Quantifying the sediment sorption of organic ultraviolet filter chemicals using solvophobic theory.

Hydrophobic organic chemicals (HOCs) that enter the aquatic environment often negatively impact organisms, endangering aquatic biodiversity. Understanding sediment sorption equilibria for these chemicals can properly direct mitigation efforts. In addition, many HOCs of environmental concern lack sufficient environmental fate data to adequately assess their risk to ecosystems and humans. In this study, a sorption method addressing solvophobic effects was used to quantify the sorption of an HOC of current environmental concern, OD-PABA (padimate O, 2-ethylhexyl-4-(dimethylamino)benzoate), to a variety of sediments. OD-PABA is an organic ultraviolet filter chemical used in commercial sun protection products; it has been shown to exhibit cytotoxic effects and is known to photochemically transform under natural sunlight conditions. Given its commercial use, it enters the aquatic environment via recreational use and wastewater treatment plant effluent. OD-PABA is strongly hydrophobic; to mitigate the adsorption of OD-PABA to the container walls during sorption experiments, a precise concentration of methanol was used to avoid solvophobic effects. This sorption method was used to determine the sorption capacities for OD-PABA of four sediment samples, each with unique geochemical characteristics. Sediment-water distribution coefficients (Kd) were quantified and were normalized to various sediment characteristics to assess the main driving force(s) for sorption of OD-PABA. Organic carbon content was found to be a main driving force, with organic carbon-normalized distribution coefficients (log Koc) ranging from 4.4 - 4.6 for sediments with total organic carbon (TOC) > 10%); the clay fraction was also found to be important, especially for sediments with low TOC. The sorption of para-aminobenzoic acid (PABA), a water-soluble analog of OD-PABA was also investigated to assess the experimental approach, yielding a log Koc of 2.1 for the sediment with the greatest TOC.

Epigenetic and Genetic Population Structure is Coupled in a Marine Invertebrate.

Delineating the relative influence of genotype and the environment on DNA methylation is critical for characterizing the spectrum of organism fitness as driven by adaptation and phenotypic plasticity. In this study, we integrated genomic and DNA methylation data for two distinct Olympia oyster (Ostrea lurida) populations while controlling for within-generation environmental influences. In addition to providing the first characterization of genome-wide DNA methylation patterns in the oyster genus Ostrea, we identified 3,963 differentially methylated loci between populations. Our results show a clear coupling between genetic and epigenetic patterns of variation, with 27% of variation in interindividual methylation differences explained by genotype. Underlying this association are both direct genetic changes in CpGs (CpG-SNPs) and genetic variation with indirect influence on methylation (mQTLs). When comparing measures of genetic and epigenetic population divergence at specific genomic regions this relationship surprisingly breaks down, which has implications for the methods commonly used to study epigenetic and genetic coupling in marine invertebrates.

Confirmation of the shell-boring oyster parasite Polydora websteri (Polychaeta: Spionidae) in Washington State, USA.

Invasions by shell-boring polychaetes such as Polydora websteri Hartman have resulted in the collapse of oyster aquaculture industries in Australia, New Zealand, and Hawaii. These worms burrow into bivalve shells, creating unsightly mud blisters that are unappealing to consumers and, when nicked during shucking, release mud and detritus that can foul oyster meats. Recent findings of mud blisters on the shells of Pacific oysters (Crassostrea gigas Thunberg) in Washington State suggest a new spionid polychaete outbreak. To determine the identity of the polychaete causing these blisters, we obtained Pacific oysters from two locations in Puget Sound and examined them for blisters and burrows caused by polychaete worms. Specimens were also obtained from eastern oysters (Crassostrea virginica Gmelin) collected in New York for morphological and molecular comparison. We compared polychaete morphology to original descriptions, extracted DNA and sequenced mitochondrial (cytochrome c oxidase I [mtCOI]) and nuclear (small subunit 18S rRNA [18S rRNA]) genes to determine a species-level molecular identification for these worms. Our data show that Polydora websteri are present in the mud blisters from oysters grown in Puget Sound, constituting the first confirmed record of this species in Washington State. The presence of this notorious invader could threaten the sustainability of oyster aquaculture in Washington, which currently produces more farmed bivalves than any other US state.

