Evidence that Pacific tuna mercury levels are driven by marine methylmercury production and anthropogenic inputs.

Pacific Ocean tuna is among the most-consumed seafood products but contains relatively high levels of the neurotoxin methylmercury. Limited observations suggest tuna mercury levels vary in space and time, yet the drivers are not well understood. Here, we map mercury concentrations in skipjack tuna across the Pacific Ocean and build generalized additive models to quantify the anthropogenic, ecological, and biogeochemical drivers. Skipjack mercury levels display a fivefold spatial gradient, with maximum concentrations in the northwest near Asia, intermediate values in the east, and the lowest levels in the west, southwest, and central Pacific. Large spatial differences can be explained by the depth of the seawater methylmercury peak near low-oxygen zones, leading to enhanced tuna mercury concentrations in regions where oxygen depletion is shallow. Despite this natural biogeochemical control, the mercury hotspot in tuna caught near Asia is explained by elevated atmospheric mercury concentrations and/or mercury river inputs to the coastal shelf. While we cannot ignore the legacy mercury contribution from other regions to the Pacific Ocean (e.g., North America and Europe), our results suggest that recent anthropogenic mercury release, which is currently largest in Asia, contributes directly to present-day human mercury exposure.

Mercury stable isotopes constrain atmospheric sources to the ocean.

Human exposure to toxic mercury (Hg) is dominated by the consumption of seafood1,2. Earth system models suggest that Hg in marine ecosystems is supplied by atmospheric wet and dry Hg(II) deposition, with a three times smaller contribution from gaseous Hg(0) uptake3,4. Observations of marine Hg(II) deposition and Hg(0) gas exchange are sparse, however5, leaving the suggested importance of Hg(II) deposition6 ill-constrained. Here we present the first Hg stable isotope measurements of total Hg (tHg) in surface and deep Atlantic and Mediterranean seawater and use them to quantify atmospheric Hg deposition pathways. We observe overall similar tHg isotope compositions, with median Δ200Hg signatures of 0.02‰, lying in between atmospheric Hg(0) and Hg(II) deposition end-members. We use a Δ200Hg isotope mass balance to estimate that seawater tHg can be explained by the mixing of 42% (median; interquartile range, 24-50%) atmospheric Hg(II) gross deposition and 58% (50-76%) Hg(0) gross uptake. We measure and compile additional, global marine Hg isotope data including particulate Hg, sediments and biota and observe a latitudinal Δ200Hg gradient that indicates larger ocean Hg(0) uptake at high latitudes. Our findings suggest that global atmospheric Hg(0) uptake by the oceans is equal to Hg(II) deposition, which has implications for our understanding of atmospheric Hg dispersal and marine ecosystem recovery.

Persistent osteoarticular pain in children: early clinical and laboratory findings suggestive of acute lymphoblastic leukemia (a multicenter case-control study of 147 patients).

BACKGROUND: The aim of this study was to identify early clinical and laboratory features that distinguish acute lymphoblastic leukemia (ALL) from juvenile idiopathic arthritis (JIA) in children presenting with persistent bone or joint pain for at least 1 month. METHODS: We performed a multicenter case-control study and reviewed medical records of children who initially presented with bone or joint pain lasting for at least 1 month, all of whom were given a secondary diagnosis of JIA or ALL, in four French University Hospitals. Each patient with ALL was paired by age with two children with JIA. Logistic regression was used to compare clinical and laboratory data from the two groups. RESULTS: Forty-nine children with ALL and 98 with JIA were included. The single most important feature distinguishing ALL from JIA was the presence of hepatomegaly, splenomegaly or lymphadenopathy; at least one of these manifestations was present in 37 cases with ALL, but only in 2 controls with JIA, for an odds ratio (OR) of 154 [95%CI: 30-793] (regression coefficient: 5.0). If the presence of these findings is missed or disregarded, multivariate analyses showed that non-articular bone pain and/or general symptoms (asthenia, anorexia or weight loss) (regression coefficient: 4.8, OR 124 [95%CI: 11.4-236]), neutrophils < 2 × 109/L (regression coefficient: 3.9, OR 50 [95%CI: 4.3-58]), and platelets < 300 × 109/L (regression coefficient: 2.6, OR 14 [95%CI: 2.3-83.9]) were associated with the presence of ALL (area under the ROC curve: 0.96 [95%CI: 0.93-0.99]). CONCLUSIONS: Based on our findings we propose the following preliminary decision tree to be tested in prospective studies: in children presenting with at least 1 month of osteoarticular pain and no obvious ALL in peripheral smear, perform a bone marrow examination if hepatomegaly, splenomegaly or lymphadenopathy is present. If these manifestations are absent, perform a bone marrow examination if there is fever or elevated inflammatory markers associated with non-articular bone pain, general symptoms (asthenia, anorexia or weight loss), neutrophils < 2 × 109/L or platelets < 300 × 109/L.

