Possibilities for the future of global mental health: a scenario planning approach.

BACKGROUND: Global mental health is a widely used term describing initiatives in policies, research and practice to improve the mental health of people worldwide. It has been gaining momentum over the last 10 years, reflected in increasing funding opportunities, training programmes, and publications. In light of the rising importance of global mental health and the various uncertainties about its future directions, this paper explores what the future may hold for global mental health in 30 years' time. METHOD: A scenario planning method was used, involving a workshop with experts from four continents and a range of backgrounds, including clinical and academic psychiatry, psychology, art and music therapy, service user advisory role, funder of global health research and post-graduate students. RESULTS: Six distinct scenarios that describe potential future situations were developed: universal standards for care; worldwide coordination of research; making use of diversity; focus on social factors; globalised care through technology; mental health as a currency in global politics. CONCLUSIONS: These scenarios consider different social, economic, scientific and technological drivers and focus on distinct aspects. Some reflect a global application of possible trends in mental health, whilst others apply general global developments to mental health care. They are not fixed forecasts, but instead may help to promote discussion and debate about further developments and decisions

Bioformulation of microbial biocontrol agents for a sustainable agriculture

The application of microbial based biopesticides has become a sustainable alternative to the use of chemicals to prevent yield losses due to plant pathogens. However, microbial based biopesticides are often unsuccessfully formulated and do not meet the demanding regulatory standards required by the agencies, which hinders their commercialization. Hence, an outline on the approaches to attain more effective formulations might be useful for the development of future more effective products. With this aim, this chapter reports the current state of biocontrol strategies and describes the principles of microbial biocontrol formulations. Emphasis is placed on techniques and tools available for the development and characterisation of microbial products. To provide glimpses on the possible formulations, the different existing additives, carriers, inoculation techniques and formulation types are exhaustively reviewed. Finally, requirements and principles for efficacy evaluation of plant protection products in the European Union are include

Transportations of space, time and self: the role of reading groups in managing mental distress in the community

Background: The practice of reading and discussing literature in groups is long established, stretching back into classical antiquity. Although benefits of therapeutic reading groups have been highlighted, research into participants’ perceptions of these groups has been limited. Aims: To explore the experiences of those attending therapeutic reading groups, considering the role of both the group, and the literature itself, in participants’ ongoing experiences of distress. Method: Eleven participants were recruited from two reading groups in the South-East of England. One focus group was run, and eight individuals self-selected for individual interviews. The data were analysed together using a thematic analysis drawing on dialogical theories. Results: Participants described the group as an anchor, which enabled them to use fiction to facilitate the discussion of difficult emotional topics, without referring directly to personal experience. Two aspects of this process are explored in detail: the use of narratives as transportation, helping to mitigate the intensity of distress; and using fiction to explore possibilities, alternative selves and lives. Conclusions: For those who are interested and able, reading groups offer a relatively de-stigmatised route to exploring and mediating experiences of distress. Implications in the present UK funding environment are discussed

Listeriolysin O Is Necessary and Sufficient to Induce Autophagy during Listeria monocytogenes Infection

Recent studies have suggested that autophagy is utilized by cells as a protective mechanism against Listeria monocytogenes infection.However we find autophagy has no measurable role in vacuolar escape and intracellular growth in primary cultured bone marrow derived macrophages (BMDMs) deficient for autophagy (atg5-/-). Nevertheless, we provide evidence that the pore forming activity of the cholesterol-dependent cytolysin listeriolysin O (LLO) can induce autophagy subsequent to infection by L. monocytogenes. Infection of BMDMs with L. monocytogenes induced microtubule-associated protein light chain 3 (LC3) lipidation, consistent with autophagy activation, whereas a mutant lacking LLO did not. Infection of BMDMs that express LC3-GFP demonstrated that wild-type L. monocytogenes was encapsulated by LC3-GFP, consistent with autophagy activation, whereas a mutant lacking LLO was not. Bacillus subtilis expressing either LLO or a related cytolysin, perfringolysin O (PFO), induced LC3 colocalization and LC3 lipidation. Further, LLO-containing liposomes also recruited LC3-GFP, indicating that LLO was sufficient to induce targeted autophagy in the absence of infection. The role of autophagy had variable effects depending on the cell type assayed. In atg5-/- mouse embryonic fibroblasts, L. monocytogenes had a primary vacuole escape defect. However, the bacteria escaped and grew normally in atg5-/- BMDMs.We propose that membrane damage, such as that caused by LLO, triggers bacterial-targeted autophagy, although autophagy does not affect the fate of wild-type intracellular L. monocytogenes in primary BMDMs