Carryover effects of temperature and pCO2 across multiple Olympia oyster populations.

Predicting how populations will respond to ocean change across generations is critical to effective conservation of marine species. One emerging factor is the influence of parental exposures on offspring phenotype, known as intergenerational carryover effects. Parental exposure may deliver beneficial or detrimental characteristics to offspring that can influence larval recruitment patterns, thus shaping how populations and community structure respond to ocean change. Impacts of adult exposure to elevated winter temperature and pCO2 on reproduction and offspring viability were examined in the Olympia oyster (Ostrea lurida) using three populations of adult, hatchery-reared O. lurida, plus an additional cohort spawned from one of the populations. Oysters were sequentially exposed to elevated temperature (+4°C, at 10°C), followed by elevated pCO2 (+2,204 µatm, at 3,045 µatm) during winter months. Male gametes were more developed after elevated temperature exposure and less developed after high pCO2 exposure, but there was no impact on female gametes or sex ratios. Oysters previously exposed to elevated winter temperature released larvae earlier, regardless of pCO2 exposure. Those exposed to elevated winter temperature as a sole treatment released more larvae on a daily basis but, when also exposed to high pCO2 , there was no effect. These combined results indicate that elevated winter temperature accelerates O. lurida spermatogenesis, resulting in earlier larval release and increased production, with elevated pCO2 exposure negating effects of elevated temperature. Altered recruitment patterns may therefore follow warmer winters due to precocious spawning, but these effects may be masked by coincidental high pCO2 . Offspring were reared in common conditions for 1 yr, then deployed for 3 months in four estuarine bays with distinct environmental conditions. Offspring of parents exposed to elevated pCO2 had higher survival rates in two of the four bays. This carryover effect demonstrates that parental conditions can have substantial ecologically relevant impacts that should be considered when predicting impacts of environmental change. Furthermore, Olympia oysters may be more resilient in certain environments when progenitors are pre-conditioned in stressful conditions. Combined with other recent studies, our work suggests that the Olympia may be more equipped than other oysters for the challenge of a changing ocean.

Pacific geoduck (Panopea generosa) resilience to natural pH variation.

Pacific geoduck aquaculture is a growing industry, however, little is known about how geoduck respond to varying environmental conditions, or how the industry will fare under projected climate conditions. To understand how geoduck production may be impacted by low pH associated with ocean acidification, multi-faceted environmental heterogeneity needs to be included to understand species and community responses. In this study, eelgrass habitats and environmental heterogeneity across four estuarine bays were leveraged to examine low pH effects on geoduck under different natural regimes, using targeted proteomics to assess physiology. Juvenile geoduck were deployed in eelgrass and adjacent unvegetated habitats for 30 days while pH, temperature, dissolved oxygen, and salinity were monitored. Across the four bays, pH was lower in unvegetated habitats compared to eelgrass habitats. However this did not impact geoduck growth, survival, or proteomic abundance patterns in gill tissue. Temperature and dissolved oxygen differences across all locations corresponded to differences in growth and targeted protein abundance patterns. Specifically, three protein abundance levels (trifunctional-enzyme ß-subunit, puromycin-sensitive aminopeptidase, and heat shock protein 90-α) and shell growth positively correlated with dissolved oxygen variability and inversely correlated with mean temperature. These results demonstrate that geoduck may be resilient to low pH in a natural setting, but other abiotic factors (i.e. temperature, dissolved oxygen variability) may have a greater influence on geoduck physiology. In addition this study contributes to the understanding of how eelgrass patches influences water chemistry.

Everyday functioning of people with Parkinson's disease and impairments in executive function: a qualitative investigation.

