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1.
BMC Psychiatry ; 23(1): 920, 2023 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-38066477

RESUMO

Attention deficit hyperactivity disorder (ADHD) is the most prevalent neuropsychiatric disorder in the world. Currently, the diagnosis is based mainly on interviews, resulting in uncertainties in the clinical assessment. While some neuropsychological tests are used, their specificity and selectivity are low, and more reliable biomarkers are desirable. Previous research indicates that ADHD is associated with morphological changes in the cerebellum, which is essential for motor ability and timing. Here, we compared 29 children diagnosed with ADHD to 96 age-matched controls on prism adaptation, eyeblink conditioning, and timed motor performance in a finger tapping task. Prism adaptation and timing precision in the finger tapping task, but not performance on eyeblink conditioning, differed between the ADHD and control groups, as well as between children with and without Deficits in Attention, Motor control, and Perception (DAMP) - a more severe form of ADHD. The results suggest finger tapping can be used as a cheap, objective, and unbiased biomarker to complement current diagnostic procedures.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Criança , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Desempenho Psicomotor , Cerebelo , Testes Neuropsicológicos
2.
Neuroimage ; 237: 118095, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34000402

RESUMO

Brain activation mapping using functional magnetic resonance imaging (fMRI) has been extensively studied in brain gray matter (GM), whereas in large disregarded for probing white matter (WM). This unbalanced treatment has been in part due to controversies in relation to the nature of the blood oxygenation level-dependent (BOLD) contrast in WM and its detectability. However, an accumulating body of studies has provided solid evidence of the functional significance of the BOLD signal in WM and has revealed that it exhibits anisotropic spatio-temporal correlations and structure-specific fluctuations concomitant with those of the cortical BOLD signal. In this work, we present an anisotropic spatial filtering scheme for smoothing fMRI data in WM that accounts for known spatial constraints on the BOLD signal in WM. In particular, the spatial correlation structure of the BOLD signal in WM is highly anisotropic and closely linked to local axonal structure in terms of shape and orientation, suggesting that isotropic Gaussian filters conventionally used for smoothing fMRI data are inadequate for denoising the BOLD signal in WM. The fundamental element in the proposed method is a graph-based description of WM that encodes the underlying anisotropy observed across WM, derived from diffusion-weighted MRI data. Based on this representation, and leveraging graph signal processing principles, we design subject-specific spatial filters that adapt to a subject's unique WM structure at each position in the WM that they are applied at. We use the proposed filters to spatially smooth fMRI data in WM, as an alternative to the conventional practice of using isotropic Gaussian filters. We test the proposed filtering approach on two sets of simulated phantoms, showcasing its greater sensitivity and specificity for the detection of slender anisotropic activations, compared to that achieved with isotropic Gaussian filters. We also present WM activation mapping results on the Human Connectome Project's 100-unrelated subject dataset, across seven functional tasks, showing that the proposed method enables the detection of streamline-like activations within axonal bundles.


Assuntos
Conectoma/métodos , Imagem de Tensor de Difusão/métodos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Substância Branca , Adulto , Humanos , Modelos Teóricos , Substância Branca/anatomia & histologia , Substância Branca/diagnóstico por imagem , Substância Branca/fisiologia
3.
Cardiovasc Diabetol ; 20(1): 240, 2021 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-34937562

RESUMO

BACKGROUND: Post-stroke functional recovery is severely impaired by type 2 diabetes (T2D). This is an important clinical problem since T2D is one of the most common diseases. Because weight loss-based strategies have been shown to decrease stroke risk in people with T2D, we aimed to investigate whether diet-induced weight loss can also improve post-stroke functional recovery and identify some of the underlying mechanisms. METHODS: T2D/obesity was induced by 6 months of high-fat diet (HFD). Weight loss was achieved by a short- or long-term dietary change, replacing HFD with standard diet for 2 or 4 months, respectively. Stroke was induced by middle cerebral artery occlusion and post-stroke recovery was assessed by sensorimotor tests. Mechanisms involved in neurovascular damage in the post-stroke recovery phase, i.e. neuroinflammation, impaired angiogenesis and cellular atrophy of GABAergic parvalbumin (PV)+ interneurons were assessed by immunohistochemistry/quantitative microscopy. RESULTS: Both short- and long-term dietary change led to similar weight loss. However, only the latter enhanced functional recovery after stroke. This effect was associated with pre-stroke normalization of fasting glucose and insulin resistance, and with the reduction of T2D-induced cellular atrophy of PV+ interneurons. Moreover, stroke recovery was associated with decreased T2D-induced neuroinflammation and reduced astrocyte reactivity in the contralateral striatum. CONCLUSION: The global diabetes epidemic will dramatically increase the number of people in need of post-stroke treatment and care. Our results suggest that diet-induced weight loss leading to pre-stroke normalization of glucose metabolism has great potential to reduce the sequelae of stroke in the diabetic population.


