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Lupus nephritis is a potentially fatal autoimmune disease for which the current treatment is ineffective and often toxic. To develop mechanistic hypotheses of disease, we analyzed kidney samples from patients with lupus nephritis and from healthy control subjects using single-cell RNA sequencing. Our analysis revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid cells, T cells, natural killer cells and B cells that demonstrated both pro-inflammatory responses and inflammation-resolving responses. We found evidence of local activation of B cells correlated with an age-associated B-cell signature and evidence of progressive stages of monocyte differentiation within the kidney. A clear interferon response was observed in most cells. Two chemokine receptors, CXCR4 and CX3CR1, were broadly expressed, implying a potentially central role in cell trafficking. Gene expression of immune cells in urine and kidney was highly correlated, which would suggest that urine might serve as a surrogate for kidney biopsies.
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Rim/imunologia , Nefrite Lúpica/imunologia , Biomarcadores , Biópsia , Análise por Conglomerados , Biologia Computacional/métodos , Células Epiteliais/metabolismo , Citometria de Fluxo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Imunofenotipagem , Interferons/metabolismo , Rim/metabolismo , Rim/patologia , Leucócitos/imunologia , Leucócitos/metabolismo , Nefrite Lúpica/genética , Nefrite Lúpica/metabolismo , Nefrite Lúpica/patologia , Linfócitos/imunologia , Linfócitos/metabolismo , Anotação de Sequência Molecular , Células Mieloides/imunologia , Células Mieloides/metabolismo , Análise de Célula Única , TranscriptomaRESUMO
To define the cell populations that drive joint inflammation in rheumatoid arthritis (RA), we applied single-cell RNA sequencing (scRNA-seq), mass cytometry, bulk RNA sequencing (RNA-seq) and flow cytometry to T cells, B cells, monocytes, and fibroblasts from 51 samples of synovial tissue from patients with RA or osteoarthritis (OA). Utilizing an integrated strategy based on canonical correlation analysis of 5,265 scRNA-seq profiles, we identified 18 unique cell populations. Combining mass cytometry and transcriptomics revealed cell states expanded in RA synovia: THY1(CD90)+HLA-DRAhi sublining fibroblasts, IL1B+ pro-inflammatory monocytes, ITGAX+TBX21+ autoimmune-associated B cells and PDCD1+ peripheral helper T (TPH) cells and follicular helper T (TFH) cells. We defined distinct subsets of CD8+ T cells characterized by GZMK+, GZMB+, and GNLY+ phenotypes. We mapped inflammatory mediators to their source cell populations; for example, we attributed IL6 expression to THY1+HLA-DRAhi fibroblasts and IL1B production to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis.
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Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Perfilação da Expressão Gênica , Membrana Sinovial/metabolismo , Transcriptoma , Artrite Reumatoide/patologia , Autoimunidade/genética , Biomarcadores , Biologia Computacional/métodos , Estudos Transversais , Citocinas/metabolismo , Fibroblastos/metabolismo , Citometria de Fluxo , Expressão Gênica , Perfilação da Expressão Gênica/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/imunologia , Humanos , Leucócitos/imunologia , Leucócitos/metabolismo , Monócitos/imunologia , Monócitos/metabolismo , Transdução de Sinais , Análise de Célula Única/métodos , Membrana Sinovial/patologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Fluxo de TrabalhoRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Systemic lupus erythematosus (SLE) is prototypical autoimmune disease driven by pathological T cell-B cell interactions1,2. Expansion of T follicular helper (TFH) and T peripheral helper (TPH) cells, two T cell populations that provide help to B cells, is a prominent feature of SLE3,4. Human TFH and TPH cells characteristically produce high levels of the B cell chemoattractant CXCL13 (refs. 5,6), yet regulation of T cell CXCL13 production and the relationship between CXCL13+ T cells and other T cell states remains unclear. Here, we identify an imbalance in CD4+ T cell phenotypes in patients with SLE, with expansion of PD-1+/ICOS+ CXCL13+ T cells and reduction of CD96hi IL-22+ T cells. Using CRISPR screens, we identify the aryl hydrocarbon receptor (AHR) as a potent negative regulator of CXCL13 production by human CD4+ T cells. Transcriptomic, epigenetic and functional studies demonstrate that AHR coordinates with AP-1 family member JUN to prevent CXCL13+ TPH/TFH cell differentiation and promote an IL-22+ phenotype. Type I interferon, a pathogenic driver of SLE7, opposes AHR and JUN to promote T cell production of CXCL13. These results place CXCL13+ TPH/TFH cells on a polarization axis opposite from T helper 22 (TH22) cells and reveal AHR, JUN and interferon as key regulators of these divergent T cell states.
