Examination of mercury contamination from a recent coal ash spill into the Dan River, North Carolina, United States.

Coal ash spills occasionally occur due to the accidental failure of surface impoundments, and toxic metal-laden ash can pose a serious health threat to adjacent aquatic ecosystems. Here, we performed an investigation into longitudinal variations of mercury (Hg) contamination in the Dan River (North Carolina, United States) about 17 and 29 months after a February 2014 coal ash spill incident, in which the reported Hg concentrations in the spilled coal ash (210 ng/g) were 1-2 orders of magnitude higher than the river sediments (2-61 ng/g). We examined total Hg (THg) and methyl Hg (MeHg) in sediments from 0 to 65 km downstream of the spill, and found that most of the variations of THg and MeHg in surface sediments (0-16 cm) could be well accounted by the organic matter content and appeared to be not contaminated by Hg derived from coal ash. In examining MeHg bioaccumulation in invertebrates (aquatic and riparian) and fish in the Dan River and fish in a reservoir downstream of Dan River, we found no evidence of elevated MeHg bioaccumulation due to the 2014 coal ash spill. Thus, we concluded that Hg contamination from the coal ash spill is largely absent in the Dan River for both surface sediments and biota within the first three years of spill (until 2017), even though the majority of coal ash may be buried deeper in the sediment in the river channel and/or the downstream reservoir. Alternatively, the Hg associated with the coal ash is largely not bioavailable for extensive microbial Hg methylation. The findings provide useful insights into remediation strategies for this incident and other coal ash spills.

Peer Support for Individuals with Major Limb Loss: a Scoping Review.

BACKGROUND: Major limb loss can have profound physical and psychosocial implications for individuals, impacting their quality of life and well-being. Despite the effectiveness of peer support in improving outcomes for various chronic conditions, its impact on individuals with major limb loss remains understudied. OBJECTIVES: This review aims to explore the existing literature on peer support for individuals with major limb loss. Specifically, exploring how the literature defines peer support; examining its implementation, identifying outcomes measured in peer support interventions, assessing the benefits for individuals with major limb loss, and identifying barriers associated with peer support provision. STUDY DESIGN: This review followed Arksey and O'Malley's methodological framework, analysing relevant literature to identify evidence, definitions, and key factors related to peer support for individuals with major limb loss. METHODOLOGY: A comprehensive search in January 2023 utilized databases: MEDLINE, PsychInfo, Embase, and CINAHL. After a two-phase screening process, articles meeting specific criteria were included. Thematic and descriptive numerical analyses were applied to the extracted data. FINDINGS: Twenty-two articles were reviewed. Peer support was described as an opportunity to provide education, advice, and encouragement between individuals with lived experiences. Across the two intervention-based studies investigating peer support programs, outcome measures included physical, psychological, social, and quality of life. Qualitative studies described perceived benefits as improved psychosocial well-being and the opportunity to exchange knowledge. Perceived barriers included a lack of formal training and male-dominated groups, which deterred individuals with amputation from participating. CONCLUSION: The evidence from the findings of the review sheds light on the current understanding of peer support for individuals with amputation. Due to the limited number of studies available, future research is necessary to develop and evaluate the effectiveness of peer support interventions tailored to this population.

Effect of Various Surface Treatments on Ti-Base Coping Retention.

CLINICAL RELEVANCE: Mechanical surface roughening of the titanium-abutment base is necessary to increase the pull-off bond strength of the lithium disilicate abutment material. Additional chemical surface treatment may further increase the bond strength, but the effects are product specific.

Antimalarial drugs and pregnancy.

