Insights into growth kinetics and roles of enzymes of Krebs' cycle and sulfur oxidation during exochemolithoheterotrophic growth of Achromobacter aegrifaciens NCCB 38021 on succinate with thiosulfate as the auxiliary electron donor.

Achromobacter aegrifaciens NCCB 38021 was grown heterotrophically on succinate versus exochemolithoheterotrophically on succinate with thiosulfate as auxiliary electron donor. In batch culture, no significant differences in specific molar growth yield or specific growth rate were found for the two growth conditions, but in continuous culture in the succinate-limited chemostat, the maximum specific growth yield coefficient increased by 23.3% with thiosulfate present, consistent with previous studies of endo- and exochemolithoheterotrophs and thermodynamic predictions. Thiosulfate oxidation was coupled to respiration at cytochrome c551, and thiosulfate-dependent ATP biosynthesis occurred. Specific activities of cytochrome c-linked thiosulfate dehydrogenase (E.C. 1.8.2.2) and two other enzymes of sulfur metabolism were significantly higher in exochemolithoheterotrophically grown cell extracts, while those of succinyl-transferring 2-oxoglutarate dehydrogenase (E.C. 1.2.4.2), fumarate hydratase (E.C. 4.2.1.2) and malate dehydrogenase (NAD+, E.C. 1.1.1.37) were significantly lower-presumably owing to less need to generate reducing equivalents during Krebs' cycle, since they could be produced from thiosulfate oxidation.

Preoperative sentinel lymph node identification, biopsy and localisation using contrast enhanced ultrasound (CEUS) in patients with breast cancer: a systematic review and meta-analysis.

AIM: To evaluate whether contrast-enhanced ultrasound (CEUS)-guided core biopsy of the sentinel lymph node (SLN) could identify metastatic nodes preoperatively and reduce the number of surgical SLN biopsies in patients with breast cancer and normal axillary B-mode ultrasound; and to establish whether CEUS SLN identification and localisation is a viable alternative to standard lymphatic mapping using isotope and blue dye. MATERIALS AND METHODS: A search of several electronic databases was performed and identified studies were assessed using QUADAS-2 for methodological quality. Pooled estimates of sensitivity and specificity for identification of nodal metastases were calculated. RESULTS: Eleven prospective studies and one retrospective study with 1,520 participants were included. The SLN identification and localisation rate for CEUS-guided skin marking was 70-100%, CEUS guided-wire localisation was 89-97%, and CEUS-guided iodine-125 (125I) seed localisation was 60%. Across the four studies that evaluated preoperative CEUS-guided SLN biopsy, pooled sensitivity for identification of nodal metastases was 54% (95% confidence interval [CI]: 47-61) and pooled specificity 100% (95% CI: 99-100). CONCLUSION: CEUS is a promising technique for preoperative staging of the axilla. CEUS-guided core biopsy has the potential to identify nodal metastases in over half (54%) of patients with normal axillary B-mode ultrasound. CEUS-guided identification and localisation of the SLN may offer a viable alternative to standard lymphatic mapping using isotope and blue dye; however, further prospective studies with larger samples are warranted.

Physiological niche and geographical range in European diving beetles (Coleoptera: Dytiscidae).

Geographical ranges vary greatly in size and position, even within recent clades, but the factors driving this remain poorly understood. In aquatic beetles, thermal niche has been shown to be related to both the relative range size and position of congeners but whether other physiological parameters play a role is unknown. Metabolic plasticity may be critical for species occupying more variable thermal environments and maintaining this plasticity may trade-off against other physiological processes such as immunocompetence. Here we combine data on thermal physiology with measures of metabolic plasticity and immunocompetence to explore these relationships in Deronectes (Dytiscidae). While variation in latitudinal range extent and position was explained in part by thermal physiology, aspects of metabolic plasticity and immunocompetence also appeared important. Northerly distributed, wide-ranging species apparently used different energy reserves under thermal stress from southern endemic congeners and differed in their antibacterial defences. This is the first indication that these processes may be related to geographical range, and suggests parameters that may be worthy of exploration in other taxa.

Antioxidant Responses in Relation to Persistent Organic Pollutants and Metals in a Low- and a High-Exposure Population of Seabirds.

