Comprehensive Analysis of Adverse Events Associated with Gastric Peroral Endoscopic Myotomy: An International Multicenter Study.

BACKGROUND: Gastric peroral endoscopic myotomy (G-POEM) has emerged as an effective management approach for patients with refractory gastroparesis. This study aims to comprehensively study the safety of G-POEM and describe the predictive factors of adverse events (AEs) occurrence. METHODS: This study is a retrospective study involving 13 tertiary care centers (7 USA, 1 South America, 4 Europe, and 1 Asia). Patients who underwent G-POEM for refractory gastroparesis were included. Cases were identified by the occurrence of AEs. For each case, two controls were randomly selected and matched for age (± 10 years), gender, and etiology of gastroparesis. RESULTS: A total of 216 patients underwent G-POEM for gastroparesis. Overall, 31 (14%) AEs were encountered [mild 24 (77%), moderate 5 (16%), and severe 2 (6%)] during the duration of the study. The most common AE was abdominal pain (n = 16), followed by mucosotomy (n = 5) and capnoperitoneum (n = 4), and AEs were most commonly identified within the first 48-h post-procedure 18 (58%). The risk of adverse event occurrence was significantly higher for endoscopists with experience of < 20 G-POEM procedures (OR 3.03 [1.03-8.94], p < 0.05). CONCLUSION: G-POEM seems to be a safe intervention for refractory gastroparesis. AEs are most commonly mild and managed conservatively. Longitudinal mucosal incision, use of hook knife, use of clips for mucosal closure and endoscopist's experience with > 20 G-POEM procedures is significantly associated with decreased incidence of AEs.

Evaluation of water displacement energetics in protein binding sites with grid cell theory.

Excess free energies, enthalpies and entropies of water in protein binding sites were computed via classical simulations and Grid Cell Theory (GCT) analyses for three pairs of congeneric ligands in complex with the proteins scytalone dehydratase, p38α MAP kinase and EGFR kinase respectively. Comparative analysis is of interest since the binding modes for each ligand pair differ in the displacement of one binding site water molecule, but significant variations in relative binding affinities are observed. Protocols that vary in their use of restraints on protein and ligand atoms were compared to determine the influence of protein-ligand flexibility on computed water structure and energetics, and to assess protocols for routine analyses of protein-ligand complexes. The GCT-derived binding affinities correctly reproduce experimental trends, but the magnitude of the predicted changes in binding affinities is exaggerated with respect to results from a previous Monte Carlo Free Energy Perturbation study. Breakdown of the GCT water free energies into enthalpic and entropic components indicates that enthalpy changes dominate the observed variations in energetics. In EGFR kinase GCT analyses revealed that replacement of a pyrimidine by a cyanopyridine perturbs water energetics up three hydration shells away from the ligand.

Per- and polyfluoroalkyl substances (PFAS), trace elements and life history parameters of mass-stranded common dolphins (Delphinus delphis) in New Zealand.

Profiles of 33 PFAS analytes and 12 essential and non-essential trace elements were measured in livers of stranded common dolphins (Delphinus delphis) from New Zealand. PFAS concentrations reported were largely comparable to those measured in other marine mammal species globally and composed mostly of long-chain compounds including perfluorooctanesulfonic acid (PFOS), perfluorododecanoic acid (PFDoDA), perfluorotridecanoic acid (PFTrDA) and perfluorooctanesulfonamide (FOSA). PFAS profiles did not vary significantly by location, body condition, or life history. Notably, significant positive correlations were observed within respective PFAS and trace elements. However, only negative correlations were evident between these two contaminant types, suggesting different exposure and metabolic pathways. Age-associated concentrations were found for PFTrDA and four trace elements, i.e. silver, mercury, cadmium, selenium, indicating differences in the bioaccumulation biomagnification mechanisms. Overall, our results contribute to global understanding of accumulation of PFAS by offering first insights of PFAS exposure in cetaceans living within South Pacific Australasian waters.

Bioaccumulation of persistent organic pollutants in female common dolphins (Delphinus delphis) and harbour porpoises (Phocoena phocoena) from western European seas: geographical trends, causal factors and effects on reproduction and mortality.

Concentrations of polychlorinated biphenyls (PCBs) in blubber of female common dolphins and harbour porpoises from the Atlantic coast of Europe were frequently above the threshold at which effects on reproduction could be expected, in 40% and 47% of cases respectively. This rose to 74% for porpoises from the southern North Sea. PCB concentrations were also high in southern North Sea fish. The average pregnancy rate recorded in porpoises (42%) in the study area was lower than in the western Atlantic but that in common dolphins (25%) was similar to that of the western Atlantic population. Porpoises that died from disease or parasitic infection had higher concentrations of persistent organic pollutants (POPs) than animals dying from other causes. Few of the common dolphins sampled had died from disease or parasitic infection. POP profiles in common dolphin blubber were related to individual feeding history while those in porpoises were more strongly related to condition.

