Prospective, multicentre study of screening, investigation and management of hyponatraemia after subarachnoid haemorrhage in the UK and Ireland

Background: Hyponatraemia often occurs after subarachnoid haemorrhage (SAH). However, its clinical significance and optimal management are uncertain. We audited the screening, investigation and management of hyponatraemia after SAH. Methods: We prospectively identified consecutive patients with spontaneous SAH admitted to neurosurgical units in the United Kingdom or Ireland. We reviewed medical records daily from admission to discharge, 21 days or death and extracted all measurements of serum sodium to identify hyponatraemia (<135 mmol/L). Main outcomes were death/dependency at discharge or 21 days and admission duration >10 days. Associations of hyponatraemia with outcome were assessed using logistic regression with adjustment for predictors of outcome after SAH and admission duration. We assessed hyponatraemia-free survival using multivariable Cox regression. Results: 175/407 (43%) patients admitted to 24 neurosurgical units developed hyponatraemia. 5976 serum sodium measurements were made. Serum osmolality, urine osmolality and urine sodium were measured in 30/166 (18%) hyponatraemic patients with complete data. The most frequently target daily fluid intake was >3 L and this did not differ during hyponatraemic or non-hyponatraemic episodes. 26% (n/N=42/164) patients with hyponatraemia received sodium supplementation. 133 (35%) patients were dead or dependent within the study period and 240 (68%) patients had hospital admission for over 10 days. In the multivariable analyses, hyponatraemia was associated with less dependency (adjusted OR (aOR)=0.35 (95% CI 0.17 to 0.69)) but longer admissions (aOR=3.2 (1.8 to 5.7)). World Federation of Neurosurgical Societies grade I–III, modified Fisher 2–4 and posterior circulation aneurysms were associated with greater hazards of hyponatraemia. Conclusions: In this comprehensive multicentre prospective-adjusted analysis of patients with SAH, hyponatraemia was investigated inconsistently and, for most patients, was not associated with changes in management or clinical outcome. This work establishes a basis for the development of evidence-based SAH-specific guidance for targeted screening, investigation and management of high-risk patients to minimise the impact of hyponatraemia on admission duration and to improve consistency of patient care

GREEN SYNTHESIS OF SILVER NANOPARTICLES FROM THE LEAF EXTRACT OF ADHATODA VASICA NEES. AND ASSESSMENT OF ITS ANTIBACTERIAL ACTIVITY

Introduction: Green synthesis of nanoparticles has been an exploring research topic in recent days due to their advanced uses in biomedical, chemical,and related fields.Objective: The objective of the present study was to rapidly synthesize silver nanoparticles (AgNPs) using Adhatoda vasica leaf extract. The nanoparticlesobtained have been characterized with various techniques like ultraviolet-visible spectrum, Fourier transform (FT) infrared spectrometry, scanningelectron microscopy, energy dispersive spectroscopy, X-ray diffraction, atomic force microscopy, and FT-Raman spectroscopy.Results: These techniques showed the formation of AgNPs with an average size of 21.1-29.1 nm. Phytochemicals present in the plant were responsiblefor the quick reduction of Ag+ ions to Ag0 nanoparticles. The synthesized AgNPs had the potential to mitigate the bacterial and fungal cell proliferationparticularly Staphylococcus aureus, Pseudomonas auroginosa, Bacillus thuringiensis, Escherichia coli, Klebsiella pneumoniae and fungal specieswere Aspergillus niger, Aspergillus flavous, Pencillium chrysogenum, and Trichoderm harizanum. The results were compared with ciprofloxacin andfluconazole as positive controls.Conclusion: A. vasica being a crucial medicinal plant widely used in the treatment of cancer, the present study shows that the plant can be used as bestsource for synthesis of AgNPs for further research in the cancer field.Keywords: Adhatoda vasica, Phytochemials, Phenols, Fourier transform Raman spectroscopy, Atomic force microscopy

Biosynthesis and characterization of Dillenia indica-mediated silver nanoparticles and their biological activity

