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Objective: To describe determinants of persisting humoral and cellular immune response to the second COVID‐19 vaccination among patients with myeloma. Methods: This is a prospective, observational study utilising the RUDYstudy.org platform. Participants reported their second and third COVID‐19 vaccination dates. Myeloma patients had an Anti‐S antibody level sample taken at least 21 days after their second vaccination and a repeat sample before their third vaccination. Results: 60 patients provided samples at least 3 weeks (median 57.5 days) after their second vaccination and before their third vaccination (median 176.0 days after second vaccine dose). Low Anti‐S antibody levels (<50 IU/mL) doubled during this interval (p =.023) and, in the 47 participants with T‐spot data, there was a 25% increase negative T‐spot tests (p =.008). Low anti–S antibody levels prior to the third vaccination were predicted by lower Anti‐S antibody level and negative T‐spot status after the second vaccine. Independent determinants of a negative T‐spot included increasing age, previous COVID infection, high CD4 count and lower percentage change in Anti‐S antibody levels. Conclusions: Negative T‐spot results predict low Anti‐S antibody levels (<50 IU/mL) following a second COVID‐19 vaccination and a number of biomarkers predict T cell responses in myeloma patients. [ABSTRACT FROM AUTHOR]

Summary: Treatment advances have greatly improved survival, but myeloma is among the worst of all cancers for delayed diagnosis, causing serious morbidities and early deaths. This delay is largely because the symptom profile of myeloma has very low specificity, and in primary care, myeloma is rare. However, initiating the journey to diagnosis simply requires considering myeloma and sending blood to test for monoclonal immunoglobulin. Laboratory tests reliably detect monoclonal immunoglobulin, which is present in 99% of myeloma cases, so why do health care systems have such a problem with delayed diagnosis? The Myeloma UK early diagnosis programme has brought together diverse expertise to investigate this problem, and this article was prepared by the programme's working group for laboratory best practice. It reviews evidence for test requesting, analysis and reporting, for which there is large variation in practice across the United Kingdom. It presents a 'GP Myeloma diagnostic tool' and how it can be integrated into laboratory practice alongside a laboratory best practice tool. It proposes improved requesting and integration with haematology services for reporting and interpretation. Here the laboratory has a central role in creating efficient and cost‐effective pathways for appropriate and timely bone marrow examination for myeloma diagnosis. [ABSTRACT FROM AUTHOR]

Chlorpyrifos has been used extensively for decades to control crop pests and disease-transmitting insects; its contribution to increasing food security and minimizing the spread of diseases has been well documented. Pymetrozine and Avermectin (also known as abamectin) have been used to replace the toxic organophosphate insecticides (e.g., Chlorpyrifos) applied to rice crops in China, where the overuse of pesticides has occurred. In addition, climate change has exacerbated pesticide use and pollution. Thus, farmers and communities are at risk of exposure to pesticide pollution. This study reviews the contamination, exposure, and health risks through environmental and biological monitoring of the legacy pesticide Chlorpyrifos and currently used insecticides Pymetrozine and Avermectin in China; it investigates whether changes in pesticide usage from Chlorpyrifos to Pymetrozine and Avermectin reduce pesticide contamination and health hazards to communities and residents. In addition, this review discusses whether Pymetrozine and Avermectin applications could be recommended in other countries where farmers largely use Chlorpyrifos and are exposed to high health risks under climate change scenarios. Although Chlorpyrifos is now banned in China, farmers and residents exposed to Chlorpyrifos are still experiencing adverse health effects. Local farmers still consider Chlorpyrifos an effective pesticide and continue to use it illegally in some areas. As a result, the concentration levels of Chlorpyrifos still exceed risk-based thresholds, and the occurrence of Chlorpyrifos with high toxicity in multiple environmental routes causes serious health effects owing to its long-term and wide application. The bioaccumulation of the currently used insecticides Pymetrozine and Avermectin in the environment is unlikely. Pymetrozine and Avermectin used in paddy water and soil for crop growth do not pose a significant hazard to public health. A change in pesticide use from Chlorpyrifos to Pymetrozine and Avermectin can reduce the pesticide contamination of the environment and health hazards to communities and residents. Finally, we recommend Pymetrozine and Avermectin in other countries, such as Vietnam, and countries in Africa, such as Ghana, where farmers still largely use Chlorpyrifos. [ABSTRACT FROM AUTHOR]

