Effects of Harmful Algal Blooms on Fish and Shellfish Species: A Case Study of New Zealand in a Changing Environment

Harmful algal blooms (HABs) have wide-ranging environmental impacts, including on aquatic species of social and commercial importance. In New Zealand (NZ), strategic growth of the aquaculture industry could be adversely affected by the occurrence of HABs. This review examines HAB species which are known to bloom both globally and in NZ and their effects on commercially important shellfish and fish species. Blooms of Karenia spp. have frequently been associated with mortalities of both fish and shellfish in NZ and the sub-lethal effects of other genera, notably Alexandrium spp., on shellfish (which includes paralysis, a lack of byssus production, and reduced growth) are also of concern. Climate change and anthropogenic impacts may alter HAB population structure and dynamics, as well as the physiological responses of fish and shellfish, potentially further compromising aquatic species. Those HAB species which have been detected in NZ and have the potential to bloom and harm marine life in the future are also discussed. The use of environmental DNA (eDNA) and relevant bioassays are practical tools which enable early detection of novel, problem HAB species and rapid toxin/HAB screening, and new data from HAB monitoring of aquaculture production sites using eDNA are presented. As aquaculture grows to supply a sizable proportion of the world’s protein, the effects of HABs in reducing productivity is of increasing significance. Research into the multiple stressor effects of climate change and HABs on cultured species and using local, recent, HAB strains is needed to accurately assess effects and inform stock management strategies

Prediction of melanoma metastasis by the Shields index based on lymphatic vessel density

<p>Abstract</p> <p>Background</p> <p>Melanoma usually presents as an initial skin lesion without evidence of metastasis. A significant proportion of patients develop subsequent local, regional or distant metastasis, sometimes many years after the initial lesion was removed. The current most effective staging method to identify early regional metastasis is sentinel lymph node biopsy (SLNB), which is invasive, not without morbidity and, while improving staging, may not improve overall survival. Lymphatic density, Breslow's thickness and the presence or absence of lymphatic invasion combined has been proposed to be a prognostic index of metastasis, by Shields et al in a patient group.</p> <p>Methods</p> <p>Here we undertook a retrospective analysis of 102 malignant melanomas from patients with more than five years follow-up to evaluate the Shields' index and compare with existing indicators.</p> <p>Results</p> <p>The Shields' index accurately predicted outcome in 90% of patients with metastases and 84% without metastases. For these, the Shields index was more predictive than thickness or lymphatic density. Alternate lymphatic measurement (hot spot analysis) was also effective when combined into the Shields index in a cohort of 24 patients.</p> <p>Conclusions</p> <p>These results show the Shields index, a non-invasive analysis based on immunohistochemistry of lymphatics surrounding primary lesions that can accurately predict outcome, is a simple, useful prognostic tool in malignant melanoma.</p

Alternative splicing of TIA-1 in human colon cancer regulates VEGF isoform expression, angiogenesis, tumour growth and bevacizumab resistance

© 2014 The Authors. The angiogenic capability of colorectal carcinomas (CRC), and their susceptibility to anti-angiogenic therapy, is determined by expression of vascular endothelial growth factor (VEGF) isoforms. The intracellular protein T-cell Intracellular Antigen (TIA-1) alters post-transcriptional RNA processing and binds VEGF-A mRNA. We therefore tested the hypothesis that TIA-1 could regulate VEGF-A isoform expression in colorectal cancers. TIA-1 and VEGF-A isoform expression was measured in colorectal cancers and cell lines. We discovered that an endogenous splice variant of TIA-1 encoding a truncated protein, short TIA-1 (sTIA-1) was expressed in CRC tissues and invasive K-Ras mutant colon cancer cells and tissues but not in adenoma cell lines. sTIA-1 was more highly expressed in CRC than in normal tissues and increased with tumour stage. Knockdown of sTIA-1 or over-expression of full length TIA-1 (flTIA-1) induced expression of the anti-angiogenic VEGF isoform VEGF-A 165 b. Whereas flTIA-1 selectively bound VEGF-A 165 mRNA and increased translation of VEGF-A 165 b, sTIA-1 prevented this binding. In nude mice, xenografted colon cancer cells over-expressing flTIA-1 formed smaller, less vascular tumours than those expressing sTIA-1, but flTIA-1 expression inhibited the effect of anti-VEGF antibodies. These results indicate that alternative splicing of an RNA binding protein can regulate isoform specific expression of VEGF providing an added layer of complexity to the angiogenic profile of colorectal cancer and their resistance to anti-angiogenic therapy

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Adipose derived stem cell extracellular vesicles modulate primary human macrophages to an anti‐inflammatory phenotype in vitro