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Fatores de Transcrição Hélice-Alça-Hélice Básicos , Linfócitos T CD4-Positivos , Quimiocina CXCL13 , Interferon Tipo I , Lúpus Eritematoso Sistêmico , Proteínas Proto-Oncogênicas c-jun , Receptores de Hidrocarboneto Arílico , Feminino , Humanos , Masculino , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Diferenciação Celular , Quimiocina CXCL13/metabolismo , Epigenômica , Perfilação da Expressão Gênica , Interferon Tipo I/imunologia , Interferon Tipo I/metabolismo , Interleucina 22/imunologia , Interleucina 22/metabolismo , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/genética , Proteínas Proto-Oncogênicas c-jun/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismoRESUMO
OBJECTIVE: Autoantibodies and autoimmune diseases after SARS-CoV-2 infection are widely reported. Given evolving variants, milder infections, and increasing population vaccination, we hypothesized that SARS-CoV-2 infection earlier in the pandemic would be associated with more autoimmune connective tissue disease (CTD) symptoms and immunologic abnormalities. METHODS: Patients ≥18 years old with COVID-19 3/1/2020-8/15/2022 completed the CTD Screening Questionnaire and were tested for 27 autoimmune serologies, SARS-CoV-2 serologies, cell-bound complement activation products (CB-CAPs), and T and B lymphocyte immunophenotypes by flow cytometry. We assessed relationships between symptoms, serologies, and immunophenotypes in earlier (3/1/2020-1/31/2021) vs. later (2/1/2021-8/15/2022) periods, with different predominating SARS-CoV-2 viruses. RESULTS: 57 subjects had earlier and 23 had later pandemic COVID-19. 35 % of earlier vs. 17 % of later pandemic patients had CTD symptoms (p 0.18). More patients were antinuclear antibody (ANA) positive (44 % vs. 13 %, p 0.01) and had lupus anticoagulant (11 % vs. 4 %, p 0.67). After adjustment for age, race, and sex, earlier (vs. later) COVID-19 was associated with increased ANA positivity (OR 4.60, 95%CI 1.17, 18.15). No subjects had positive CB-CAPs. T and B cell immunophenotypes and SARS-CoV-2 serologies did not differ by group. In heatmap analyses, higher autoantibody variety was seen among those with infection in the early pandemic. CONCLUSION: In this sample, having COVID-19 infection in the earlier (pre-2/1/2021) vs. later pandemic was associated with more CTD symptoms, ANA positivity, and autoantibody reactivities. Earlier SARS-CoV-2 variants circulating in a less vaccinated population with less natural immunity may have been more immunogenic.