The use of chloroquine and hydroxychloroquine during pregnancy is controversial. These 4-aminoquinoline drugs cross the placenta and have been reported to cause fetal abnormalities, including loss of vision, ototoxicity, and cochleovestibular dysfunction. However, other reports suggest that 4-aminoquinoline drugs can be taken safely during pregnancy, even in dosages used to control systemic connective tissue diseases. We retrospectively studied eight patients who took antimalarial drugs continuously throughout pregnancy. There was a total of 14 pregnancies in women receiving these drugs; three occurred during periods of disease activity and all of these resulted in failure to complete pregnancy successfully. Of the remaining 11 pregnancies exposed to antimalarial drugs, one resulted in stillbirth; four resulted in spontaneous abortion; and six had normal full-term standard deliveries. None of the live births demonstrated any congenital abnormalities. Hence, it is possible for women to produce normal live babies despite taking large doses of these drugs. If patients with systemic lupus erythematosus are already taking antimalarial drugs when they become pregnant, it is believed that the risk of disease flare and loss of pregnancy from discontinuing therapy outweighs any risks to fetuses from continuing the medication.

The thrombotic diathesis associated with the presence of phospholipid antibodies may be due to low levels of free protein S.

PURPOSE: To determine if abnormalities in the protein C/protein S anticoagulant system exist in patients with phospholipid antibodies who had the primary clinical complaint of fetal wastage. PATIENTS AND METHODS: Eleven patients with fetal wastage and phospholipid antibodies were selected for study. Some patients also gave a history of previous thrombotic events related to oral contraceptives and/or pregnancy, but patients were not selected because of a history of clinical thrombosis. The levels of protein C (chromogenic assay), protein S (both free and bound) (Laurell rocket), and C4b-binding protein (Laurell rocket) were measured, and assays for the presence of antibodies against protein S or protein C were performed. RESULTS: Seven of the 11 patients were found to have low levels of free protein S. Total protein S and protein C levels were within the normal range in all patients. Antibodies to protein C and protein S were not found in any patient. These findings suggest that free protein S levels may be abnormally low in some patients with phospholipid antibodies. CONCLUSION: Free protein S levels are abnormally low in some patients with phospholipid antibodies, and this abnormality may be a factor contributing to the thrombotic diathesis associated with phospholipid antibodies.

Autoantibodies in patients with primary pulmonary hypertension: association with anti-Ku.

PURPOSE: Patients with primary pulmonary hypertension (PPH) frequently have Raynaud's phenomenon, serum antinuclear antibodies (ANAs), and/or pulmonary vascular lesions similar to those seen in certain connective tissue diseases, especially scleroderma. A number of relatively disease-specific autoantibodies have been described in connective tissue diseases but have not been studied in patients with PPH. Therefore, sera from PPH patients were studied for a variety of autoantibodies, seeking a possible link between this pulmonary disorder and connective tissue diseases. PATIENTS AND METHODS: Sera from 31 patients with PPH and 24 with secondary pulmonary hypertension (SPH) were studied for the following autoantibodies: anti-centromere (indirect immunofluorescence of Hep-2 cells), anti-CENP-B by immunoblotting and enzyme immunoassay (EIA) using cloned CENP-B fusion protein, anti-topoisomerase I (Scl-70), anti-Ku using immunoblotting of affinity purified antigens, anti-cardiolipin using EIA, and anti-Ro (SS-A), La (SS-B), Sm, nRNP, Jo-1, PM-Scl, and Mi-2 by counter-current immunoelectrophoresis. RESULTS: Anti-Ku antibodies were found in 23% of patients with PPH, 4% with SPH, and none of 24 normal controls (PPH versus SPH, p = 0.06: PPH versus controls, p = 0.01). Antibodies to CENP-B were found in one patient each with PPH and SPH, anti-topoisomerase I in one with SPH, and anti-Ro (SS-A) and La (SS-B) in one with PPH. Overall, 12 patients (39%) with PPH had Raynaud's phenomenon or positive ANA results, with 9 (29%) having more specific autoantibodies associated with connective tissue diseases. CONCLUSIONS: These results further suggest a link between at least a subgroup of patients with PPH and autoimmune connective tissue diseases, with anti-Ku antibodies being a possible new serologic marker.

Basiliximab (Simulect) for the treatment of steroid-resistant rejection in pediatric liver transpland recipients: a preliminary experience.