Below the surface: Twenty-five years of seafloor litter monitoring in coastal seas of North West Europe (1992-2017).

Marine litter presents a global problem, with increasing quantities documented in recent decades. The distribution and abundance of marine litter on the seafloor off the United Kingdom's (UK) coasts were quantified during 39 independent scientific surveys conducted between 1992 and 2017. Widespread distribution of litter items, especially plastics, were found on the seabed of the North Sea, English Channel, Celtic Sea and Irish Sea. High variation in abundance of litter items, ranging from 0 to 1835 pieces km-2 of seafloor, was observed. Plastic tems such as bags, bottles and fishing related debris were commonly observed across all areas. Over the entire 25-year period (1992-2017), 63% of the 2461 trawls contained at least one plastic litter item. There was no significant temporal trend in the percentage of trawls containing any or total plastic litter items across the long-term datasets. Statistically significant trends, however, were observed in specific plastic litter categories only. These trends were all positive except for a negative trend in plastic bags in the Greater North Sea - suggesting that behavioural and legislative changes could reduce the problem of marine litter within decades.

Membrane proteins: Aquaporins--channels without ions.

Recently determined structures have shed new light on the way that aquaporins act as passive, but selective, pores for the transport of small molecules--such as water or glycerol--across membranes.

Trace elements, PCBs and organochlorine pesticides in New Zealand common dolphins (Delphinus sp.).

Trace elements, polychlorinated biphenyls (PCBs) and organochlorine (OC) pesticide levels were determined in tissues collected from stranded and bycaught common dolphins (Delphinus sp.) from New Zealand waters between 1999 and 2005. The concentrations of mercury (Hg), selenium (Se), chromium (Cr), zinc (Zn), nickel (Ni), cadmium (Cd), cobalt (Co), manganese (Mn), iron (Fe), copper (Cu), tin (Sn), lead (Pb), arsenic (As) and silver (Ag) were determined in blubber, liver and kidney tissue. PCBs (45 congeners) and a range of OC pesticides including dieldrin, hexachlorocyclohexane (HCH) and dichlorodiphenyltrichloroethane (DDT) and its metabolites DDE and DDD were determined in blubber samples. Cr and Ni were not detected in any of the samples and concentrations of Co, Sn and Pb were generally low. Concentrations of Hg ranged from 0.17 to 110 mg/kg wet weight. Organochlorine pesticides dieldrin, HCB, o,p'-DDT and p,p'-DDE were present at the highest concentrations. Sum DDT concentrations in the blubber ranged from 17 to 337 and 654 to 4430 microg/kg wet weight in females and males, respectively. Similarly, Sigma45CB concentrations ranged from 49 to 386 and 268 to 1634 microg/kg wet weight in females and males, respectively. The mean transmission of SigmaDDTs and ICES7CBs between a genetically determined mother-offspring pair was calculated at 46% and 42%, respectively. Concentrations of organochlorine pesticides determined in the present study are within similar range to those reported for Hector's dolphins (Cephalorhyncus hectori) from inshore New Zealand waters.

Biological and ecological factors related to trace element levels in harbour porpoises (Phocoena phocoena) from European waters.

Selected trace elements (Cd, Cu, Hg, Se, Zn) were measured in the kidneys and the liver of 104 harbour porpoises (Phocoena phocoena) stranded along the coasts of France, Galicia (Spain), Ireland, Scotland (UK), and the Netherlands. Generally, relatively low concentrations of toxic elements were encountered in the tissues of European porpoises, except for two individuals, which displayed high hepatic Hg concentrations. Also, elevated Cd levels obtained in Scottish porpoises could be related to their feeding preferences and this result suggests an increase of the proportion of cephalopods in their diet with latitude. Moreover, significant geographical differences were seen in hepatic Zn concentrations; the elevated Zn concentrations displayed by porpoises from the Netherlands may relate their poor health status. Variation in metal concentrations within porpoises from the North Sea is likely to reflect a long-term segregation between animals from northern (Scotland) and southern areas (the Netherlands), making trace elements powerful ecological tracers.

Observation of nonlinear optical phenomena in air and fused silica using a 100 GW, 1.54 mum source.