Glucocorticoids prescribed to limit inflammation, have significant adverse effects. As 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates active glucocorticoid, we investigated whether 11β-HSD1 inhibition with AZD4017 could mitigate adverse glucocorticoid effects without compromising their anti-inflammatory actions. We conducted a proof-of-concept, randomized, double-blind, placebo-controlled study at Research Unit, Churchill Hospital, Oxford, UK (NCT03111810). 32 healthy male volunteers were randomized to AZD4017 or placebo, alongside prednisolone treatment. Although the primary endpoint of the study (change in glucose disposal during a two-step hyperinsulinemic, normoglycemic clamp) wasn't met, hepatic insulin sensitivity worsened in the placebo-treated but not in the AZD4017-treated group. Protective effects of AZD4017 on markers of lipid metabolism and bone turnover were observed. Night-time blood pressure was higher in the placebo-treated but not in the AZD4017-treated group. Urinary (5aTHF+THF)/THE ratio was lower in the AZD4017-treated but remained the same in the placebo-treated group. Most anti-inflammatory actions of prednisolone persisted with AZD4017 co-treatment. Four adverse events were reported with AZD4017 and no serious adverse events. Here we show that co-administration of AZD4017 with prednisolone in men is a potential strategy to limit adverse glucocorticoid effects. Glucocorticoids prescribed to limit inflammation, have significant adverse effects. Here the authors show that co-administration of AZD4017 with prednisolone in men is a potential strategy to limit adverse glucocorticoid effects. [ABSTRACT FROM AUTHOR]

Pymetrozine is one of the most commonly used insecticides in China. This study was conducted to analyse Pymetrozine's potential exposures through various environmental routes beyond the treatment areas. The aim was to estimate the potential health risk for communities due to non-dietary exposures to Pymetrozine in soil and paddy water. Data on registration of pesticides in China, government reports, questionnaires, interviews and literature reviews as well as toxicological health investigations were evaluated to determine the hazard and dose–response characteristics of Pymetrozine. These were based on the US EPA exposure and human health risk assessment methods and exposure data from soil and paddy water samples collected between 10 and 20 m around the resident's location. The exposure doses from dermal contact through soil and paddy water were estimated. The potential cancer risk from the following exposure routes was evaluated: ingestion through soil; dermal contact exposure through soil; dermal contact exposure through paddy water. The potential total cancer risk for residents was estimated to be less than 1 × 10−6. These were relatively low and within the acceptable risk levels. The potential hazard quotient (HQ) from acute and lifetime exposure by dermal contact through paddy water and soil and acute and lifetime exposure by soil ingestion for residents was less than 1, indicating an acceptable risk level. This study suggested that there were negligible cancer risk and non-cancer risks based on ingestion and dermal contact routes of exposure to residents. [ABSTRACT FROM AUTHOR]

Myasthenia gravis (MG) and congenital myasthenic syndromes (CMS) are a group of disorders with a well characterised autoimmune or genetic and neurophysiological basis. We reviewed the literature from the last 20 years assessing the utility of various neurophysiological, immunological, provocative and genetic tests in MG and CMS. Diagnostic sensitivity of repetitive nerve stimulation test ranges between 14 and 94% and specificity between 73 and 100%; sensitivity of single-fibre EMG (SFEMG) test ranges between 64 and 100% and specificity between 22 and 100%; anti-acetylcholine receptor (AChR) antibody sensitivity ranges from 13 to 97% and specificity ranges from 95 to 100%. Overall, SFEMG has the highest sensitivity while positive anti-AChR antibodies have the highest specificity. Newer testing strategies that have been investigated over the last couple of decades include ocular vestibular-evoked myogenic potentials, otoacoustic emissions and disease-specific circulating miRNAs in serum for autoimmune myasthenia, as well as next-generation sequencing for genetic testing of CMS. While there has been significant progress in developing newer testing strategies for diagnosing MG and CMS over the last couple of decades, more research is needed to assess the utility of these newer tools regarding their sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Pesticides play an important role in agricultural development. However, pesticide application can result in both acute and chronic human toxicities, and the adverse effects of pesticides on the environment and human health remain a serious problem. There is therefore a need to discuss the application methods for pesticides, the routes of pesticide exposure, and the health risks posed by pesticide application. The health problems related to pesticide application and exposure in developing countries are of particular concern. The purpose of this paper is to provide scientific information for policymakers in order to allow the development of proper pesticide application technics and methods to minimize pesticide exposure and the adverse health effects on both applicators and communities. Studies indicate that there are four main pesticide application methods, including hydraulic spraying, backpack spraying, basal trunk spraying, and aerial spraying. Pesticide application methods are mainly selected by considering the habits of target pests, the characteristics of target sites, and the properties of pesticides. Humans are directly exposed to pesticides in occupational, agricultural, and household activities and are indirectly exposed to pesticides via environmental media, including air, water, soil, and food. Human exposure to pesticides occurs mainly through dermal, oral, and respiratory routes. People who are directly and/or indirectly exposed to pesticides may contract acute toxicity effects and chronic diseases. Although no segment of the general population is completely protected against exposure to pesticides and their potentially serious health effects, a disproportionate burden is shouldered by people in developing countries. Both deterministic and probabilistic human health risk assessments have their advantages and disadvantages and both types of methods should be comprehensively implemented in research on exposure and human health risk assessment. Equipment for appropriate pesticide application is important for application efficiency to minimize the loss of spray solution as well as reduce pesticide residuals in the environment and adverse human health effects due to over-spraying and residues. Policymakers should implement various useful measures, such as integrated pest management (IPM) laws that prohibit the use of pesticides with high risks and the development of a national implementation plan (NIP) to reduce the adverse effects of pesticides on the environment and on human health. [ABSTRACT FROM AUTHOR]