PURPOSE: Executive function is the key area of cognitive impairment in Parkinson's disease. This study investigated how cognitive difficulties impact on everyday life of people with Parkinson's disease and their carers, and whether they explicitly mention executive-type difficulties. METHODS: Semistructured interviews with 11 people with Parkinson's disease and six carers were analyzed thematically. People with Parkinson's disease performed within the normal range on cognitive screening tests, but all had abnormal scores on tests of executive function. RESULTS: Despite relatively mild executive deficits and no global cognitive impairment, participants described executive-type difficulties as well as a range of problems in other cognitive domains, such as memory, processing speed and apathy. Cognitive difficulties had a far-reaching impact on everyday life and their significance depended on personal circumstances, such as the level of responsibilities of the person with Parkinson's disease and the extent of available support. CONCLUSIONS: By presenting subjective accounts of living with Parkinson's disease and cognitive difficulties, this study improves our understanding of how the observed level of cognitive impairment translates into everyday functioning. The study results have implications for recognizing cognitive difficulties and for planning support for people with Parkinson's disease and their families, and can help identify ways of promoting effective self-management. Implications for rehabilitation Treatment of Parkinson's disease tends to focus on the movement disorder, meaning that cognitive difficulties and their impact can be overlooked. Participants in this study had only relatively mild executive deficits but described a range of cognitive problems, including executive-type difficulties. Cognitive difficulties have an emotional impact and can cause a range of challenges in everyday life, adding to the burden of physical symptoms of Parkinson's disease. Results of this study provide insights into how executive functions impairments translate into everyday difficulties in Parkinson's disease and have implications for planning support for people with Parkinson's disease and their families.

Photolysis and cellular toxicities of the organic ultraviolet filter chemical octyl methoxycinnamate and its photoproducts.

Organic ultraviolet filter chemicals (UVFCs) are the active ingredients used in many sunscreens to protect the skin from UV light; these chemicals have been detected in numerous aquatic environments leading to concerns about how they might affect aquatic organisms and humans. One commonly used organic UVFC is octyl methoxycinnamate (OMC), better known by its commercial name, octinoxate. Upon exposure to UV light, OMC degrades rapidly, forming numerous photoproducts, some of which have been previously identified. In this study, we isolated and completely characterized the major products of OMC photolysis, including the two major stable OMC cyclodimers. One of these cyclodimers is a δ-truxinate, resulting from a head-to-head dimerization of two OMC molecules, and the other cyclodimer is an α-truxillate, resulting from a head-to-tail dimerization of two OMC molecules. Additionally, the cellular toxicities of the individual photoproducts were determined; it was found that the parent UVFC, OMC, 4-methoxybenzaldehyde, and two cyclodimers are significantly toxic to cells. The photoproduct 2-ethylhexanol is not cytotoxic, demonstrating that different components of OMC photolysate contribute differently to its cellular toxicity. This study thus provides an enhanced understanding of OMC photolysis and gives toxicity data that can be used to better evaluate OMC as a sunscreen agent.

A liquid chromatography-tandem mass spectrometry assay for the detection and quantification of trehalose in biological samples.

Trehalose is an important disaccharide that is used as a cellular protectant by many different organisms, helping these organisms better survive extreme conditions, such as dehydration, oxidative stress, and freezing temperatures. Methods to detect and accurately measure trehalose from different organisms will help us gain a better understanding of the mechanisms behind trehalose's ability to act as a cellular protectant. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay using selected reaction monitoring mode for the detection and quantification of trehalose using maltose as an internal standard has been developed. This assay uses a commercially available LC column for trehalose separation and a standard triple quadrupole mass spectrometer, thus allowing many scientists to take advantage of this simple assay. The calibration curve from 3 to 100µM trehalose was fit best by a single polynomial. This LC-MS/MS assay directly detects and accurately quantifies trehalose, with an instrument limit of detection (LOD) that is 2-1000 times more sensitive than the most commonly-used assays for trehalose detection and quantification. Furthermore, this assay was used to detect and quantify endogenous trehalose produced by Escherichia coli (E. coli) cells, which were found to have an intracellular concentration of 8.5±0.9mM trehalose. This method thus shows promise for the reliable detection and quantification of trehalose from different biological sources.

Research Priorities for Fertility and Conception Research as Identified by Multidisciplinary Health Care Practitioners and Researchers.

