There is increasing emphasis on the need for effective ways of sharing knowledge to enhance environmental management and sustainability. Knowledge exchange (KE) are processes that generate, share ...and/or use knowledge through various methods appropriate to the context, purpose, and participants involved. KE includes concepts such as sharing, generation, coproduction, comanagement, and brokerage of knowledge. This paper elicits the expert knowledge of academics involved in research and practice of KE from different disciplines and backgrounds to review research themes, identify gaps and questions, and develop a research agenda for furthering understanding about KE. Results include 80 research questions prefaced by a review of research themes. Key conclusions are: (1) there is a diverse range of questions relating to KE that require attention; (2) there is a particular need for research on understanding the process of KE and how KE can be evaluated; and (3) given the strong interdependency of research questions, an integrated approach to understanding KE is required. To improve understanding of KE, action research methodologies and embedding evaluation as a normal part of KE research and practice need to be encouraged. This will foster more adaptive approaches to learning about KE and enhance effectiveness of environmental management.
Purpose
Acute graft versus host disease (aGVHD) is a major cause of non-relapse morbidity and mortality post-allogenic hematopoietic stem cell transplant (HSCT). Using conventional literature search ...and computational approaches, our objective was to identify oral and gut bacterial species associated with aGVHD, potentially affecting drug treatment via lipopolysaccharide (LPS) pathways.
Methods
Medline, PubMed, PubMed Central, and Google Scholar were searched using MeSH terms. The top 100 hits per database were curated, and 25 research articles were selected to examine oral and gut microbiomes associated with health, HSCT, and aGVHD. Literature search validation, aGVHD drug targets, and microbial metabolic pathway identification were completed using BioReader, MACADAM, KEGG, and STRING programs.
Results
Our review determined that (1) oral genera
Rothia
,
Solobacterium
, and
Veillonella
were identified in HSCT patients’ stool and associated with aGVHD; (2) shifts in gut
enterococci
profiles were determined in HSCT-associated aGVHD; (3) gut microbiome dysbiosis prior or during HSCT and lower Shannon diversity index at time of HSCT were also associated with increased risk of aGVHD and transplant related death; and (4) Coriobacteriaceae family was negatively correlated with gut aGVHD, whereas
Eubacterium limosum
was associated with decreased risk of chronic GVHD relapse.
Additionally, we identified molecular pathways related to TLR4/ LPS, including candidate aGVHD drug targets, impacted by oral and gut bacterial taxa.
Conclusion
Reduced microbial diversity reflects higher severity and mortality rate in HSCT patients with aGVHD. Multi-omics approaches to decipher oral and gut microbiome associations will be critical for developing aGVHD preventive therapies.
Highlights•5-year FFBF was 92% in patients with intermediate risk prostate cancer treated with 15 Gy HDR boost. •5-year MFS was 96% in patients with intermediate risk prostate cancer treated with ...15 Gy HDR boost.
Aim
This systematic review aimed to provide an overview of (inter)national guidelines on the treatment of peritoneal metastases of colorectal cancer origin (PMCRC) and to determine the degree of ...consensus and available evidence with identification of topics for future research.
Method
A systematic search of MEDLINE, Embase, PubMed as well as Tripdatabase, National Guideline Clearinghouse, BMJ Best Practice and Guidelines International Network was performed to identify (inter)national guidelines and consensus statements from oncological or surgical societies on PMCRC. The quality of guidelines was assessed using the AGREE‐II score. Topics followed by recommendations were extracted from the guidelines. The recommendations, highest level of supporting evidence and the degree of consensus were determined for each topic.
Results
Twenty‐one guidelines were included, in most (15) of which cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) was recommended in selected patients based on level 1b evidence. Substantial consensus was also reached on the benefit of multidisciplinary team discussion and the achievability of a (near) complete cytoreduction (CC0‐1) without supporting evidence. Both evidence and consensus were lacking regarding other aspects including preoperative positron emission tomography/CT, second look surgery in high risk patients, the optimal patient selection for CRS/HIPEC, procedural aspects of HIPEC and (perioperative) systemic therapy.
