A synthesis of patterns of environmental mercury inputs, exposure and effects in New York State.

Mercury (Hg) pollution is an environmental problem that adversely affects human and ecosystem health at local, regional, and global scales-including within New York State. More than two-thirds of the Hg currently released to the environment originates, either directly or indirectly, from human activities. Since the early 1800s, global atmospheric Hg concentrations have increased by three- to eight-fold over natural levels. In the U.S., atmospheric emissions and point-source releases to waterways increased following industrialization into the mid-1980s. Since then, water discharges have largely been curtailed. As a result, Hg emissions, atmospheric concentrations, and deposition over the past few decades have declined across the eastern U.S. Despite these decreases, Hg pollution persists. To inform policy efforts and to advance public understanding, the New York State Energy Research and Development Authority (NYSERDA) sponsored a scientific synthesis of information on Hg in New York State. This effort includes 23 papers focused on Hg in atmospheric deposition, water, fish, and wildlife published in Ecotoxicology. New York State experiences Hg contamination largely due to atmospheric deposition. Some landscapes are inherently sensitive to Hg inputs driven by the transport of inorganic Hg to zones of methylation, the conversion of inorganic Hg to methylmercury, and the bioaccumulation and biomagnification along food webs. Mercury concentrations exceed human and ecological risk thresholds in many areas of New York State, particularly the Adirondacks, Catskills, and parts of Long Island. Mercury concentrations in some biota have declined in the Eastern Great Lakes Lowlands and the Northeastern Highlands over the last four decades, concurrent with decreases in water releases and air emissions from regional and U.S. sources. However, widespread changes have not occurred in other ecoregions of New York State. While the timing and magnitude of the response of Hg levels in biota varies, policies expected to further diminish Hg emissions should continue to decrease Hg concentrations in food webs, yielding benefits to the fish, wildlife, and people of New York State. Anticipated improvements in the Hg status of aquatic ecosystems are likely to be greatest for inland surface waters and should be roughly proportional to declines in atmospheric Hg deposition. Efforts that advance recovery from Hg pollution in recent years have yielded significant progress, but Hg remains a pollutant of concern. Indeed, due to this extensive compilation of Hg observations in biota, it appears that the extent and intensity of the contamination on the New York landscape and waterscape is greater than previously recognized. Understanding the extent of Hg contamination and recovery following decreases in atmospheric Hg deposition will require further study, underscoring the need to continue existing monitoring efforts.

Circulating tumor DNA predicts survival in patients with resected high-risk stage II/III melanoma.

Background: Patients with high-risk stage II/III resected melanoma commonly develop distant metastases. At present, we cannot differentiate between patients who will recur or those who are cured by surgery. We investigated if circulating tumor DNA (ctDNA) can predict relapse and survival in patients with resected melanoma. Patients and methods: We carried out droplet digital polymerase chain reaction to detect BRAF and NRAS mutations in plasma taken after surgery from 161 stage II/III high-risk melanoma patients enrolled in the AVAST-M adjuvant trial. Results: Mutant BRAF or NRAS ctDNA was detected (≥1 copy of mutant ctDNA) in 15/132 (11%) BRAF mutant patient samples and 4/29 (14%) NRAS mutant patient samples. Patients with detectable ctDNA had a decreased disease-free interval [DFI; hazard ratio (HR) 3.12; 95% confidence interval (CI) 1.79-5.47; P < 0.0001] and distant metastasis-free interval (DMFI; HR 3.22; 95% CI 1.80-5.79; P < 0.0001) versus those with undetectable ctDNA. Detectable ctDNA remained a significant predictor after adjustment for performance status and disease stage (DFI: HR 3.26, 95% CI 1.83-5.83, P < 0.0001; DMFI: HR 3.45, 95% CI 1.88-6.34, P < 0.0001). Five-year overall survival rate for patients with detectable ctDNA was 33% (95% CI 14%-55%) versus 65% (95% CI 56%-72%) for those with undetectable ctDNA. Overall survival was significantly worse for patients with detectable ctDNA (HR 2.63; 95% CI 1.40-4.96); P = 0.003) and remained significant after adjustment for performance status (HR 2.50, 95% CI 1.32-4.74, P = 0.005). Conclusion: ctDNA predicts for relapse and survival in high-risk resected melanoma and could aid selection of patients for adjuvant therapy. Clinical trial number: ISRCTN 81261306.

Urinary retention and syndrome of inappropriate antidiuretic hormone secretion (SIADH) secondary to impacted gravid uterus.