The Robinson Research Institute of the University of Adelaide convened a multidisciplinary group of n = 33 clinicians, researchers and representatives of government organisations on the 2 October 2014 for a workshop entitled "Promoting fertility and healthy conception. How do we generate greater reproductive health awareness?" The key aim of the workshop was to assess the body of knowledge that informs clinical practice and government policy, and to identify questions and additional information needed by health practitioners and government representatives working in the field of reproductive health and to frame future research and policy. The workshop identified topics that fell mostly into three categories: lifestyle-related, societal and biological factors. The lifestyle topics included nutrition and diet, exercise, obesity, shift work and other factors deemed to be modifiable at the level of the individual. The societal topics included discussions of matters that are structural, and resistant to change by individuals, including specific ethical issues, social disadvantage, government and educational policies. The biological factors are intrinsic physical states of the individual, and included many factors where there is a dense body of scientific knowledge which may not be readily accessible in less academic language. This workshop thus provided an opportunity to identify further actions that could be undertaken to meet the needs of diverse organisations and groups of professionals with an interest in human fertility. Since so many factors in our social and biological environment can impact fertility and preconception health, it is imperative to involve many disciplines or levels of government or societal organisations that have not traditionally been involved in this area.

Screening and subsequent management for thyroid dysfunction pre-pregnancy and during pregnancy for improving maternal and infant health.

BACKGROUND: Thyroid dysfunction pre-pregnancy and during pregnancy (both hyper- and hypothyroidism) is associated with increased risk of adverse outcomes for mothers and infants in the short- and long-term. Managing the thyroid dysfunction (e.g. thyroxine for hypothyroidism, or antithyroid medication for hyperthyroidism) may improve outcomes. The best method of screening to identify and subsequently manage thyroid dysfunction pre-pregnancy and during pregnancy is unknown. OBJECTIVES: To assess the effects of different screening methods (and subsequent management) for thyroid dysfunction pre-pregnancy and during pregnancy on maternal and infant outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (14 July 2015) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials, comparing any screening method (e.g. tool, program, guideline/protocol) for detecting thyroid dysfunction (including hypothyroidism, hyperthyroidism, and/or thyroid autoimmunity) pre-pregnancy or during pregnancy with no screening, or alternative screening methods. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility of studies, extracted and checked data accuracy, and assessed the risk of bias of included studies. MAIN RESULTS: We included two randomised controlled trials (involving 26,408 women) - these trials were considered to be at low risk of bias. Universal screening (screening all women) versus case finding (screening only those at perceived increased risk) in pregnancy for thyroid dysfunctionOne trial (4562 women) compared universal screening with case finding for thyroid dysfunction. Before 11 weeks' gestation, women in the universal screening group, and 'high-risk' women in the case finding group had their sera tested for TSH (thyroid stimulating hormone), fT4 (free thyroxine) and TPO-Ab (thyroid peroxidase antibody); women with hypothyroidism (TSH > 2.5 mIU/litre) received levothyroxine; women with hyperthyroidism (undetectable TSH and elevated fT4) received antithyroid medication.In regards to this review's primary outcomes, compared with the case finding group, more women in the universal screening group were diagnosed with hypothyroidism (risk ratio (RR) 3.15, 95% confidence interval (CI) 1.91 to 5.20; 4562 women; GRADE: high quality evidence), with a trend towards more women being diagnosed with hyperthyroidism (RR 4.50, 95% CI 0.97 to 20.82; 4562 women; P = 0.05; GRADE: moderate quality evidence). No clear differences were seen in the risks of pre-eclampsia (RR 0.87, 95% CI 0.64 to 1.18; 4516 women; GRADE: moderate quality evidence), or preterm birth (RR 0.99, 95% CI 0.80 to 1.24; 4516 women; GRADE: high quality evidence) between groups. This trial did not report on neurosensory disability for the infant as a child.Considering this review's secondary outcomes, more women in the universal screening group received pharmacological treatment for thyroid dysfunction (RR 3.15, 95% CI 1.91 to 5.20; 4562 women). No clear differences between groups were observed for miscarriage (RR 0.90, 95% CI 0.68 to 1.19; 4516 women; GRADE: moderate quality evidence), fetal and neonatal death (RR 0.92, 95% CI 0.42 to 2.02; 4516 infants; GRADE: moderate quality evidence), or other secondary outcomes: pregnancy-induced hypertension, gestational diabetes, congestive heart failure, thyroid storm, mode of birth (caesarean section), preterm labour, placental abruption, respiratory distress syndrome, low birthweight, neonatal intensive care unit admission, or other congenital malformations. The trial did not report on a number of outcomes including adverse effects associated with the intervention. Universal screening versus no screening in pregnancy for hypothyroidismOne trial (21,846 women) compared universal screening with no screening for hypothyroidism. Before 15 + 6 weeks' gestation, women in the universal screening group had their sera tested; women who screened 'positive' (TSH > 97.5th percentile, fT4 < 2.5th percentile, or both) received levothyroxine.Considering primary review outcomes, compared with the no screening group, more women in the universal screening screened 'positive' for hypothyroidism (RR 998.18, 95% CI 62.36 to 15,978.48; 21,839 women; GRADE: high quality evidence). No data were provided for the outcome pre-eclampsia, and for preterm birth, the trial reported rates of 5.6% and 7.9% for the screening and no screening groups respectively (it was unclear if these percentages related to the entire cohort or women who screened positive). No clear difference was seen for neurosensory disability for the infant as a child (three-year follow-up IQ score < 85) (RR 0.85, 95% CI 0.60 to 1.22; 794 infants; GRADE: moderate quality evidence).More women in the universal screening group received pharmacological treatment for thyroid dysfunction (RR 1102.90, 95% CI 69.07 to 17,610.46; 1050 women); 10% had their dose lowered because of low TSH, high fT4 or minor side effects. No clear differences were observed for other secondary outcomes, including developmental delay/intellectual impairment at three years. Most of our secondary outcomes, including miscarriage, fetal or neonatal death were not reported. AUTHORS' CONCLUSIONS: Based on the existing evidence, though universal screening for thyroid dysfunction in pregnancy increases the number of women diagnosed with hypothyroidism who can be subsequently treated, it does not clearly impact (benefit or harm) maternal and infant outcomes.While universal screening versus case finding for thyroid dysfunction increased diagnosis and subsequent treatment, we found no clear differences for the primary outcomes: pre-eclampsia or preterm birth. No clear differences were seen for secondary outcomes, including miscarriage and fetal or neonatal death; data were lacking for the primary outcome: neurosensory disability for the infant as a child, and for many secondary outcomes. Though universal screening versus no screening for hypothyroidism similarly increased diagnosis and subsequent treatment, no clear difference was seen for the primary outcome: neurosensory disability for the infant as a child (IQ < 85 at three years); data were lacking for the other primary outcomes: pre-eclampsia and preterm birth, and for the majority of secondary outcomes.For outcomes assessed using the GRADE approach the evidence was considered to be moderate or high quality, with any downgrading of the evidence based on the presence of wide confidence intervals crossing the line of no effect.More evidence is needed to assess the benefits or harms of different screening methods for thyroid dysfunction in pregnancy, on maternal, infant and child health outcomes. Future trials should assess impacts on use of health services and costs, and be adequately powered to evaluate the effects on short- and long-term outcomes.