Evaluation of an oral analgesia protocol for upper-limb fracture reduction in the paediatric emergency department: Prospective study of 101 patients.

BACKGROUND: Upper limb injuries are common in children. When required, closed fracture reduction can be performed in the emergency department without general anaesthesia but causes pain. The primary objective of this study was to assess an oral analgesia protocol for fracture reduction without general anaesthesia. The secondary objectives were to look for associations linking pain intensity to age, sex, and waiting time and to determine the frequency of secondary displacement requiring closed reduction or internal fixation under general anaesthesia at the 1-week follow-up visit. HYPOTHESIS: An oral analgesia protocol combining a loading dose of morphine with other medications would provide sufficient pain control to obviate the need for general anaesthesia. MATERIAL AND METHODS: A prospective observational single-centre study was conducted over a 15-month period (July 2017-October 2018) in consecutive patients younger than 16 years who required reduction of a displaced upper-limb fracture. All patients received the same oral combination of paracetamol (15mg/kg), ibuprofen (7.5-10mg/kg), and a loading morphine dose (0.5mg/kg, up to 20mg) 1hour before the procedure. Patients given morphine more than 2hours before the procedure and those with persistent pain were given an additional morphine dose (0.2mg/kg, up to 10mg). An equimolar mixture of oxygen and nitrous oxide was administered during reduction. An appropriate scale was used to measure pain intensity before, during, and 15minutes after the procedure. Cases of secondary displacement requiring further reduction or internal fixation under general anaesthesia at the 1-week follow-up visit were recorded. RESULTS: The 101 study patients (73 male and 28 female) had a mean age of 9.4 years (range, 2-15 years). Mean pain scores were 5.0±2.6 at admission and 2.1±2.3, 2.6±3.3, and 1.3±2.2 before, during, and after reduction, respectively. Pain intensity during reduction was significantly associated with age. The analgesia was deemed satisfactory by 94 patients and 90 parents. General anaesthesia for further treatment was required in 10 (9.9%) patients, either on the day after the initial treatment, due to inadequate reduction (n=8), or at the 1-week visit, due to secondary displacement (n=2). DISCUSSION: Oral morphine in a sufficient dosage given in combination with other medications was effective and well tolerated when used to control pain during upper-limb fracture reduction. Pain intensity was not significantly associated with sex. In contrast, pain was significantly more severe in the patients older than 10 years of age. The proportions of patients requiring further reduction or internal fixation were consistent with previously published data. Most patients and parents were satisfied with the analgesia protocol. CONCLUSION: A multimodal oral analgesia protocol provides sufficient pain relief to allow closed reduction of upper-limb fractures in children at the emergency department. This management strategy provided high satisfaction rates in both the patients and their parents. LEVEL OF EVIDENCE: II, prospective observational study.

Reversible cerebral vasoconstriction syndrome in paediatric patients with systemic lupus erythematosus: implications for management.

Microvascular brain injury is well recognized in neuropsychiatric systemic lupus erythematosus (SLE), but cerebral large artery involvement is being debated. Three females with SLE, aged 9 to 14 years, had immunosuppressive treatment intensification because of lupus nephritis. Within the following days or weeks, they presented with intense cephalalgia - isolated or associated with neurological symptoms - and no or mild hypertension. Magnetic resonance angiography showed multiple stenoses within the circle of Willis. One patient had subsequent small subcortical cerebral infarction. Two patients were treated for neuropsychiatric SLE; one patient was treated for reversible cerebral vasoconstriction syndrome (RCVS). Angiography normalized within a few weeks in all three patients. Retrospectively, clinical and radiological features suggest that RCVS was the most likely diagnosis in all patients. Multidisciplinary analysis of clinical and angiographic features is recommended, as RCVS is rare in children and its recognition may help to adjust treatment. WHAT THIS PAPER ADDS: Reversible vasoconstriction syndrome was observed in paediatric systemic lupus erythematosus. Thorough imaging analysis was necessary to address this diagnosis in paediatric patients.

