From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways

The human body hosts an enormous abundance and diversity of microbes, which perform a range of essential and beneficial functions. Our appreciation of the importance of these microbial communities to many aspects of human physiology has grown dramatically in recent years. We know, for example, that animals raised in a germ-free environment exhibit substantially altered immune and metabolic function, while the disruption of commensal microbiota in humans is associated with the development of a growing number of diseases. Evidence is now emerging that, through interactions with the gut-brain axis, the bidirectional communication system between the central nervous system and the gastrointestinal tract, the gut microbiome can also influence neural development, cognition and behaviour, with recent evidence that changes in behaviour alter gut microbiota composition, while modifications of the microbiome can induce depressive-like behaviours. Although an association between enteropathy and certain psychiatric conditions has long been recognized, it now appears that gut microbes represent direct mediators of psychopathology. Here, we examine roles of gut microbiome in shaping brain development and neurological function, and the mechanisms by which it can contribute to mental illness. Further, we discuss how the insight provided by this new and exciting field of research can inform care and provide a basis for the design of novel, microbiota-targeted, therapies.GB Rogers, DJ Keating, RL Young, M-L Wong, J Licinio, and S Wesseling

Field comparison of OraQuick ADVANCE Rapid HIV-1/2 antibody test and two blood-based rapid HIV antibody tests in Zambia.

BACKGROUND: Zambia's national HIV testing algorithm specifies use of two rapid blood based antibody assays, DetermineHIV-1/2 (Inverness Medical) and if positive then Uni-Gold Recombigen HIV-1/2 (Trinity Biotech). Little is known about the performance of oral fluid based HIV testing in Zambia. The aims of this study are two-fold: 1) to compare the diagnostic accuracy (sensitivity and specificity) under field conditions of the OraQuick ADVANCE Rapid HIV-1/2 (OraSure Technologies, Inc.) to two blood-based rapid antibody tests currently in use in the Zambia National Algorithm, and 2) to perform a cost analysis of large-scale field testing employing the OraQuick. METHODS: This was a operational retrospective research of HIV testing and questionnaire data collected in 2010 as part of the ZAMSTAR (Zambia South Africa TB and AIDS reduction) study. Randomly sampled individuals in twelve communities were tested consecutively with OraQuick test using oral fluid versus two blood-based rapid HIV tests, Determine and Uni-Gold. A cost analysis of four algorithms from health systems perspective were performed: 1) Determine and if positive, then Uni-Gold (Determine/Uni-Gold); based on current algorithm, 2) Determine and if positive, then OraQuick (Determine/OraQuick), 3) OraQuick and if positive, then Determine (OraQuick/Determine), 4) OraQuick and if positive, then Uni-Gold (OraQuick/Uni-Gold). This information was then used to construct a model using a hypothetical population of 5,000 persons with varying prevalence of HIV infection from 1-30%. RESULTS: 4,458 participants received both a Determine and OraQuick test. The sensitivity and specificity of the OraQuick test were 98.7 (95%CI, 97.5-99.4) and 99.8 (95%CI, 99.6-99.9), respectively when compared to HIV positive serostatus. The average unit costs per algorithm were US$3.76, US$4.03, US$7.35, and US$7.67 for Determine/Uni-Gold, Determine/OraQuick, OraQuick/Determine, and OraQuick/Uni-Gold, respectively, for an HIV prevalence of 15%. CONCLUSIONS: An alternative HIV testing algorithm could include OraQuick test which had a high sensitivity and specificity. The current Determine/Uni-Gold testing algorithm is the least expensive when compared to Determine/OraQuick, OraQuick/Determine, and OraQuick/Uni-Gold in the Zambian setting. From our field experience, oral fluid based testing offers many advantages over blood-based testing, especially with self testing on the horizon

Rapid responses of root traits and productivity to phosphorus and cation additions in a tropical lowland forest in Amazonia

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordSoil nutrient availability can strongly affect root traits. In tropical forests, phosphorus (P) is often considered the main limiting nutrient for plants. However, support for the P paradigm is limited, and N and cations might also control tropical forests functioning. We used a large-scale experiment to determine how the factorial addition of nitrogen (N), P and cations affected root productivity and traits related to nutrient acquisition strategies (morphological traits, phosphatase activity, arbuscular mycorrhizal colonisation and nutrient contents) in a primary rainforest growing on low-fertility soils in Central Amazonia after one year of fertilisation. Multiple root traits and productivity were affected. Phosphorus additions increased annual root productivity and root diameter, but decreased root phosphatase activity. Cation additions increased root productivity at certain times of year, also increasing root diameter and mycorrhizal colonisation. P and cation additions increased their element concentrations in root tissues. No responses were detected with N addition. Here we show that rock-derived nutrients determine root functioning in low-fertility Amazonian soils, demonstrating not only the hypothesised importance of P, but also highlighting the role of cations. The changes in fine root traits and productivity indicate that even slow-growing tropical rainforests can respond rapidly to changes in resource availability.Brazilian National Council for Scientific and 551 Technological Development (CNPq)Natural Environment Research Council (NERC)Australian Research Council (ARC)European Research Council (ERC

Early administration of donor lymphocyte infusions upon molecular relapse after allogeneic hematopoietic stem cell transplantation for chronic myeloid leukemia: a study by the Chronic Malignancies Working Party of the EBMT.