Oxidative stress occurs when there is an imbalance between the production of reactive oxygen species (ROS) and antioxidant defense. Exposure to pollutants may increase ROS and affect antioxidant levels, and the resulting oxidative stress may negatively affect both reproduction and survival. We measured concentrations of 18 persistent organic pollutants (POPs) and 9 toxic elements in blood, as well as total antioxidant capacity (TAC), total glutathione (tGSH), and carotenoids in plasma of Baltic and Arctic female common eiders (Somateria mollissima) (N = 54) at the end of their incubation-related fasting. The more polluted Baltic population had higher TAC and tGSH concentrations compared to the Arctic population. Carotenoid levels did not differ between populations. The effect of mixtures of pollutants on the antioxidants was assessed, and the summed molar blood concentrations of 14 POPs were positively related to TAC. There was no significant relationship between the analyzed pollutants and tGSH concentrations. The adaptive improvement of the antioxidant defense system in the Baltic population may be a consequence of increased oxidative stress. However, both increased oxidative stress and energy allocation toward antioxidant defense may have adverse consequences for Baltic eiders at the incubation stage, when energy resources reach an annual minimum due to incubation-related fasting.

DNA double-strand breaks in incubating female common eiders (Somateria mollissima): Comparison between a low and a high polluted area.

Alterations in the genetic material may have severe consequences for individuals and populations. Hence, genotoxic effects of environmental exposure to pollutants are of great concern. We assessed the impact of blood concentrations of persistent organic pollutants (POPs) and mercury (Hg) on DNA double-strand break (DSB) frequency, in blood cells of a high-exposed Baltic, and lower exposed Arctic population of common eiders (Somateria mollissima). Furthermore, we examined whether the genotoxic response was influenced by antioxidant concentration (plasma total glutathione (tGSH) and total antioxidant capacity) and female body mass. The DNA DSB frequency did not differ between the two populations. We found significant positive relationships between Hg and DNA DSB frequency in Baltic, but not in Arctic eiders. Although both p,p'-DDE and PCB 118 had a lesser effect than Hg, they exhibited a positive association with DNA DSB frequency in Baltic eiders. Antioxidant levels were not important for the genotoxic effect, suggesting alternative mechanisms other than GSH depletion for the relationship between Hg and DNA DSBs. Hence, the Baltic population, which is considered to be endangered and is under the influence of several environmental stressors, may be more susceptible to genotoxic effects of environmental exposure to Hg than the Arctic population.

Hyperbaric oxygen enhances neutrophil apoptosis and their clearance by monocyte-derived macrophages.

Neutrophil apoptosis and clearance by macrophages are essential for wound healing. Evidence suggests that hyperbaric oxygen (HBO) exposure may enhance neutrophil apoptosis, but HBO effects leading to neutrophil clearance by macrophages are still unclear. In the current study, bovine neutrophils and monocyte-derived macrophages (MDMΦ) were co-cultured under HBO (97.9% O2, 2.1% CO2 at 2.4 atm absolute (ATA)) (1 atm = 101.325 kPa), hyperbaric normoxia (8.8% O2 at 2.4 ATA), normobaric hyperoxia (95% O2, 5% CO2), normoxia (air), and normobaric hypoxia (5% O2, 5% CO2). Phagocytosis of fresh and 22 h aged neutrophils by MDMΦ was increased after HBO pre-treatment, assessed using flow cytometry and light microscopy. Enhanced clearance of neutrophils was accompanied by an increase in H2O2 levels following HBO pre-treatment with upregulation of IL-10 (anti-inflammatory cytokine) mRNA expression in LPS-stimulated MDMΦ that had ingested aged neutrophils. TNF-α (pro-inflammatory cytokine) gene expression did not change in LPS-stimulated MDMΦ that had ingested fresh or aged neutrophils after HBO, pressure, and hyperoxia. These findings suggest that HBO-activated MDMΦ participate in the clearance of apoptotic cells. Uptake of neutrophils by MDMΦ exposed to HBO may contribute to resolution of inflammation, because HBO induced up-regulation of IL-10 mRNA expression.

Comparison of intermittent and continuous exposures to inorganic mercury in the mussel, Mytilus edulis: accumulation and sub-lethal physiological effects.