Urinary retention is an emergency that rarely occurs during pregnancy. Previous case reports have suggested multiple risk factors that can cause the gravid uterus to become impacted in the pelvis leading to lower bladder or urethral compression with subsequent urinary retention. However, no cases of urinary obstruction in a pregnancy that was complicated with severe electrolyte imbalance have been reported. To our knowledge, we report the first case of a 31-year-old woman presenting at 8 weeks' gestation with acute urinary retention caused by a retroflexed, retroverted uterus with a 6-cm posterior uterine fibroid leading to syndrome of inappropriate antidiuretic hormone secretion and severe hyponatremia requiring intensive care unit admission. The cornerstones of effective management of urinary retention should include: (i) urgent bladder catheterization; (ii) assessment of sodium levels to rule out syndrome of inappropriate antidiuretic hormone secretion, and prompt treatment before neurological damage occurs; (iii) reduction of the impacted uterus; and (iv) monitoring for post-obstructive diuresis.

Respiratory complex III dysfunction in humans and the use of yeast as a model organism to study mitochondrial myopathy and associated diseases.

The bc1 complex or complex III is a central component of the aerobic respiratory chain in prokaryotic and eukaryotic organisms. It catalyzes the oxidation of quinols and the reduction of cytochrome c, establishing a proton motive force used to synthesize adenosine triphosphate (ATP) by the F1Fo ATP synthase. In eukaryotes, the complex III is located in the inner mitochondrial membrane. The genes coding for the complex III have a dual origin. While cytochrome b is encoded by the mitochondrial genome, all the other subunits are encoded by the nuclear genome. In this review, we compile an exhaustive list of the known human mutations and associated pathologies found in the mitochondrially-encoded cytochrome b gene as well as the fewer mutations in the nuclear genes coding for the complex III structural subunits and accessory proteins such as BCS1L involved in the assembly of the complex III. Due to the inherent difficulties of studying human biopsy material associated with complex III dysfunction, we also review the work that has been conducted to study the pathologies with the easy to handle eukaryotic microorganism, the yeast Saccharomyces cerevisiae. Phenotypes, biochemical data and possible effects due to the mutations are also discussed in the context of the known three-dimensional structure of the eukaryotic complex III. This article is part of a Special Issue entitled: Respiratory complex III and related bc complexes.

Mortality, morbidity and evidence-based management amongst patients in regional New Zealand with severe left ventricular systolic dysfunction (1997-2011).

BACKGROUND: Heart failure and its management represents a significant health burden, the extent of which is poorly understood in regional New Zealand. AIMS: To investigate mortality, quality of life, hospitalisation, and evidence-based medical and device management of severe left ventricular (LV) systolic dysfunction in a regional New Zealand setting. METHODS: A retrospective case series was undertaken of 1126 patients with a LV ejection fraction <36% on transthoracic echocardiograms performed between 1 October 1997 and 31 March 2011 in Nelson Marlborough District Health Board. All-cause mortality and hospitalisation data were analysed for all participants. Substudies were undertaken regarding pharmacotherapy, demographics, implantable cardioverter-defibrillator implantation rates and quality of life based on the EQ-5D questionnaire and New York Heart Association class. RESULTS: Five-year cumulative survival was 44.5%. The mean annual medical admission rate was 204/100 000; 54.84% of which were readmissions in the same year. Prescription rates for angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers, beta-blockers and spironolactone were 68.3%, 74.2% and 24.9%, respectively, with only 17.6%, 19.0% and 16.4% on maximum recommended doses. implantable cardioverter-defibrillator devices were inserted in 11.5% of eligible patients. Quality of life was impaired in patients <70 years relative to the age-approximated New Zealand index population. Mean EQ-5D visual analogue score was 72.6 ± 0.032 and self-reported New York Heart Association class 2.09 ± 0.107 CONCLUSION: Patients with severe LV systolic dysfunction in this regional New Zealand community experience similar mortality and first hospitalisation rates to those seen elsewhere in patients with clinical heart failure, but a greater number of readmissions. Medical and device therapy utilisation was suboptimal, and quality of life impaired, together supporting the need for a dedicated heart failure service.

Influence of exercise on nutritional requirements.