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OBJECTIVE: To determine the incidence and baseline factors associated with breakthrough coronavirus disease 2019 (COVID-19) after preexposure prophylaxis (PrEP) with tixagevimab/cilgavimab among patients with systemic autoimmune rheumatic diseases (SARDs). METHODS: We performed a retrospective cohort study among patients with SARDs who received tixagevimab/cilgavimab between January 2, 2022, and November 16, 2022. The primary outcome was breakthrough COVID-19 after tixagevimab/cilgavimab. We performed multivariable Cox regression models adjusted for baseline factors to identify risk factors for breakthrough COVID-19. RESULTS: We identified 444 patients with SARDs who received tixagevimab/cilgavimab (mean age 62.0 years, 78.2% female). There were 83 (18.7%) breakthrough COVID-19 cases (incidence rate 31.5/1000 person-months, 95% CI 24.70-38.24), 7 (1.6%) hospitalizations, and 1 (0.2%) death. Older age was inversely associated with breakthrough COVID-19 (adjusted hazard ratio [aHR] 0.86/10 years, 95% CI 0.75-0.99). Higher baseline spike antibody levels were associated with lower risk of breakthrough COVID-19 (aHR 0.42, 95% CI 0.18-0.99 for spike antibody levels > 200 vs < 0.4 units). CD20 inhibitor users had a similar risk of breakthrough COVID-19 (aHR 1.05, 95% CI 0.44-2.49) compared to conventional synthetic disease-modifying antirheumatic drug (DMARD) users. CONCLUSION: We found that patients with SARDs had frequent breakthrough COVID-19, but the proportion experiencing severe COVID-19 was low. DMARD type, including CD20 inhibitors, did not significantly affect risk of breakthrough COVID-19. Evidence of prior humoral immunity was protective against breakthrough infection, highlighting the continued need for a multimodal approach to prevent severe COVID-19 as novel PrEP therapies are being developed.
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Anticorpos Monoclonais , Antirreumáticos , COVID-19 , Doenças Reumáticas , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Antirreumáticos/uso terapêutico , Doenças Reumáticas/complicações , Doenças Reumáticas/tratamento farmacológicoRESUMO
SerpinB1, a protease inhibitor and neutrophil survival factor, was recently linked with IL-17-expressing T cells. Here, we show that serpinB1 (Sb1) is dramatically induced in a subset of effector CD4 cells in experimental autoimmune encephalomyelitis (EAE). Despite normal T cell priming, Sb1-/- mice are resistant to EAE with a paucity of T helper (TH) cells that produce two or more of the cytokines, IFNγ, GM-CSF, and IL-17. These multiple cytokine-producing CD4 cells proliferate extremely rapidly; highly express the cytolytic granule proteins perforin-A, granzyme C (GzmC), and GzmA and surface receptors IL-23R, IL-7Rα, and IL-1R1; and can be identified by the surface marker CXCR6. In Sb1-/- mice, CXCR6+ TH cells are generated but fail to expand due to enhanced granule protease-mediated mitochondrial damage leading to suicidal cell death. Finally, anti-CXCR6 antibody treatment, like Sb1 deletion, dramatically reverts EAE, strongly indicating that the CXCR6+ T cells are the drivers of encephalitis.
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Linfócitos T CD4-Positivos/imunologia , Encefalomielite Autoimune Experimental/patologia , Receptores CXCR6/metabolismo , Serpinas/fisiologia , Linfócitos T Auxiliares-Indutores/imunologia , Animais , Citocinas/metabolismo , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/metabolismo , Interferon gama/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores CXCR6/genéticaRESUMO
More than 1 million apheresis platelet collections are performed annually in the United States. After 2 healthy plateletpheresis donors were incidentally found to have low CD4+ T-lymphocyte counts, we investigated whether plateletpheresis causes lymphopenia. We conducted a cross-sectional single-center study of platelet donors undergoing plateletpheresis with the Trima Accel, which removes leukocytes continuously with its leukoreduction system chamber. We recruited 3 groups of platelet donors based on the total number of plateletpheresis sessions in the prior 365 days: 1 or 2, 3 to 19, or 20 to 24. CD4+ T-lymphocyte counts were <200 cells per microliter in 0/20, 2/20, and 6/20 donors, respectively (P = .019), and CD8+ T-lymphocyte counts were low in 0/20, 4/20, and 11/20 donors, respectively (P < .001). The leukoreduction system chamber's lymphocyte-extraction efficiency was â¼15% to 20% for all groups. Immunophenotyping showed decreases in naive CD4+ T-lymphocyte and T helper 17 (Th17) cell percentages, increases in CD4+ and CD8+ effector memory, Th1, and regulatory T cell percentages, and stable naive CD8+ and Th2 percentages across groups. T-cell receptor repertoire analyses showed similar clonal diversity in all groups. Donor screening questionnaires supported the good health of the donors, who tested negative at each donation for multiple pathogens, including HIV. Frequent plateletpheresis utilizing a leukoreduction system chamber is associated with CD4+ and CD8+ T-cell lymphopenia in healthy platelet donors. The mechanism may be repeated extraction of these cells during plateletpheresis. The cytopenias do not appear to be harmful.