Changes in plasma and erythrocyte omega-6 and omega-3 fatty acids in response to intravenous supply of omega-3 fatty acids in patients with hepatic colorectal metastases.

BACKGROUND: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are functionally the most important omega-3 polyunsaturated fatty acids (PUFAs). Oral supply of these fatty acids increases their levels in plasma and cell membranes, often at the expense of the omega-6 PUFAs arachidonic acid (ARA) and linoleic acid. This results in an altered pattern of lipid mediator production to one which is less pro-inflammatory. We investigated whether short term intravenous supply of omega-3 PUFAs could change the levels of EPA, DHA, ARA and linoleic acid in plasma and erythrocytes in patients with hepatic colorectal metastases. METHODS: Twenty patients were randomised to receive a 72 hour infusion of total parenteral nutrition with (treatment group) or without (control group) omega-3 PUFAs. EPA, DHA, ARA and linoleic acid were measured in plasma phosphatidylcholine (PC) and erythrocytes at several times points up to the end of infusion and 5 to 12 days (mean 9 days) after stopping the infusion. RESULTS: The treatment group showed increases in plasma PC EPA and DHA and erythrocyte EPA and decreases in plasma PC and erythrocyte linoleic acid, with effects most evident late in the infusion period. Plasma PC and erythrocyte EPA and linoleic acid all returned to baseline levels after the 5-12 day washout. Plasma PC DHA remained elevated above baseline after washout. CONCLUSIONS: Intravenous supply of omega-3 PUFAs results in a rapid increase of EPA and DHA in plasma PC and of EPA in erythrocytes. These findings suggest that infusion of omega-3 PUFAs could be used to induce a rapid effect especially in targeting inflammation.

