A Comparative Study of Mercury Bioaccumulation in Bivalve Molluscs from a Shallow Estuarine Embayment.

In estuarine food webs, bivalve molluscs transfer nutrients and pollutants to higher trophic levels. Mercury (Hg) pollution is ubiquitous, but it is especially elevated in estuaries historically impacted by industrial activities, such as those in the U.S. Northeast. Monomethylmercury (MeHg), the organic form of Hg, is highly bioaccumulative and transferable in the food web resulting in the highest concentrations in the largest and oldest marine predators. Patterns of Hg concentrations in marine bivalve molluscs, however, are poorly understood. In this study, inorganic Hg (iHg), MeHg, and the total Hg (THg) in soft tissues of the northern quahogs (Mercenaria mercenaria), eastern oysters (Crassostrea virginica), and ribbed mussels (Geukensia demissa) from eastern Long Island sound, a temperate estuary of the western North Atlantic Ocean was investigated. In all three species, concentrations of THg remained similar between the four sampling months (May, June, July, and September), and were mostly independent of animal size. In quahogs, MeHg and iHg displayed significant (p < 0.05) positive (iHg in May and June) and negative (MeHg in July and September) changes with shell height. Variability in concentrations of THg, MeHg, and iHg, both inter- and intra-specifically was high and greater in quahogs and oysters (THg: 37, 39%, MeHg: 28, 39%, respectively) than in mussels (THg: 13%, MeHg: 20%). The percentage of THg that was MeHg (%MeHg) was also highly variable in the three species (range: 10-80%), highlighting the importance of measuring MeHg and not only THg in molluscs.

Significant elevation of human methylmercury exposure induced by the food trade in Beijing, a developing megacity.

Methylmercury (MeHg) poses health risks to humans worldwide. The investigation of a longer chain of biogeochemical MeHg transport from production to consumption than that addressed in previous studies could provide additional scientific foundation for the reduction of risks. The main objective of this study is to identify the impacts of the interregional food trade along with the age, gender and socioeconomic status of people on human MeHg exposure in a developing megacity. Based on a field investigation, sampling and measurements, we provide experimental evidence regarding the substantial displacement of human MeHg exposure from production areas to consumption areas induced by the food trade. In 2018, 20% and 64% of the exposure in Beijing originated from the international and interprovincial food trade, respectively. Meanwhile, the ingestion of fish contributed 79% to the total exposure, followed by rice (4.4%), crab (3.8%) and shrimp (2.7%), and the exposure risk in urban districts was higher than that in rural areas by a factor of 2.2. A significantly higher contribution of imported deep-sea species to exposure among young people than among older people was observed (P < 0.01**), and a larger contribution of the international food trade to the MeHg exposure risk for women of childbearing age (average: 27%) than that among other groups (average: 10%) was found. Overall, our efforts demonstrate the dramatic impact of the food trade on MeHg exposure in a developing megacity, and we suggest that MeHg-susceptible populations in China should choose indigenous fish species (e.g., hairtail, yellow croaker and carp species) rather than imported deep-sea species as their dietary protein source.

MRI of trunk muscles and motor and respiratory function in patients with myotonic dystrophy type 1.

BACKGROUND: Myotonic Dystrophy 1 (DM1) causes progressive myopathy of extremity muscles. DM1 may also affect muscles of the trunk. The aim of this study was to investigate fat infiltration and muscle size in trunk muscles in DM1 patients, and in an age and gender matched control group. Further, explore how fat infiltration and degree of atrophy in these muscles are associated with motor and respiratory function in DM1 patients. METHOD: We measured fat infiltration and trunk muscle size by MRI in 20 patients with genetically confirmed classic form of DM1, and compared these cases with 20 healthy, age and gender matched controls. In the DM1 group, we investigated correlations between MRI findings and clinical measures of muscle strength, mobility and respiration. We used sum scores for fat infiltration and muscle size in trunk flexors and trunk extensors in the analysis of group differences and correlations. RESULTS: Significant differences between cases and controls were present for fat infiltration in trunk flexors (p = 0.001) and trunk extensors (p = < 0.001), and for muscle size in trunk flexors (p = 0.002) and trunk extensors (p = 0.030). Fat infiltration in trunk flexors were significant correlated to back extension strength (rho = - 0.523 p = 0.018), while muscle size in trunk flexors was significantly correlated to trunk flexion strength (rho = 0.506 p = 0.023). Fat infiltration in trunk flexors was significantly correlated with lower general mobility (rho = - 0.628, p = 0.003), reduced balance (rho = 0.630, p < 0.003) and forced vital capacity (rho - 0.487 p = 0.040). CONCLUSIONS: Trunk muscles in DM1 patients had significant higher levels of fat infiltration and reduced muscle size compared to age and gender matched controls. In DM1 patients, fat infiltration was associated with reduced muscle strength, mobility, balance and lung function, while muscle size was associated with reduced muscle strength and lung function. These findings are of importance for clinical management of the disease and could be useful additional outcome measures in future intervention studies.