Aquatic organisms are often subject to intermittent exposure to pollutants in real ecosystems. This study aimed to compare mercury accumulation and the physiological responses of mussels, Mytilus edulis during continuous and intermittent exposure to the metal. Mussels were treated in a semi-static, triplicated design to either a control (no added Hg) or 50 µg l(-1) Hg as HgCl2 in continuous (daily) or intermittent (2 day exposure, 2 days in clean seawater alternately) exposure for 14 days. A time-dependent increase in Hg accumulation was observed in the continuous exposure, while the intermittent treatment showed step-wise changes in Hg concentrations with the exposure profile, especially in the gills. At the end of the experiment, tissue Hg concentrations were significantly increased in the continuous compared to the intermittent exposure for digestive gland (4 fold), gonad and remaining soft tissue (>2 fold), but not for the gill and adductor muscle. There was no observed oxidative damage at the end of the experiment as measured by the thiobarbituric acid reactive substances (TBARS) concentrations in tissues from all treatments. However, total glutathione was significantly decreased in the gill and digestive gland of both the continuous and intermittent exposure by the end of the experiment. The neutral red retention ability of the haemocytes was not affected, but total haemocyte counts were significantly decreased (<2 fold) in the intermittent compared to the continuous exposure. Histopathological examinations showed less pathology in the gill, but more inflammation in the digestive gland of mussels for the intermittent compared to the continuous exposure. Overall, the results showed that Hg accumulation from intermittent exposure was less than that of the continuous exposure regime, but the sub-lethal responses are sometimes more severe than expected in the former.

Is community treatment best? a randomised trial comparing delivery of cancer treatment in the hospital, home and GP surgery.

BACKGROUND: Care closer to home is being explored as a means of improving patient experience as well as efficiency in terms of cost savings. Evidence that community cancer services improve care quality and/or generate cost savings is currently limited. A randomised study was undertaken to compare delivery of cancer treatment in the hospital with two different community settings. METHODS: Ninety-seven patients being offered outpatient-based cancer treatment were randomised to treatment delivered in a hospital day unit, at the patient's home or in local general practice (GP) surgeries. The primary outcome was patient-perceived benefits, using the emotional function domain of the EORTC quality of life (QOL) QLQC30 questionnaire evaluated after 12 weeks. Secondary outcomes included additional QOL measures, patient satisfaction, safety and health economics. RESULTS: There was no statistically significant QOL difference between treatment in the combined community locations relative to hospital (difference of -7.2, 95% confidence interval: -19·5 to +5·2, P=0.25). There was a significant difference between the two community locations in favour of home (+15·2, 1·3 to 29·1, P=0.033). Hospital anxiety and depression scale scores were consistent with the primary outcome measure. There was no evidence that community treatment compromised patient safety and no significant difference between treatment arms in terms of overall costs or Quality Adjusted Life Year. Seventy-eight percent of patients expressed satisfaction with their treatment whatever their location, whereas 57% of patients preferred future treatment to continue at the hospital, 81% at GP surgeries and 90% at home. Although initial pre-trial interviews revealed concerns among health-care professionals and some patients regarding community treatment, opinions were largely more favourable in post-trial interviews. INTERPRETATION: Patient QOL favours delivering cancer treatment in the home rather than GP surgeries. Nevertheless, both community settings were acceptable to and preferred by patients compared with hospital, were safe, with no detrimental impact on overall health-care costs.

Large changes in NAD levels associated with CD38 expression during HL-60 cell differentiation.

NAD is an important cofactor involved in multiple metabolic reactions and as a substrate for several NAD-dependent signalling enzymes. One such enzyme is CD38 which, alongside synthesising Ca(2+)-releasing second messengers and acting as a cell surface receptor, has also been suggested to play a key role in NAD(+) homeostasis. CD38 is well known as a negative prognostic marker in B-CLL but the role of its enzymatic activity has not been studied in depth to date. We have exploited the HL-60 cell line as a model of inducible CD38 expression, to investigate CD38-mediated regulation intracellular NAD(+) levels and the consequences of changes in NAD(+) levels on cell physiology. Intracellular NAD(+) levels fell with increasing CD38 expression and this was reversed with the CD38 inhibitor, kuromanin confirming the key role of CD38 in NAD(+) homeostasis. We also measured the consequences of CD38 expression during the differentiation on a number of functions linked to NAD(+) and we show that some but not all NAD(+)-dependent processes are significantly affected by the lowered NAD(+) levels. These data suggest that both functional roles of CD38 might be important in the pathogenesis of B-CLL.

