Other outcomes were postoperative complications within 30 days of surgery, measured using the Clavien\u2013Dindo classification system. Results: A total of 3288 patients were included in the analysis, of whom 301 (9\ub72 per cent) were discharged before the return of bowel function. The median duration of hospital stay for patients discharged before and after return of bowel function was 5 (i.q.r. 4\u20137) and 7 (6\u20138) days respectively (P < 0\ub7001). There were no significant differences in rates of readmission between these groups (6\ub76 versus 8\ub70 per cent; P = 0\ub7499), and this remained the case after multivariable adjustment for baseline differences (odds ratio 0\ub790, 95 per cent c.i. 0\ub755 to 1\ub746; P = 0\ub7659). Rates of postoperative complications were also similar in those discharged before versus after return of bowel function (minor: 34\ub77 versus 39\ub75 per cent; major 3\ub73 versus 3\ub74 per cent; P = 0\ub7110). Conclusion: Discharge before return of bowel function after elective colorectal surgery appears to be safe in appropriately selected patients

Safety and efficacy of non-steroidal anti-inflammatory drugs to reduce ileus after colorectal surgery

Background: Ileus is common after elective colorectal surgery, and is associated with increased adverse events and prolonged hospital stay. The aim was to assess the role of non-steroidal anti-inflammatory drugs (NSAIDs) for reducing ileus after surgery. Methods: A prospective multicentre cohort study was delivered by an international, student- and trainee-led collaborative group. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The primary outcome was time to gastrointestinal recovery, measured using a composite measure of bowel function and tolerance to oral intake. The impact of NSAIDs was explored using Cox regression analyses, including the results of a centre-specific survey of compliance to enhanced recovery principles. Secondary safety outcomes included anastomotic leak rate and acute kidney injury. Results: A total of 4164 patients were included, with a median age of 68 (i.q.r. 57\u201375) years (54\ub79 per cent men). Some 1153 (27\ub77 per cent) received NSAIDs on postoperative days 1\u20133, of whom 1061 (92\ub70 per cent) received non-selective cyclo-oxygenase inhibitors. After adjustment for baseline differences, the mean time to gastrointestinal recovery did not differ significantly between patients who received NSAIDs and those who did not (4\ub76 versus 4\ub78 days; hazard ratio 1\ub704, 95 per cent c.i. 0\ub796 to 1\ub712; P = 0\ub7360). There were no significant differences in anastomotic leak rate (5\ub74 versus 4\ub76 per cent; P = 0\ub7349) or acute kidney injury (14\ub73 versus 13\ub78 per cent; P = 0\ub7666) between the groups. Significantly fewer patients receiving NSAIDs required strong opioid analgesia (35\ub73 versus 56\ub77 per cent; P < 0\ub7001). Conclusion: NSAIDs did not reduce the time for gastrointestinal recovery after colorectal surgery, but they were safe and associated with reduced postoperative opioid requirement