An assessment of the impact of artisanal and commercial gold mining on mercury and methylmercury levels in the environment and fish in Cote d'Ivoire.

Artisanal and small-scale gold mining (ASGM) activities are an important source of mercury (Hg) to the atmosphere globally, and in most countries in West Africa, where gold production has increased dramatically in the last decade from both commercial and ASGM activities. This study focused on examining the concentrations of Hg and methylmercury (MeHg) in water, sediments and fish in four regions associated with gold mining activities in Cote d'Ivoire to assess the potential exposure of the local communities to MeHg from fish consumption. Concentrations of dissolved total Hg and MeHg in water and sediment were elevated at some locations sample and were indicative of local contamination. Several locations had sediment total Hg above 100 ng g-1 and sediment %MeHg ranged from 0.03 to 4.4%. Fish concentrations exceeded 0.3 µg/ g wet wt., especially for carnivores and fish caught in the western region of the country. Bioaccumulation factors, relative to dissolved MeHg, were higher for carnivores than omnivores and varied with region, suggesting other factors besides MeHg concentration alone were impacting uptake and trophic transfer. Given that people in Cote d'Ivoire consume fish at a higher level than other countries, the levels in fish were sufficient to exceed the US EPA's guidance criteria even at average consumption levels, and particularly for people consuming fish at a higher rate. Overall, this study provides compelling evidence that ASGM activities in Cote d'Ivoire are leading to elevated exposure and likely impacting the health of the local populations in regions where such activity is occurring.

Coordination of services for dual diagnosis clients in the interface between specialist and community care.

PURPOSE: The aim of this article is to study the coordination of comprehensive services for clients with concurrent substance abuse and mental health disorders (dual diagnosis), which is a very complex client group. In order to achieve comprehensive care and treatment, the service providers need to cooperate and coordinate, but the questions here, are how this is done and how appropriate the coordination is. DATA AND METHODS: Data were collected from group interviews during a 1-day workshop with clients, relatives, and employees from the various services involved. RESULTS: Information exchange between the services was generally in writing. Coordination between substance abuse and mental health services was experienced as fragmented. Employees had an unclear perception of the work and expertise of the other service providers involved. There were examples of disparity between the services a municipality could offer and client needs. A coordinator, if available, was emphasized by both clients and service providers as serving an important function in coordination and relationship building. CONCLUSION: Predominantly written communication and unclear division of responsibilities and duties resulted in employees creating stereotypes of each other, both within specialist health services and between specialist and municipal health services. A coordinator was able to coordinate various inputs, often through informal contact, with a view to establishing appropriate services for individual clients. Coordination in interagency meeting points, such as "responsibility teams", was the most successful solution, but this will involve a greater degree of networking than is common today.

Prevalence of juvenile myoclonic epilepsy in people <30 years of age-A population-based study in Norway.