Summary: Myeloma patients frequently respond poorly to bacterial and viral vaccination. A few studies have reported poor humoral immune responses in myeloma patients to COVID‐19 vaccination. Using a prospective study of myeloma patients in the UK Rudy study cohort, we assessed humoral and interferon gamma release assay (IGRA) cellular immune responses to COVID‐19 vaccination post second COVID‐19 vaccine administration. We report data from 214 adults with myeloma (n = 204) or smouldering myeloma (n = 10) who provided blood samples at least three weeks after second vaccine dose. Positive Anti‐spike antibody levels (> 50 iu/ml) were detected in 189/203 (92.7%), positive IGRA responses were seen in 97/158 (61.4%) myeloma patients. Only 10/158 (6.3%) patients were identified to have both a negative IGRA and negative anti‐spike protein antibody response. In all, 95/158 (60.1%) patients produced positive results for both anti‐spike protein serology and IGRA. After adjusting for disease severity and myeloma therapy, poor humoral immune response was predicted by male gender. Predictors of poor IGRA included anti‐CD38/anti‐BCMA (B‐cell maturation antigen) therapy and Pfizer‐BioNTech vaccination. Further work is required to understand the clinical significance of divergent cellular response to vaccination. [ABSTRACT FROM AUTHOR]

All patients who had had a previous infection had a robust antibody response to the first dose of COVID-19 vaccine and 60% of patients had an optimal immune response to the first dose of COVID-19 vaccination. COVID symptoms, testing, shielding impact on patient-reported outcomes and early vaccine responses in individuals with multiple myeloma Keywords: myeloma; COVID-19; vaccination; wellbeing; shielding EN myeloma COVID-19 vaccination wellbeing shielding 95 98 4 12/27/21 20220101 NES 220101 Patients with myeloma have been shielded and self-isolated since the start of the COVID-19 pandemic, due to the concern for and subsequent reports of higher risk of severe COVID-19 disease and mortality.1 In addition, guidelines have encouraged attenuation of myeloma therapeutics or a switch to oral therapies, ostensibly to reduce hospital foot-fall, facilitate shielding and potentially to limit further treatment-related immune suppression.2 Myeloma requires ongoing immune-suppressive chemotherapy, frequent medical visits and has previously demonstrated universally poor response to vaccinations.3 The protective titre of antibodies required to prevent re-infection is unclear, as is the ability to protect patients from SARS-CoV-2 virus variants of concern (VoC). [Extracted from the article]