Dillenia indica L. is a traditional medicinal plant well known for its ability to cure various human diseases. In the current study, silver nanoparticles have been synthesized by simple and eco-friendly method using Dillenia indica extract. The green synthesized nanoparticles were characterized by Fourier transform infrared (FTIR), UV-visible spectroscopy, Atomic force microscopy (AFM), High-resolution transmission electron microscopy (HR-TEM), Zeta Potential and Size Distribution. UV-visible and FTIR spectra, AFM, HR-TEM and Zeta Potential readings and size distribution conformed that the synthesized silver particles were in the size of nano. The green synthesized silver nanoparticles were subjected for antibacterial activity against Gram-positive bacteria Enterococcus faecalis and Gram-negative bacteria Escherichia coli by agar well diffusion method. The synthesized AgNPs exhibited significant inhibition of 27 and 16 mm against the test bacteria at 0.25 mg/ml. Further the antibacterial activity was confirmed by live and dead cell assay by fluorescence microscopy and morphological changes of bacteria were studied by Scanning electron microscope (SEM). The study recommends that the synthesized silver nanoparticles using Dillenia indica extract have potential application in inhibition of bacteria owing to their potent antibacterial activity

MAP2K1 and MAP3K1 mutations in langerhans cell histiocytosis

Langerhans cell histiocytosis (LCH) is now understood to be a neoplastic disease in which over 50% of cases have somatic activating mutations of BRAF. However, the extracellular signal-related (ERK) pathway is activated in all cases including those with wild type BRAF alleles. Here, we applied a targeted massively parallel sequencing panel to 30 LCH samples to test for the presence of additional genetic alterations that might cause ERK pathway activation. In 20 BRAF wild type samples, we found 3 somatic mutations in MAP2K1 (MEK1) including C121S and C121S/G128D in the kinase domain, and 56_61QKQKVG>R, an in-frame deletion in the N-terminal regulatory domain. All three variant proteins constitutively phosphorylated ERK in in vitro kinase assays. The C121S/G128D and 56_61QKQKVG>R variants were resistant to the mitogen-activated protein kinase kinase (MEK) inhibitor trametinib in vitro. Within the entire sample set, we found 3 specimens with mutations in MAP3K1 (MEKK1), including two truncation mutants, T779fs and T1481fs; T1481fs encoded an unstable and nonfunctional protein when expressed in vitro. T779fs was present in a specimen carrying BRAF V600E. The third variant was a single nucleotide substitution, E1286V, which was fully functional and is likely a germline polymorphism. These results indicate that LCH cells can harbor additional genetic alterations in the RAS-RAF-MEK pathway which, in the case of MAP2K1, may be responsible for ERK activation in a wild type BRAF setting. The resistance of some of these variants to trametinib may also have clinical implications for the combined use of RAF and MEK inhibitors in LCH. © 2015 Wiley Periodicals, In

MAP2K1 and MAP3K1 mutations in langerhans cell histiocytosis

Langerhans cell histiocytosis (LCH) is now understood to be a neoplastic disease in which over 50% of cases have somatic activating mutations of BRAF. However, the extracellular signal-related (ERK) pathway is activated in all cases including those with wild type BRAF alleles. Here, we applied a targeted massively parallel sequencing panel to 30 LCH samples to test for the presence of additional genetic alterations that might cause ERK pathway activation. In 20 BRAF wild type samples, we found 3 somatic mutations in MAP2K1 (MEK1) including C121S and C121S/G128D in the kinase domain, and 56_61QKQKVG>R, an in-frame deletion in the N-terminal regulatory domain. All three variant proteins constitutively phosphorylated ERK in in vitro kinase assays. The C121S/G128D and 56_61QKQKVG>R variants were resistant to the mitogen-activated protein kinase kinase (MEK) inhibitor trametinib in vitro. Within the entire sample set, we found 3 specimens with mutations in MAP3K1 (MEKK1), including two truncation mutants, T779fs and T1481fs; T1481fs encoded an unstable and nonfunctional protein when expressed in vitro. T779fs was present in a specimen carrying BRAF V600E. The third variant was a single nucleotide substitution, E1286V, which was fully functional and is likely a germline polymorphism. These results indicate that LCH cells can harbor additional genetic alterations in the RAS-RAF-MEK pathway which, in the case of MAP2K1, may be responsible for ERK activation in a wild type BRAF setting. The resistance of some of these variants to trametinib may also have clinical implications for the combined use of RAF and MEK inhibitors in LCH. © 2015 Wiley Periodicals, In