OBJECTIVE: Despite juvenile myoclonic epilepsy (JME) being considered one of the most common epilepsies, population-based prevalence studies of JME are lacking. Our aim was to estimate the prevalence of JME in a Norwegian county, using updated diagnostic criteria. METHODS: This was a cross-sectional study, based on reviews of the medical records of all patients with a diagnosis of epilepsy at Drammen Hospital in the period 1999-2013. The study population consisted of 98,152 people <30 years of age. Subjects diagnosed with JME, unspecified genetic generalized epilepsy, or absence epilepsy were identified. All of these patients were contacted and asked specifically about myoclonic jerks. Electroencephalography (EEG) recordings and medical records were reevaluated for those who confirmed myoclonic jerks. Information about seizure onset was obtained from the medical records, and annual frequency of new cases was estimated. RESULTS: A total of 55 subjects fulfilled the diagnostic criteria for JME. The point prevalence was estimated at 5.6/10,000. JME constituted 9.3% of all epilepsies in the age group we investigated. Of subjects diagnosed with either unspecified genetic generalized epilepsy or absence epilepsy, 21% and 12%, respectively, had JME. We identified 21 subjects with JME (38%) who had not been diagnosed previously. Six subjects (11%) had childhood absence epilepsy evolving into JME. Between 2009 and 2013, the average frequency of JME per 100,000 people of all ages per year was estimated at 1.7. SIGNIFICANCE: A substantial portion of people with JME seem to go undiagnosed, as was the case for more than one third of the subjects in this study. By investigating subjects diagnosed with unspecified genetic generalized epilepsy or absence epilepsy, we found a prevalence of JME that was considerably higher than previously reported. We conclude that JME may go undiagnosed due to the underrecognition of myoclonic jerks. To make a correct diagnosis, clinicians need to ask specifically about myoclonic jerks.

Chronic inflammatory demyelinating polyradiculoneuropathy occurring after autologous haematopoietic stem cell transplantation for multiple sclerosis.

We describe the case of a man in his 40 s with aggressive multiple sclerosis (MS) who received autologous haematopoietic stem cell transplantation (AHSCT) and subsequently developed probable, if not definite, Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) and haematological complications. Autoimmune conditions occurring as a side effect of allogenic transplantations are well known in the context of haematological malignancies, but only rarely reported for autologous transplantations. Our case demonstrates that although AHSCT may be effective for suppressing MS inflammatory activity, the profound changes to the immune repertoire may lead to other clinically relevant autoimmune phenomena. A careful benefit-risk evaluation should be conducted in all cases where AHSCT is considered.

Prevalence and etiology of epilepsy in a Norwegian county-A population based study.

OBJECTIVE: Epilepsy represents a substantial personal and social burden worldwide. When addressing the multifaceted issues of epilepsy care, updated epidemiologic studies using recent guidelines are essential. The aim of this study was to find the prevalence and causes of epilepsy in a representative Norwegian county, implementing the new guidelines and terminology suggested by the International League Against Epilepsy (ILAE). METHODS: Included in the study were all patients from Buskerud County in Norway with a diagnosis of epilepsy at Drammen Hospital and the National Center for Epilepsy at Oslo University Hospital. The study period was 1999-2014. Patients with active epilepsy were identified through a systematic review of medical records, containing information about case history, electroencephalography (EEG), cerebral magnetic resonance imaging (MRI), genetic tests, blood samples, treatment, and other investigations. Epilepsies were classified according to the revised terminology suggested by the ILAE in 2010. RESULTS: In a population of 272,228 inhabitants, 1,771 persons had active epilepsy. Point prevalence on January 1, 2014 was 0.65%. Of the subjects registered with a diagnostic code of epilepsy, 20% did not fulfill the ILAE criteria of the diagnosis. Epilepsy etiology was structural-metabolic in 43%, genetic/presumed genetic in 20%, and unknown in 32%. Due to lack of information, etiology could not be determined in 4%. SIGNIFICANCE: Epilepsy is a common disorder, affecting 0.65% of the subjects in this cohort. Every fifth subject registered with a diagnosis of epilepsy was misdiagnosed. In those with a reliable epilepsy diagnosis, every third patient had an unknown etiology. Future advances in genetic research will probably lead to an increased identification of genetic and hopefully treatable causes of epilepsy.

Acetazolamide improves oxygenation in patients with respiratory failure and metabolic alkalosis.

