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BackgroundAlthough evidence points to a role for histamine and serotonin in visceral hypersensitivity, activation of calcium channels such as transient receptor potential vanilloid 4 (TRPV4) also causes visceral hypersensitivity. We hypothesised that TRPV4 is important for the generation of hypersensitivity, mediating histamine- and serotonin-induced visceral hypersensitivity.MethodsIn response to histamine, serotonin and/or TRPV4 agonist (4αPDD), calcium signals and TRPV4 localisation studies were performed on dorsal root ganglia (DRG) neurons projecting from the colon. To evaluate visceral nociception, colorectal distension (CRD) was performed in mice treated with serotonin or histamine and with 4αPDD. Intrathecal injection of TRPV4 silencer RNA (SiRNA) or mismatch SiRNA was used to target TRPV4 expression.ResultsPre-exposure of DRG neurons projecting from the colon, to histamine or serotonin, increased Ca2+ responses induced by 4αPDD by a protein kinase C (PKC), phospholipase Cβ (PLCβ), mitogen-activated protein kinase kinase (MAPKK) and phospholipase A2 (PLA2)-dependent mechanisms. Serotonin or histamine treatments enhanced TRPV4 expression at the plasma membrane by a MAPKK mechanism. Hypersensitivity induced by serotonin or histamine were both significantly inhibited by TRPV4 SiRNA intrathecal injection. Administration of sub-nociceptive doses of serotonin or histamine potentiated 4αPDD-induced hypersensitivity in response to CRD.ConclusionsSerotonin and histamine sensitise TRPV4 response to 4αPDD both in vivo (increased visceral hypersensitivity) and in vitro, in sensory neurons, by a PKC, PLA2, PLCβ and MAPKK-dependent mechanism. Serotonin and histamine caused a MAPKK-dependent increase in TRPV4 expression in colonic sensory neurons plasma membranes. Further, histamine- or serotonin-mediated visceral hypersensitivity depend on TRPV4 expression in sensory neurons. TRPV4 appears as a common mechanism to several known mediators of visceral hypersensitivity.

The objective of this study was to evaluate the effect of different intercropping and spacing arrangements of corn (Zea mays L) and crotalaria (Crotalaria spp) on the agronomic characteristics, chemical composition and forage digestibility. The experiment was distributed in a randomized complete block design with a 2 × 2 + 1 factorial scheme. The treatments were two cultivation systems (corn + Crotalaria juncea (CCJ) intercropping, and corn + Crotalaria ochroleuca (CCO) intercropping), in two spacing arrangements (A1 (corn and crotalaria sown in the same row) and A2 (corn and crotalaria sown in alternate rows)) plus control (single corn monocropping (CSC)), with six replicates per treatment, for 2 years. Forage plants were harvested when the corn grain reached the doughy-farinaceous phenological stage. Forage mass (total and of each species), morphological composition, chemical composition and in vitro digestibility were evaluated. The forage accumulation was higher for the A1 spatial arrangement. In the second year, the highest total forage mass was verified in the CCO intercropping (11 140 kg/ha). The highest corn mass (9402 kg/ha) was observed for CSC. The highest crotalaria mass was observed in the CCJ intercropping in both years. Regarding the chemical composition, CCJ and CCO intercropping had the highest crude protein concentration. The lowest acid detergent fibre concentration was observed in CSC and CCO intercropping, directly reflecting the in vitro dry matter digestibility coefficients. It is concluded that C. ochroleuca, sown between corn rows, had higher forage accumulation and nutritive value among the treatments tested in this experiment.