Human health risk assessments of exposures to non-carcinogenic occupational and environmental toxicants have mostly been undertaken using the Hazard Quotient (HQ) approach, which largely ignores variabilities in both exposures and associated adverse health outcomes, unlike probabilistic approaches. Chlorpyrifos is a neurotoxic insecticide that is commonly applied by farmers in Ghana with limited research on associated health risks among applicators. The objective of this study was to assess health risks associated with chlorpyrifos exposure among applicators on rice farms in Ghana, using advanced probabilistic approaches that incorporate variability in both exposure doses and adverse response doses obtained from human epidemiological studies. Urine samples obtained from the applicators were analyzed for 3,5,6-trichloro-2-pyridinol (TCP)from which Absorbed Daily Dose (ADD) and Lifetime Average Daily Dose (LADD) levels of chlorpyrifos were estimated. The scientific literature was searched to identify human epidemiological data from studies that have reported chlorpyrifos adverse effects and their corresponding exposure levels. Equivalent ADD and LADD of chlorpyrifos were estimated from the human epidemiological data to obtain chlorpyrifos Toxicant Sensitivity Distributions (TSDs). Using the applicators' chlorpyrifos dose distribution and TSDs, adverse health risks among the applicators were characterized using the probabilistic approaches, Overall Risk Probability (ORP) and Monte Carlo Simulation (MCS). The probabilities of chlorpyrifos adverse health effects occurring under the chronic exposure scenarios ranged from 1 to 8%, while those for acute exposure scenarios ranged from 31 to 34%. This study indicates that while the risks of chronic adverse health effects from chlorpyrifos exposure among the applicators were low, acute health risks were high. [ABSTRACT FROM AUTHOR]

Soil-transmitted helminth (STH) infections are endemic in Indonesia. However, prevalence data for many parts of the country are incomplete. The aim of this study was to determine human STH prevalence and knowledge and practices relating to STH risk behaviour, to provide a current view of the status of STH infection in rural communities in Central Java. A cross-sectional survey of 16 villages was conducted in Semarang, Central Java in 2015. Demographic and household data together with information about knowledge and practices relating to STH and hygiene were elicited through face-to-face interviews. Stool samples were collected and examined using the flotation method. Children (aged 2–12 years) also had their haemoglobin (Hb) levels, height and weight data collected, and BMI estimated. Data were analysed using univariate logistic regression analysis. A total of 6,466 individuals with a mean age of 33.5 years (range: 2–93) from 2,195 households were interviewed. The overall prevalence of STH was 33.8% with Ascaris lumbricoides (roundworm) the predominant nematode identified (prevalence = 26.0%). Hookworm and Trichuris trichiura (whipworm) were found in 7.9% and 1.8% of participants, respectively. Females were at increased odds of infection with A. lumbricoides (adjusted OR 1.14, 95% CI [1.02–1.29], p = 0.02). Adults in age groups 51–60 and over 60 years had the highest odds of being infected with hookworm (adjusted OR 3.01, 95% CI [1.84–4.91], p<0.001 and adjusted OR 3.79, 95% CI [2.30–6.26], p<0.001, respectively) compared to 6–12 year olds. Farmers also had higher odds of being infected with hookworm (adjusted OR 2.36, 95% CI [1.17–4.76], p = 0.02) compared to other occupation categories. Poverty (OR 2.14, 95% CI [1.77–2.58], p<0.001), overcrowding (OR 1.35, 95% CI [1.27–1.44], p<0.001), goat ownership (OR 1.61, 95% CI [1.10–2.41], p = 0.02) and the presence of dry floor space in the home (OR 0.73, 95% CI [0.58–0.91], p = 0.01) were all household factors significantly associated with an increased odds of infection. Infection with STH was not significantly associated with the gastrointestinal illness (p>0.05), BMI or Hb levels; however, one third of all 2–12 year olds surveyed were found to be anaemic (i.e. Hb concentrations below 110g/l or 115g/l for children under 5 and 5 years or older, respectively), with a greater proportion of school-age children at risk. Knowledge and behaviour related to hygiene and gastrointestinal diseases varied widely and were generally not associated with STH infection. The study revealed that STH infection remains endemic in Central Java despite ongoing deworming programs. Current control efforts would benefit from being re-evaluated to determine a more effective way forward. Author summary: Among the major NTDs, STH are one of the most common disabling chronic infections. Currently available drug treatments, whilst considered safe and generally well tolerated, do not confer protection against new infections. In Indonesia, prevalences of STH of up to 90% have been reported but these estimates are based on data from the 1980s and 90s. More up-to-date STH prevalence estimates are urgently needed to help guide future control efforts. A cross-sectional survey was conducted in rural villages in Semarang, Central Java to determine human STH prevalence and associated risk factors. One-third of all cohort participants were positive for STH with prevalences of 26%, 7.9% and 1.8% identified for Ascaris lumbricoides, hookworm and Trichuris trichiura at 7.9% and 1.8%, respectively. Risk of A. lumbricoides infection was higher for females, whilst farmers and adults over 50 had an increased risk of hookworm infection. Poverty, overcrowding in the home and goat ownership were also associated with an increased risk at the household level. Soil-transmitted helminthiases remains a significant health problem in Central Java, Indonesia, exacerbated by limited knowledge about STH, poor sanitation and hygiene and poverty prevalent in the region. Control efforts would benefit from an integrated approach emphasising WASH, health education and chemotherapy. Further studies investigating environmental contamination with STH in and around homes in endemic areas could provide further insight into links between household factors and STH identified in our study. [ABSTRACT FROM AUTHOR]

