Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Dabrafenib-Panobinostat Salt: Improving Dissolution Rate and Inhibition of BRAF Melanoma Cells

Cocrystallization of the drug−drug salt-cocrystal of the histone deacetylase inhibitor (HDACi) panobinostat (PAN) and b-rapidly accelerated fibrosarcoma (BRAF) inhibitor dabrafenib (DBF) afforded single crystals of a two-drug salt stabilized by N+−H···O and N+−H···N− hydrogen bonds between the ionized panobinostat ammonium donor and dabrafenib sulfonamide anion acceptor in a 12-member ring motif. A faster dissolution rate for both drugs was achieved through the salt combination compared to the individual drugs in an aqueous acidic medium. The dissolution rate exhibited a peak concentration (Cmax) of approximately 310 mg cm−2 min−1 for PAN and 240 mg cm−2 min−1 for DBF at a Tmax of less than 20 min under gastric pH 1.2 (0.1 N HCl) compared to the pure drug dissolution values of 10 and 80 mg cm−2 min−1, respectively. The novel and fast-dissolving salt DBF−·PAN+ was analyzed in BRAFV600E melanoma cells Sk-Mel28. DBF−·PAN+ reduced the dose−response from micromolar to nanomolar concentrations and lowered IC50 (21.9 ± 7.2 nM) by half compared to PAN alone (45.3 ± 12.0 nM). The enhanced dissolution and lower survival rate of melanoma cells show the potential of novel DBF−·PAN+ salt in clinical evaluation

Bicentric bipolar hip prosthesis: A radiological study of movement at the interprosthetic joint

Background: The bipolar hip prostheses after some time functions as a unipolar device. There is a need to change the design of bipolar hip prostheses to make it function as a bipolar device over a prolonged period of time. A bicentric bipolar hip prosthesis was used as an implant for various conditions of the hip. We evaluated the movement of this newly developed prosthesis at the interprosthetic joint radiologically at periodic intervals. Materials and Methods: Fifty two cases were operarted with the Bicentric bipolar prosthesis for indications like fracture neck of femur and various other diseases of the hip and were followed up with serial radiographs at periodic intervals to evaluate, what fraction of the total abduction at the hip was occurring at the interprosthetic joint. Results: In cases of intracapsular fracture neck of femur, the percentage of total abduction occurring at the interprosthetic joint at 3 months follow-up was 33.74% (mean value of all the patients), which fell to 25.66% at 1.5 years. In indications for bipolar hemireplacement other than fracture neck of femur, the percentage of total abduction occurring at the interprosthetic joint at 3 months follow-up was 71.71% (mean value) and at 1.5 years it was 67.52%. Conclusion: This study shows the relative preservation of inner bearing movement in the bipolar hip prosthesis with time probably due its refined design. Further refinements are needed to make the prosthesis work better in patients of intracapsular fracture neck femur

N,N-Bis(2-cyano­eth­yl)-p-toluene­sulfonamide

In the title compound, C13H15N3O2S, the geometric parameters are in the normal ranges. The amide N atom is coordinated in an almost trigonal-planar fashion

Vapour phase methylation of phenol over nanocrystalline ZnFe_2-xAl_xO₄(x= 0, 0.25, 0.5, 0.75 and 1.0) ferrospinel system

493-498The alkylation of phenol with methanol was carried out over ZnFe2-xAlxO4 (x = 0, 0.25, 0.5, 0.75 and 1.0) type spinel systems in a fixed bed, down flow reactor. The influence of surface acidity, cation distribution in the spinel lattice and various reaction parameters are discussed. A maximum yield of 70.9 and 22.9% with selectivity of 73.5 and 23.3% was obtained for 2,6-xylenol and o-cresol respectively, giving a total ortho selectivity of 96.8% over ZnFeAlO4 at 350oC, methanol to phenol molar ratio of 5 and WHSV of 0.6 h–1. Catalyst characterization was made by XRD, Mössbauer spectroscopy, ammonia desorption and BET surface area measurements. Mössbauer spectroscopy reveals isomorphic substitution of Fe3+ by smaller Al3+ into the octahedral sites leading to lattice distortion, unsymmetrical charge distribution and charge transfer from iron to oxygen making it more basic and proton attracting. This helps vertical adsorption of phenol and formation of 2,6-xylenol. It has been concluded that catalyst acidity plays major role in the reaction as compared to surface area

Cerebrospinal fluid cytokines and matrix metalloproteinases in human immunodeficiency seropositive and seronegative patients of tuberculous meningitis

Background: Some important clinical differences exist between human immunodeficiency virus (HIV)-seropositive and HIV-seronegative patients. Alterations in the cerebrospinal fluid (CSF) cytokines and matrix metalloproteinase have been noted in tuberculous meningitis. In HIV-infected patients, the immunopathogenesis is expected to be different. Materials and Methods: In this study, 64 patients of tuberculous meningitis (28 HIV seropositive and 36 seronegative) were included. The patients were followed up for six months. Cerebrospinal fluid (CSF) samples of tuberculous meningitis patients and 20 controls were subjected to tissue necrosis factor (TNF)-α, interleukin (IL)-1β, interferon (IFN)-γ, IL-10, matrix metalloproteinase (MMP)-2, and MMP-9 estimations. The levels were correlated with the patients′ baseline clinical characteristics, CSF parameters, neuroimaging findings, and the outcome. The outcome was assessed and modified with the Barthel index. Results: The CSF cytokines and MMP levels were significantly elevated in tuberculous meningitis when compared with the controls. There was no significant difference seen between HIV seropositive and seronegative tuberculous meningitis, except for the IL-1β level, which was significantly lower in the HIV-infected patients. The cytokine and MMP levels did not correlate with the baseline clinical characteristics, disease severity, cerebrospinal fluid characteristics, neuroimaging findings, and outcome. Conclusion: In conclusion, HIV infection did not affect a majority of the CSF cytokines and MMP levels in tuberculous meningitis except for IL-1β level. None of the estimated inflammatory parameters correlated with the outcome