Total synthesis and biological evaluation of the tetramic acid based natural product harzianic acid and its stereoisomers

Financial support for this project was provided by Cancer Research UK (Grant No. C21383/A6950)The bioactive natural product harzianic acid was prepared for the first time in just six steps (longest linear sequence) with an overall yield of 22%. The identification of conditions to telescope amide bond formation and a Lacey-Dieckmann reaction into one pot proved important. The three stereoisomers of harzianic acid were also prepared, providing material for comparison of their biological activity. While all of the isomers promoted root growth, improved antifungal activity was unexpectedly associated with isomers in the enantiomeric series opposite that of harzianic acid.Publisher PDFPeer reviewe

Piperazinium Chlorocuprates(I)

The formation from aqueous solution of networks containing piperazinium hydrochlorides with copper(I) chloride is described. Four new X-ray crystal structures are reported: (H2Pip)[Cu2Cl4] (two isomeric phases: 1A and 1B), (H2MePip)[Cu3Cl5] (2), and (H2Me2Pip)[Cu4Cl6] (3) (Pip = piperazine, MePip = N-methylpiperazine, Me2Pip = N,N′-dimethylpiperazine. In 1A (P-1, a = 6.3141(2), b = 6.8248(2), c = 6.9067(2), α = 90.707(2), β = 110.748(2), γ = 110.799(2), V = 256.918(13), Z = 2) corner-sharing Cu2Cl2 rhomboid dimers form infinite chains running parallel to the a-axis. In 1B (Pbcn, a = 9.9442(6), b = 8.0622(5), c = 13.1301(7), V = 1052.67(11), Z = 8) the Cu2Cl2 dimers are linked by μ-Cl into Cu6Cl8 rings which form hexagonally tiled sheets running parallel to the a,b-plane. In 2 (P-1, a = 8.0815(7), b = 9.6584(9), c = 9.7900(8), α = 70.231(4), β = 77.180(4), γ = 70.587(4), V = 673.05(10), Z = 2) alternating Cu3Cl3 and Cu4Cl4 rings are fused to form ribbons that run parallel to the a-axis. Copper-copper interactions are present. In 3 (C2/c, a = 17.4026(6), b = 10.5295(4), c = 11.7501(8), β = 131.5490(10), V = 1611.35(14), Z = 8) relatively long Cu···Cl interactions connect Cu4Cl6 “adamantane” units into chains running parallel to the c-axis. In all cases the piperazinium ions are independent from the chlorocuprate structures, but they do show N–H···Cl interactions

Bromelain and Cardiovascular Risk Factors in Diabetes: An Exploratory Randomized, Placebo Controlled, Double Blind Clinical Trial

Objective: The objective of this trial was to assess whether the dietary supplement (bromelain) had the potential to reduce plasma fibrinogen and other Cardiovascular Disease (CVD) risk factors in patients with diabetes. Methods: This randomized placebo controlled, double blind, parallel design, efficacy study was carried out in China and investigated the effect of 12 weeks of bromelain (1.05g/day) on plasma fibrinogen . This randomized controlled trial (RCT) recruited 68 Chinese diabetic patients (32 males and 36 females; Han origin, mean age of 61.26 years (Standard Deviation, 12.62 years)) with at least one CVD risk factor. Patients were randomized into either bromelain or placebo group. While bromelain group received bromelain capsule, the placebo group received placebo capsule which consisted inert ingredient and has no treatment effect. Patients and researcher were blinded and did not know whether they received bromelain or placebo capsules. Plasma fibrinogen, CVD risk factors and anthropometric indicators were determined at baseline and at 12 weeks. Results: The change in the fibrinogen level in the placebo group at the end of the study showed a mean reduction of 0.36g/L (Standard Deviation (SD) 0.96g/L) compared with the mean reduction of 0.13g/L (SD 0.86g/L) for the bromelain group. However, there was no significant difference in the mean change in fibrinogen between the placebo and bromelain groups (mean difference=0.23g/L (SD 0.22g/L), p=0.291). Similarly, the difference in mean change in other CVD risk factors (blood lipids, blood pressure), blood glucose, C - reactive protein (CRP) and anthropometric measures between the bromelain and placebo groups was also not statistically significant. Conclusions: This RCT failed to show a beneficial effect in reducing fibrinogen or influencing other selected CVD risk factors but suggests other avenues for subsEquent research on bromelain

Modificación hidrotérmica del almidón de yuca para su empleo como estabilizador de helados

En el trabajo se desarrolla un procedimiento de modificación física de almidón nativo de yuca a través de un tratamiento hidrotérmico en la zona previa a la gelatinización, de la cual no existen reportes de experimentación. El objetivo es determinar la influencia de las principales variables del proceso sobre el comportamiento reológico, con el propósito de ser empleado como estabilizador en la Industria heladera. Se alcanzaron buenos resultados reológicos con una concentración de 6% p/p de almidón nativo a 56 0C. El material obtenido se usó en formulaciones de helados, sustituyendo parte de los productos convencionales con efectos muy positivos en cuanto a la evaluación sensorial y el índice de aireación. Los resultados alcanzados permiten establecer perspectivas para el empleo de almidones modificados de yuca cuyo tratamiento hidrotérmico en la zona previa a la gelatinización ofrece efectos positivos, como estabilizante de suspensiones acuosas, similares a los que se alcanzan con almidones pregelatinizados, además con la ventaja de obtener el producto modificado con mayor facilidad