There is no consensus on the best diet for exercise, as many variables influence it. We propose an approach that is based on the total energy expenditure of exercise and the specific macro- and micronutrients used. di Prampero quantified the impact of intensity and duration on the energy cost of exercise. This can be used to determine the total energy needs and the balance of fats and carbohydrates (CHO). There are metabolic differences between sedentary and trained persons, thus the total energy intake to prevent overfeeding of sedentary persons and underfeeding athletes is important. During submaximal sustained exercise, fat oxidation (FO) plays an important role. This role is diminished and CHO's role increases as exercise intensity increases. At super-maximal exercise intensities, anaerobic glycolysis dominates. In the case of protein and micronutrients, specific recommendations are required. We propose that for submaximal exercise, the balance of CHO and fat favors fat for longer exercise and CHO for shorter exercise, while always maintaining the minimal requirements of each (CHO: 40% and fat: 30%). A case for higher protein (above 15%) as well as creatine supplementation for resistance exercise has been proposed. One may also consider increasing bicarbonate intake for exercise that relies on anaerobic glycolysis, whereas there appears to be little support for antioxidant supplementation. Insuring minimal levels of substrate will prevent exercise intolerance, while increasing some components may increase exercise tolerance.

Chlorinated hydrocarbon pollutants and photosynthesis of marine phytoplankton: a reassessment.

The chlorinated hydrocarbons DDT and PCB's (polychlorinated biphenyls), ubiquitous pollutants of the marine environment, have been observed to reduce the cell division rate of marine phytoplankton, thereby indirectly reducing the total photosynthetic carbon fixation in treated cultures. The photosynthetic capacity of each cell was not affected. Total marine photosynthesis will likely remain undiminished by these compounds, although alterations in phytoplankton communities through selective toxicity could effect herbivore populations.

The assimilation of elements ingested by marine copepods.

The efficiency with which a variety of ingested elements (Ag, Am, C, Cd, P, S, Se, and Zn) were assimilated in marine calanoid copepods fed uniformly radiolabeled diatoms ranged from 0.9% for Am to 97.1% for Se. Assimilation efficiencies were directly related to the cytoplasmic content of the diatoms. This relation indicates that the animals obtained nearly all their nutrition from this source. The results suggest that these zooplankton, which have short gut residence times, have developed a gut lining and digestive strategy that provides for assimilation of only soluble material. Because the fraction of total cellular protein in the cytoplasm of the diatoms increased markedly with culture age, copepods feeding on senescent cells should obtain more protein than those feeding on rapidly dividing cells. Elements that are appreciably incorporated into algal cytoplasm and assimilated in zooplankton should be recycled in surface waters and have longer oceanic residence times than elements bound to cell surfaces.

Polychlorinated biphenyls and DDT alter species composition in mixed cultures of algae.

Either DDT or polychlorinated biphenyls were added to mixed cultures containing a marine diatom and a marine green alga that were sensitive and resistant, respectively, to these organochlorine compounds. The diatom grew faster and was therefore dominant in control cultures, but its dominance diminished in treated cultures, even at concentrations of chlorinated hydrocarbons that had no apparent effect in pure cultures. Such stable pollutants could disrupt the species composition of phytoplankton communities, thereby affecting whole eco-systems.

Polychlorinated biphenyls: toxicity to certain phytoplankters.

The growth rates of two species of marine diatoms were reduced by polychlorinated biphenyls (PCB's), widespread pollutants of the marine environment, at concentrations as low as 10 to 25 parts per billion. In contrast, a marine green alga and two species of freshwater algae were not inhibited at these or higher concentrations. The sensitivity of these species to PCB's paralleled their sensitivity to DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane].

Influences of dietary uptake and reactive sulfides on metal bioavailability from aquatic sediments.

Understanding how animals are exposed to the large repository of metal pollutants in aquatic sediments is complicated and is important in regulatory decisions. Experiments with four types of invertebrates showed that feeding behavior and dietary uptake control bioaccumulation of cadmium, silver, nickel, and zinc. Metal concentrations in animal tissue correlated with metal concentrations extracted from sediments, but not with metal in porewater, across a range of reactive sulfide concentrations, from 0.5 to 30 micromoles per gram. These results contradict the notion that metal bioavailability in sediments is controlled by geochemical equilibration of metals between porewater and reactive sulfides, a proposed basis for regulatory criteria for metals.

Seroepidemiology of hepatitis C antibodies among dentists and their self-reported use of infection control measures.