Fructooligosacharides Reduce Pseudomonas aeruginosa PAO1 Pathogenicity through Distinct Mechanisms

Pseudomonas aeruginosa is ubiquitously present in the environment and acts as an opportunistic pathogen on humans, animals and plants. We report here the effects of the prebiotic polysaccharide inulin and its hydrolysed form FOS on this bacterium. FOS was found to inhibit bacterial growth of strain PAO1, while inulin did not affect growth rate or yield in a significant manner. Inulin stimulated biofilm formation, whereas a dramatic reduction of the biofilm formation was observed in the presence of FOS. Similar opposing effects were observed for bacterial motility, where FOS inhibited the swarming and twitching behaviour whereas inulin caused its stimulation. In co-cultures with eukaryotic cells (macrophages) FOS and, to a lesser extent, inulin reduced the secretion of the inflammatory cytokines IL-6, IL-10 and TNF- a . Western blot experiments indicated that the effects mediated by FOS in macrophages are associated with a decreased activation of the NF- k B pathway. Since FOS and inulin stimulate pathway activation in the absence of bacteria, the FOS mediated effect is likely to be of indirect nature, such as via a reduction of bacterial virulence. Further, this modulatory effect is observed also with the highly virulent ptxS mutated strain. Co-culture experiments of P. aeruginosa with IEC18 eukaryotic cells showed that FOS reduces the concentration of the major virulence factor, exotoxin A, suggesting that this is a possible mechanism for the reduction of pathogenicity. The potential of these compounds as components of antibacterial and anti-inflammatory cocktails is discussed.The authors acknowledge financial support from FEDER funds and Fondo Social Europeo through grants from the Spanish Ministry of Economy and Competitiveness (grants SAF2011-22922, SAF2011-22812) the Andalusian regional government Junta de Andalucía (grant CVI-7335) and the Centre of Networked Biomedical Research on Hepatic and Digestive Diseases (CIBERehd) which is funded by the Carlos III Health Institute and the Ramón Areces Foundation, Spain

Multicenter retrospective analysis of 581 patients with primary intestinal non-hodgkin lymphoma from the Consortium for Improving Survival of Lymphoma (CISL)