Comparison of intermittent and continuous exposures to cadmium in the blue mussel, Mytilus edulis: accumulation and sub-lethal physiological effects.

Little is known about the bioaccumulation responses of shellfish to metals during intermittent compared to continuous exposure. There is also the concern that the toxicity of intermittent events may not be the same as that from the steady-state continuous exposures. The aim of the present study was to determine whether there was any difference between cadmium (Cd) accumulation, or Cd-dependent biological responses, in tissues of blue mussels (Mytilus edulis) during intermittent compared to continuous Cd exposure. Tissues and hemolymph were collected from M. edulis exposed for 14 days to either control (no added Cd, only seawater), or 50 µg/l Cd as CdCl2 in continuous or intermittent profile (2 day exposure, 2 days in clean seawater alternately); and sub-lethal responses examined using a suite of assays including total glutathione, thiobarbituric acid reactive substances (TBARS), neutral red retention, total hemocyte counts, hemolymph Na(+) and K(+), plasma glucose and histopathology. A time-dependent accumulation of the Cd was observed in tissues of mussels after continuous exposure, while the intermittent exposure showed step-wise changes in the hemolymph and gonad. Tissue Cd concentration in the continuous exposure was significantly increased (≥2 fold) for most tissues compared to the intermittent exposure. No clear differences were seen between the continuous and intermittent exposure for most end points measured apart from a 2 fold significant increase in hemocyte infiltration in the digestive gland of the continuous exposure compared to the intermittent exposure. Overall, the data showed that the Cd accumulation was generally greater in the continuous exposure regime, but despite this, most of the biological responses being similar in both regimes.

Limited DNA damage in human endothelial cells after hyperbaric oxygen treatment and protection from subsequent hydrogen peroxide exposure.

BACKGROUND: In vitro studies on hyperbaric oxygen (HBO) therapy suggest that HBO may cause DNA damage, but this has not been evaluated using endothelial cells. METHODS: Human umbilical cord endothelial cells (HUVECs) were exposed either to H(2)O(2) or to HBO for 90 min, with or without subsequent H(2)O(2) exposure. Measurements included the comet assay for DNA damage, and reduced and oxidised glutathione levels. RESULTS: HUVECs showed sensitivity to H(2)O(2) (EC(50) of 0.2mM for DNA migration). A single 90 min HBO treatment at 2.2 ATA caused a statistically significant (ANOVA, P<0.05) increase of DNA migration in HUVECs to 6.8 ± 0.3% (mean ± SEM, n=8), which returned to normal levels (4.9 ± 0.1%, n=6) after 24h. Further exposure to 0.2mM H(2)O(2) after HBO treatment significantly increased the DNA migration in HBO-treated cells immediately post-treatment; but 24h later the cells showed 22% less DNA damage and higher glutathione than controls. CONCLUSION: A single HBO exposure causes limited DNA damage to HUVECs, which repairs quickly. HBO treatment protects against H(2)O(2)-induced DNA damage and involves cellular glutathione. SIGNIFICANCE: Endothelial cells are unlikely to be compromised during HBO therapy.

A randomised study evaluating the use of pyridoxine to avoid capecitabine dose modifications.

BACKGROUND: Pyridoxine is frequently used to treat capecitabine-induced hand-foot syndrome (HFS), although the evidence of benefit is lacking. We performed a randomised placebo-controlled trial to determine whether pyridoxine could avoid the need for capecitabine dose modifications and improve outcomes. METHODS: A total of 106 patients planned for palliative single-agent capecitabine (53 in each arm, 65%/35% colorectal/breast cancer) were randomised to receive either concomitant pyridoxine (50 mg po) or matching placebo three times daily. RESULTS: Compared with placebo, pyridoxine use was associated with an increased rate of avoiding capecitabine dose modifications (37% vs 23%, relative risk 0.59, 95% CI 0.29, 1.20, P=0.15) and fewer grade 3/4 HFS-related adverse events (9% vs 17%, odds ratio 0.51, 95% CI 0.15-1.6, P=0.26). Use of pyridoxine did not improve response rate or progression-free survival. CONCLUSION: Pyridoxine may reduce the need for capecitabine dose modifications and the incidence of severe HFS, but does not impact on antitumour effect.