OBJECTIVES: To determine the prevalence of hepatitis C virus (HCV) antibodies among dentists graduated from various countries and assess the use of infection control measures in their dental practice. RESEARCH DESIGN: The study included 301 Israeli dentists who attended an annual dental conference. Participants filled out a structured questionnaire regarding demographic (age, gender, number of siblings, number of children) and occupational characteristics. Venous blood was examined for presence of HCV antibodies by enzyme immunoassay and confirmed by a third generation line immunoassay, which assesses antibodies to HCV-core antigens (INN-LIA HCV Ab III update, 100% sensitivity, 100% specificity). RESULTS: The prevalence of HCV antibodies among Israeli dentists was 1/301 (0.33%), similar to the prevalence range (0.1-0.5%) among the general Israeli population. The studied population included dentists (30.6%) who immigrated from Asia, Eastern Europe and the former USSR, where HCV prevalence ranges from 3.1% to 26.5%. Dentists routinely used gloves (99.6%), gown (93.3%), autoclaves (90.3%), dry heat (29.1%) and mask (81%). Dentists who graduated after 1985 used a mask or gown significantly more often than dentists who graduated before 1985 (p < 0.001 and p = 0.004, respectively). CONCLUSION: It seems that dentists who usually adhere to basic infection control measures are not at an increased risk for HCV.

Mobilization of endothelial progenitor cells into the circulation in burned patients.

BACKGROUND: Bone marrow-derived endothelial progenitor cells (EPCs) have been detected in the peripheral blood of patients following thermal injury. EPCs migrate to sites of active neovascularization in response to mediators released after trauma, contributing to wound healing. The aim was to characterize levels and kinetics of EPCs in burned patients, then relate these to key mobilizing factors, vascular endothelial growth factor (VEGF) and the chemokine (C-X-C motif) ligand 12 (CXCL 12), and compare them with those in healthy subjects. METHODS: The study included 19 adult patients with superficial or full-thickness burns and 50 blood donor volunteer controls. EPCs, identified by cell surface markers CD45(dim/-), CD133+, CD144+ and VEGF receptor 2, were quantified by four-colour flow cytometry. Plasma VEGF and CXCL12 were measured using enzyme-linked immunosorbent assay. RESULTS: Burned patients showed a rapid rise in EPC levels within 24 h, a ninefold increase compared with controls, returning to basal levels by 72 h. Body surface area burned correlated strongly with the degree of mobilization. EPC levels correlated significantly with rises in plasma VEGF and CXCL12. CONCLUSION: Thermal injury induced a rapid rise in EPCs that was proportional to the extent of the burn and significantly correlated with levels of angiogenic cytokines. Such cytokines may be used to stimulate EPCs as a future therapeutic target in burned patients.

Quantification of circulating cell-free plasma DNA and endothelial gene RNA in patients with burns and relation to acute thermal injury.

BACKGROUND: Major burn represents a multi-system insult to the human body. Despite improvements in mortality and morbidity, reliable predictors of outcome are lacking. Raised levels of cell-free nucleic acids have been detected in various pathological processes including burns. We quantified circulating nucleic acids as potential objective measures of burn severity with predictive and prognostic value. METHODS: Expression of endothelial specific cell-free mRNA and cell-free DNA were measured in plasma of 19 burn patients at days 1-3 and week 10 following acute thermal injury and in 19 healthy controls by real-time quantitative PCR. RESULTS: Expression of endothelial specific mRNA was higher in burn patients compared to controls (p<0.001). DNA levels were significantly higher in the burn population in the first 48 h following injury. Plasma RNA and DNA levels related to %TBSA burn in the first 24h and to the levels of circulating endothelial progenitor cells. CONCLUSIONS: We show that plasma levels of endothelial specific mRNA and DNA are elevated acutely following burns, and relate to severity in terms of %TBSA burnt.

The Glasgow alcoholic hepatitis score identifies patients who may benefit from corticosteroids.

INTRODUCTION: There is no consensus on the pharmacological treatment of alcoholic hepatitis. The Glasgow alcoholic hepatitis score (GAHS) has been shown to be more accurate than the modified Maddrey's discriminant function (mDF) in the prediction of outcome from alcoholic hepatitis. This study aimed to determine whether the GAHS was able to identify those patients who would benefit from corticosteroids. METHODS: 225 patients with an mDF greater than or equal to 32 from five hospital centres in the United Kingdom were reviewed. Patient survival relative to the GAHS and the use of corticosteroids was recorded. RESULTS: 144 patients with an mDF greater than or equal to 32 (64%) also had a GAHS greater than or equal to 9. There was no difference in survival between untreated or corticosteroid-treated patients for those with a GAHS less than 9. For patients with a GAHS greater than or equal to 9 the 28-day survival for untreated and corticosteroid-treated patients was 52% and 78% (p = 0.002), and 84-day survival was 38% and 59% (p = 0.02), respectively. CONCLUSIONS: Among patients with an mDF greater than or equal to 32, there was no appreciable benefit from treatment with corticosteroids in patients with a GAHS less than 9. Patients with a GAHS greater than or equal to 9 have an extremely poor prognosis if they are not treated with corticosteroids, or if such treatment is contraindicated.