Background: The measurement of monoclonal free light chains is being increasingly utilized since the introduction of serum-based assays. It is important for laboratories to determine their own reference ranges in order to reflect the local population. The aim of this study was to determine if age-adjusted reference ranges for serum free light chains would have implications for demand management of further laboratory investigations including immunofixation. Methods: After certain exclusions, 4293 samples from individuals seen in primary care across Oxfordshire between 2014 and 2016 were identified for analysis of patient characteristics, serum free light chain results and estimated glomerular filtration rate. Results: We found age to be an independent variable when considering serum free light chain concentrations, ratio and estimated glomerular filtration rate. The reference ranges derived from our data differ markedly from the original Binding Site ranges. When the age-specific ranges are retrospectively applied to our population, there is a 38% decrease in follow-up testing with no loss of specificity. Conclusion: We feel confident implementing new age-specific serum free light chain reference ranges in our laboratory. We have developed a simple algorithm for evaluating serum free light chains based on age and estimated glomerular filtration rate. We encourage laboratories to establish their own local reference ranges using large cohorts and their chosen serum free light chain assay platform. [ABSTRACT FROM AUTHOR]

The article discusses clinical management and diagnosis of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) that manifest with osteoporosis and fragility fractures. Topics explored include the increasing prevalence of osteoporosis and fractures in the elderly, the standardized incidence ratio of osteoporotic fracture in patients with MGUS, and the screening guidelines for myeloma bone disease and MGUS.

The concentration level related to toxicities of trace elements in drinking water, rice, wheat flour, and their associated negative impacts on human health have become an emergent issue in China. Because Xinjiang is the largest province in China with the majority of arable pasture land available for cultivation, it is important to analyze the concentrations of trace elements in relation to their toxicities in water, rice, and wheat flour and to investigate the health risk differences between agricultural and pastoral areas in Bay County, Xinjiang. The study results showed that (1) metal concentrations from drinking water, rice, and wheat flour were within the permissible limits; (2) concentration levels of trace elements and their total risk from drinking water and rice were higher in the agricultural areas than those in the pastoral areas, whereas concentration levels of trace elements and their total risk from wheat flour were higher in the pastoral areas than those in the agricultural areas; (3) the concentration level of the trace elements in rice were higher than in the wheat flour, but the risk from the wheat flour was higher than the risk from rice; (4) total non-cancer risk from the flour (HIf) in both areas exceeded the respective safe reference doses; (5) total cancer risk from the wheat flour, rice, and water exceeded the safety limit (1 × 10−4); (6) for the exposed population, arsenic was suggested as the most evident pollutant leading to carcinogenic concerns regarding the water, rice, and wheat flour; (7) the risk index from the wheat flour made up the highest percentage both in the total cancer risk and the non-cancer risk, followed by rice and then water; and (8) the human health risk was attributed to influence from the local environment in the agriculture areas, while it was attributed to the external environment in the pastoral areas. [ABSTRACT FROM AUTHOR]

Chlorpyrifos is a neurotoxic insecticide that is widely used in the agricultural sector of Ghana. The main objective of this study was to evaluate the levels of chlorpyrifos exposure and health risk among applicators (n = 21) on irrigated rice farms in Ghana, based on a typical application event. Pre- and post-application urine samples (24-h) were collected from the applicators and analysed for 3,5,6-trichloro-2-pyridinol (TCP), using LC-MS/MS. The levels of chlorpyrifos-absorbed dose with the applicators were estimated from the urinary TCP levels. Prior to application, the median absorbed dose of chlorpyrifos (background exposure) with the applicators was 0.2 μg/kg/day (range 0.05 to 2 μg/kg/day). Following application, the median absorbed dose of chlorpyrifos (application exposure) increased 30-fold to 6 μg/kg/day (range 0.7 to 74 μg/kg/day). The mean elimination half-life (t1/2) of chlorpyrifos was calculated to be 50 h. Hazard quotient (HQ) values (HQ > 1) obtained with the chronic (10 μg/kg/day) and acute (100 μg/kg/day) guideline values of the WHO suggested no risk of chronic or acute health effects, respectively, among both the median and 5% highly exposed groups. However, HQ values (HQ > 1) obtained with the chronic (0.3 μg/kg/day) and acute (5 μg/kg/day) guideline values of the USEPA suggested risk of chronic and acute health effects, respectively, among both the median and 5% highly exposed groups. The quantity of chlorpyrifos formulation applied, spraying duration, and the number of spray tanks applied significantly correlated with the absorbed dose levels of chlorpyrifos from application exposure. Therefore, these factors suggest means to reduce exposure and consequent health risk among the applicators. [ABSTRACT FROM AUTHOR]