Strong associations of short-chain perfluoroalkyl acids with serum albumin and investigation of binding mechanisms.

Interactions of perfluoroalkyl acids (PFAAs) with tissue and serum proteins likely contribute to their tissue distribution and bioaccumulation patterns. Protein-water distribution coefficients (K(PW) ) based on ligand associations with bovine serum albumin (BSA) as a model protein were recently proposed as biologically relevant parameters to describe the environmental behavior of PFAAs, yet empirical data on such protein binding behavior are limited. In the present study, associations of perfluoroalkyl carboxylates (PFCAs) with two to 12 carbons (C2-C12) and perfluoroalkyl sulfonates with four to eight carbons (C4, C6, and C8) with BSA are evaluated at low PFAA:albumin mole ratios and various solution conditions using equilibrium dialysis, nanoelectrospray ionization mass spectrometry, and fluorescence spectroscopy. Log K(PW) values for C4 to C12 PFAAs range from 3.3 to 4.3. Affinity for BSA increases with PFAA hydrophobicity but decreases from the C8 to C12 PFCAs, likely due to steric hindrances associated with longer and more rigid perfluoroalkyl chains. The C4-sulfonate exhibits increased affinity relative to the equivalent chain-length PFCA. Fluorescence titrations support evidence that an observed dependence of PFAA-BSA binding on pH is attributable to conformational changes in the protein. Association constants determined for perfluorobutanesulfonate and perfluoropentanoate with BSA are on the order of those for long-chain PFAAs (K(a) ∼106/M), suggesting that physiological implications of strong binding to albumin may be important for short-chain PFAAs.

Aqueous photolysis of the organic ultraviolet filter chemical octyl methoxycinnamate.

Organic UV filter chemicals are the active ingredients in personal care products designed to protect the skin from UV radiation, and hundreds of tons are estimated to be produced annually. Despite their entrance into the aquatic environment by both direct and indirect routes and their detection in surface waters and fish, little is known about their environmental fate. UV filter chemicals are designed to be photostable, but some undergo transformation upon exposure to UV light. Octyl methoxycinnamate (OMC), a commonly used UV filter chemical, degrades rapidly by direct photolysis; previous studies have focused on its photoisomerization, and a few investigators have reported the formation of cyclodimers. Here, we present the kinetics and quantum efficiency of the direct photolysis of OMC and confirm that dimerization occurs as a result of direct photolysis in aqueous solution. Likely identities of the dimers are offered based on comparison to reported results for other cinnamate derivatives. We have identified additional products of direct photolysis that have not been previously reported and investigated their photostability, as well as the mechanism of product formation. There is also some evidence of indirect photolysis in the presence of dissolved natural organic matter.

Development of a fluorescence model for the binding of medium- to long-chain perfluoroalkyl acids to human serum albumin through a mechanistic evaluation of spectroscopic evidence.

A novel model for measuring the strength of perfluoroalkyl acid (PFAA) binding to human serum albumin (HSA) by use of the protein's native fluorescence is described. The model is derived from published properties of HSA and its interactions with other surfactants; it is consistent with these properties and experimental observations. The model's validity has been tested with both medium- to long-chain PFAAs (perfluoroheptanoate, perfluorooctanoate, perfluorononanoate, perfluorodecanoate, perfluoroundecanoate, perfluorohexanesulfonate, and perfluorooctanesulfonate) and short-chain PFAAs (perfluorohexanoate and perfluorobutanesulfonate). These experiments confirm the model as a valid description for the binding of medium- to long-chain PFAAs to HSA. Results indicate at least 2-3 PFAAs bind to each protein with affinity on the order of 10(4) M(-1). These binding strengths exhibit a dependence on protein concentration. Measured PFAA binding constants are approximately 10% of those values reported for fatty acids of similar chain length; correcting for protein concentration suggests the binding strengths may be as low as 2-3% of the corresponding fatty acids' affinities. Like fatty acids, the carboxylate PFAAs exhibit a trend of generally increasing binding strength with increased chain length. The model does not appear valid for the binding of short-chain PFAAs to HSA. Hill binding coefficients, fluorescence intensity measurements, and wavelengths of maximum emission suggest short-chain PFAAs associate with HSA differently and fail to promote the same conformational changes in the protein's tertiary structure as the medium- to long-chain PFAAs.