Assuntos
Glicemia/metabolismo , Encéfalo/fisiopatologia , Diabetes Mellitus Tipo 2/dietoterapia , Infarto da Artéria Cerebral Média/dietoterapia , Obesidade/dietoterapia , Acidente Vascular Cerebral/dietoterapia , Redução de Peso , Animais , Comportamento Animal , Biomarcadores/sangue , Encéfalo/metabolismo , Encéfalo/patologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Dieta Hiperlipídica , Modelos Animais de Doenças , Controle Glicêmico , Infarto da Artéria Cerebral Média/sangue , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Obesidade/sangue , Obesidade/fisiopatologia , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/fisiopatologia , Fatores de Tempo
4.
Cardiovasc Diabetol ; 18(1): 91, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307484

RESUMO

BACKGROUND: Glucagon-like peptide-1 (GLP-1) treatment has been shown to reduce stroke incidence in diabetes and also to be neuroprotective in experimental stroke models. The prognostic value of endogenous levels of GLP-1 in the recovery phase after stroke remains to be elucidated. The aim of the study was to investigate the potential association between GLP-1 levels and functional outcome after stroke and to determine whether GLP-1 is altered in the acute phase of stroke compared to 3 months post stroke and to healthy controls. METHODS: Fasting GLP-1 was measured on hospital day 2-4 in patients without previously known diabetes (n = 59) that received recombinant tissue plasminogen activator (rtPA) for ischemic stroke. Fasting GLP-1 was measured again after 3 months and neurologic outcome was measured as modified Rankin Scale (mRS). mRS ≥ 2 was considered as unfavorable outcome. A control group of healthy individuals (n = 27) was recruited and their fasting GLP-1 was measured. RESULTS: Fasting GLP-1 was higher in the patients that suffered a stroke compared to healthy controls (25.1 vs. 18.0 pmol/L; p = 0.004). The GLP-1 levels did not change significantly at the 3-month follow up OGTT (25.8 vs. 25.6; p = 0.80). There was no significant association between GLP-1 levels and unfavorable mRS (OR 1.03, 95% CI 0.95-1.12, p = 0.50). CONCLUSIONS: Endogenous GLP-1 levels in patients that recently suffered an ischemic stroke are higher than in healthy controls and remained unchanged at the 3 months follow-up, possibly indicating an elevation of the levels of GLP-1 already pre-stroke. However, no association between endogenous GLP-1 and functional outcome of stroke 3 months post stroke was found.


Assuntos
Isquemia Encefálica/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Acidente Vascular Cerebral/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/fisiopatologia , Estudos de Casos e Controles , Avaliação da Deficiência , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/fisiopatologia , Terapia Trombolítica , Fatores de Tempo , Ativador de Plasminogênio Tecidual/uso terapêutico , Regulação para Cima
5.
Acta Neurol Scand ; 140(6): 443-448, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31518433