Background and objectives Helicobacter pylori ( H.pylori ) plasminogen binding protein (PBP) has been proposed as an antigen triggering autoimmune pancreatitis (AIP), the pancreatic manifestation of IgG4-related disease (IgG4-RD). We investigated exposure to H. pylori infection, cytokine response and immunological memory to H. pylori PBP in a prospective IgG4-RD cohort in the UK. Methods Clinical and endoscopic evidence of peptic ulceration, serological H. pylori exposure and serum IgG4 levels were obtained in 55 IgG4-RD patients and 52 disease controls (DC) with autoimmune or inflammatory conditions with an elevated serum IgG4. Gastric and duodenal tissues were assessed for H. pylori and immunostained for IgG4. B and T cell ELISpot and cytokine luminex assays were used to detect immune responses to H. pylori PBP. Results 85% of IgG4-RD patients had pancreatic and/or biliary disease, 89% had extra-pancreatic manifestations, and 84% had an increased serum IgG4. Clinical dyspepsia (35.2%), gastritis (58%), peptic ulceration (7.4%) and H. pylori colonisation (24%) in IgG4-RD was similar to DC. In IgG4-RD, gastric tissue contained a chronic inflammatory infiltrate with a low IgG4+ plasma-cell count (<10/HPF; range 1–4/HPF), and duodenal specimens had an increased IgG4 count (>10/HPF; range 7–54) compared with DC (p < 0.01). Th1 and Th2 cytokine response and immunological B-cell memory to H. pylori PBP did not differ between IgG4-RD and DC. Conclusions In a prospective UK cohort, the prevalence of gastric ulceration, exposure to H. pylori, cytokine response and immunological memory to H. pylori PBP did not differ in IgG4-RD patients compared with DC. This study does not support a role for H. pylori PBP as a microbial antigen in IgG4-RD. Keywords for abstract Peptic ulceration, Antigens, B cells, T cells, Interleukins, Helicobacter pylori . [ABSTRACT FROM AUTHOR]

Background IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory condition, characterised by an elevated serum IgG4 concentration and abundant IgG4-positive plasma cells in the involved organs. An important question is whether the elevated IgG4 response is causal or a reflection of immune-regulatory mechanisms of the disease. Objectives To investigate if the IgG4 response in IgG4-RD represents a generalised polyclonal amplification by examining the response to common environmental antigens. Methods Serum from 24 patients with IgG4-RD (14 treatment-naive, 10 treatment-experienced), 9 patients with primary sclerosing cholangitis and an elevated serum IgG4 (PSC-high IgG4), and 18 healthy controls were tested against egg white and yolk, milk, banana, cat, peanut, rice and wheat antigens by radioimmunoassay. Results We demonstrated an elevated polyclonal IgG4 response to multiple antigens in patients with IgG4-RD and in PSC-high IgG4, compared with healthy controls. There was a strong correlation between serum IgG4 and antigen-specific responses. Responses to antigens were higher in treatment-naive compared with treatment-experienced patients with IgG4-RD. Serum electrophoresis and immunofixation demonstrated polyclonality. Conclusions This is the first study to show enhanced levels of polyclonal IgG4 to multiple antigens in IgG4-RD. This supports that elevated IgG4 levels reflect an aberrant immunological regulation of the overall IgG4 response, but does not exclude that causality of disease could be antigen-driven. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 58-year-old man with X-linked immunodeficiency with Magnesium defect, Epstein-Barr virus infection and Neoplasia (XMEN) disease, discussing the course of his illness over a period of more than 20 years. Topics include the mutation found in his magnesium cation transporter protein 1 (MAGT1) gene and his lymphoproliferative disease symptoms.