Noncovalent interactions of long-chain perfluoroalkyl acids with serum albumin.

Preferential distribution of long-chain perfluoroalkyl acids (PFAAs) in the liver, kidney, and blood of organisms highlights the importance of PFAA-protein interactions in PFAA tissue distribution patterns. A serum protein association constant may be a useful parameter to characterize the bioaccumulative potential and in vivo bioavailability of PFAAs. In this work, association constants (K(a)) and binding stoichiometries for PFAA-albumin complexes are quantified over a wide range of PFAA:albumin mole ratios. Primary association constants for perfluorooctanoate (PFOA) or perfluorononanoate (PFNA) with the model protein bovine serum albumin (BSA) determined via equilibrium dialysis are on the order of 10(6) M(-1) with one to three primary binding sites. PFNA was greater than 99.9% bound to BSA or human serum albumin (HSA) at a physiological PFAA:albumin mole ratio (<10(-3)), corresponding to a high protein-water distribution coefficient (log K(PW) > 4). Nanoelectrospray ionization mass spectrometry (nanoESI-MS) data reveal PFAA-BSA complexes with up to eight occupied binding sites at a 4:1 PFAA:albumin mole ratio. Association constants estimated by nanoESI-MS are on the order of 10(5) M(-1) for PFOA and PFNA and 10(4) M(-1) for perfluorodecanoate and perfluorooctanesulfonate. The results reported here suggest binding through specific high affinity interactions at low PFAA:albumin mole ratios.

Binding of perfluorocarboxylates to serum albumin: a comparison of analytical methods.

Perfluorochemicals are globally pervasive contaminants that are persistent, bioaccumulative, and toxic. Perfluorocarboxylic acids (PFCAs) with 8-13 carbons accumulate in the liver and blood of aquatic organisms; PFCA-protein interactions may explain this accumulation pattern. Here, the interactions between PFCAs with 8-11 carbons and serum albumin are examined using three experimental approaches: surface tension titrations, (19)F NMR spectroscopy, and fluorescence spectroscopy. Surface tension titrations indicate complex formation at high (mM) PFCA concentrations. Secondary association constants ranging from 10(2) to 10(4) M(-1) were determined from (19)F NMR titrations at high PFCA:albumin mole ratios. Fluorescence measurements indicate that PFCA-albumin interactions alter the protein conformation at low PFCA:albumin mole ratios (up to 5:1) and suggest two binding classes with association constants around 10(5) and 10(2) M(-1). While (19)F NMR and fluorescence provide both qualitative and quantitative information about PFCA-albumin interactions, surface tension provides only qualitative information. Limitations associated with instrumentation and methods require high PFCA concentrations in both surface tension and (19)F NMR experiments; in contrast, fluorescence allows for analysis of a wider range of PFCA concentrations and PFCA:albumin mole ratios. Results from this study indicate that fluorescence, though an indirect method, offers a more comprehensive picture of the nature of PFCA-albumin interactions.

The effect of omega-3 FAs on tumour angiogenesis and their therapeutic potential.