INTRODUCTION: Coexistent respiratory failure and metabolic alkalosis is a common finding. Acidotic diuretics cause a fall in pH that may stimulate respiration. OBJECTIVE: The purpose of the study was to evaluate the effectiveness of short-term treatment with acetazolamide for combined respiratory failure and metabolic alkalosis. METHODS: A randomised, placebo-controlled and double-blind parallel group trial where oral acetazolamide 250 mg three times a day for 5 days were administered to patients hospitalised for respiratory failure because of a pulmonary disease (Pa O2 ≤ 8 kPa and/or Pa CO2 ≥ 7 kPa) who had concurrent metabolic alkalosis [base excess (BE) ≥ 8 mmol/L]. Pa O2 after 5 days was the primary effect variable. Secondary effect variables were Pa CO2 , BE and pH on day 5, and the total number of days in hospital. RESULTS: Of 70 patients enrolled (35 in each group), data from 54 were analysed per protocol, while last observation carried forward was used for the remaining 16. During the 5-day treatment, Pa O2 increased on average 0.81 kPa in the placebo group and 1.41 kPa in the acetazolamide group. After adjustment for baseline skewness, the difference was statistically significant (adjusted mean difference 0.55 kPa, 95% confidence interval 0.03-1.06). Pa CO2 decreased in both groups, but the difference was not statistically significant. As expected, pH and BE decreased markedly in the acetazolamide group. CONCLUSION: Acetazolamide may constitute a useful adjuvant treatment mainly to be considered in selected patients with respiratory failure combined with prominent metabolic alkalosis or where non-invasive ventilation is insufficient or infeasible.

Airway complications after lung transplantation: long-term outcome of silicone stenting.

BACKGROUND: Airway complications remain a significant cause of morbidity after lung transplantation. The majority of the centres that have published their results have used metal stents. OBJECTIVES: We report the long-term outcome of silicone stenting and subsequent stent removal in lung transplant recipients with stenotic airway complications. METHOD: From 1990 to 2008, 279 patients received 88 single, 170 double, and 21 heart-and-lung transplantations. Of 470 anastomoses at risk, 44 airway complications developed and were treated in 35 patients. Six lesions were treated with Nd:YAG laser and balloon dilatations only. Thirty-two silicone stents of Hood or Dumont type were inserted in 27 patients. RESULTS: Symptoms were relieved and FEV(1) increased in all patients (median 0.7 litres, range 0.1-1.8 litres, p < 0.0001). In 8 patients, stents had to be repositioned or reinserted, in 19 patients only one insertion and one removal procedure were necessary. One patient suffered a serious complication with haemorrhage and pneumonectomy, 3 patients had minor airway wall injuries resolving spontaneously. Six patients died with the stents from causes not related to the airway complications. Twenty-five stents could be removed after a median of 6 months (range 1-22) in 21 patients, and 22 airways remained patent. Median FEV(1) was 2.3 litres immediately after stent removal, and remained 2.3 litres after 24 months. CONCLUSION: Stenotic airway complications after lung transplantation can be successfully treated with silicone stents, which can ultimately be removed, leaving a patent airway.

Transbronchial laser ablation of benign and malignant tumors.

An overview is given over different methods for thermal ablation in central airways. The most widely used method, endoscopic laser photocoagulation (Nd:YAG laser) is described in some detail. Other methods are electrocautery, argon plasma coagulation, photodynamic treatment and cryotherapy. Thermal ablation is usually a palliative treatment, but is sometimes performed with a curative intent. Such treatment should be performed in specialized centres for interventional bronchoscopy, with a broad range of methods available.

Statistical dissection of cytogenetic patterns in lung cancer reveals multiple modes of karyotypic evolution independent of histological classification.