In the last decade, the introduction of the serum-free light-chain (sFLC) assay has been an important advance in the diagnosis and management of plasma cell dyscrasias, particularly monoclonal light-chain diseases. The immunoassay was developed to detect free light chains in serum by using anti-FLC antibodies which specifically recognised epitopes on light chains that were ‘hidden’ in intact immunoglobulins. Since its introduction in 2001, there have been several publications in the English language literature discussing the clinical utility as well as analytical limitations of the sFLC assay. These studies have highlighted both positive and negative aspects of the assay particularly with regard to its sensitivity and specificity and the technical challenges that can affect its performance. The contribution and significance of the sFLC assay in the management of light-chain myeloma, primary amyloid light-chain (AL) amyloidosis and non-secretory myeloma are well recognised and will be addressed in this review. The aim of this article is to also review the published literature with a view to providing a clear understanding of its utility and limitations in the diagnosis, prognosis and monitoring of plasma dyscrasias including intact immunoglobulin multiple myeloma (MM) and monoclonal gammopathy of unknown significance (MGUS). The increasing interest in using this assay in other haematological conditions will also be briefly discussed. [ABSTRACT FROM AUTHOR]

Purpose: Hypoxia is known to induce the release of microparticles in vitro. However, few publications have addressed the role of hypoxia in vivo on circulating levels of microparticles. This randomised, controlled, crossover trial aimed to determine the effect of mild hypoxia on in vivo levels of circulating microparticles in healthy individuals. Methods: Blood was obtained from 51 healthy male volunteers (mean age of 26.9 years) at baseline altitude (490 m) and after 24 and 48 h at moderate altitude (2,590 m). The order of altitude exposure was randomised. Flow cytometry was used to assess platelet-poor plasma for levels of circulating microparticles derived from platelets, endothelial cells, leucocytes, granulocytes, monocytes, red blood cells and procoagulant microparticles. Results: Mean (standard deviation) oxygen saturation was significantly lower on the first and second day after arrival at 2,590 m, 91.0 (2.0) and 92.0 (2.0) %, respectively, compared to 490 m, 96 (1.0) %, p < 0.001 for both comparisons. A significant decrease in the levels of procoagulant microparticles (annexin V+ −221/μl 95 % CI −370.8/−119.0, lactadherin+ −202/μl 95 % CI −372.2/−93.1), platelet-derived microparticles (−114/μl 95 % CI −189.9/−51.0) and red blood cell-derived microparticles (−81.4 μl 95 % CI −109.9/−57.7) after 48 h at moderate altitude was found. Microparticles derived from endothelial cells, granulocytes, monocytes and leucocytes were not significantly altered by exposure to moderate altitude. Conclusions: In healthy male individuals, mild hypobaric hypoxia, induced by a short-term stay at moderate altitude, is associated with lower levels of procoagulant microparticles, platelet-derived microparticles and red blood cell-derived microparticles, suggesting a reduction in thrombotic potential. [ABSTRACT FROM AUTHOR]

There is a general lack of knowledge as regards the effects of climate change on pollutant behavior. This is particularly true of the Asia-Pacific Region (APR). This region has major significance in terms of global pollutant emission and also displays a wide variety of environments. This review presents the authors' opinions on possible implications of climate change for pollutant behavior in the APR. Although differing responses can be expected across the region, there are clear implications as regards the short- and long-term behavior of pollutants. Effects can be predicted through modeling, but further data are required for model calibration. Nevertheless, it can be predicted that climate change will affect processes including global distillation of persistent organic pollutants, airborne transport of heavy metals, half-life of readily degradable pollutants, and eutrophication in water bodies. Particulates are expected to play a central role in mediating the effects of climate change, and successful predictive models will need to be based on particulate-mediated transport and behavior. Climate change also has the potential to cause an increase in the intensity and frequency of harmful algal blooms in aquatic environments throughout the region, with significant implications for supply of both food and drinking water. [ABSTRACT FROM AUTHOR]

