Suicide first aid guidelines for Indonesia: a Delphi consensus study

Background: The concept that "suicide is preventable" is fairly recent in Indonesia. Suicide prevention training is also new for community leaders and laypeople. On the other side, in a collectivistic society like Indonesia, community leaders, neighbours, and friends are essential parts of someone's life. Therefore, guidelines to assist first aiders in preventing suicide is urgently needed. Aim: This study aimed to develop guidelines to recognise key warning signs and provide first aid support to Indonesians at potential immediate risk for suicide. Methods: The guidelines was developed through three steps: (i) systematic literature review; (ii) focus group discussions and interviews; and (iii) expert consensus using the Delphi approach. These steps were taken to ensure that the final guidelines reflected the cultural beliefs and norms of the Indonesian context. Results: Three rounds of Delphi resulted in 460 accepted items out of 539 items generated from the literature search and group and individual interviews. Some key differences with other countries where similar studies were carried out were highlighted. Conclusions: This study emphasised the need for gatekeeper training as the ideal way of educating community members on the guidelines

A bayesian meta-analysis of multiple treatment comparisons of systemic regimens for advanced pancreatic cancer

© 2014 Chan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: For advanced pancreatic cancer, many regimens have been compared with gemcitabine (G) as the standard arm in randomized controlled trials. Few regimens have been directly compared with each other in randomized controlled trials and the relative efficacy and safety among them remains unclear

Impaired natural killer cell phenotype and function in idiopathic and heritable pulmonary arterial hypertension

BACKGROUND: Beyond their role as innate immune effectors, natural killer (NK) cells are emerging as important regulators of angiogenesis and vascular remodeling. Pulmonary arterial hypertension (PAH) is characterized by severe pulmonary vascular remodeling and has long been associated with immune dysfunction. Despite this association, a role for NK cells in disease pathology has not yet been described. METHODS AND RESULTS: Analysis of whole blood lymphocytes and isolated NK cells from PAH patients revealed an expansion of the functionally defective CD56(-)/CD16(+) NK subset that was not observed in patients with chronic thromboembolic pulmonary hypertension. NK cells from PAH patients also displayed decreased levels of the activating receptor NKp46 and the killer immunoglobulin-like receptors 2DL1/S1 and 3DL1, reduced secretion of the cytokine macrophage inflammatory protein-1β, and a significant impairment in cytolytic function associated with decreased killer immunoglobulin-like receptor 3DL1 expression. Genotyping patients (n=222) and controls (n=191) for killer immunoglobulin-like receptor gene polymorphisms did not explain these observations. Rather, we show that NK cells from PAH patients exhibit increased responsiveness to transforming growth factor-β, which specifically downregulates disease-associated killer immunoglobulin-like receptors. NK cell number and cytotoxicity were similarly decreased in the monocrotaline rat and chronic hypoxia mouse models of PAH, accompanied by reduced production of interferon-γ in NK cells from hypoxic mice. NK cells from PAH patients also produced elevated quantities of matrix metalloproteinase 9, consistent with a capacity to influence vascular remodeling. CONCLUSIONS: Our work is the first to identify an impairment of NK cells in PAH and suggests a novel and substantive role for innate immunity in the pathobiology of this disease

A cross-cultural study of attitudes toward suicide among young people in India, Italy and Australia

Background: An understanding of the cultural aspects of suicidal behavior is essential for the development of culturally appropriate suicide prevention and intervention strategies. Aims: This study explored the attitudes toward youth suicide in 686 Italian, Indian and Australian undergraduate students (18-24 years old). Method: A 21-item suicide attitude inventory titled Attitude towards Youth Suicide (AtYS) Scale was used in the three samples. Results: Four factors were extracted, labelled negative attitudes toward suicide, belief that suicide was not preventable, suicide as acceptable and normal, and the existence of risk signs for suicide. Country differences were found for all four subscales, with Indian students having the most negative attitudes toward suicide. Sex differences were found in all three countries with women, on the whole, having less negative attitudes toward suicide, more belief in the preventability of suicide in India and more belief in risk signs for suicide in Italy. Conclusions: Attitudes are linked to suicide in a complex manner. More quantitative and qualitative studies, including in lower-income and non-English speaking Western societies, are needed

Myeloma cells suppress osteoblasts through sclerostin secretion

Wingless-type (Wnt) signaling through the secretion of Wnt inhibitors Dickkopf1, soluble frizzled-related protein-2 and -3 has a key role in the decreased osteoblast (OB) activity associated with multiple myeloma (MM) bone disease. We provide evidence that another Wnt antagonist, sclerostin, an osteocyte-expressed negative regulator of bone formation, is expressed by myeloma cells, that is, human myeloma cell lines (HMCLs) and plasma cells (CD138+ cells) obtained from the bone marrow (BM) of a large number of MM patients with bone disease. We demonstrated that BM stromal cells (BMSCs), differentiated into OBs and co-cultured with HMCLs showed, compared with BMSCs alone, reduced expression of major osteoblastic-specific proteins, decreased mineralized nodule formation and attenuated the expression of members of the activator protein 1 transcription factor family (Fra-1, Fra-2 and Jun-D). Moreover, in the same co-culture system, the addition of neutralizing anti-sclerostin antibodies restored OB functions by inducing nuclear accumulation of β-catenin. We further demonstrated that the upregulation of receptor activator of nuclear factor κ-B ligand and the downregulation of osteoprotegerin in OBs were also sclerostin mediated. Our data indicated that sclerostin secretion by myeloma cells contribute to the suppression of bone formation in the osteolytic bone disease associated to MM