RESUMO

OBJECTIVES: Hyperglycemia is a predictor for poor stroke outcome. Hyperglycemic stroke patients treated with thrombolysis have an increased risk of intracranial hemorrhage. Insulin is the gold standard for treating hyperglycemia but comes with a risk of hypoglycemia. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are drugs used in type 2 diabetes that have a low risk of hypoglycemia and have been shown to exert neuroprotective effects. The primary objective was to determine whether prehospital administration of the GLP-1RA exenatide could lower plasma glucose in stroke patients. Secondary objective was to study tolerability and safety. MATERIALS & METHODS: Randomized controlled trial comparing exenatide administrated prehospitally with a control group receiving standard care for hyperglycemia. Patients with Face Arm Speech Test ≥1 and glucose ≥8 mmol/L were randomized. Glucose was monitored for 24 hours. All adverse events were recorded. RESULTS: Nineteen patients were randomized, eight received exenatide. An interim recruitment failure analysis with subsequent changes of the protocol was made. The study was stopped prematurely due to slow inclusion. No difference was observed in the main outcome of plasma glucose at 4 hours, control vs exenatide (mean, SD); 7.0 ± 1.9 vs 7.6 ± 1.6; P = .56). No major adverse events were reported. CONCLUSIONS: We found no evidence that prehospital exenatide had effect on hyperglycemia. However, it was given without adverse events in this study with limited sample size that was prematurely stopped due to slow inclusion.


Assuntos
Glicemia/efeitos dos fármacos , Exenatida/administração & dosagem , Hiperglicemia/prevenção & controle , Hipoglicemiantes/administração & dosagem , Acidente Vascular Cerebral/sangue , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hiperglicemia/complicações , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações
6.
FASEB J ; 31(8): 3288-3297, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28404742

RESUMO

A single bout of low-frequency electroacupuncture (EA) causing muscle contractions increases whole-body glucose uptake in insulin-resistant rats. We explored the underlying mechanism of this finding and whether it can be translated into clinical settings. Changes in glucose infusion rate (GIR) were measured by euglycemic-hyperinsulinemic clamp during and after 45 min of low-frequency EA in 21 overweight/obese women with polycystic ovary syndrome (PCOS) and 21 controls matched for age, weight, and body mass index (experiment 1) and in rats receiving autonomic receptor blockers (experiment 2). GIR was higher after EA in controls and women with PCOS. Plasma serotonin levels and homovanillic acid, markers of vagal activity, decreased in both controls and patients with PCOS. Adipose tissue expression of pro-nerve growth factor (proNGF) decreased, and the mature NGF/proNGF ratio increased after EA in PCOS, but not in controls, suggesting increased sympathetic-driven adipose tissue metabolism. Administration of α-/ß-adrenergic receptor blockers in rats blocked the increase in GIR in response to EA. Muscarinic and dopamine receptor antagonist also blocked the response but with slower onset. In conclusion, a single bout of EA increases whole-body glucose uptake by activation of the sympathetic and partly the parasympathetic nervous systems, which could have important clinical implications for the treatment of insulin resistance.-Benrick, A., Kokosar, M., Hu, M., Larsson, M., Maliqueo, M., Marcondes, R. R., Soligo, M., Protto, V., Jerlhag, E., Sazonova, A., Behre, C. J., Højlund, K., Thorén, P., Stener-Victorin, E. Autonomic nervous system activation mediates the increase in whole-body glucose uptake in response to electroacupuncture.


Assuntos
Sistema Nervoso Autônomo/fisiologia , Glicemia , Eletroacupuntura , Glucose/metabolismo , Antagonistas Adrenérgicos alfa/farmacologia , Adulto , Animais , Antagonistas de Dopamina/farmacologia , Feminino , Técnica Clamp de Glucose , Humanos , Antagonistas Muscarínicos/farmacologia , Antagonistas de Entorpecentes/farmacologia , Síndrome do Ovário Policístico/metabolismo , Ratos , Adulto Jovem
7.
EJNMMI Res ; 14(1): 13, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38319478

RESUMO

BACKGROUND: Peptide receptor radionuclide therapy is effective in treating neuroendocrine tumours, but treatment may be limited by kidney and bone marrow toxicity. In this work, the absorbed dose burden to the bone marrow was estimated using image-based dosimetry and its potential use for predicting treatment-altering toxicity was studied. Peripheral blood samples taken before and after 229 treatments with 177Lu-DOTATATE in 59 patients were studied. In connection to the treatments, a total of 940 blood sample occasions provided data on white blood cell, neutrophil granulocyte, platelet, erythrocyte and haemoglobin concentrations. SPECT/CT image data were collected at two or three time points after each treatment. Absorbed doses to bone marrow were calculated from the activity concentration in a metastasis-free lumbar vertebra. The rate of delayed and aborted treatments was analysed based on medical records. RESULTS: The average absorbed dose to the bone marrow was 0.42 Gy (median 0.33 Gy, SD 0.27 Gy) per treatment. Dose-response relationships between white blood cells, neutrophil granulocytes and haemoglobin concentrations were observed, most prominently at 31-45 days after each treatment. The correlations were stronger in patients with skeletal metastases. The rates of haematological toxicity-related delays and aborted treatments were 6% and 12%, respectively. None of the studied bone marrow dosimetric parameters could clearly predict treatment-related toxicity. However, patients with skeletal metastases had higher risk of treatment-altering toxicity (odds ratio = 6.0). CONCLUSIONS: Treatment-altering haematological toxicity in peptide receptor radionuclide therapy is relatively rare and appears difficult to fully predict from post-therapeutic image-based dosimetry. However, for patients with skeletal metastases, the haematological dose-response relationships are stronger. Future studies may focus on this patient group, to further investigate the usefulness of dosimetry in predicting decreases in blood values.