<p>Abstract</p> <p>Background</p> <p>Primary intestinal non-Hodgkin lymphoma (NHL) is a heterogeneous disease with regard to anatomic and histologic distribution. Thus, analyses focusing on primary intestinal NHL with large number of patients are warranted.</p> <p>Methods</p> <p>We retrospectively analyzed 581 patients from 16 hospitals in Korea for primary intestinal NHL in this retrospective analysis. We compared clinical features and treatment outcomes according to the anatomic site of involvement and histologic subtypes.</p> <p>Results</p> <p>B-cell lymphoma (n = 504, 86.7%) was more frequent than T-cell lymphoma (n = 77, 13.3%). Diffuse large B-cell lymphoma (DLBCL) was the most common subtype (n = 386, 66.4%), and extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) was the second most common subtype (n = 61, 10.5%). B-cell lymphoma mainly presented as localized disease (Lugano stage I/II) while T-cell lymphomas involved multiple intestinal sites. Thus, T-cell lymphoma had more unfavourable characteristics such as advanced stage at diagnosis, and the 5-year overall survival (OS) rate was significantly lower than B-cell lymphoma (28% versus 71%, P < 0.001). B symptoms were relatively uncommon (20.7%), and bone marrow invasion was a rare event (7.4%). The ileocecal region was the most commonly involved site (39.8%), followed by the small (27.9%) and large intestines (21.5%). Patients underwent surgery showed better OS than patients did not (5-year OS rate 77% versus 57%, P < 0.001). However, this beneficial effect of surgery was only statistically significant in patients with B-cell lymphomas (P < 0.001) not in T-cell lymphomas (P = 0.460). The comparison of survival based on the anatomic site of involvement showed that ileocecal regions had a better 5-year overall survival rate (72%) than other sites in consistent with that ileocecal region had higher proportion of patients with DLBCL who underwent surgery. Age > 60 years, performance status ≥ 2, elevated serum lactate dehydrogenase, Lugano stage IV, presence of B symptoms, and T-cell phenotype were independent prognostic factors for survival.</p> <p>Conclusions</p> <p>The survival of patients with ileocecal region involvement was better than that of patients with involvement at other sites, which might be related to histologic distribution, the proportion of tumor stage, and need for surgical resection.</p

Platelet-Activating Factor Induces TLR4 Expression in Intestinal Epithelial Cells: Implication for the Pathogenesis of Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in neonatal intensive care units, however its pathogenesis is not completely understood. We have previously shown that platelet activating factor (PAF), bacteria and TLR4 are all important factors in the development of NEC. Given that Toll-like receptors (TLRs) are expressed at low levels in enterocytes of the mature gastrointestinal tract, but were shown to be aberrantly over-expressed in enterocytes in experimental NEC, we examined the regulation of TLR4 expression and signaling by PAF in intestinal epithelial cells using human and mouse in vitro cell lines, and the ex vivo rat intestinal loop model. In intestinal epithelial cell (IEC) lines, PAF stimulation yielded upregulation of both TLR4 mRNA and protein expression and led to increased IL-8 secretion following stimulation with LPS (in an otherwise LPS minimally responsive cell line). PAF stimulation resulted in increased human TLR4 promoter activation in a dose dependent manner. Western blotting and immunohistochemical analysis showed PAF induced STAT3 phosphorylation and nuclear translocation in IEC, and PAF-induced TLR4 expression was inhibited by STAT3 and NFκB Inhibitors. Our findings provide evidence for a mechanism by which PAF augments inflammation in the intestinal epithelium through abnormal TLR4 upregulation, thereby contributing to the intestinal injury of NEC

Left Bundle Branch Block, an Old–New Entity

Left bundle branch block (LBBB) is generally associated with a poorer prognosis in comparison to normal intraventricular conduction, but also in comparison to right bundle branch block which is generally considered to be benign in the absence of an underlying cardiac disorder like congenital heart disease. LBBB may be the first manifestation of a more diffuse myocardial disease. The typical surface ECG feature of LBBB is a prolongation of QRS above 0.11 s in combination with a delay of the intrinsic deflection in leads V5 and V6 of more than 60 ms and no septal q waves in leads I, V5, and V6 due to the abnormal septal activation from right to left. LBBB may induce abnormalities in left ventricular performance due to abnormal asynchronous contraction patterns which can be compensated by biventricular pacing (resynchronization therapy). Asynchronous electrical activation of the ventricles causes regional differences in workload which may lead to asymmetric hypertrophy and left ventricular dilatation, especially due to increased wall mass in late-activated regions, which may aggravate preexisting left ventricular pumping performance or even induce it. Of special interest are patients with LBBB and normal left ventricular dimensions and normal ejection fraction at rest but who may present with an abnormal increase in pulmonary artery pressure during exercise, production of lactate during high-rate pacing, signs of ischemia on myocardial scintigrams (but no coronary artery narrowing), and abnormal ultrastructural findings on myocardial biopsy. For this entity, the term latent cardiomyopathy had been suggested previously