A 100-GW optical parametric chirped-pulse amplifier system is used to study nonlinear effects in the 1.54 mum regime. When focusing this beam in air, strong third-harmonic generation (THG) is observed, and both the spectra and efficiency are measured. Broadening is observed on only the blue side of the third-harmonic signal and an energy conversion efficiency of 0.2% is achieved. When propagated through a 10-cm block of fused silica, a collimated beam is seen to collapse and form multiple filaments. The measured spectral features span 400-2100 nm. The spectrum is dominated by previously unobserved Stokes emissions and broad emissions in the visible.

Baseline survey of marine sediments collected from the State of Kuwait: PAHs, PCBs, brominated flame retardants and metal contamination.

A geographically extensive baseline survey of sediment contamination was undertaken at twenty nine locations around Kuwait. Samples were assessed in relation to a wide range of industrial pollutants, including metals, PAHs, PCBs, PBDEs and HBCDs. The data generated indicated that levels of pollutants were generally low and below commonly applied sediment quality guidelines (SQGs). However, naturally high background concentrations of certain metals present in sediment from the region may prohibit the direct assessment against some of the routinely applied SQGs. Hot spots of contamination were identified for PAHs, PCBs and PBDEs, that were mainly associated with the Shuaiba Industrial Area, located south of the city, and known to contain a diverse mix of both light and heavy industry.

Stress on stress response of wild mussels, Mytilus edulis and Mytilus trossulus, as an indicator of ecosystem health.

Mussels' health as indicated by the survival time of 50% of sampled animals (LT(50)) when maintained in air at 15 degrees C was examined at three sites in Halifax Harbour with expected differing levels of contamination. Condition and gonad indices, lipid content and the body burden of polycyclic aromatic compounds (PACs) were compared with this stress response in 60 groups of mussels covering two species. At each sampling time, the bioaccumulation of PACs, lipid content and condition indices were higher within Mytilus edulis and Mytilus trossulus displaying shorter survival than at the other sites. M. edulis was generally more tolerant than M. trossulus (for n=11, LT(50) of 9.3 and 7.9 days), with indications of shorter and later gonad development in M. trossulus. Minimum and maximum tolerance was apparent in June and October (LT(50) spanning 3-14 days), respectively. Our results indicate that the stress on stress response provides a simple and sensitive indicator of environmental health, which could be integrated with mussel watch studies.

Levels of short and medium chain length polychlorinated n-alkanes in environmental samples from selected industrial areas in England and Wales.

Electron capture or negative ion chemical ionisation gas chromatography-mass spectrometry was employed to measure concentrations of short and medium chain length polychlorinated n-alkanes extracted from samples of water, river sediment, benthos, fish, soil, digested sewage and earthworms. Analysis of samples from 20 aquatic and eight agricultural sites indicated that short and medium chain length polychlorinated alkanes were present in the following concentration ranges: sediment < 0.2-65.1 mg/kg dry weight, water < 0.1-1.7 micrograms/l, fish < 0.1-5.2 mg/kg wet weight, benthos < 0.05-0.8 mg/kg wet weight, digested sewage 1.8-93.1 mg/kg dry weight, soil < 0.1 mg/kg dry weight, and earthworms < 0.1-1.7 mg/kg wet weight. It is clear from this study that these compounds are widely distributed in the UK environment, although it is not yet possible to fully assess the risks posed to either wildlife or humans by their continued use. Further study of these compounds is indicated.

Organochlorine contaminants in Caspian and harbour seal blubber.

Organochlorine contaminants (pesticides and individual polychlorinated biphenyl congeners, PCBs) were measured in Caspian (Phoca caspica) seal blubber and compared with concentrations in Harbour (Phoca vitulina) seal blubber. Concentrations of total dichlorodiphenyltrichloroethane (DDT) and its metabolites were significantly higher in Caspian seal than Harbour seal samples, whereas PCB congeners were significantly higher in Harbour than Caspian seals. Our finding suggests that Caspian seals are exposed to high levels of DDT pesticides. In contrast, PCBs are circulating in this population at much lower levels than in marine mammals from the North Sea.

Organochlorine levels in common seals (Phoca vitulina) which were victims and survivors of the 1988 phocine distemper epizootic.

We compared concentrations of organochlorines in the blubber of common seals (Phoca vitulina) found dead during the 1988 phocine distemper epizootic with levels in animals which survived it. There were highly significant differences between the live and dead animals, and between sample sites. These were not fully accounted for by seasonal and condition-related changes in blubber thickness.

Investigating potential associations between chronic exposure to polychlorinated biphenyls and infectious disease mortality in harbour porpoises from England and Wales.