8.
Genome Biol Evol ; 16(6)2024 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-38795367

RESUMO

Sheep are among the earliest domesticated livestock species, with a wide variety of breeds present today. However, it remains unclear how far back this diversity goes, with formal documentation only dating back a few centuries. North European short-tailed (NEST) breeds are often assumed to be among the oldest domestic sheep populations, even thought to represent relicts of the earliest sheep expansions during the Neolithic period reaching Scandinavia <6,000 years ago. This study sequenced the genomes (up to 11.6X) of five sheep remains from the Baltic islands of Gotland and Åland, dating from the Late Neolithic (∼4,100 cal BP) to historical times (∼1,600 CE). Our findings indicate that these ancient sheep largely possessed the genetic characteristics of modern NEST breeds, suggesting a substantial degree of long-term continuity of this sheep type in the Baltic Sea region. Despite the wide temporal spread, population genetic analyses show high levels of affinity between the ancient genomes and they also exhibit relatively high genetic diversity when compared to modern NEST breeds, implying a loss of diversity in most breeds during the last centuries associated with breed formation and recent bottlenecks. Our results shed light on the development of breeds in Northern Europe specifically as well as the development of genetic diversity in sheep breeds, and their expansion from the domestication center in general.


Assuntos
Genoma , Animais , Ovinos/genética , Variação Genética , Carneiro Doméstico/genética , DNA Antigo/análise
10.
Endocrine ; 79(3): 455-458, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36374446

RESUMO

CONTEXT: Diclofenac is commonly used as pain relief. Hypoglycemia has rarely been reported due to aspirin and indomethacin use but not of any other nonsteroidal anti-inflammatory drugs. CASE REPORT: A 69-years old endocrinologist participated as a control in a glucagon-like peptide-1 (GLP-1) study. He decreased his plasma glucose to 1.8 mmol/L and developed full-blown hypoglycemic symptoms during an oral glucose tolerance test (OGTT). He had taken a 50 mg diclofenac tablet at 10 pm the evening before for a harmless muscle stretch in the lower back. Apart from well-controlled hypothyroidism he was healthy. During medical school he often had reactive hypoglycemia which came after intake of a carbohydrate rich but otherwise poor breakfast followed by bicycling. However, he had never experienced problems later in life after more decent meals containing slower absorbable carbohydrates. A 3-day continuous glucose monitoring (CGM) was performed three weeks after the OGTT test. A glucose value of 3.1 mmol/L was registered on the third CGM day in the afternoon after intake of 500 mg aspirin in the early morning the same day. Otherwise, all values were normal. A second OGGT where no medications apart from levothyroxine had been taken during at least a 2-week period adjacent was normal. Detailed analyses of the OGTTs showed that the GLP-1 levels before the test were higher after diclofenac exposure while the insulin levels increased after the glucose challenge which suggesting uncoupling. CONCLUSION: With this case report we would like to draw attention to that diclofenac may cause hypoglycemia.