Conclusion
In currently available guidelines, evidence and consensus on the treatment strategy for PMCRC are lacking. Updates of guidelines are ongoing and future (randomized) clinical trials should contribute to multidisciplinary and international consensus on treatment strategies for PMCRC.
To assess the efficacy of high-intensity interval training (HIIT) for improving cardiorespiratory fitness (CRF) in patients awaiting resection for urological malignancy within four weeks.
A ...randomised control trial of consecutive patients aged (>65 years) scheduled for major urological surgery in a large secondary referral centre in a UK hospital. The primary outcome is change in anaerobic threshold (VO
) following HIIT vs. standard care.
Forty patients were recruited (mean age 72 years, male (39): female (1)) with 34 completing the protocol. Intention to treat analysis showed significant improvements in anaerobic threshold (VO
; mean difference (MD) 2.26 ml/kg/min (95% CI 1.25-3.26)) following HIIT. Blood pressure (BP) also significantly reduced in following: HIIT (SBP: -8.2 mmHg (95% CI -16.09 to -0.29) and DBP: -6.47 mmHg (95% CI -12.56 to -0.38)). No reportable adverse safety events occurred during HIIT and all participants achieved >85% predicted maximum heart rate during sessions, with protocol adherence of 84%.
HIIT can improve CRF and cardiovascular health, representing clinically meaningful and achievable pre-operative improvements. Larger randomised trials are required to investigate the efficacy of prehabilitation HIIT upon different cancer types, post-operative complications, socio-economic impact and long-term survival.
A genomic and bioactivity informed analysis of the metabolome of the extremophile Amycolatopsis sp. DEM30355 has allowed for the discovery and isolation of the polyketide antibiotic tatiomicin. ...Identification of the biosynthetic gene cluster was confirmed by heterologous expression in Streptomyces coelicolor M1152. Structural elucidation, including absolute stereochemical assignment, was performed using complementary crystallographic, spectroscopic and computational methods. Tatiomicin shows antibiotic activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Cytological profiling experiments suggest a putative antibiotic mode-of-action, involving membrane depolarisation and chromosomal decondensation of the target bacteria.
•APP4 was predictive of metastatic failure after curative prostate cancer treatment.•APP4 was predictive of ADT use for biochemical failure after prostate cancer treatment.•APP4 was predictive of ...biochemical failure after curative prostate cancer treatment.•Optimized cutpoints for APP4 were found in this study.
To identify if, in intermediate risk prostate cancer (IR-PCa), the absolute percentage of biopsied tissue positive for pattern 4 disease (APP4) may be a predictor of outcome.
411 patients with IR-PCa were retrospectively reviewed. APP4 was calculated based on biopsy reports. Multivariable competing risk analysis was then performed on optimized APP4 cutpoints to predict for biochemical failure (BF), androgen deprivation use for BF (ADT-BF) and development of metastases (MD).
Median follow-up for the cohort was 5.2 (Inter Quartile Range: 2.9–6.6) years. Median baseline PSA was 7.3 (5.3–9.8) ng/mL. 234 (56.9%) patients had T1 and 177 (43.1%) had T2 disease. Median APP4 was 2.00 (0.75–7.50)%.
38 (9.3%) patients experienced BF. The optimal cutpoint of APP4 for BF was >3.3% with an area under the curve (AUC) of 0.66. 17 (4.1%) received ADT-BF. The ADT-BF cutpoint was >6.6% with an AUC of 0.72. Eight (2.0%) developed MD. The MD cutpoint was >17.5% with an AUC of 0.86.
Using APP4 >3.3 vs ≤ 3.3, log-transformed baseline PSA ln(PSA) (HR 2.5, 1.1–6.1; p = 0.037) and APP4 (HR 2.3, 1.1–4.7; p = 0.031) predicted for BF. Using APP4 >6.6 vs ≤ 6.6, ln(PSA) (HR 4.2, 1.4–12.4; p = 0.010) and APP4 (HR 3.7, 1.4–10.0; p = 0.009) were predictive of ADT-BF. APP4 >17.5 vs ≤ 17.5 alone was predictive of MD (HR 25.7, 4.9–135.3; p < 0.001).