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Doadores de Sangue/estatística & dados numéricos , Plaquetas/citologia , Linfopenia/etiologia , Plaquetoferese/efeitos adversos , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Prognóstico , Adulto JovemRESUMO
Objectives: The study aimed to evaluate the feasibility of a blood flow restriction (BFR) training regimen in patients with rheumatoid arthritis (RA); and to compare the effects of 4 weeks of BFR training with low-intensity strength training on muscle strength, muscle endurance, and joint pain in patients with RA.Method: In this non-blinded pilot randomized controlled trial, 18 women with RA aged 18-65 years performed low-intensity strength training for the lower limbs three times a week for 4 weeks, and were randomized to train with or without occlusion bands. The primary outcomes were registration of the recruitment process, compliance with training sessions, side effects, perceived pain, and a satisfaction survey. The secondary outcomes were changes in muscle strength, muscle endurance, and joint pain.Results: The findings of this pilot study included a challenging recruitment process, well tolerated training and test protocols, overall good patient satisfaction, no serious side effects, and high compliance. Both groups achieved significant improvements in knee extensor strength from baseline to follow-up, with a change of 11.5 kg [interquartile range (IQR) 9.8;13.0] in the intervention group and 8.4 kg (IQR 5.5;12.4) in the control group, and a significant between-group difference in favour of the intervention group (p = 0.0342).Conclusions: The feasibility results of this study indicated a challenging recruitment process, general satisfaction with the BFR and exercises, good compliance, and only expected non-serious side effects. BFR training may improve knee extensor strength in women with RA, compared low-intensity strength training without BFR.
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Artrite Reumatoide/terapia , Terapia por Exercício/métodos , Articulação do Joelho/fisiopatologia , Força Muscular/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Adulto , Idoso , Artrite Reumatoide/fisiopatologia , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Treinamento Resistido/métodos , Resultado do TratamentoRESUMO
OBJECTIVE: To develop a Core Outcome Set (COS) for treatment of perinatal depression. DESIGN: Systematic overview of outcomes reported in the literature and consensus development study. SETTING: International. POPULATION: Two hundred and twenty-two participants, mainly patients, healthcare professionals and researchers, representing 13 countries. METHODS: A systematic overview of outcomes reported in recently published research, a two-round Delphi survey and a consensus meeting at which the final COS was decided using modified nominal group technique. MAIN RESULTS: In the literature search, 1772 abstracts were identified and evaluated, and 165 studies were finally included in the review. In all, 106 outcomes were identified and included in the Delphi survey. In all, 222 participants registered for the first round of the Delphi survey and 151 (68%) responded. In the second round, 123 (55%) participants responded. Thirteen participants attended the consensus meeting, where the following nine outcomes were agreed upon for inclusion in the final COS: self-assessed symptoms of depression, diagnosis of depression by a clinician, parent to infant bonding, self-assessed symptoms of anxiety, quality of life, satisfaction with intervention, suicidal thoughts, attempted or committed suicide, thoughts of harming the baby, and adverse events. CONCLUSIONS: The relevant stakeholders prioritised outcomes and reached consensus on a COS comprising nine outcomes. We expect that this COS will contribute to the consistency and uniformity of outcome selection and reporting in future clinical trials involving treatment of perinatal depression. TWEETABLE ABSTRACT: Development of a core outcome set regarding treatment for perinatal depression by @SBU_en.