Haematopoietic cell transplant activity in the 28 countries comprising Latin America is poorly defined. We conducted a voluntary survey of members of the Latin American Bone Marrow Transplantation Group regarding transplant activity 2009–2012. Collated responses were compared with data of transplant rates from the Worldwide Network for Blood and Marrow Transplantation for other geographic regions. Several socio-economic variables were analysed to determine correlations with transplant rates. In total, 94 teams from 12 countries reported 11 519 transplants including 7033 autotransplants and 4486 allotransplants. Annual activity increased from 2517 transplants in 2009 to 3263 in 2012, a 30% increase. Median transplants rate (transplant per million inhabitants) in 2012 was 64 (autotransplants, median 40; allotransplants, median 24). This rate is substantially lower than that in North America and European regions (482 and 378) but higher than that in the Eastern Mediterranean and Asia Pacific regions (30 and 45). However, the Latin America transplant rate is 5–8-fold lower than that in America and Europe, suggesting a need to increase transplant availability. Transplant team density in Latin America (teams per million population; 1.8) is 3–4-fold lower than that in North America (6.2) or Europe (7.6). Within Latin America, there is substantial diversity in transplant rates by country partially explained by diverse socio-economic variables including per capita gross national income, health expenditure and physician density. These data should help inform future health-care policy in Latin America.

Capiaçu is a cultivar of elephant grass (Pennisetum purpureum Schum.), which is a promising species for use in ruminant feed and presents a high potential for biomass production. However, as this grass became subjected to different management strategies, fluctuations in biomass production were observed, reflecting on its nutritive value. The objective was to verify the effect of cutting age and nitrogen (N) application on the productivity and nutritional value of BRS Capiaçu. A randomized block design was used in a 3 × 3 factorial scheme: three cutting ages (60, 90, and 120 days) and three levels of nitrogen fertilization (0, 100, and 200 kg N/ha/year). The variables evaluated were: productivity and chemical composition of the leaf, stem, and whole plant fractions, besides the production of nutrients and efficiency of utilization of applied nitrogen (EUAN). There were interaction effects between cutting ages and N application on dry matter (DM), crude protein (CP), cellulose, hemicellulose, and lignin production. Plants cut every 120 days and fertilized with 100 or 200 kg N/ha had the highest annual DM production. Nitrogen fertilization was efficient in increasing the percentage of leaves and the production of CP and DM digestibility of the grass. The highest CP production (in kg/ha/year) was observed for the 60- and 90-days old grass fertilized with 200 kg of N/ha/year. Grasses that were cut every 90 days and that received nitrogen fertilization of 100 kg N/ha/year were the ones that presented the highest EUAN. The cutting at 90 days of age, associated with N fertilization of 100 kg N/ha/year, is the best strategy for BRS Capiaçu.

The conservation of elephant grass cultivar Capiaçu in the form of total mixed ration (TMR) silage can help to improve the quality of the fermentative process and optimize feed management. However, the best cutting age of grass and the necessity of using microbes-enzymatic additives to aid in the process have not been determined thus far. Therefore, the objective of this study was to evaluate cutting age and different microbes-enzymatic additives on the fermentative and nutritional quality of total mixed ration (TMR) silages based on BRS Capiaçu. A completely randomized design was used in a 3×3 factorial scheme, with three cutting ages of grass (60, 90, and 120 days of regrowth), associated with three types of additives [CON (control), HOM (homofermentative inoculant + fibrolytic enzyme), and COMBO (homofermentative inoculant + heterofermentative inoculant + fibrolytic enzyme)]. The fermentative losses, the production of organic acids, chemical composition, and the aerobic stability of the tested silages were measured. The TMR silages containing 60-day-old grass showed the lowest dry matter contents, highest effluent production, and lower aerobic stability. The COMBO inoculant application provided higher acetic acid contents and greater aerobic stability of the 90- and 120-day-old grass silages. The highest lactic acid concentrations were observed in silages produced with the 60- and 90-day-old grass silages. It is concluded that the TMR produced with BRS Capiaçu at 90 days of age and in association with COMBO is the best option to balance the nutritional and fermentative quality of this type of silage.