Patients with chronic myeloid leukemia relapsing after allogeneic hematopoietic stem cell transplantation may be treated by tyrosine kinase inhibitors and/or by donor lymphocyte infusions. The best strategies and timing of administration of lymphocytes are unclear. We analyzed 155 patients who relapsed after allogeneic stem cell transplantation with disease detectable only by molecular methods and who subsequently received lymphocytes. Transplants were performed in first chronic phase (n=125) or in advanced disease (n=29) from identical siblings (n=84) or unrelated donors (n=71) between 1986 and 2003. They received lymphocytes either during molecular relapse (n=85) or upon progression to more advanced disease (1993 to 2004). The median interval from relapse to lymphocyte infusion was 210 (0-1673) days. The median follow up after it was 46 (3-135) months. Overall survival was 76 +/- 4% at five years after lymphocyte infusions (89 +/- 8% with sibling donors and 63 +/- 13% with unrelated donors (P=0.003)). Survival was 69 +/- 14% when lymphocytes were given within six months of the detection of molecular relapse and 81 +/- 10% (P=0.061) when given later; 81 +/- 11% if given at molecular relapse versus 71 +/- 12% (P=0.26) with more advanced disease. In multivariate analysis survival was worse if the donor was unrelated (HR 2.54 (95% CI: 1.15-5.53), P=0.021) and better with lymphocyte infusions beyond six months from molecular relapse (HR 0.4 (95% CI: 0.19-0.84), P=0.018). These data confirm the remarkable efficacy of lymphocyte infusions for this disease. There appears to be no advantage from administering it early upon detection of molecular relapse in patients who received allogeneic stem cell transplantation for chronic myeloid leukemia

Open-access upper gastrointestinal endoscopy a decade after the introduction of proton pump inhibitors and helicobacter pylori eradication: a shift in endoscopic findings.

Contains fulltext : 51695.pdf (publisher's version ) (Closed access)BACKGROUND/AIM: Over the past 15 years, there were considerable changes in factors associated with the development and treatment of upper gastrointestinal symptoms, of which the introduction of proton pump inhibitors and Helicobacter pylori eradication in guidelines for treatment of patients with dyspepsia are the most prominent: findings at open-access upper gastrointestinal endoscopy have not been evaluated properly ever since. This study aims to compare the current prevalence of upper gastrointestinal endoscopic findings to the prevalence 15 years ago. METHODS: Data about endoscopic findings of consecutive patients for the first time referred for open-access upper gastrointestinal endoscopy between January 2002 and December 2004 was collected from medical files. The prevalence of each specific finding was compared with data described in three historical populations about 15 years ago. RESULTS: The current and historical study population consisted of 1,286 and 3,062 subjects, respectively. The prevalence of peptic ulcer disease and duodenitis significantly decreased by 12.6% (95% CI: 14.5-10.7) and 2.9% (95% CI: 4.5-1.3), respectively. On the other hand, the prevalence of reflux esophagitis and Barrett's esophagus both significantly increased by 6.9% (95% CI: 4.2-9.6) and 2.1% (95% CI: 0.8-4.4), respectively. CONCLUSIONS: Compared to 15 years ago, the prevalence of specific findings at open-access upper gastrointestinal endoscopy has changed considerably

NOD2 polymorphisms predict severe acute graft-versus-host and treatment-related mortality in T-cell-depleted haematopoietic stem cell transplantation.

Contains fulltext : 80954.pdf (publisher's version ) (Closed access)Single nucleotide polymorphisms (SNPs) in the NOD2 gene have significant impact on both treatment-related mortality (TRM) and acute GVHD (aGVHD) in haematopoietic stem cell transplantation (HSCT). The effect of these polymorphisms when using T-cell-depleted grafts has been poorly studied. We retrospectively analysed NOD2 polymorphisms in a cohort of 85 patients and donors who received an HLA-identical sibling partially T-cell-depleted HSCT (0.5 x 10(6) CD3+ T cells per kg) following idarubicin-containing conditioning regimens. NOD2 polymorphisms were present in 14 of 85 (16.5%) of patients and 18 of 85 (21%) of donors. The risk of severe aGVHD (grade III-IV) and the 1-year TRM was significantly higher in the presence of NOD2 polymorphisms (hazard ratio (HR) 6.0, P=0.02 for severe aGVHD and HR 3.3, P=0.02 for TRM, respectively) and was most prominent in cases where patient and donor both had a polymorphism (HR 10.5, P=0.002 and HR 3.9, P=0.002). There was also a trend towards increased risk of bacteraemia due to coagulase-negative staphylococci in patients with an NOD2 polymorphism. We conclude that NOD2 polymorphism screening should be used to optimize donor selection and antimicrobial prophylaxis to reduce the occurrence of aGVHD and TRM following allogeneic HSCT

FRAX provides robust fracture prediction regardless of socioeconomic status

The authors investigated the fracture risk assessment tool (FRAX) Canada calibration and discrimination according to income quintile in 51,327 Canadian women, with and without a competing mortality framework. The data shows that, under a competing mortality framework, FRAX provides robust fracture prediction and calibration regardless of socioeconomic status (SES)