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Ansiedade/psicologia , Depressão/tratamento farmacológico , Assistência Perinatal/normas , Gestantes/psicologia , Qualidade de Vida/psicologia , Consenso , Técnica Delphi , Depressão/diagnóstico , Depressão Pós-Parto/diagnóstico , Depressão Pós-Parto/tratamento farmacológico , Determinação de Ponto Final/métodos , Feminino , Humanos , Avaliação de Resultados em Cuidados de Saúde/métodos , Gravidez , Resultado do TratamentoRESUMO
BACKGROUND: The literature on planning ability in individuals with intellectual disability (ID) provides no clarity on whether their ability matches their mental age (MA) or not. Perhaps can planning experience explain the mixed results. The current study investigated to what extent cognitive abilities and life experience can explain everyday planning ability in individuals with ID and to what extent results from everyday planning tasks support the developmental or the difference model of ID. METHOD: Planning tests, cognitive ability tasks and a self-rated life experience form were administered to 71 adolescents with ID and 62 children with a typical development matched on MA. RESULTS: Adolescents with ID exhibited planning ability according to their MA. Regression analyses showed that the predictors of planning differed between the groups. The cognitive measures could predict planning in both groups, but life experience only contributed positively to planning in the MA group, whereas chronological age was negatively correlated with successful planning in the ID group. CONCLUSIONS AND DISCUSSION: The results support the difference model of ID. When matched on MA, the individuals with ID will solve the planning task in a qualitatively different manner. Additionally, the participants with ID could not utilise their life experience when solving the planning task, contrary to the MA group. Practitioners should be aware that individuals with ID might need more everyday planning training throughout adolescence. To support adolescents with ID, practitioners may focus on supporting the individual's cognitive abilities rather than relying on their prior knowledge.
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Comportamento do Adolescente/fisiologia , Disfunção Cognitiva/fisiopatologia , Função Executiva/fisiologia , Deficiência Intelectual/fisiopatologia , Acontecimentos que Mudam a Vida , Pensamento/fisiologia , Adolescente , Remediação Cognitiva , Feminino , Humanos , Masculino , SuéciaRESUMO
Forest harvest in the boreal zone can increase the input of terrestrial materials such as dissolved organic carbon (DOC) and nitrate (NO3- ) into nearby aquatic ecosystems, with potential effects on phytoplankton growth through enhanced nutrient (i.e., positive) or reduced light availability (i.e., negative), which may affect ecosystem productivity and consumer resource use. Here, we conducted forest clear-cutting experiments in the catchments of four small, humic, and nitrogen-limited unproductive boreal lakes (two controls and two clear-cut, 18% and 44% of area cut) with one reference and two impact years. Our aim was to assess the effects of forest clear-cutting on pelagic biomass production and consumer resource use. We found that pelagic biomass production did not change after two years of forest clear-cutting: Pelagic primary and bacterial production (PP, BP), PP:BP ratio, chl a, and seston carbon (seston C) were unaffected by clear-cutting; neither did tree harvest affect seston stoichiometry (i.e., N:phosphorus [P], C:P) nor induce changes in zooplankton resource use, biomass, or community composition. In conclusion, our findings suggest that pelagic food webs of humic lakes (DOC > 15 mg/L) might be resilient to a moderate form of forest clear-cutting, at least two years after tree removal, before mechanical site preparation (e.g., mounding, plowing) and when leaving buffer strips along lakes and incoming streams. Thus, pelagic food web responses to forest clear-cutting might not be universal, but could depend on factors such as the time scale, share of catchment logged, and the forest practices involved, including the application of buffer strips and site preparation.