Assuntos
Glicemia , Hipoglicemia , Masculino , Humanos , Idoso , Glicemia/análise , Diclofenaco/efeitos adversos , Insulina , Automonitorização da Glicemia , Hipoglicemia/induzido quimicamente , Glucose , Peptídeo 1 Semelhante ao Glucagon
11.
BMJ Open ; 13(2): e064374, 2023 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-36813503

RESUMO

OBJECTIVE: To assess the efficacy of inhaled ciclesonide in reducing the duration of oxygen therapy (an indicator of time to clinical improvement) among adults hospitalised with COVID-19. DESIGN: Multicentre, randomised, controlled, open-label trial. SETTING: 9 hospitals (3 academic hospitals and 6 non-academic hospitals) in Sweden between 1 June 2020 and 17 May 2021. PARTICIPANTS: Adults hospitalised with COVID-19 and receiving oxygen therapy. INTERVENTION: Inhaled ciclesonide 320 µg two times a day for 14 days versus standard care. MAIN OUTCOME MEASURES: Primary outcome was duration of oxygen therapy, an indicator of time to clinical improvement. Key secondary outcome was a composite of invasive mechanical ventilation/death. RESULTS: Data from 98 participants were analysed (48 receiving ciclesonide and 50 receiving standard care; median (IQR) age, 59.5 (49-67) years; 67 (68%) men). Median (IQR) duration of oxygen therapy was 5.5 (3-9) days in the ciclesonide group and 4 (2-7) days in the standard care group (HR for termination of oxygen therapy 0.73 (95% CI 0.47 to 1.11), with the upper 95% CI being compatible with a 10% relative reduction in oxygen therapy duration, corresponding to a <1 day absolute reduction in a post-hoc calculation). Three participants in each group died/received invasive mechanical ventilation (HR 0.90 (95% CI 0.15 to 5.32)). The trial was discontinued early due to slow enrolment. CONCLUSIONS: In patients hospitalised with COVID-19 receiving oxygen therapy, this trial ruled out, with 0.95 confidence, a treatment effect of ciclesonide corresponding to more than a 1 day reduction in duration of oxygen therapy. Ciclesonide is unlikely to improve this outcome meaningfully. TRIAL REGISTRATION NUMBER: NCT04381364.


Assuntos
COVID-19 , Pregnenodionas , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Feminino , SARS-CoV-2 , Oxigênio , Resultado do Tratamento
12.
Front Med (Lausanne) ; 9: 954033, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36111117

RESUMO

Introduction: Ectopic Cushing's syndrome (ECS) is an uncommon disorder. Recently, however, a larger proportion of patients with endogenous Cushing's syndrome (CS) had ECS than has previously been reported. Objective: The aim of this study was to determine whether ECS is an underdiagnosed disorder in patients with small-cell lung cancer (SCLC). Materials and methods: Medical records from consecutive patients diagnosed with SCLC at our hospital between 2013 and 2019 were reviewed (N = 213; mean age 69.5 ± 9 years; range, 36-89 years). The probability of having ECS was evaluated by review of biochemical and clinical features, including presence of recent onset diabetes mellitus, therapy resistant hypertension and/or spontaneous hypokalaemia. Results: Of 213 identified patients with SCLC, one (0.5%) patient had confirmed ECS, two (1%) patients had probable ECS, and twenty-three (11%) patients had possibly ECS. Patients with SCLC and possibly or probable ECS exhibited a significantly shorter survival than patients only with SCLC (8 vs. 14 months, respectively). Conclusions: Our findings indicate that ECS is underdiagnosed in patients with SCLC. Given the serious consequences of untreated ECS, the low detection rate highlights the need to improve endocrine work-up of patients with SCLC who present with biochemical and clinical features associated with ECS. Prospective studies are needed to establish a reliable assessment of the incidence of ECS and to optimise early detection strategies.