Hyperoxia-induced ciliary loss and oxidative damage in an in vitro bovine model: the protective role of antioxidant vitamins E and C.

Although elevated oxygen fraction is used in intensive care units around the world, pathological changes in pulmonary tissue have been shown to occur with prolonged exposure to hyperoxia. In this work a bovine bronchus culture model has been successfully used to evaluate the effects of hyperoxia on ciliated epithelium in vitro. Samples were cultured using an air interface method and exposed to normoxia, 21% O(2) or hyperoxia, 95% O(2). Cilial coverage was assessed using scanning electron microscopy (SEM). Tissue damage (lactate dehydrogenase, LDH, in the medium), lipid peroxidation (thiobarbituric acid reactive substances, TBARS), DNA damage (comet assay), protein oxidation (OxyBlot kit) and antioxidant status (total glutathione) were used to assess whether the hyperoxia caused significant oxidative stress. Hyperoxia caused a time-dependent decline (t(½)=3.4d compared to 37.1d under normoxia) in cilial coverage (P<0.0001). This was associated with a significant increase in the number of cells (2.80 ± 0.27 × 10(6) compared to 1.97 ± 0.23 × 10(6)ml(-1) after 6d), many apparently intact, in the medium (P<0.05); LDH release (1.06 ± 0.29 compared to 0.83 ± 0.36 µmol min(-1)g(-1) after 6d; P<0.001); lipid peroxidation (352 ± 16 versus 247 ± 11 µmol MDA g(-1) for hyperoxia and normoxia, respectively); % tail DNA (18.7 ± 2.2 versus 11.1 ± 1.5); protein carbonyls (P<0.05); and total glutathione (229 ± 20 µmol g(-1) versus 189 ± 15 µmol g(-1)). Vitamins E (10(-7)M) and C (10(-6) or 10(-7)M) alone or in combination (10(-7)M and 10(-6)M, respectively) had a significant protective effect on the hyperoxia-induced reduction in percentage cilial coverage (P<0.05). In conclusion, hyperoxia caused damage to cultured bovine bronchial epithelium and denudation of cilia. The antioxidant vitamins E and C significantly protected against hyperoxia-induced cilia loss.

Merging nano-genotoxicology with eco-genotoxicology: an integrated approach to determine interactive genotoxic and sub-lethal toxic effects of C(60) fullerenes and fluoranthene in marine mussels, Mytilus sp.

Whilst there is growing concern over the potential detrimental impact of engineered nanoparticles (ENPs) on the natural environment, little is known about their interactions with other contaminants. In the present study, marine mussels (Mytilus sp.) were exposed for 3 days to C(60) fullerenes (C(60); 0.10-1 mg l(-1)) and a model polycyclic aromatic hydrocarbon (PAH), fluoranthene (32-100 µg l(-1)), either alone or in combination. The first two experiments were conducted by exposing the organisms to different concentrations of C(60) and fluoranthene alone, in order to determine the effects on total glutathione levels (as a measure of generic oxidative stress), genotoxicity (DNA strand breaks using Comet assay in haemocytes), DNA adduct analyses (using (32)P-postlabelling method) in different organs, histopathological changes in different tissues (i.e. adductor muscle, digestive gland and gills) and physiological effects (feeding or clearance rate). Subsequently, in the third experiment, a combined exposure of C(60) plus fluoranthene (0.10 mg l(-1) and 32 µg l(-1), respectively) was carried out to evaluate all endpoints mentioned above. Both fluoranthene and C(60) on their own caused concentration-dependent increases in DNA strand breaks as determined by the Comet assay. Formation of DNA adducts however could not be detected for any exposure conditions. Combined exposure to C(60) and fluoranthene additively enhanced the levels of DNA strand breaks along with a 2-fold increase in the total glutathione content. In addition, significant accumulation of C(60) was observed in all organs, with highest levels in digestive gland (24.90 ± 4.91µg C(60) g(-1) ww). Interestingly, clear signs of abnormalities in adductor muscle, digestive gland and gills were observed by histopathology. Clearance rates indicated significant differences compared to the control with exposure to C(60), and C(60)/fluoranthene combined treatments, but not after fluoranthene exposure alone. This study demonstrated that at the selected concentrations, both C(60) and fluoranthene evoke toxic responses and genetic damage. The combined exposure produced enhanced damage with additive rather than synergistic effects.