Among children, infections with soil-transmitted helminths (STH) can cause anemia, impaired growth, and absence from school. Sustainable control of STH infection requires that appropriate latrines be integrated with health-promotion education. We report a pilot study of the effects of a combined latrine-education intervention in Central Java, Indonesia. The participants were 99 children (3-13 years old) in two villages (intervention and control) south of Semarang city. Stool samples were collected from the children and were examined for the presence of helminth eggs. After baseline data were collected, latrines were constructed and health education was given in the intervention village. Then, in both villages, all children who had STH infection at baseline were given 400 mg of albendazole. Eight months later, follow-up stool samples were collected and examined. In both villages, 20% of the children had STH infection at baseline. At follow-up, the incidence of STH infection was much lower in the intervention village than in the control village (4.0% vs. 20.4%; p<0.02). The results of this small pilot study give some confidence that a scaled-up study involving many more children and cluster-randomization of the intervention will be feasible and could provide more conclusive evidence of the intervention's effectiveness. [ABSTRACT FROM AUTHOR]

Rationale: Serum mesothelin is a new biomarker for the diagnosis of mesothelioma. Patients with mesothelioma commonly present with pleural effusions. To define the clinical utility of mesothelin quantification in pleural fluid, we assessed its additional value over pleural fluid cytology and its short-term reproducibility and reliability after pleural inflammatory processes, including pleurodesis.Objectives: To assess the diagnostic role of pleural fluid mesothelin and the effect of common clinical factors that may influence measurement accuracy.Methods: Mesothelin was quantified in 424 pleural fluid and 64 serum samples by ELISA. Fluid was collected prospectively from 167 patients who presented with pleural effusions for investigation. Serial pleural fluid samples were obtained from patients (n = 33) requiring repeated drainage. Mesothelin levels were also measured in patients (n = 32) prepleurodesis and postpleurodesis.Measurements and Main Results: Pleural fluid mesothelin concentrations were significantly higher in patients with mesothelioma (n = 24) relative to those with metastatic carcinomas (n = 67) and benign effusions (n = 75): median (interquartile range, 25th-75th percentile) = 40.3 (18.3-68.1) versus 6.1 (1.5-13.2) versus 3.7 (0.0-12.4) nM, respectively, P < 0.0001. Mesothelin measurement was superior to cytological examination in the diagnosis and exclusion of mesothelioma (sensitivity, 71 vs. 35%; specificity, 89 vs. 100%; negative predictive value, 95 vs. 82%, respectively). In patients with "suspicious" cytology, pleural fluid mesothelin was 100% specific for mesothelioma, and in cytology-negative effusions (n = 105) offered a negative predictive value of 94%. Intraindividual reproducibility of pleural fluid mesothelin was excellent: mean (+/-SD) variation, -0.15 (+/-8.41) nM in samples collected within 7 days from patients with mesothelioma. Measurements remained reliable after pleurodesis and were not affected by the presence of bacteria.Conclusions: Pleural fluid mesothelin provides additional diagnostic value relative to cytological examination. Mesothelin measurements are reproducible and not affected by inflammatory pleural processes. [ABSTRACT FROM AUTHOR]

Out of 247 traditional Chinese medicines (TCM) investigated, a proportion were contaminated with arsenic (5-15%), lead (∼5%), and mercury (∼65%). Some preparations exceeded the tolerable daily intake (TDI) for males and females for arsenic (4 and 5 products, respectively), lead (1 and 2 products), and mercury (5 and 7 products). These exceedances were as high as 2760-fold, which posed a potential danger to public health. As many users are known to self-prescribe, there is a substantial risk of poisoning from the consumption of these contaminated TCM. [ABSTRACT FROM AUTHOR]

Cyanobacteria can produce groups of structurally and functionally unrelated but highly potent toxins. Cyanotoxins are used in multiple research endeavours, either for direct investigation of their toxicologic properties, or as functional analogues for various biochemical and physiological processes. This paper presents occupational safety guidelines and recommendations for personnel working in field, laboratory or industrial settings to produce and use purified cyanotoxins and toxic cyanobacteria, from bulk harvesting of bloom material, mass culture of laboratory isolates, through routine extraction, isolation and purification. Oral, inhalational, dermal and parenteral routes are all potential occupational exposure pathways during the various stages of cyanotoxin production and application. Investigation of toxicologic or pharmacologic properties using in vivo models may present specific risks if radiolabelled cyanotoxins are employed, and the potential for occupational exposure via the dermal route is heightened with the use of organic solvents as vehicles. Inter- and intra-national transport of living cyanobacteria for research purposes risks establishing feral microalgal populations, so disinfection of culture equipment and destruction of cells by autoclaving, incineration and/or chlorination is recommended in order to prevent viable cyanobacteria from escaping research or production facilities. [ABSTRACT FROM AUTHOR]