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Cadeia Alimentar , Lagos , Animais , Ecossistema , Florestas , ZooplânctonRESUMO
BACKGROUND: Clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG. PARTICIPANTS AND METHODS: A genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10 543 mothers and 16 317 offspring of European origin, with replication in 10 660 mothers and 7561 offspring. Additional analyses determined the proportion of variability in GWG from maternal and fetal common genetic variants and the overlap of established genome-wide significant variants for phenotypes relevant to GWG (for example, maternal body mass index (BMI) and glucose, birth weight). RESULTS: Approximately 20% of the variability in GWG was tagged by common maternal genetic variants, and the fetal genome made a surprisingly minor contribution to explain variation in GWG. Variants near the pregnancy-specific beta-1 glycoprotein 5 (PSG5) gene reached genome-wide significance (P=1.71 × 10-8) for total GWG in the offspring genome, but did not replicate. Some established variants associated with increased BMI, fasting glucose and type 2 diabetes were associated with lower early, and higher later GWG. Maternal variants related to higher systolic blood pressure were related to lower late GWG. Established maternal and fetal birth weight variants were largely unrelated to GWG. CONCLUSIONS: We found a modest contribution of maternal common variants to GWG and some overlap of maternal BMI, glucose and type 2 diabetes variants with GWG. These findings suggest that associations between GWG and later offspring/maternal outcomes may be due to the relationship of maternal BMI and diabetes with GWG.
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Feto/fisiologia , Ganho de Peso na Gestação/genética , Gravidez/genética , Feminino , Estudo de Associação Genômica Ampla , Ganho de Peso na Gestação/fisiologia , Humanos , Gravidez/fisiologia , Gravidez/estatística & dados numéricosRESUMO
OBJECTIVES: To describe the long-term perspective regarding prevalence of risk factors, secondary stroke prevention, and lifestyle indices after stroke. METHODS: From a population-based one-year cohort (n = 416), we performed an observational study of 145 survivors at 16 months and 10 years after stroke (age 27-97 years) regarding secondary prevention including reaching acceptable treatment goals; nutritional status with focus on underweight; and the lifestyle indices: living situation, level of dependence, and self-assessed health condition. RESULTS: Ten years after stroke, 50% of the subjects with hypertension diagnosis and 55% of those without hypertension diagnosis were within the blood pressure goal <140/90 compared with 32% (P = .008) and 37% (N.S.) at 16 months. Acceptable HbA1c levels among subjects with diabetes mellitus diagnosis increased from 35% to 45% (N.S.). Among those without diabetes diagnosis, satisfactory HbA1c levels decreased from 98% to 79% (P < .001). Underweight increased from 9% to 17% (P = .019). Among patients with cerebral infarction, the prevalence of atrial fibrillation increased from 22% to 29% (P = .004), and treatment with oral anticoagulants from 75% to 78% (N.S.). Acceptable LDL cholesterol levels increased from 59% to 80% (P = .033) among subjects on lipid lowering treatment, and from 18% to 40% among untreated (P = .010). At 10 years, 90% still lived in their own home. Health condition was reported as good/very good/excellent by 65%. Age, female sex, and living situation were associated with intensity of secondary prevention measures and underweight. CONCLUSIONS: The proportion of individuals within treatment goals improved over time, but secondary prevention still needed additional consideration 10 years after stroke.
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Prevenção Secundária/métodos , Acidente Vascular Cerebral/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Acidente Vascular Cerebral/complicaçõesRESUMO
Molybdenum is toxic to ruminants when present in high levels in forage, causing physiological copper deficiency. A critical level for ruminants is 3-10 mg Mo kg-1 dry matter. The average Mo level varies considerably between different arable soils, depending mainly on soil parent material. This study investigated the possibility of using various existing sources of geospatial information (geophysical, biogeochemical and soil chemical) to develop a geography-based risk assessment system. Forage samples (n = 173) were collected in 2006-2007. Three types of national geoscientific datasets were tested: (1) SEPA topsoil, comprising data from arable land within the Swedish environmental monitoring programme; (2) SGU biogeochemical, containing data from aquatic plant root material collected in small streams; and (3) SGU geophysical, consisting of data from airborne gamma-ray scanning. The digital postcode area map was used for geocoding, with Mo concentrations in forage assigned to arable parts of the corresponding postcode area. By combining this with the three national geoscientific databases, it was possible to construct a risk map using fuzzy classification depicting High-risk, Intermediate-risk, Low-risk and Very-low-risk areas. The map was validated using 42 randomly selected samples. All samples but one with Mo > 3 mg kg-1 were found in postcode areas designated High risk. Thus, the risk map developed seems to be useful as a decision support system on where standard forage analyses need to be supplemented with Mo analyses.