FLAIR MRI biomarkers of the normal appearing brain matter are related to cognition.

A novel biomarker panel was proposed to quantify macro and microstructural biomarkers from the normal-appearing brain matter (NABM) in multicentre fluid-attenuation inversion recovery (FLAIR) MRI. The NABM is composed of the white and gray matter regions of the brain, with the lesions and cerebrospinal fluid removed. The primary hypothesis was that NABM biomarkers from FLAIR MRI are related to cognitive outcome as determined by MoCA score. There were three groups of features designed for this task based on 1) texture: microstructural integrity (MII), macrostructural damage (MAD), microstructural damage (MID), 2) intensity: median, skewness, kurtosis and 3) volume: NABM to ICV volume ratio. Biomarkers were extracted from over 1400 imaging volumes from more than 87 centres and unadjusted ANOVA analysis revealed significant differences in means of the MII, MAD, and NABM volume biomarkers across all cognitive groups. In an adjusted ANCOVA model, a significant relationship between MoCA categories was found that was dependent on subject age for MII, MAD, intensity, kurtosis and NABM volume biomarkers. These results demonstrate that structural brain changes in the NABM are related to cognitive outcome (with different relationships depending on the age of the subjects). Therefore these biomarkers have high potential for clinical translation. As a secondary hypothesis, we investigated whether texture features from FLAIR MRI can quantify microstructural changes related to how "structured" or "damaged" the tissue is. Based on correlation analysis with diffusion weighted MRI (dMRI), it was shown that FLAIR MRI texture biomarkers (MII and MAD) had strong correlations to mean diffusivity (MD) which is related to tissue degeneration in the GM and WM regions. As FLAIR MRI is routinely collected for clinical neurological examinations, novel biomarkers from FLAIR MRI could be used to supplement current clinical biomarkers and for monitoring disease progression. Biomarkers could also be used to stratify patients into homogeneous disease subgroups for clinical trials, or to learn more about mechanistic development of dementia disease.

Detection of Aspergillus in lung and other tissue samples using the MycAssay Aspergillus real-time PCR kit.

The MycAssay™ Aspergillus real-time PCR kit was tested on tissues from patients with invasive fungal infections. Tissue samples from nine organ transplant recipients and 33 patients with haematological malignancy were from lung (n = 30), skin (n = 4), and others. Samples were preprocessed with proteinase K and lyticase, followed by DNA extraction and real-time PCR. For all samples, the sensitivity of the MycAssay Aspergillus test was 82% and specificity 79% relative to microscopy and 90% and 64%, respectively, compared with Aspergillus culture. The positive predictive value and negative predictive values compared with culture were 69% and 88% and were 88% and 69% compared with microscopy, respectively. The MycAssay Aspergillus test detected tissue invasive infections with Aspergillus fumigatus , Aspergillus flavus , and Aspergillus terreus.

The effect of material choice on biofilm formation in a model warm water distribution system.

Water distribution systems (WDS) are composed of a variety of materials and may harbour potential pathogens within surface-attached microbial biofilms. Biofilm formation on four plumbing materials, viz. copper, stainless steel 316 (SS316), ethylene propylene diene monomer (EPDM) and cross-linked polyethylene (PEX), was investigated using scanning electron microscope (SEM)/confocal microscopy, ATP-/culture-based analysis, and molecular analysis. Material 'inserts' were incorporated into a mains water fed, model WDS. All materials supported biofilm growth to various degrees. After 84 days, copper and SS316 showed no significant overall differences in terms of the level of biofilm formation observed, whilst PEX supported a significantly higher level of biofilm. EPDM exhibited gross contamination by a complex, multispecies biofilm, at a level significantly higher than was observed on the other materials, regardless of the analytical method used. PCR-DGGE analysis showed clear differences in the composition of the biofilm community on all materials after 84 days. The primary conclusion of this study has been to identify EPDM as a potentially unsuitable material for use as a major component in WDS.