13.
Br J Pharmacol ; 179(4): 677-694, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33973246

RESUMO

BACKGROUND AND PURPOSE: Glucagon-like peptide-1 (GLP-1) receptor activation decreases stroke risk in people with Type 2 diabetes (T2D), while animal studies have shown the efficacy of this strategy to counteract stroke-induced acute brain damage. However, whether GLP-1 receptor activation also improves recovery in the chronic phase after stroke is unknown. We investigated whether post-acute, chronic administration of the GLP-1 receptor agonist, exendin-4, improves post-stroke recovery and examined possible underlying mechanisms in T2D and non-T2D mice. EXPERIMENTAL APPROACH: We induced stroke via transient middle cerebral artery occlusion (tMCAO) in T2D/obese mice (8 months of high-fat diet) and age-matched controls. Exendin-4 was administered for 8 weeks from Day 3 post-tMCAO. We assessed functional recovery by weekly upper-limb grip strength tests. Insulin sensitivity and glycaemia were evaluated at 4 and 8 weeks post-tMCAO. Neuronal survival, stroke-induced neurogenesis, neuroinflammation, atrophy of GABAergic parvalbumin+ interneurons, post-stroke vascular remodelling and fibrotic scar formation were investigated by immunohistochemistry. KEY RESULTS: Exendin-4 normalised T2D-induced impairment of forepaw grip strength recovery in correlation with normalised glycaemia and insulin sensitivity. Moreover, exendin-4 counteracted T2D-induced atrophy of parvalbumin+ interneurons and decreased microglia activation. Finally, exendin-4 normalised density and pericyte coverage of micro-vessels and restored fibrotic scar formation in T2D mice. In non-T2D mice, the exendin-4-mediated recovery was minor. CONCLUSION AND IMPLICATIONS: Chronic GLP-1 receptor activation mediates post-stroke functional recovery in T2D mice by normalising glucose metabolism and improving neuroplasticity and vascular remodelling in the recovery phase. The results warrant clinical trial of GLP-1 receptor agonists for rehabilitation after stroke in T2D. LINKED ARTICLES: This article is part of a themed issue on GLP1 receptor ligands (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.4/issuetoc.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Acidente Vascular Cerebral , Animais , Atrofia , Glicemia , Cicatriz , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Exenatida/farmacologia , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/metabolismo , Masculino , Camundongos , Parvalbuminas/metabolismo , Acidente Vascular Cerebral/tratamento farmacológico , Remodelação Vascular
14.
Environ Pollut ; 289: 117828, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34358872

RESUMO

Some of the older Swedish roads contain road tar underneath a surface layer of bituminous asphalt. This road tar, also known as tar asphalt, contains large amounts of polycyclic aromatic hydrocarbons (PAHs). There is concern about PAHs spreading from the bottom layers of these older roads to the surrounding environment, and that because of this spreading road tar asphalt should not be recycled but rather placed in landfills. However, a risk assessment of PAH spreading below roads has not yet been conducted. The first aim of this study was to assess this potential spreading of PAHs from underlying tar asphalt to the sand beneath, the soil next to the roads, as well as nearby groundwater. The second aim was to measure the bioavailability and estimate the toxicity of PAHs in all relevant media using polyoxymethylene (POM) passive samplers. Four road sections and nearby groundwater in northern Sweden were investigated, including a control road without tar asphalt. PAHs were detected in all analysed solid media at varying concentrations: in asphalt from 2.3 to 4800 mg kg-1, in underlying sand from <1.5 to 460 mg kg-1 and in slope soil from <1.5 to 36 mg kg-1. However, the spread of PAHs from the asphalt to roadside soil and groundwater was very limited. Groundwater at most of the road sections contained very low or non-detectable levels of PAHs (<0.08-0.53 µg L-1, excluding one site where fuel contamination is hypothesized). The PAHs generally showed low bioavailability. Only asphalt with PAH content >1200 mg kg-1 exhibited bioavailable concentrations that exceeded threshold concentrations for serious risk. The most PAH contaminated sand and soil samples exhibited low toxicity when considering bioavailability, only in some cases exceeding chronic toxicity threshold concentrations. These results were compared with the Swedish EPA's guideline values for PAH in contaminated soil, which is shown to overpredict toxicity for these sites. Further research on the leaching and transportation processes of PAHs from subsurface tar asphalt is recommended for developing risk analysis approaches.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Poluentes do Solo , Disponibilidade Biológica , Hidrocarbonetos/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Poluentes do Solo/análise , Poluentes do Solo/toxicidade
16.
Eur J Epidemiol ; 25(6): 431-7, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20449637