Statin therapy depresses total body fat oxidation in the absence of genetic limitations to fat oxidation.

Cholesterol lowering drugs are associated with myopathic side effects in 7% of those on therapy, which is reversible in most, but not all patients. This study tested the hypothesis that total body fat oxidation (TBFO) is reduced by statins in patients with genetic deficiencies in FO, determined by white blood cells (FOwbc) and by molecular analysis of common deficiencies, and would cause intolerance in some patients. Six patients on statin therapy without myopathic side effects (tolerant) and 7 patients who had previously developed statin-induced myopathic symptoms (intolerant) (age = 58 +/- 8.25 yrs, ht. = 169 +/- 11 cm, and wt. = 75.4 +/- 14.2 kg) were tested for TBFO (Respiratory Exchange Ratio, RER) pre- and during exercise. FOwbc was not significantly different between tolerant and intolerant (0.261 +/- 0.078 vs. 0.296 +/- 0.042 nmol/h per 10(9) wbc), or normals (0.27 +/- 0.09 nmol/h per 10(9) wbc) and no common molecular abnormalities were found. Pre-exercise RER (0.73 +/- 0.05 vs. 0.84 +/- 0.05) was significantly lower in the intolerant group and the VO2 at RER = 1.0 (1.27 +/- 0.32 vs. 1.87 +/- 0.60 L/min) greater than the tolerant. Post-exercise lactates were not different between groups. Although dietary fat intake was not different, blood lipoprotein levels, particularly triglycerides were 35% lower in tolerant than previously intolerant. TBFO and blood lipoproteins were reduced in tolerant patients in spite of the absence of genetic limitations, but not in the intolerant group as hypothesized. Although not conclusive, these data suggest the need for a prospective study of the effects of statins on fat oxidation.

Sporting and physical activity following Oxford medial unicompartmental knee arthroplasty.

The purpose of this study was to evaluate and assess the sporting and physical activities of patients who had undergone an Oxford medial unicompartmental knee arthroplasty (UKA). Seventy-six patients who underwent a UKA between 2000 and 2003 were reviewed. Demographic data such as age, sex and comorbidities were recorded. University of California Los Angeles (UCLA) activity level ratings and Oxford knee scores were determined for each patient. The sporting and physical activities of all patients' pre- and post-operatively were recorded. The mean age of patients was 64 years (range 49-81) at surgery and 66 years (range 53-82) at review. The mean follow up time was 18 months (range 4-46). Following surgery there was a significant improvement in UCLA activity level scores from 4.2 to 6.5 (Wilcoxon Matched-pairs Signed-rank Test, p<0.01). Forty-two patients (64%) regularly participated in sport before they became symptomatic with significant knee pain, and thirty-nine patients (59%) regularly participated in sports after surgery. In total 93% of patients successfully returned to their regular sporting and physical activities following surgery. The published long-term survivorship of the Oxford UKA has given surgeons increasing confidence to use the prosthesis on a younger generation of patients. Our study has demonstrated that this population of patients is extremely active. A more detailed study is required to evaluate the long-term effects of sporting activity on the Oxford UKA.

Decrease in coronary blood flow reserve during hyperlipidemia is secondary to an increase in blood viscosity.

BACKGROUND: During maximal hyperemia, capillaries provide the greatest resistance to flow. A major determinant of capillary resistance is viscosity. We, therefore, hypothesized that abnormal coronary blood flow (CBF) reserve observed during hyperlipidemia is secondary to increased blood viscosity and not abnormal coronary vasomotion. METHODS AND RESULTS: Maximal hyperemia was induced in 9 dogs using adenosine. Serum triglyceride levels were increased by incremental doses of Intralipid. A good correlation was noted between serum triglyceride levels and blood viscosity (r=0.82). Neither total coronary blood volume nor myocardial blood volume changed with increasing serum triglyceride levels, indicating lack of vasomotion. Myocardial vascular resistance (MVR) increased with increasing triglyceride levels (r=0.84), while hyperemic myocardial blood flow (MBF) decreased (r=-0.64). The decrease in hyperemic MBF was associated with a decrease in blood velocity (r=-0.56). These findings were confirmed with direct intravital microscopic observations in the mice cremaster muscle. CONCLUSIONS: Increasing lipid levels in a fully dilated normal coronary bed causes no change in large or small vessel dimensions. Instead, the increase in blood viscosity causes capillary resistance to rise, which attenuates hyperemic CBF. Therefore, the abnormal CBF reserve associated with hyperlipidemia is due to increase blood viscosity and not abnormal vascular function.