Omega-3 fatty acid (omega-3 FA) consumption has long been associated with a lower incidence of colon, breast and prostate cancers in many human populations. Human trials have demonstrated omega-3 FA to have profound anti-inflammatory effects in those with cancer. In vitro and small animal studies have yielded a strong body of evidence establishing omega-3 FA as having anti-inflammatory, anti-apoptotic, anti-proliferative and anti-angiogenic effects. This review explores the evidence and the mechanisms by which omega-3 FA may act as angiogenesis inhibitors and identifies opportunities for original research trialling omega-3 FAs as anti-cancer agents in humans. The conclusions drawn from this review suggest that omega-3 FAs in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found principally in oily fish have potent anti-angiogenic effects inhibiting production of many important angiogenic mediators namely; Vascular Endothelial Growth Factor (VEGF), Platelet-Derived Growth Factor (PDGF), Platelet-Derived Endothelial Cell Growth Factor (PDECGF), cyclo-oxygenase 2 (COX-2), prostaglandin-E2 (PGE2), nitric oxide, Nuclear Factor Kappa Beta (NFKB), matrix metalloproteinases and beta-catenin.

A case of liver metastasis from an oncocytoma with a focal area of chromophobe renal cell carcinoma: a wolf in sheep's clothing.

In 2004, the World Health Organization classified the renal oncocytomas as benign neoplasms of the kidney. There are reports of subtypes of renal tumors, with similar histological morphology to oncocytoma, but with malignant potential, one of these tumors is the eosinophilic variant of chromophobe renal cell carcinoma. It is important to characterize the histological features and the subtype of tumor, as this predicts biological behavior and cancer-specific survival rate. A rare case of a liver metastasis from a focal area of eosinophilic variant of chromophobe renal cell carcinoma mixed in oncocytoma in a 69-year-old woman is reported. Although some renal tumors may contain oncocytoma and eosinophilic variant of chromophobe renal cell carcinoma histology, caution should be exercised while diagnosing oncocytomas in needle biopsies as there may be unsampled area of chromophobe carcinoma which has a potential for metastatic spread representing a wolf in sheep's clothing.

Lessons from laparoscopic liver surgery: a nine-year case series.

OBJECTIVE: This series describes a developing experience in laparoscopic liver surgery presenting results from 40 procedures including right hemihepatectomy, left lateral lobectomy, and microwave ablation therapy. METHODS: Forty patients undergoing laparoscopic liver surgery between September 1997 and November 2006 were included. The data set includes: operative procedure and duration, intraoperative blood loss, conversion to open operation rates, length of hospital stay, complications, mortality, histology of lesions/resection margins, and disease recurrence. RESULTS: Mean age of patient: 59 years, 17/40 male, 23/40 female, 23/40 of lesions were benign, and 17/40 malignant. Operations included: laparoscopic anatomical resections n = 15, nonanatomical resections n = 11, microwave ablations n = 8 and deroofing of cysts n = 7. Median anaesthetic time: 120 minutes (range 40-240), mean blood loss 78 mL and 1/40 conversions to open. Median resection margins were 10 mm (range 1-14) and median length of stay 3 days (range 1-10). Operative and 30-day mortality were zero with no local disease recurrence. CONCLUSION: Laparoscopic liver surgery appears safe and effective and is associated with reduced hospital stay. Larger studies are required to confirm it is oncologically sound.

Laparoscopic inguinal ligament tenotomy and mesh reinforcement of the anterior abdominal wall: a new approach for the management of chronic groin pain.

BACKGROUND: Chronic groin pain has an incidence of up to 6.2% and is common in people undertaking regular sports activity. A variety of surgical options exist for unresolving pain, which consist, for the most part, of a repair of the posterior abdominal wall, with or without mesh placement. We describe a new technique, which combines laparoscopic inguinal ligament tenotomy in conjunction with a mesh repair. METHODS: A retrospective analysis of the notes of 48 patients was undertaken in conjunction with a mailed questionnaire. Success of surgery was judged on return to preinjury sporting activity, severity of pain scores, frequency of pain scores, and functional limitation scores. RESULTS: There were no major complications associated with the procedure. Severity of pain, frequency of pain, and functional limitation scores were all significantly improved after surgery (P=0.0012, <0.0001, and <0.0001, respectively). Ninety-two percent of patients polled returned to normal sports activity after their surgery (n=24). The median return to strenuous sports activity was 28 days (range of 14 to 40 d). CONCLUSIONS: The success rates of laparoscopic tenotomy and mesh repair are comparable with the published literature and a lower median time interval before returning to preinjury sporting activity.