A multiple biomarker approach to investigate the effects of copper on the marine bivalve mollusc, Mytilus edulis.

While copper (Cu) is considered to be an essential trace element for many organisms, overexposure to this metal can induce a wide spectrum of effects including DNA damage. Given that Cu is a highly relevant contaminant in the marine environment, we aimed to evaluate the induction of DNA strand breaks (using the comet assay) in haemocytes and concurrently also determined biological responses at higher levels of biological organisation in bivalve molluscs, Mytilus edulis, following exposure for 5 days to a range of environmentally realistic levels of Cu (18-56 µg l(-1)). Prior to evaluation of genetic damage, the maximum tolerated concentration (MTC) was also determined, which was found to be (100 µg l(-1)) above which complete mortality over the exposure period was observed. In addition to DNA damage, levels of glutathione in adductor muscle extracts, histopathological examination of various organs (viz., adductor muscle, gills and digestive glands) and clearance rates as a physiological measure at individual level were also determined. Furthermore, tissue-specific accumulation and levels of Cu in water samples were also determined using ICP-MS. There was a strong concentration-dependant induction for DNA damage and total glutathione levels increased by 1.8-fold at 56 µg l(-1) Cu. Histological examination of the organs showed qualitatively distinct abnormalities. Clearance rate also showed a significant decrease compared to controls even at the lowest concentration (i.e. 18 µg l(-1); P=0.003). Cu levels in adductor muscle (P=0.012), digestive gland (P=0.008) and gills (P=0.002) were significantly higher than in the control. The multi-biomarker approach used here suggests that in some cases clear relationships exist between genotoxic and higher level effects, which could be adopted as an integrated tool to evaluate different short and long-term toxic effects of pollutants.

Cardiac magnetic resonance imaging: insights into developmental programming and its consequences for aging.

Cardiovascular diseases (CVD) are important consequences of adverse perinatal conditions such as fetal hypoxia and maternal malnutrition. Cardiac magnetic resonance imaging (CMR) can produce a wealth of physiological information related to the development of the heart. This review outlines the current state of CMR technologies and describes the physiological biomarkers that can be measured. These phenotypes include impaired ventricular and atrial function, maladaptive ventricular remodeling, and the proliferation of myocardial steatosis and fibrosis. The discussion outlines the applications of CMR to understanding the developmental pathways leading to impaired cardiac function. The use of CMR, both in animal models of developmental programming and in human studies, is described. Specific examples are given in a baboon model of intrauterine growth restriction (IUGR). CMR offers great potential as a tool for understanding the sequence of dysfunctional adaptations of developmental origin that can affect the human cardiovascular system.

The diagnostic performance of ultrasound-guided core biopsy in the diagnosis of head and neck lymphoma: results in 226 patients.

Many clinical guidelines for investigating lymphomas advise that surgical excision biopsy (SEB) should be performed for a confident diagnosis. It is increasingly recognized in clinical practice that ultrasound-guided core needle biopsy (USCNB) is a reliable diagnostic technique. We aimed to investigate the diagnostic efficacy of USCNB in head and neck lymphoma. A retrospective analysis of all diagnosed head and neck lymphomas between 2013 and 2018 was performed. Patient records, radiology and histopathology reports along with the biopsy technique: fine needle aspiration cytology (FNAC), USCNB, and SEB used were reviewed. The technique providing diagnosis and leading to initiation of treatment was identified. Two-hundred and thirty patients and 267 biopsy samples were included. A total of 226 patients underwent USCN. In 215 of 226 (95.1%) USCNB patients were fully diagnostic allowing for initiation of oncological treatment; 11 patients required a subsequent SEB to provide diagnosis. In four patients, SEB was the only investigation performed. Of the USCNB total number of procedures (number of patients n=230 is the same coincidentally as the number of USCNB procedures), 215 of 230 (93.5%) were fully diagnostic samples. In the majority of cases, USCNB provided a definitive diagnosis allowing initiation of oncological treatment, avoiding the need for SEB. USCNB should be considered the first-line diagnostic modality in appropriate cases, as it reduces time to initiate treatment, costs and avoids patients having to undergo unnecessary surgery and possible complications.