Patterns and motivations for method choices in suicidal thoughts and behaviour: Qualitative content analysis of a large online survey

Background Choice of suicide method can strongly influence the outcome of suicidal behaviour, and is an important aspect of the process and planning involved in a suicide attempt. Yet, the reasons why individuals consider, choose or discard particular methods are not well understood. Aims This is the first study to explore method choices among people with a history of suicidal behaviour and individuals who have experienced, but not enacted, suicidal thoughts. Method Via an online survey, we gathered open-ended data about choice of methods in relation to suicidal thoughts and behaviours, including reasons for and against specific means of harm. Results A total of 712 respondents had attempted suicide, and a further 686 experienced suicidal thoughts (but not acted on them). Self poisoning was the most commonly contemplated and used method of suicide, but most respondents had considered multiple methods. Method choices when contemplating suicide included a broader range of means than those used in actual attempts, and more unusual methods, particularly if perceived to be lethal, ‘easy’, quick, accessible and/or painless. Methods used in suicide attempts were, above all, described as having been accessible at the time, and were more commonly said to have been chosen impulsively. Key deterrents against the use of specific methods were the presence of and impact on other people, especially loved ones, and fears of injury and survival. Conclusions Exploration of method choices can offer novel insights into the transition from suicidal ideation to behaviour. Results underscore the need for preventative measures to restrict access to means and delay impulsive behaviour

Impact of B→K0∗ℓ+ℓ−B\to K^\ast_0 \ell^+\ell^- on the New Physics search in B→K∗ℓ+ℓ−B\to K^\ast \ell^+\ell^- decay

We discuss the uncertainty related to the amount of unwanted $B\to K_0^\ast (K\pi)\ell^+\ell^-$ events in the sample of $B\to K^\ast (K\pi)\ell^+\ell^-$. Those events can increase the measured differential decay rate by up to 10% in the low $q^2$ region, and can be a source of non-negligible uncertainty in the full angular distribution of the $B\to K^\ast (K\pi)\ell^+\ell^-$ decay. Although the transverse asymmetries should be unaffected by the presence of the $S$-wave $K\pi$ pairs, coming from the scalar $K_0^\ast$ meson, we show that in practice their normalization might be sensitive to those events and could entail a sizable uncertainty in transverse asymmetries around $q^2=2 GeV^2$. For other $q^2$'s that error is under about 10%.Comment: 16 pages [as published in NPB

Ran GTPase promotes cancer progression via Met receptor-mediated downstream signaling

YesIt has been shown previously that cancer cells with an activated oncogenic pathway, including Met activation, require Ran for growth and survival. Here, we show that knockdown of Ran leads to a reduction of Met receptor expression in several breast and lung cancer cell lines. This, in turn suppressed HGF expression and the Met-mediated activation of the Akt pathway, as well as cell adhesion, migration, and invasion. In a cell line model where Met amplification has previously been shown to contribute to gefitinib resistance, Ran knockdown sensitized cells to gefitinib-mediated inhibition of Akt and ERK1/2 phosphorylation and consequently reduced cell proliferation. We further demonstrate that Met reductionmediated by knockdown of Ran, occurs at the post-transcriptional level, probably via a matrix metalloproteinase. Moreover, the level of immunoreactive Ran and Met are positively associated in human breast cancer specimens, suggesting that a high level of Ran may be a prerequisite for Met overexpression. Interestingly, a high level of immunoreactive Ran dictates the prognostic significance of Met, indicating that the co-overexpression of Met and Ran may be associated with cancer progression and could be used in combination as a prognostic indicator.The authors would like to thank Cancer Research UK for the post-doctoral fellowship to H.F.Y

Lysine Scanning of Arg10-Teixobactin. Deciphering the Role of Hydrophobic and Hydrophilic Residues.

Teixobactin is a recently discovered antimicrobial cyclodepsipeptide with good activity against Gram positive bacteria. Taking Arg10-teixobactin as a reference, where the nonproteinogenic residue l-allo-enduracididine was substituted by arginine, a lysine scan was performed to identify the importance of keeping the balance between hydrophilic and hydrophobic amino acids for the antimicrobial activities of this peptide family. Thus, the substitution of four isoleucine residues present in the natural sequence by lysine led to a total loss of activity. On the other hand, the substitution of the polar noncharged residues and alanine by lysine allowed us to keep and in some cases to improve the antimicrobial activity

Insight into eco-friendly fabrication of silver nanoparticles by Pseudomonas aeruginosa and its potential impacts

Although green synthesis of nanoparticles (NPs) has replaced conventional physicochemical methods owing to eco-friendly and cost effective nature but molecular mechanism is not known completely. Elucidation of the mechanism is needed to enhance the production of control size synthesis and for understanding the biomineralization process. Here we report the facile, extracellular biosynthesis of silver nanoparticles (AgNPs) by Pseudomonas aeruginosa JP1 through nitrate reductase mediated mechanism. AgNO3 was reduced to AgNPs by cell filtrate exposure. UV-visible spectrum of the reaction mixture depicted reduction of ionic silver (Ag+) to atomic silver (Ag0) by a progressive upsurge in surface plasmon resonance (SPR) band range 435-450 nm. X-ray diffraction analysis showed the 2θ values at 38.08°, 44.52°, 64.42° and 77.44° confirming the crystalline nature and mean diameter [6.5-27.88nm (Ave = 13.44 nm)] of AgNPs. Transmission electron microscopy analysis demonstrated the spherical AgNPs with size range 5-45 nm. Stabilizing proteins and rhamnolipids were recognized by Fourier transform infrared spectroscopy. Nitrate reductase was purified and characterized (molecular weight 65 kDa and specific activity = 5.6 U/mg). To probe the plausible mechanism purified enzyme was retreated with AgNO3. Characteristic SPR bands range (435-450 nm) and Particle-induced x-ray emission results also confirmed the synthesis of AgNPs (59679.5 ppm) in solution. These results demonstrated that, nitrate reductase as a principal reducing agent in the mechanistic pathway of AgNPs synthesis, which leads to the understanding of metal transformation and biomineralization processes for controlling the biogeochemical cycles of silver and other heavy metals