SÍNDROME DE VASOCONSTRICCIÓN CEREBRAL REVERSIBLE EN PACIENTES PEDIÁTRICOS CON LUPUS ERITEMATOSO SISTÉMICO: IMPLICANCIAS PARA EL MANEJO: La lesión microvascular cerebral está bien reconocida en el Lupus eritematoso sistémico neuropsiquiátrico (LES), pero se debate la participación de las arterias cerebrales grandes. Tres mujeres con LES, de edades entre 9 y 14 años, tuvieron una intensificación del tratamiento inmunosupresión por la nefritis lúpica. Dentro de los siguientes días o semanas, presentaron cefalea intensa, aislada o asociada con síntomas neurológicos - con o sin leve hipertensión. La angiografía por resonancia magnética mostro múltiples estenosis en el círculo de Willis. Un paciente tuvo subsecuentemente un pequeño infarto cerebral subcortical.

SÍNDROME DA VASOCONSTRIÇÃO CEREBRAL REVERSÍVEL EM PACIENTES PEDIÁTRICOS COM LUPUS ERITOMATOSO SISTÊMICO: IMPLICAÇÕES PARA O MANEJO: Lesão cerebral microvascular é bem reconhecida no lupus eritomatoso sistêmico (LES) neuropsiquiátrico, mas o envolvimento arterial cerebral extenso tem sido debatido. Três meninas com LES, idades de 9 a 14 anos, tiveram intensificação do tratamento imunossupressivo devido a nefrite causada pelo lupus. Dentro dos dias ou semanas seguintes, apresentaram cefalalgia intensa - isolada ou associada com sintomas neurológicos - sem nenhuma, ou com leve hipertensão. A angiografia por ressonância magnética mostrou estenoses múltiplas no círculo de Willis. Uma paciente teve subsequente infarto cerebral subcortical pequeno. Duas pacientes foram tratadas para LES neuropsiquiátrico, uma foi tratada para síndrome da vasoconstrição cerebral reversível (SVCR). A angiografia se normalizou em algumas semanas em todas as três pacientes. Retrospectivamente, os achados clínicos e radiológicos sugerem que SVCR era o diagnóstico mais provável em todas. Análise multidisciplinar dos aspectos clínicos e angiográficos é recomendada, pois a SVCR é rara em crianças, e seu reconhecimento pode ajudar a ajustar o tratamento.

MRI assessment of tenosynovitis in children with juvenile idiopathic arthritis: inter- and intra-observer variability.

BACKGROUND: There is sparse knowledge about grading tenosynovitis using MRI. OBJECTIVE: The purpose of this study was to assess the reliability of a tenosynovitis MRI scoring system in juvenile idiopathic arthritis. MATERIALS AND METHODS: Children with juvenile idiopathic arthritis and wrist involvement were enrolled in two paediatric centres, from October 2006 to January 2010. The extensor (compartments II, IV and VI) and flexor tendons were assessed for the presence of tenosynovitis on T1-weighted postcontrast fat-saturated MR images and were scored from 0 (normal) to 2 (moderate to severe) by two observers independently. Intra- and interobserver agreement was assessed. RESULTS: Ninety children (age range: 5-18.5 years) were included, of whom 34 had tenosynovitis involving extensors and 28 had tenosynovitis involving flexors. A total of 360 tendon areas were analysed, of which 114 had tenosynovitis (86/270 extensors and 28/90 flexors). Intra-reader 1 agreement was excellent for the extensors (k = 0.82-0.91) and for the flexors (k = 0.85); intra-reader 2 agreement was moderate to good for the extensors (k = 0.51-0.72) and good for the flexors (k = 0.64). Inter-reader agreement was good for the extensors (k = 0.69-0.73) and moderate for the flexors (k = 0.49). CONCLUSION: The proposed MRI scoring system for the assessment of wrist tenosynovitis in juvenile idiopathic arthritis appears feasible with an observer agreement sufficient for clinical use.