APP4 cutpoints of >3.3%, >6.6% and >17.5% were strongly associated with increased risk of BF, ADT-BF and developing MD respectively. These findings may inform future practice when treating IR-PCa but require external validation.
The multidrug resistance-1 (MDR1) gene encodes an ATP-dependent efflux transporter that is highly expressed in the colon. In mice, loss of MDR1 function results in colitis with similarities to human ...inflammatory bowel diseases (IBD). Here, we show that MDR1 has an unexpected protective role for the mitochondria where MDR1 deficiency results in mitochondrial dysfunction with increased mitochondrial reactive oxygen species (mROS) driving the development of colitis. Exogenous induction of mROS accelerates, while inhibition attenuates colitis in vivo; these effects are amplified in MDR1 deficiency. In human IBD, MDR1 is negatively correlated to SOD2 gene expression required for mROS detoxification. To provide direct evidential support, we deleted intestinal SOD2 gene in mice and showed an increased susceptibility to colitis. We exploited the genome-wide association data sets and found many (∼5%) of IBD susceptibility genes with direct roles in regulating mitochondria homeostasis. As MDR1 primarily protects against xenotoxins via its efflux function, our findings implicate a distinct mitochondrial toxin+genetic susceptibility interaction leading to mitochondrial dysfunction, a novel pathogenic mechanism that could offer many new therapeutic opportunities for IBD.
Contact with livestock and consumption of unpasteurised dairy products are associated with an increased risk of zoonotic and foodborne infection, particularly among populations with close animal ...contact, including pastoralists and semi-pastoralists. However, there are limited data on disease risk factors among pastoralists and other populations where livestock herding, particularly of dromedary camels, is common. This cross-sectional study used a previously validated survey instrument to identify risk factors for self-reported symptoms. Adults (n = 304) were randomly selected from households (n = 171) in the Somali Region of Ethiopia, a region characterised by chronic food insecurity, population displacement, recurrent droughts and large semi-pastoralist and pastoralist populations. Multivariable logistic regression assessed associations between self-reported symptoms and type of milk consumed, controlling for demographics and human-animal interaction. Consumption of days-old unrefrigerated raw camel milk was significantly associated with symptoms in the 30 days prior to the survey (AOR = 5.07; 95% CI 2.41–10.66), after controlling for age, refugee status, sanitation, camel ownership and source of drinking water and accounting for clustering. Consumption of days-old unrefrigerated raw ruminant milk was significantly associated with symptoms (AOR = 4.00, 95% CI 1.27–12.58). Source of drinking water and camel ownership, a proxy for camel contact, were significantly associated with the outcome in each model. There were no significant associations between self-reported symptoms and fresh or soured animal milk consumption. Research is needed to identify pathogens and major routes of transmission. Tailored communication campaigns to encourage safe food preparation should also be considered.
The alternative sigma factor RpoS controls the expression of many stationary-phase genes in Escherichia coli and other bacteria. Though the RpoS regulon is a large, conserved system that is critical ...for adaptation to nutrient deprivation and other stresses, it remains incompletely characterized. In this study, we have used oligonucleotide arrays to delineate the transcriptome that is controlled by RpoS during entry into stationary phase of cultures growing in rich medium. The expression of known RpoS-dependent genes was confirmed to be regulated by RpoS, thus validating the use of microarrays for expression analysis. The total number of positively regulated stationary-phase genes was found to be greater than 100. More than 45 new genes were identified as positively controlled by RpoS. Surprisingly, a similar number of genes were found to be negatively regulated by RpoS, and these included almost all genes required for flagellum biosynthesis, genes encoding enzymes of the TCA cycle, and a physically contiguous group of genes located in the Rac prophage region. Negative regulation by RpoS is thus much more extensive than has previously been recognized, and is likely to be an important contributing factor to the competitive growth advantage of rpoS mutants reported in previous studies.
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