Severe odontogenic infections

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.Background: Severe odontogenic infections are serious potentially lethal conditions. Following the death of a patient in the authors’ institution this study was initiated to determine the risk factors, management and outcome of a consecutive series of patients. Methods: All patients admitted to the Royal Adelaide Hospital under the care of the Oral and Maxillofacial Surgery Unit with odontogenic infections in calendar year 2003 were investigated. Detailed information relative to their prepresentation history, surgical and anaesthetic management and outcome was obtained and analysed. Results: Forty-eight patients, 32M, 16F, average age 34.5, range 19 to 88 years were treated. All presented with pain and swelling, with 21 (44 per cent) having trismus. Forty-four (92 per cent) were as a result of dental neglect and four (8 per cent) were regular dental patients having endodontic treatment which failed. Of those known to have been treated prior to presentation, most had been on antibiotics. Most patients had aggressive surgical treatment with extraction, surgical drainage, high dose intravenous antibiotics and rehydration. The hospital stay was 3.3 (range 1-16) days. Patients requiring prolonged intubation and high dependency or intensive care (40 per cent) had longer hospitalization. No patient died and all fully recovered. Conclusion: Severe odontogenic infections are a serious risk to the patient’s health and life. Management is primarily surgical with skilled anaesthetic airway management. Antibiotics are required in high intravenous doses as an adjunct and not as a primary treatment.IC Uluibau, T Jaunay and AN Gos

Long-range effects of histone point mutations on DNA remodeling revealed from computational analyses of SIN-mutant nucleosome structures

The packaging of DNA into nucleosomes impedes the binding and access of molecules involved in its processing. The SWI/SNF multi-protein assembly, found in yeast, is one of many regulatory factors that stimulate the remodeling of DNA required for its transcription. Amino-acid point mutations in histones H3 or H4 partially bypass the requirement of the SWI/SNF complex in this system. The mechanisms underlying the observed remodeling, however, are difficult to discern from the crystal structures of nucleosomes bearing these so-called SIN (SWI/SNF INdependent) mutations. Here, we report detailed analyses of the conformations and interactions of the histones and DNA in these assemblies. We find that the loss of direct protein–DNA contacts near point-mutation sites, reported previously, is coupled to unexpected additional long-range effects, i.e. loss of intermolecular contacts and accompanying DNA conformational changes at sequentially and spatially distant sites. The SIN mutations seemingly transmit information relevant to DNA binding across the nucleosome. The energetic cost of deforming the DNA to the states found in the SIN-mutant structures helps to distinguish the mutants that show phenotypes in yeast from those that do not. Models incorporating these deformed dimer steps suggest ways that nucleosomal DNA may be remodeled during its biological processing

Interleukin 10 (IL-10): an immunosuppressive factor and independent predictor in patients with metastatic renal cell carcinoma

Interleukin 10 (IL-10) is an immunosuppressive factor and has been detected in tumour cell cultures of renal cell carcinoma and of malignant melanoma. IL-10 has been described as a cytokine of the Th2 response; it is able to suppress antigen-presenting cells (APCs) and may lead to down-regulation of HLA class I and II molecules on dendritic cells and to anergy of T-lymphocytes. We evaluated pretreatment serum levels of soluble IL-10 and various clinical parameters to determine their prognostic value in 80 advanced renal cell carcinoma patients seen at our institution between May 1990 and April 1996. For statistical evaluation we used both univariate and multivariate Cox proportional hazards models. An elevated pretreatment serum level of IL-10 was a statistically independent predictor of unfavourable outcome (P < 0.0028), in addition to the well-known clinical and biochemical risk factors. These data support risk stratification for future therapeutic trials and identify a predictor which needs to be validated in prospective studies and may potentially influence decision making in palliative management of patients with metastatic renal cell carcinoma. These data also suggest a potential role of IL-10 in the development of advanced renal cell carcinoma and in the future design of therapeutic strategies. © 1999 Cancer Research Campaig

Tumor-derived exosomes: potential biomarker or therapeutic target in breast cancer?

Exosomes are released by normal and tumour cells, including those involved in breast cancer, and provide a means of intercellular communications. Exosomes with diameters ranging between 30-150 nm are involved in transferring biological information, via various lipids, proteins, different forms of RNAs, and DNA from one cell to another, and this can result in reprogramming of recipient cell functions. These vesicles are present in all body fluids, e.g., blood plasma/serum, semen, saliva, cerebrospinal fluid, breast milk, and urine. It has been recently reported that these particles are involved in the development and progression of different tumor types, including breast cancer. Furthermore, it has been suggested that exosomes have the potential to be used as drug transporters, or as biomarkers. This review highlights the potential roles of exosomes in normal and breast cancer cells and their potential applications as biomarkers with special focus on their potential applications in treatment of breast cancer