BACKGROUND: The role of interleukin-2 receptor antibodies as rescue therapy in steroid-resistant rejection (SRR) has not been studied. We evaluated the safety and efficacy of an interleukin-2 receptor antibody, basiliximab (Simulect, Novartis, East Hanover, NJ), in treating SRR in pediatric liver transplant recipients. METHODS: This was a prospective study of seven pediatric liver transplant recipients with biopsy-proven SRR who would have otherwise received OKT3 or antithymocyte globulin. The primary immunosuppression consisted of cyclosporine (Neoral, Novartis), azathioprine, and prednisolone in four patients and tacrolimus and prednisolone in three patients who had undergone retransplantation for chronic rejection (n=2) and hyperacute rejection (n=1). Four patients had received two cycles of high-dose steroids, and three patients had received a single cycle; all had been converted to tacrolimus, followed by the addition of mycophenolate mofetil. RESULTS: The median time from transplant to SRR was 30 days (range, 8 days-23 months). Five children received two doses of basiliximab (10 mg, 3-7 days apart), and two children received a single dose. Aspartate aminotransferase levels normalized in three children 12, 21, and 30 days after basiliximab treatment. Aspartate aminotransferase levels decreased without normalizing in two children, but there was no further evidence of cellular rejection on repeat biopsies. All five children are rejection-free with a median follow-up of 22 months (range, 5-32 months). Biochemical abnormalities persisted in the remaining two children, and both developed chronic rejection. There were no immediate side effects associated with basiliximab. Two patients were treated empirically for possible cytomegalovirus infection 21 and 57 days after basiliximab treatment, with no evidence of cytomegalovirus disease. CONCLUSION: Five of seven pediatric liver transplant recipients with SRR experienced successful outcomes with basiliximab treatment without major side effects, indicating that it is a safe alternative to OKT3 and other antilymphocyte antibodies.

Discovery of the toxic dinoflagellate Pfiesteria in northern European waters.

Several dinoflagellate strains of the genus Pfiesteria were isolated by culturing techniques from sediment samples taken in the Oslofjord region of Norway. Pfiesteria piscicida, well known as a fish killer from the Atlantic coast of America, was identified by genetic methods and light microscopy. The related species Pfiesteria shumwayae was attracted from the sediment by the presence of fish, and has proved toxic. This present survey demonstrates the wide distribution of these potentially harmful species, but so far they have not been connected with fish kills in Europe.

Antiphospholipid antibody syndromes.

There is no doubt that in some individuals the presence of antibodies to negatively charged phospholipids currently measured as the lupus anticoagulant, a biologically false positive VDRL, and anticardiolipin antibodies is associated with certain clinical features, in particular, a predisposition to both arterial and venous thrombosis and, in women, to fetal wastage. This syndrome may be seen in patients with readily identifiable connective tissue disease, in patients with an ill-defined disease, and in clinically healthy individuals who only manifest signs of this syndrome when they are pregnant or when taking oral contraceptives. This last group have given rise to the term "subclinical" autoimmune disease, but it remains to be seen whether these women stay healthy or go on to develop overt clinical autoimmune disease states. Current recommendations for treating pregnant patients with these antibodies are based on uncontrolled studies, and there is a need for well controlled age-matched, parity-matched studies to be done. Similarly, the discrepant reports addressing the significance of these antibodies and their laboratory associations emphasize the need for standardization of the tests used to measure these antibodies with international standards for the cardiolipin assay an absolute must. These problems are being addressed. This exciting field of research that has extended the world of autoimmunity far beyond the limits of rheumatology, has given rheumatologists, hematologists and obstetricians a new challenge: to find the link between antibodies, blood clots, and babies.

Placental pathology in systemic lupus erythematosus and phospholipid antibody syndrome.

