Marine mammals as indicators of Anthropocene Ocean Health

The current state of marine mammal populations reflects increasing anthropogenic impacts on the global Ocean. Adopting a holistic approach towards marine mammal health, incorporating healthy individuals and healthy populations, these taxa present indicators of the health of the overall Ocean system. Their present deterioration at the animal, population and ecosystem level has implications for human health and the global system. In the Anthropocene, multiple planetary boundaries have already been exceeded, and quiet tipping points in the Ocean may present further uncertainties. Long and short-term monitoring of marine mammal health in the holistic sense is urgently required to assist in evaluating and reversing the impact on Ocean Health and aid in climate change mitigation

Effects of ondansetron alone and in combination with domperidone in the prevention of chemotherapy-induced nausea and vomiting in breast cancer patients

The efficacy and safety of ondansetron, administered alone and in combination with domperidone to prevent chemotherapy-induced nausea and vomiting of breast cancer patients receiving chemotherapy FAC regimen (5-fluorouracil, adriamycin and cyclophosphamide) were evaluated. A consecutive open-label interventional study was conducted on a total number of 86 female breast cancer patients who were receiving chemotherapy. Forty two patients received ondansetron (8 mg) intravenously 30 min before chemotherapy which is followed by ondansetron (8 mg) administered orally every 8 hourly for 2 days from the day of start of chemotherapy. Another 44 patients received ondansetron (8 mg) intravenously 30 min before chemotherapy followed by ondansetron (8 mg) plus domperidone (20 mg) administered orally 8 hourly for 48 hours from the day of start of chemotherapy. The number of emetic episodes, severity of nausea, assessment of appetite and adverse events were recorded at 8 hour intervals for two days study period using specific scoring criteria. Ondansetron in combination with domperidone significantly decreased the chemotherapy-induced nausea and vomiting in comparison with ondansetron administered alone (P<0.001). Appetite status was good with combination therapy (P<0.001). Improvement in appetite indicates that ondansetron plus domperidone exert protective effect against nausea and maintain normal appetite, while patients who were getting monotherapy experience loss of appetite. The common adverse event, headache was present in both the groups. No extrapyramidal reaction was observed in any group. This study showed that ondansetron plus domperidone exert more pronounced antiemetic effect in patients with breast cancer receiving moderately emetogenic chemotherapy (FAC regimen) with good appetite status and less adverse effect

Th17-to-Tfh plasticity during periodontitis limits disease pathology

Th17 cell plasticity is crucial for development of autoinflammatory disease pathology. Periodontitis is a prevalent inflammatory disease where Th17 cells mediate key pathological roles, yet whether they exhibit any functional plasticity remains unexplored. We found that during periodontitis, gingival IL-17 fate-mapped T cells still predominantly produce IL-17A, with little diversification of cytokine production. However, plasticity of IL-17 fate-mapped cells did occur during periodontitis, but in the gingiva draining lymph node. Here, some Th17 cells acquired features of Tfh cells, a functional plasticity that was dependent on IL-6. Notably, Th17-to-Tfh diversification was important to limit periodontitis pathology. Preventing Th17-to-Tfh plasticity resulted in elevated periodontal bone loss that was not simply due to increased proportions of conventional Th17 cells. Instead, loss of Th17-to-Tfh cells resulted in reduced IgG levels within the oral cavity and a failure to restrict the biomass of the oral commensal community. Thus, our data identify a novel protective function for a subset of otherwise pathogenic Th17 cells during periodontitis.</p

Th17-to-Tfh plasticity during periodontitis limits disease pathology.

Th17 cell plasticity is crucial for development of autoinflammatory disease pathology. Periodontitis is a prevalent inflammatory disease where Th17 cells mediate key pathological roles, yet whether they exhibit any functional plasticity remains unexplored. We found that during periodontitis, gingival IL-17 fate-mapped T cells still predominantly produce IL-17A, with little diversification of cytokine production. However, plasticity of IL-17 fate-mapped cells did occur during periodontitis, but in the gingiva draining lymph node. Here, some Th17 cells acquired features of Tfh cells, a functional plasticity that was dependent on IL-6. Notably, Th17-to-Tfh diversification was important to limit periodontitis pathology. Preventing Th17-to-Tfh plasticity resulted in elevated periodontal bone loss that was not simply due to increased proportions of conventional Th17 cells. Instead, loss of Th17-to-Tfh cells resulted in reduced IgG levels within the oral cavity and a failure to restrict the biomass of the oral commensal community. Thus, our data identify a novel protective function for a subset of otherwise pathogenic Th17 cells during periodontitis

Leukocyte trafficking between stromal compartments:lessons from rheumatoid arthritis

The trafficking of leukocytes from their site of production in the bone marrow through the circulation and into peripheral tissues is a highly coordinated and tightly regulated process in healthy individuals. Lymphocytes are long-lived cells that visit many lymphoid and peripheral tissues over their lifetime and can even recirculate back to the bone marrow, whereas granulocytes and monocytes are not thought to recirculate so widely. Using rheumatoid arthritis (RA) as an example, this Review explores the migratory journey of leukocytes during the establishment and resolution of disease — from the blood, through the lymphoid tissues and into peripheral sites such as the lungs and the gut before their entry into the synovium. This Review explores our current understanding of differences in the molecular processes that regulate leukocyte trafficking at different phases of disease and in different stromal compartments, which could help to explain the disease heterogeneity seen in patients with RA. Expanding our knowledge of these processes will open new avenues in the clinical management of RA, paving the way for personalized medicine that is founded on the pathological molecular signature of each patient, which varies according to their phase of disease or disease subtype