Hyponatraemia despite isotonic maintenance fluid therapy: a time series intervention study

OBJECTIVE: To examine the prevalence of dysnatraemias among children admitted for paediatric surgery before and after a change from hypotonic to isotonic intravenous maintenance fluid therapy. DESIGN: Retrospective consecutive time series intervention study. SETTING: Paediatric surgery ward at the Children's Hospital in Lund, during a 7-year period, 2010-2017. PATIENTS: All children with a blood sodium concentration measurement during the study period were included. Hypotonic maintenance fluid (40 mmol/L NaCl and 20 mmol/L KCl) was used during the first 3 years of the study (646 patients), and isotonic solution (140 mmol/L NaCl and 20 mmol/L KCl) was used during the following period (807 patients). MAIN OUTCOME MEASURES: Primary outcomes were sodium concentration and occurrence of hyponatraemia (145 mmol/L). RESULTS: Overall, the change from hypotonic to isotonic intravenous maintenance fluid therapy was associated with a decreased prevalence of hyponatraemia from 29% to 22% (adjusted OR 0.65 (0.51-0.82)) without a significantly increased odds for hypernatraemia (from 3.4% to 4.3%, adjusted OR 1.2 (0.71-2.1)). Hyponatraemia <130 mmol/L decreased from 6.2% to 2.6%, and hyponatraemia <125 mmol/L decreased from 2.0% to 0.5%. CONCLUSIONS: Routine use of intravenous isotonic maintenance fluids was associated with lower prevalence of hyponatraemia, although hyponatraemia still occurred in over 20% of patients. We propose that the composition and the volume of administered fluid need to be addressed

Threaded Structure and Blue Luminescence of (CuCN)20(Piperazine)7

The structurally unique and highly luminescent 20 : 7 complex of CuCN with piperazine (Pip) was formed under aqueous conditions; its structure reveals two interpenetrated 2D sub-networks in 6 : 1 ratio: (CuCN)2(Pip) and (CuCN)8(Pip), the latter consisting of Cu18(CN)16(Pip)2 macrocycles

Implementation of duty of candour within neurosurgery: a national survey and framework for improved application in clinical practice

INTRODUCTION: Statutory duty of candour was introduced in November 2014 for NHS bodies in England. Contained within the regulation were definitions regarding the threshold for what constitutes a notifiable patient safety incident. However, it can be difficult to determine when the process should be implemented. The aim of this survey was to evaluate the interpretation of these definitions by British neurosurgeons. MATERIALS AND METHODS: All full (consultant) members of the Society of British Neurological Surgeons were electronically invited to participate in an online survey. Surgeons were presented with 15 cases and asked to decide in the case of each one whether they would trigger the process of duty of candour. Cases were stratified according to their likelihood and severity. RESULTS: In all, 106/357 (29.7%) members participated in the survey. Responses varied widely, with almost no members triggering the process of duty of candour in cases where adverse events were common (greater than 10% likelihood) and required only outpatient follow-up (7/106; 6.6%), and almost all members doing so in cases where adverse events were rare (less than 0.1% likelihood) and resulted in death (102/106; 96.2%). However, there was clear equipoise in triggering the process of duty of candour in cases where adverse events were uncommon (0.1-10% likelihood) and resulted in moderate harm (38/106; 35.8%), severe harm (57/106; 53.8%) or death (49/106; 46.2%). CONCLUSION: There is considerable nationwide variation in the interpretation of definitions regarding the threshold for duty of candour. To this end, we propose a framework for the improved application of duty of candour in clinical practice

Selective medium for culture of Mycoplasma hyopneumoniae

The fastidious porcine respiratory pathogen Mycoplasma hyopneumoniae has proven difficult to culture since it was first isolated in 1965. A reliable solid medium has been particularly challenging. Moreover, clinical and pathological samples often contain the fast-growing M. hyorhinis which contaminates and overgrows M. hyopneumoniae in primary culture. The aim of this study was to optimise the culture medium for recovery of M. hyopneumoniae and to devise a medium for selection of M. hyopneumoniae from clinical samples also containing M. hyorhinis. The solid medium devised by Niels Friis was improved by use of Purified agar and incorporation of DEAE-dextran. Addition of glucose or neutralization of acidity in liquid medium with NaOH did not improve the final yield of viable organisms or alter the timing of peak viability. Analysis of the relative susceptibility of M. hyopneumoniae and M. hyorhinis strains to four antimicrobials showed that M. hyopneumoniae is less susceptible than M. hyorhinis to kanamycin. This was consistent in all UK and Danish strains tested. A concentration of 2 μg/ml of kanamycin selectively inhibited the growth of all M. hyorhinis tested, while M. hyopneumoniae was able to grow. This forms the basis of an effective selective culture medium for M. hyopneumoniae.(Résumé d'auteur

Positronium Hyperfine Splitting in Non-commutative Space at the Order α6\alpha^6

We obtain positronium Hyperfine Splitting owing to the non-commutativity of space and show that, in the leading order, it is proportional to $\theta \alpha^6$ where, $\theta$ is the parameter of non-commutativity. It is also shown that spatial non-commutativity splits the spacing between $n=2$ triplet excited levels $E(2^3S_1)\to E(2^3P_2)$ which provides an experimental test on the non-commutativity of space.Comment: 7 pages, 2 figures, to appear in Phys. Rev.