Lung carcinomas are cytogenetically highly complex. In spite of this, patterns of recurrent chromosome aberrations have emerged. Apart from the frequent loss of 3p, losses of 4q, 5q, 8p, 9p, 10q, 13q, and 17p are common and gains often include 1q, 3q, 5p, and 8q. In the present study, we retrieved all aberrant lung carcinoma karyotypes, in total 432 cases, from the Mitelman Database of Chromosome Aberrations in Cancer and identified the most frequent imbalances. Each case was then classified with respect to the presence or absence of these imbalances and the data were statistically analyzed by means of principal component analysis, multidimensional scaling, and hierarchical cluster analysis. The analyses suggest that lung cancer develops through three pathways, initiated by +7, 3p-, and +12, respectively, and that the 3p- pathway is dominated by losses and the +12 pathway by gains. Gain of chromosome 7 was shown to be both important in the 3p- pathway and also forming a group of tumors containing +7 and +20 (with few additional changes). The distribution of the number of imbalances per tumor indicated that the karyotypic evolution might pass through three different phases. Phase I is characterized by tumors with few changes and by well-separated 3p- and +12 pathways. Phase II cases have an increased number of imbalances and exhibit less distinct 3p- and +12 pathways. Phase III tumors are polyploid and highly complex. No marked differences between the karyotypic profiles were found among morphologic subtypes, suggesting that lung cancer morphology is independent of the particular cytogenetic pathway operating in the tumor cells.

Dissecting karyotypic patterns in renal cell carcinoma: an analysis of the accumulated cytogenetic data.

Renal cell carcinoma (RCC) is one of the most frequent malignancies in Western societies. The most common subtypes are conventional (clear-cell) and papillary carcinomas, which account for about 75 and 10% of cases, respectively. Cytogenetically, conventional RCC is the best-studied subtype and is characterized by chromosomal losses: loss of the short arm of chromosome 3 being the most common. Papillary tumors frequently show gains of chromosomes 7 and 17, and the more progressed forms have, in addition, gains of chromosomes 16, 12, and 20. In the present investigation we used 796 RCC karyotypes to identify the most frequent genomic imbalances. Tumor cases were then classified with respect to the presence or absence of these imbalances and statistically analyzed to assess the order of appearance of chromosomal imbalances, as well as possible karyotypic pathways and cytogenetic subtypes. We established a temporal order by which the different imbalances occur and showed that at least two cytogenetic pathways exist in RCC, one hypodiploid characterized by presence of 3p- and one hyperdiploid characterized by the presence of +7. The data suggest that conventional-type tumors predominantly evolve through the hypodiploid pathway but that an alternative route may be by hyperdiploidy if 3p- is present. Tumors with a papillary growth pattern predominantly progress through the hyperdiploid pathway. The analyses also revealed three possible cytogenetic subtypes of the papillary tumors, one characterized by the presence of +10, a second by +17 and +3q, and a third by +16, +20, and +12.

A model for karyotypic evolution in testicular germ cell tumors.

Testicular germ cell tumor karyotypes are characterized by near-triploidy, with chromosome numbers ranging from 50 to 70, and by the frequent appearance of i(12p). The high chromosome number has been attributed to the formation of tetraploid carcinoma in situ cells followed by chromosomal losses that ultimately lead to tumor forms that are more advanced. In the present investigation, we show by analysis of the accumulated cytogenetic data on testicular germ cell tumors and computer simulations that two distinct processes are operating in the karyotypic evolution of these tumors. The results suggest that whole-chromosome changes originate from a multipolar cell division of a tetraploid cell, whereas imbalances caused by structural changes accumulate in a stepwise manner.

Statistical analyses of karyotypic complexity in head and neck squamous cell carcinoma.

More than 250 head and neck squamous cell carcinomas (HNSCCs) with clonal chromosomal abnormalities have been reported. Even though the pattern of aberrations is nonrandom, no specific primary or secondary karyotypic abnormalities have been identified. One explanation for the still-rudimentary understanding of the cytogenetic evolution in HNSCC could be the pronounced karyotypic complexity seen in these tumors. In an attempt to overcome this difficulty, we have applied several statistical methods such as hierarchical cluster analysis, multidimensional scaling, and k-means clustering, which allow the identification and interpretation of karyotypic pathways, as well as establishing a temporal order of chromosomal imbalances on 241 published and 70 previously unpublished HNSCC karyotypes. From the analysis of the distribution of the number of imbalances per tumor we suggest that the carcinomas evolve through three phases representing different stages of chromosomal instability. Two major cytogenetic pathways, one dominated by gains and another by losses, were identified by means of principal component analysis. These were initiated by +7 and by any of the aberrations 1p-, 3p-, or 7q-, respectively.