RESUMO

National Longitudinal data of thoracolumbar fracture incidence, trends or mortality rates are lacking. The correlation between admissions and operations of thoracolumbar vertebral fractures has not been investigated. The aim of our nationwide population-based epidemiological study was to analyse the incidence, admissions, operations, and case fatality rate among patients with thoracolumbar vertebral fractures admitted to hospital in Sweden. The Swedish Hospital Discharge Register (SHDR) and the Cause of Death Register (CDR) were linked to determine the incidence of surgical interventions, trends, characteristics of the patients, and case fatality rate for thoracolumbar vertebral fractures based on comprehensive national data. The annual incidence of thoracolumbar fractures was on average 30 per 100,000 inhabitants and did not change considerably during the study period. Among patients younger than 60 years of age the annual incidence was 13 per 100,000 and was twice as high in men compared to women. The proportion operated on was 15%. In the age-group 60 years and older the majority were women. In this group two percent were operated on. However, males were operated on twice as often as women. The 90-day case-fatality rate after surgery was 1.4%. This information may assist health care providers in health care planning. Moreover, these data can also be used for power calculations when planning future clinical studies.


Assuntos
Vértebras Lombares/lesões , Fraturas da Coluna Vertebral/epidemiologia , Vértebras Torácicas/lesões , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Estudos Longitudinais , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Admissão do Paciente/estatística & dados numéricos , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/cirurgia , Análise de Sobrevida , Suécia/epidemiologia , Vértebras Torácicas/cirurgia , Adulto Jovem
17.
Diabetes ; 69(9): 1961-1973, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32540876

RESUMO

The interplay between obesity and type 2 diabetes (T2D) in poststroke recovery is unclear. Moreover, the impact of glucose control during the chronic phase after stroke is undetermined. We investigated whether obesity-induced T2D impairs neurological recovery after stroke by using a clinically relevant experimental design. We also investigated the potential efficacy of two clinically used T2D drugs: the dipeptidyl peptidase 4 inhibitor linagliptin and the sulfonylurea glimepiride. We induced transient middle cerebral artery occlusion (tMCAO) in T2D/obese mice (after 7 months of high-fat diet [HFD]) and age-matched controls. After stroke, we replaced HFD with standard diet for 8 weeks to mimic the poststroke clinical situation. Linagliptin or glimepiride were administered daily from 3 days after tMCAO for 8 weeks. We assessed neurological recovery weekly by upper-limb grip strength. Brain damage, neuroinflammation, stroke-induced neurogenesis, and atrophy of parvalbumin-positive (PV+) interneurons were quantified by immunohistochemistry. T2D/obesity impaired poststroke neurological recovery in association with hyperglycemia, neuroinflammation, and atrophy of PV+ interneurons. Both drugs counteracted these effects. In nondiabetic mice, only linagliptin accelerated recovery. These findings shed light on the interplay between obesity and T2D in stroke recovery. Moreover, they promote the use of rehabilitative strategies that are based on efficacious glycemia regulation, even if initiated days after stroke.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 2/complicações , Infarto da Artéria Cerebral Média/complicações , Obesidade/complicações , Recuperação de Função Fisiológica/efeitos dos fármacos , Acidente Vascular Cerebral/complicações , Animais , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dieta , Modelos Animais de Doenças , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Infarto da Artéria Cerebral Média/sangue , Infarto da Artéria Cerebral Média/tratamento farmacológico , Linagliptina/farmacologia , Linagliptina/uso terapêutico , Masculino , Camundongos , Obesidade/sangue , Obesidade/tratamento farmacológico , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/tratamento farmacológico , Compostos de Sulfonilureia/farmacologia , Compostos de Sulfonilureia/uso terapêutico , Resultado do Tratamento
18.
Food Chem Toxicol ; 111: 207-267, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29155356

RESUMO

Relatively few studies are available on realistic cumulative risk assessments for dietary pesticide exposure. Despite available studies showing low risk, public concern remains. A method to estimate realistic residue levels based on information from spraying journals and supervised residue trials was described in a previous publication. The present article proposes a new method to estimate average residue levels in imported foods based on residue monitoring data and knowledge about agronomic practices. The two methods were used in combination to estimate average pesticide residue levels in 47 commodities on the Danish market. The chronic consumer exposure was estimated in six Danish diets. The Hazard Index (HI) method was used to assess consumer risk. Despite the conservative (cautious) risk assessment approach, low HI values where obtained. The HI was 16% for adults and 44% for children, combining the risk of all pesticides in the diet. CONCLUSION: the present study adds support to the evidence showing that adverse health effects of chronic pesticide residue exposure in the Danish population are very unlikely. The HI for pesticides for a Danish adult was on level with that of alcohol for a person consuming the equivalent of 1 glass of wine every seventh year.