Bioaccumulation of immunosuppressive organochlorines like polychlorinated biphenyls (PCBs) may pose a threat to the health and viability of cetacean populations. To investigate possible associations between chronic exposure to PCBs and infectious disease mortality in harbour porpoises Phocoena phocoena in UK waters, blubber concentrations of 25 individual chlorobiphenyl (CB) congeners in 34 healthy harbour porpoises that died due to physical trauma (mainly by-catch) were compared with CB concentrations in 33 animals that died due to infectious disease. The infectious disease group had significantly greater total 25 CBs (sigma 25CBs) concentrations than the physical trauma group (P < 0.001). The mean sigma 25CBs concentration in animals that died due to physical trauma was 13.6 mg kg-1 extractable lipid whereas the mean concentration in the infectious disease group was 31.1 mg kg-1 extractable lipid. The relationship between higher sigma 25CBs and the infectious disease group was not confounded by age, sex, nutritional status, season, location or year of stranding. In addition, adult females had significantly lower sigma 25CBs levels than adult males (P < 0.05) due to maternal transfer of CBs to offspring. These findings are consistent with the hypothesis that chronic PCB exposure predisposes harbour porpoises in UK waters to infectious disease mortality, although further research is required to test these associations more robustly.

Exposure to heavy metals and infectious disease mortality in harbour porpoises from England and Wales.

We investigate whether long-term exposure to heavy metals, including immunosuppressive metals like mercury (Hg), is associated with infectious disease in a wild cetacean. Post-mortem investigations on 86 harbour porpoises, Phocoena phocoena, found dead along the coasts of England and Wales revealed that 49 of the porpoises were healthy when they died as a consequence of physical trauma (most frequently entrapment in fishing gear). In contrast, 37 porpoises died of infectious diseases caused by parasitic, bacterial, fungal and viral pathogens (most frequently pneumonia caused by lungworm and bacterial infections). We found that mean liver concentrations of Hg, selenium (Se), the Hg:Se molar ratio, and zinc (Zn) were significantly higher in the propoises that died of infectious disease compared to healthy porpoises that died from physical trauma. Liver concentrations of lead (Pb), cadmium (Cd), copper (Cu) and chromium (Cr) did not differ between the two groups. Hg, Se, and the Hg:Se molar ratio were also positively correlated with age. The association between Zn concentration and disease status may result from Zn redistribution in response to infection. Further work is required to evaluate whether chronic exposure to Hg may have presented a toxic challenge to the porpoises that succumbed to infectious disease.

Uptake of organochlorines (chlorobiphenyls, dieldrin; total PCB & DDT) in bottlenose dolphins (Tursiops truncatus) from Cardigan Bay, west Wales.

High concentrations of organochlorine compounds (particularly PCB and chlorobiphenyls) have been found in three bottlenose dolphins from the vicinity of New Quay in West Wales. Although few in number, the animals ranged in age from 10 months to 23 years. The occurrence of high contaminant concentrations in all of these animals suggests that a high level of uptake of these compounds occurs in food after weaning as well as by transfer from mother to calf. In order to investigate this further we have tried to model the uptake using a bioenergetics-based approach. Using estimates of feeding rate we have calculated the concentrations of these contaminants in average prey items necessary to maintain the dolphin's body burden during the juvenile growth stage. The data available to date are too few for a rigorous test of this approach, however these preliminary studies suggest that the contaminant concentrations in local food items analysed to date are not sufficiently high to explain the high concentrations found in dolphin blubber. Further information is needed on the contaminant burdens of bottlenose dolphins in Cardigan Bay, and of their relationships and diet (including seasonal and migratory components), in order to validate this approach.

Polybrominated diphenyl ethers in two species of marine top predators from England and Wales.

During an earlier study, polybrominated diphenyl ethers were detected at high concentrations in fish and sediments downstream of a manufacturing site in NE England. We have now undertaken analysis of 14 tri- to heptabromodiphenyl ether congeners in tissues of two species of marine top predators exposed to these compounds through their consumption of fish. In this paper we report data for 47 cormorants and 60 harbour porpoises from England and Wales, sampled during the period 1996-2000. Concentrations of the summed congeners ranged from 1.8 to 140 microg kg(-1) wet weight in cormorant livers, and from not detected to 6900 microg kg(-1) wet weight in porpoise blubber. The major congeners present were generally BDE47, BDE99 and BDE100. There was little correlation between concentrations of chlorobiphenyls (as the sum of 25 individual congeners) and the sum of the 14 BDE congeners determined, particularly for the porpoises.