Fetal loss is increased in women who meet the Arthritis and Rheumatism Association criteria for systemic lupus erythematosus (SLE) and in women who have phospholipid antibody syndrome (APS). There are multiple causes for this fetal loss, and in patients with SLE, disease activity appears to be an important contributing factor. In APS patients, it appears that some individuals will experience recurrent fetal loss and will continuously fail to complete pregnancy naturally. Placental examination has helped to elucidate some of the pathology that may be contribute to this fetal loss and our studies have shown that the same pathology is repeated in subsequent pregnancies. Placental examination in SLE or APS patients with recurrent fetal loss is vital if we are going to be able to determine appropriate therapy to prevent fetal loss.

Antimalarial drugs in systemic lupus erythematosus: use in pregnancy.

The 4-aminoquinoline radical containing antimalarial drugs are also used in the management of various connective tissue diseases including systemic lupus erythematosus (SLE) and rheumatoid arthritis. These agents are particularly useful for the management of inflammatory polyarthritis and skin disease. By raising the pH in intracellular compartments, these drugs interfere with normal phagocytic function which consequently enables them to interfere with antigen processing. Other actions include inhibition of platelet aggregation, this is advantageous in patients with phospholipid antibodies (aPL) which are known to predispose patients to recurrent arterial and venous clinical thrombotic events. Hydroxychloroquine has also been demonstrated to reduce serum lipid levels including cholesterol, triglycerides and low density lipoproteins. As it is now known that patients with SLE are at risk for accelerated artherogenesis and premature heart disease, this action may be an added benefit for these patients. The use of the 4-aminoquinoline radical containing antimalarial drugs during pregnancy is controversial. It is known that these agents can cross the placenta and are deposited in fetal pigmented tissues. These findings have led to the recommendation that these agents should be discontinued in pregnancy for patients with connective tissue diseases even though they have long been recommended for malarial prophylaxis in pregnant women travelling to malarial infested areas. Flares of SLE disease have been documented when these agents are discontinued and as flares of SLE disease activity are known to be detrimental to pregnancy outcome in patients with SLE, it is our opinion that these drugs should not be discontinued during pregnancy in a patient with lupus, particularly when the known terminal elimination half life is 1 to 2 months.

Subclinical autoimmunity in recurrent aborters.

Thirty-four women with habitual abortion (HA) were evaluated for the presence of lupus-associated autoantibodies, antisperm antibodies, and evidence of complement abnormalities. A control group of women who had only successful pregnancy outcomes also was studied. Fourteen HA women had anatomic, genetic, or hormonal causes for their pregnancy losses ("explained losses"), and 20 had no apparent causative factors ("unexplained losses"). Fifty percent of HA women with unexplained losses and 34% of women with explained losses had at least one abnormal result, but multiple autoimmune abnormalities were found only in women with unexplained losses. Anticardiolipin antibodies were found most commonly (30% of all HA women and 8% of controls). Two clinically normal HA women had multiple autoantibodies detected. This study suggests that recurrent pregnancy loss may be a marker for subclinical autoimmune disease.

Lupus-related mitral valve disease: embolic coronary occlusion as a unique cause of myocardial infarction.

Early diagnosis and greatly improved treatment have markedly altered the clinical evolution of systemic lupus erythematosus; the pattern of cardiac involvement in lupus has also changed. To illustrate this, a young woman who died from severe mitral valve disease, including a coronary embolus from verrucous endocarditis, is presented. Mitral valve involvement in lupus is no longer limited to the small benign lesions described by Libman and Sacks.

A double-blind study comparing sodium aurothiomalate and auranofin in patients with rheumatoid arthritis previously stabilized on sodium aurothiomalate.