Whole-genome characterisation in clinical microbiology enables to detect trends in infection dynamics and disease transmission. Here, we report a case of bacteraemia due to Campylobacter fetus subsp. fetus in a rural worker under cancer treatment that was diagnosed with cellulitis; the patient was treated with antibiotics and recovered. The routine typing methods were not able to identify the microorganism causing the infection, so it was further analysed by molecular methods and whole-genome sequencing. The multi-locus sequence typing (MLST) revealed the presence of the bovine-associated ST-4 genotype. Whole-genome comparisons with other C. fetus strains revealed an inconsistent phylogenetic position based on the core genome, discordant with previous ST-4 strains. To the best of our knowledge, this is the first C. fetus subsp. fetus carrying the ST-4 isolated from humans and represents a probable case of zoonotic transmission from cattle.

Background/Objectives: Short-chain fatty acids (SCFAs) produced by gut microbiota from dietary fiber fermentation play crucial roles in health and disease. While most research focuses on individual fibers, this study investigated whether a fiber mixture could synergistically increase SCFAs, exceeding the expected average production of individual contributions and microbial signatures associated with this phenomenon. Methods: We quantified synergistic SCFA production using secondary analysis of in vitro fecal fermentation data from 33 participants across four health conditions (healthy controls, Crohn’s disease, ulcerative colitis, and Parkinson’s disease), by comparing observed fiber mixture output to expected additive contributions from individual components and identified microbial signatures associated with synergistic SCFA production through differential abundance and network analyses. Results: The fiber mixture consistently outperformed most individual fibers and demonstrated synergistic SCFA production, yielding 32.8 ± 20.1% more total SCFAs than expected. This synergistic effect was observed across all four health conditions studied, with many individuals showing >50% synergy and some exceeding 80%. Differential abundance analysis revealed that individuals exhibiting synergistic responses were enriched in taxa from Lachnospiraceae and Ruminococcaceae families, key butyrate-producing groups that likely facilitate cooperative interactions. Network analysis confirmed these families as central hubs in synergy-associated microbial interactions. Conclusions: These findings suggest that fiber mixtures can harness cooperative microbial interactions to synergistically enhance SCFA production regardless of health status, offering potential for developing more effective prebiotics for superior therapeutic outcomes.

Autologous peripheral blood stem cell (PBSC) transplantation is a standard treatment of multiple myeloma (MM), Hodgkin lymphoma and various subtypes of non-Hodgkin lymphoma. Cryopreservation of hematopoietic stem cells is standard practice that allows time for delivery of conditioning regimen prior to cell infusion. The aim of this Worldwide Network for Blood & Marrow Transplantation (WBMT) work was to assess existing evidence on non-cryopreserved autologous transplants through a systematic review/meta-analysis, to study feasibility and safety of this approach. We searched PubMed, Web of Science and SCOPUS for studies that utilized non-cryopreserved autologous PBSC transplantation. Identified literature was reviewed for information on mobilization, apheresis, preservation and viability, conditioning regimen, engraftment, response, and survival. Results highlight collective experience from 19 transplant centers (1686 patients), that performed autologous transplants using non-cryopreserved PBSCs. The mean of infused CD34+ was 5.6 × 10 6 /kg. Stem cell viability at transplantation was >90% in MM and >75% in lymphomas, after a storage time of 24–144 h at +4 °C. Mean time-to-neutrophil engraftment was 12 days and 15.3 days for platelets. Pooled proportion estimates of day 100 transplant-related mortality and graft failure were 1% and 0%, respectively. Non-cryopreservation of apheresed autologous PBSCs appears feasible and safe.

Correction to: Bone Marrow Transplantation (2017) 52, 671–677; doi:10.1038/bmt.2016.361; published online 23 January 2017 Since the online publication of this article, the authors realised there were errors in the legends for Figures 1 and 2. The original legend for Figure 1 was: ‘Reasons for auto (left) (N=2057) and allotransplants (right) (N=1206).