Wilms tumors develop through two distinct karyotypic pathways.

Wilms tumor is an embryonic neoplasm characterized by a large variation in histologic patterns. Cytogenetic investigations have identified nonrandom chromosomal changes characteristic for this tumor type, of which numerical changes, mostly trisomies for chromosomes 7, 8, and 12, are particularly frequent. Despite the abundance of cytogenetic information, with more than 350 published karyotypes, very little is known about the mode of karyotypic evolution. In this investigation, we have used 355 karyotypes of Wilms tumor to identify frequent imbalances. The most frequent were +1q, +6, +7q, +8, +12, +13, -11, and -16. Tumor cases were then classified with respect to the presence or absence of these imbalances and statistically analyzed to assess the order of appearance of chromosomal imbalances, as well as possible karyotypic pathways. We show that Wilms tumors develop through one major mode of karyotypic evolution, common to both low- and high-complex tumors, and that polyploid cases are relatively rare. We also establish a temporal order by which the different imbalances occur and show that at least two cytogenetic pathways exist, one dominated by gains and another by losses. We also show that these pathways are well separated and do not share a common set of late imbalances.

Dissecting karyotypic patterns in malignant melanomas: temporal clustering of losses and gains in melanoma karyotypic evolution.

Malignant melanomas can be divided into two major subtypes, involving either the skin or eye melanomas. Both tumor forms exhibit highly complex karyotypes with nonrandom recurrent chromosomal imbalances. Loss of chromosome 3, the short arm of chromosome 1, and gain of 8q have been suggested to be associated with eye melanomas, whereas gain of 6p and loss of 6q have been more often seen in skin melanomas. Imbalances implicated in tumor progression include among others, -10 and +7. In spite of the abundance of cytogenetic information, with more than 300 published karyotypes, very little is known about the mode of karyotypic evolution or of the presence of possible cytogenetic pathways. In our investigation, we have used 362 melanoma karyotypes, including both the skin and eye subtypes, to identify the most frequently occurring imbalances. Tumor cases were then classified with respect to the presence or absence of these imbalances and statistically analyzed in order to assess the order of appearance of chromosomal imbalances, the presence of karyotypic pathways, as well as possible cytogenetic subtypes. We show that the melanomas develop through one mode of karyotypic evolution, common to both low and high complexity karyotypes, and we establish the temporal order by which the different imbalances occur. By applying several statistical methods, we show that at least two cytogenetic pathways of clonal evolution exist in malignant melanomas, one initiated with -3 and one with +6p, and that these pathways operate in both skin and eye melanomas.

Ovarian carcinoma develops through multiple modes of chromosomal evolution.

Ovarian carcinoma has the highest mortality of all of the gynecologic cancers. The chromosomal changes in this tumor type are highly complex, and the karyotypes typically show severe aneuploidy. Despite the abundance of cytogenetic information, with approximately 400 published karyotypes, very little is known about the mode of karyotypic evolution and the possible presence of cytogenetic pathways related to tumor development. In the present investigation we used 387 ovarian carcinoma karyotypes to identify the most frequent genomic imbalances. Tumor cases were then classified with respect to the presence or absence of these imbalances and statistically analyzed to assess the order of appearance of chromosomal imbalances, as well as possible karyotypic pathways and cytogenetic subtypes. We establish the temporal order by which the different imbalances occur and show that at least two cytogenetic pathways exist, one characterized by +7, +8q, and +12, and one by 6q- and 1q-. We show that ovarian carcinomas develop through at least three phases of karyotypic evolution. At the early stages, Phase I, the karyotypic evolution seems to proceed though step-wise acquisition of changes. The transition to Phase II showed signs of an increased chromosomal instability, most probably caused by extensive telomere crisis and the onset of breakage-fusion-bridge cycles. This process was linked to the presence of imbalances characteristic for the 6q-/1q- pathway. The transition to Phase III involved triploidization and was also linked to the presence of the 6q-/1q- pathway.