Abstract EVs released by adipose derived stem cells (ADSCs) have shown promise as a therapeutic for tissue repair because of their purported immune‐regulatory properties. Extracellular vesicles (EVs) from ADSCs could be beneficial in improving graft retention rates for autologous fat grafting (AFG) post‐mastectomy as, currently, grafted tissue rates are variable. Enriching grafted tissue with ADSC‐EVs may improve retention rates by modulating macrophages resident within both the breast and lipoaspirate. We aimed to identify key macrophage phenotypes that are modulated by ADSC‐EVs in vitro. ADSCs were isolated from lipoaspirates of women undergoing AFG and characterised by flow cytometry and differentiation potential. ADSC‐EVs were isolated from culture media and characterised by tuneable resistive pulse sensing, transmission electron microscopy and Western blot. Primary monocyte‐derived macrophages were polarized to an M1‐like (GM‐CSF, IFNγ), M2‐like phenotype (M‐CSF, IL‐4) or maintained (M0‐like; M‐CSF) and ADSC‐EVs were co‐cultured with macrophages for 48 h. Flow cytometry and high‐dimensional analysis clustered macrophages post co‐culture. A manual gating strategy was generated to recapitulate these clusters and was applied to a repeat experimental run. Both runs were analysed to examine the prevalence of each cluster, representing a unique macrophage phenotype, with and without ADSC‐EVs. Following the addition of ADSC‐EVs, M0‐like macrophages demonstrated a reciprocal shift of cell distribution from a cluster with a ‘high inflammatory profile’ (CD36+++CD206+++CD86+++; 16.5 ± 7.0%; p < 0.0001) to a cluster with a ‘lower inflammatory profile’ (CD36+CD206+CD86+; 35  ± 21.5%; p < 0.05). M1‐like macrophages shifted from a cluster with a ‘high inflammatory profile’ (CD206++CD11b++CD36++CD163++; 26.1 ± 9.4%; p = 0.0024) to a ‘lower inflammatory profile’ (CD206+CD11b+CD36+CD163+; 72.8  ± 8.7%; p = 0.0007). There was no shift in M2‐like clusters following ADSC‐EV treatment. ADSC‐EVs are complex regulators of macrophage phenotype that can shift macrophages away from a heightened pro‐inflammatory state

Volumetric assessment of fat graft retention over implant by MRI

**Background**: Autologous fat grafting (AFG) is an increasingly popular adjunct to post-mastectomy breast reconstruction as it can produce a natural cosmetic outcome and alleviate undesirable radiotherapy-associated consequences, with low surgical risk. However, graft retention rates are variable and unpredictable. In order to improve and understand what influences graft retention rates, accurate and consistent methods for the measurement of graft retention must be developed. **Methods**: Twenty patients who were undergoing AFG following a previous mastectomy were prospectively enrolled. Of these, six women suitable for immediate breast reconstruction (IBR) with implant underwent MRI pre- and three months post-AFG. **Results**: All patients had a net gain in volume at three months post-procedure with a mean of 123.6 ± 56.07cm^3^; however, the percentage retention ranged from 30.0 to 104.7 per cent. **Conclusions**: This study has demonstrated the feasibility of measuring AFG retention over implant using MRI, as well as confirming variable tissue retention rates. This is an important step forward for studies on improving overall graft survival

Association between VEGF Splice Isoforms and Progression-Free Survival in Metastatic Colorectal Cancer Patients Treated with Bevacizumab

PURPOSE: Bevacizumab improves survival for metastatic colorectal cancer patients with chemotherapy, but no proven predictive markers exist. The VEGF-A splice form, VEGF(165)b, anti-angiogenic in animal models, binds bevacizumab. We tested the hypothesis that prolonged progression-free survival (PFS) would occur only in patients with low relative VEGF(165)b levels treated with bevacizumab. METHODS: Blinded tumor samples from the phase-III trial of FOLFOX4±bevacizumab were assessed for VEGF(165)b and VEGF(total) by immunohistochemistry and scored relative to normal tissue. A predictive index (PI) was derived from the ratio of VEGF(165)b:VEGF(total) for 44 samples from patients treated with FOLFOX+bevacizumab (Arm A) and 53 samples from patients treated with FOLFOX4 (Arm B), and PFS, and overall survival (OS) analysed based on PI relative to median ratio. RESULTS: Unadjusted analysis of PFS showed significantly better outcome for individuals with VEGF(165)b:VEGF(total) ratio scores below median treated with FOLFOX4+bevacizumab compared to FOLFOX4 alone (median 8.0 months vs 5.2 months, p<0.02), but no effect of bevacizumab on PFS in patients with VEGF(165)b:VEGF(total) ratio >median (5.9 months vs 6.3 months). These findings held after adjustment for other clinical and demographic features. Overall survival (OS) was increased in Arm A (median 13.6 months) compared with Arm B (10.6 months) in the low VEGF(165)b group, but this did not reach statistical significance. There was no difference in the high VEGF(165)b:VEGF(total) group between FOLFOX+bevacizumab (10.8 months) and FOLFOX alone (11.3months). CONCLUSION: Low VEGF(165)b:VEGF(total) ratio may be a predictive marker for bevacizumab in metastatic colorectal cancer, and individuals with high relative levels may not benefit