Auranofin, an orally active gold preparation, was compared with sodium aurothiomalate in a double-blind trial in patients with rheumatoid arthritis fulfilling the ARA criteria, who had been stabilized on sodium aurothiomalate for at least six months. Twenty-four patients have so far been entered in the trial, of whom fourteen have been randomly allocated to receive auranofin and ten to receive sodium aurothiomalate. After initial stabilization, patients receive either auranofin 6 mg daily and placebo injection, or sodium aurothiomalate 50 mg monthly and placebo tablets. Five patients have completed one year on auranofin. The remaining nine patients were withdrawn because of loss of efficacy (two), side-effects, (five), loss of efficacy and side-effects (one) and default (one). Four patients have completed one year's treatment with sodium aurothiomalate. Of the remaining six patients, two were withdrawn because of side-effects, three because of poor disease control and one because of side-effects and poor disease control. Diarrhoea occurred in eight patients receiving auranofin. Rashes occurred in both groups but otherwise there were no serious side-effects. The efficacy of both drugs appeared similar, there being no significant differences in morning stiffness, fatiguability, visual analogue pain score, grip strength and articular index. There were also no significant differences in laboratory parameters of efficacy. Auranofin appears to control disease activity in rheumatoid arthritis but diarrhoea is a frequent side-effect.

Chemical-induced inflammation and inflammatory diseases.

It is now known that human exposure to certain chemicals e.g. benzene, halocarbons, ketones, nitrosamines, etc. can result in adverse health effects that are often not easily recognised as manifestations of chemical toxicity. These are inflammatory states, such as hepatitis, nephritis, scleroderma, and lupus, due to production of reactive oxygen species (ROS) through activation of cytochrome P4502E1 by the chemical, or by metabolism of the chemical to reactive intermediates and neoantigens which initiate immunotoxic effects. Intracellular glutathione (GSH), vitamins C, E and A protect against this ROS toxicity and inflammation; fasting and consumption of alcohol exacerbate it. Chronic inflammatory states may subsequently develop, including rheumatoid disease, atherosclerosis, diabetes, infertility and birth defects, multiple system organ failure (MSOF), Alzheimer's disease, and cancer.

Sjögren's syndrome: a women's health problem.

Like many other systemic connective tissue diseases, Sjögren's syndrome (SS) occurs more frequently in women, with a female to male ratio of 9:1. Unlike other diseases, such as systemic lupus erythematosus, this syndrome occurs more frequently in menopausal and postmenopausal women, although there is now evidence to suggest some patients may have autoimmune diathesis years before they develop sicca complaints. Several clinical features of SS have particular relevance for the female patient. An abnormal pregnancy, as occurs in the neonatal lupus syndrome, may be the initial manifestation of an autoimmune diathesis. Dyspareunia and chronic fatigue are important complaints that are not taken seriously. This paper will address the clinical manifestations of SS, with particular emphasis on those features that demonstrate that SS is a women's health problem.

Twenty-year follow-up: an unusual case of nephropathy of antiphospholipid syndrome.

Nephropathy of antiphospholipid antibody syndrome (NAPS) is an increasingly well-recognized aspect of antiphospholipid syndrome. The most characteristic histopathology is that of thrombotic microangiopathy, and thrombosis occurring in the renal vasculature is thought to be the initiating event. Other less common pathologies have been reported, and the mechanisms of these are unclear. Therapy has been largely empiric. We report a case of NAPS in a patient with atypical pathology, who has declined therapy with immunosuppressive agents and anticoagulants and who has maintained normal renal function in 20 years of follow-up.

Drug exposure, pregnancy outcome and fetal and childhood development occurring in the offspring of mothers with systemic lupus erythematosus and other chronic autoimmune diseases.

Most autoimmune diseases occur more commonly in females and many of these young women wish to become mothers. For pregnancy to proceed successfully immunomodulation and physiological changes preparing the reproductive system need to occur. Pregnancy occurring in a chronically ill mother who requires medications in order to maintain her own health and who may have already incurred significant organ pathology gives rise to several problems and so four questions arise: 1) What will be the effect of the pregnancy on the underlying disease? 2) What will be the effect of the disease on the outcome of pregnancy? 3) How to manage the disease, just prior to, throughout and immediately after the pregnancy? 4) The long term fetal and childhood effects of maternal disease and its management. This paper reviews the current literature pertaining to these questions in patients with systemic lupus erythematosus (SLE) and other chronic rheumatic and autoimmune diseases.