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Monitoramento Ambiental/métodos , Molibdênio/análise , Medição de Risco/métodos , Solo/químicaRESUMO
OBJECTIVES: Post-stroke cognitive impairment (PSCI) has considerable impact on patients and society. However, long-term studies on PSCI are scarce and may be influenced by assessment methods and selection bias. We aimed to (i) assess the prevalence of long-term PSCI; (ii) compare two common cognitive assessment instruments; and (iii) compare cognitive function of long-term stroke survivors with non-stroke persons. METHODS: Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were administered to 10-year survivors from a population-based cohort of first-ever stroke patients included in the Lund Stroke Register, Sweden, in 2001-2002. PSCI was defined as MMSE<27 and/or MoCA<25 and severe cognitive impairment as MMSE<23. Age- and sex-matched non-stroke control subjects who had performed MMSE (but not MoCA) were recruited from the longitudinal population study "Good Ageing in Skåne." The odds of having cognitive impairment for stroke survivors compared to controls were examined with logistic regression analyses adjusting for education. RESULTS: Of 145 stroke survivors after 10 years, 127 participated. MMSE showed PSCI in 46%, whereas MoCA displayed PSCI in 61%. Among the stroke survivors with MoCA<25, 35% had MMSE≥27 (P<.001). The odds of having severe cognitive impairment defined as MMSE<23 were higher among the stroke survivors compared to 354 controls (education-adjusted; OR=2.5; P=.004). CONCLUSIONS: Post-stroke cognitive impairment was prevalent among 10-year stroke survivors, and the odds of having severe cognitive impairment were higher among the stroke survivors compared to non-stroke persons. The burden of long-term PSCI might have been underestimated previously, and MoCA may be more suitable than MMSE to detect long-term PSCI.
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Transtornos Cognitivos/epidemiologia , Cognição , Acidente Vascular Cerebral/complicações , Idoso , Transtornos Cognitivos/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/epidemiologia , SuéciaRESUMO
BACKGROUND: In recent years, large trials have increased the level of evidence for intravenous (IV) fluid therapy, at least in the intensive care setting. It is less clear whether this change in the evidence base has been associated with changes in IV fluid use in different hospital departments. METHODS: We obtained details from the regional pharmacy regarding IV fluids issued to hospital departments in the Danish Capitol Region from January 2012 to May 2015. We used paired Wilcoxon's signed-rank test to analyse changes in the issuing in different departments. RESULTS: Total regional issuing of IV fluids showed increase in crystalloid solutions (9%; P = 0.001) and decrease in colloid solutions (59%; P = 0.005). Subtype analysis showed increased issuing of buffered crystalloids (36%; P = 0.001), human albumin (30%; P < 0.0001) and decreased issuing in synthetic colloid solutions (82%; P < 0.0001) from Q1 2012 to Q2 2015. At the departmental level, the issuing of synthetic colloid solutions decreased markedly to all settings. The issuing of buffered crystalloids increased to orthopaedic (226%; P = 0.03) and to general surgery departments (686%; P = 0.002). Albumin solutions were increasingly issued to anaesthesia departments (63%; P = 0.005) and was rarely issued to general surgery and orthopaedic departments. CONCLUSIONS: The issuing of IV fluid solutions to hospital departments has changed markedly over the last years to less colloid, in particular the synthetic solutions, and relatively more issuing of crystalloids, in particular the buffered solutions.