Assuntos
Exposição Dietética , Contaminação de Alimentos , Frutas/química , Resíduos de Praguicidas/toxicidade , Verduras/química , Adulto , Criança , Produtos Agrícolas , Dinamarca , Dieta , Análise de Alimentos , Humanos , Resíduos de Praguicidas/química , Fatores de Risco
19.
BMJ Open ; 7(10): e016311, 2017 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-29084788

RESUMO

OBJECTIVES: Acute stroke management has changed dramatically over the recent years, where a timely assessment is driven by the expanding treatment options of acute ischaemic stroke. This increases the risk in treating non-stroke patients (stroke mimics) with a possibly hazardous intravenous thrombolysis treatment (IVT). SETTING: Patients of the thrombolysis registry of Södersjukhuset AB, a secondary health centre in Stockholm, were retrospectively studied to determine complications and outcome after IVT in strokes and stroke mimics. PARTICIPANTS: Consecutively, 674 recruited patients from 1 January 2008 to 1 December 2013 were analysed regarding demographics and outcome at 3 months after onset of symptoms. RESULTS: Ischaemic stroke was confirmed in 625 patients (93%), and 48 patients (7%) were stroke mimics. Patients with strokes were older than stroke mimics 72 (IQR: 64-81) vs 54 years (IQR 40-67), p<0.0001. Antihypertensive and antithrombotic treatment were more common in patients with stroke (p<0.0001 and p=0.006, respectively). National Institute of Health Stroke Scale did not differ at time of presentation. Excellent outcome defined as modified Rankin Scale score 0-1, at 3 months, was less common in stroke than in stroke mimics (50% vs 87.5%, p<0.0001). No stroke mimic had a symptomatic intracerebral haemorrhage. Age of less than 40 years may be a predictor for a patient to be a stroke mimic (OR: 8.7, 95% CI: 3.2 to 24.0, p<0.0001). CONCLUSIONS: Stroke mimics receiving IVT had a more favourable outcome compared with patients with stroke, and showed no haemorrhagic complications. Age below 40 years may be a predictor for stroke mimics.


Assuntos
Isquemia Encefálica/terapia , Fibrinolíticos , Acidente Vascular Cerebral/terapia , Terapia Trombolítica/efeitos adversos , Administração Intravenosa , Adulto , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/epidemiologia , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/etiologia , Estudos de Coortes , Diagnóstico Diferencial , Feminino , Fibrinólise , Fibrinolíticos/efeitos adversos , Fibrinolíticos/uso terapêutico , Hospitais de Ensino , Hospitais Urbanos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Sistema de Registros , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Suécia/epidemiologia , Resultado do Tratamento
20.
Food Chem Toxicol ; 105: 407-428, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28499824

RESUMO

Relatively few studies are available on the combined risk of realistic dietary pesticide exposure. Despite available studies showing low risk, public concern remains. Recent methods used to estimate realistic exposure levels have a number of drawbacks, and better methods are needed. Using a novel approach, we estimated the combined exposure in the Danish population, resulting from pesticide usage in Danish agriculture. The complete Danish spraying journal data from 2014, and supervised trial residue levels reported by EFSA, were used in combination, generating residue estimates in 25 crops. Cumulative risk assessments were made for six typical Danish consumer diets. In terms of intake of cereals, sugar, fruits and vegetables, the 25 crops included accounted 70% of the diets of Danish consumers. The Hazard Index (HI) method was used to assess the consumer risk. Despite the conservative (cautious) approach, low HI values where obtained. Highest HI was 14% of the Acceptable Daily Intake (ADI) for Children. The main advantages of the new exposure estimation method are 1) comprehensive use data not relying on random samples, 2) coverage of all pesticides used, and 3) more precise estimates of residues that are below the standard reporting limits in the national monitoring program.


Assuntos
Produtos Agrícolas/química , Contaminação de Alimentos/análise , Resíduos de Praguicidas/análise , Adolescente , Adulto , Idoso , Qualidade de Produtos para o Consumidor , Dinamarca , Dieta , Humanos , Pessoa de Meia-Idade , Resíduos de Praguicidas/metabolismo , Resíduos de Praguicidas/toxicidade , Adulto Jovem
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