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1.
J Environ Manage ; 299: 113658, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34523536

RESUMO

Spatial planning of Blue-Green Infrastructure (BGI) should ideally be based on well-evaluated and context specific solutions. One important obstacle to reach this goal relates to adequate provisioning of data to ensure good governance of BGI, i.e., appropriate planning, design, construction, and maintenance. This study explores the gap between data availability and implementation of BGI in urban planning authorities in Sweden. A multi method approach including brainstorming, semi-structured interviews with urban planners and experts on BGI and Geographical Information System (GIS), and validating workshops were performed to develop a framework for structured and user-friendly data collection and use. Identified challenges concern data availability, data management, and GIS knowledge. There is a need to improve the organisation of data management and the skills of trans-disciplinary cooperation to better understand and interpret different types of data. Moreover, different strategic goals require different data to ensure efficient planning of BGI. This calls for closer interactions between development of strategic political goals and data collection. The data management framework consists of three parts: A) Ideal structure of data management in relation to planning process, data infrastructure and organisational structure, and B) A generic list of data needed, and C) The development of structures for data gathering and access. We conclude that it is essential to develop pan-municipal data management systems that bridge sectors and disciplines to ensure efficient management of the urban environment, and which is able to support the involvement of citizens to collect and access relevant data. The framework can assist in such development.


Assuntos
Planejamento de Cidades , Gerenciamento de Dados , Organizações , Planejamento Estratégico , Suécia
2.
Br J Surg ; 106(12): 1623-1631, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31386195

RESUMO

BACKGROUND: Paediatric surgical care is increasingly being centralized away from low-volume centres, and prehospital delay is considered a risk factor for more complicated appendicitis. The aim of this study was to determine the incidence of paediatric appendicitis in Sweden, and to assess whether distance to the hospital was a risk factor for complicated disease. METHODS: A nationwide cohort study of all paediatric appendicitis cases in Sweden, 2001-2014, was undertaken, including incidence of disease in different population strata, with trends over time. The risk of complicated disease was determined by regression methods, with travel time as the primary exposure and individual-level socioeconomic determinants as independent variables. RESULTS: Some 38 939 children with appendicitis were identified. Of these, 16·8 per cent had complicated disease, and the estimated risk of paediatric appendicitis by age 18 years was 2·5 per cent. Travel time to the treating hospital was not associated with complicated disease (adjusted odds ratio (OR) 1·00 (95 per cent c.i. 0·96 to 1·05) per 30-min increase; P = 0·934). Level of education (P = 0·177) and family income (P = 0·120) were not independently associated with increased risk of complicated disease. Parental unemployment (adjusted OR 1·17, 95 per cent c.i. 1·05 to 1·32; P = 0·006) and having parents born outside Sweden (1 parent born in Sweden: adjusted OR 1·12, 1·01 to 1·25; both parents born outside Sweden: adjusted OR 1·32, 1·18 to 1·47; P < 0·001) were associated with an increased risk of complicated appendicitis. CONCLUSION: Every sixth child diagnosed with appendicitis in Sweden has a more complicated course of disease. Geographical distance to the surgical facility was not a risk factor for complicated appendicitis.


ANTECEDENTES: La atención quirúrgica pediátrica está cada vez más centralizada lejos de los centros de bajo volumen, y el retraso pre-hospitalario se considera un factor de riesgo para las apendicitis más complicadas. El objetivo de este estudio fue determinar la incidencia de apendicitis pediátrica en Suecia y evaluar si la distancia al hospital era un factor de riesgo para una enfermedad complicada. MÉTODOS: Se analizó un estudio de cohortes a nivel nacional que incluyó todos los casos de apendicitis pediátrica en Suecia durante el periodo 2001-2014, incluida la incidencia de la enfermedad en diferentes estratos de la población y las tendencias a lo largo del tiempo. El riesgo de enfermedad complicada se determinó mediante métodos de regresión, con el tiempo de viaje como exposición primaria y los determinantes socioeconómicos a nivel individual como variables independientes. RESULTADOS: Se identificaron 38.939 casos de apendicitis pediátrica. De estos, el 17% eran complicados y el riesgo estimado de apendicitis pediátrica a los 18 años era del 2,5%. El tiempo de viaje al hospital de tratamiento no se asoció con una enfermedad complicada (razón de oportunidades, odds ratio OR ajustada 1,00 (i.c. del 95%: 0,96 a 1,05) por aumentos de 30 minutos, P = 0,93). El nivel de educación (P = 0,18) y los ingresos familiares (P = 0,120) no se asociaron de forma independiente con un aumento del riesgo de enfermedad complicada. El desempleo de los padres (OR ajustada 1,17 (1,05 a 1,32), P = 0,006) y tener padres nacidos fuera de Suecia se asociaron con un mayor riesgo de apendicitis complicada (P < 0,001; un progenitor nacido en Suecia: OR ajustada 1,12 (1,01 a 1,25), ambos progenitores nacidos fuera de Suecia: OR ajustada 1,32 (1,18 a 1,47)). CONCLUSIÓN: Uno de cada seis niños diagnosticados de apendicitis en Suecia sufre un curso de enfermedad más complicado. La distancia geográfica al hospital donde se llevó a cabo la cirugía no fue un factor de riesgo para la apendicitis complicada.


Assuntos
Apendicite/epidemiologia , Apendicite/cirurgia , Acessibilidade aos Serviços de Saúde , Adolescente , Distribuição por Idade , Apendicite/complicações , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Fatores de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Fatores Socioeconômicos , Suécia/epidemiologia , Tempo para o Tratamento
3.
J Environ Manage ; 240: 47-56, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30928794

RESUMO

This study focuses on drivers for changing urban flood risk. We suggest a framework for guiding climate change adaptation action concerning flood risk and manageability in cities. The identified key drivers of changing flood hazard and vulnerability are used to provide an overview of each driver's impact on flood risk and manageability at the city level. We find that identified drivers for urban flood risk can be grouped in three different priority areas with different time horizon. The first group has high impact but is manageable at city level. Typical drivers in this group are related to the physical environment such as decreasing permeability and unresponsive engineering. The second group of drivers is represented by public awareness and individual willingness to participate and urbanization and urban sprawl. These drivers may be important and are manageable for the cities and they involve both short-term and long-term measures. The third group of drivers is related to policy and long-term changes. This group is represented by economic growth and increasing values at risk, climate change, and increasing complexity of society. They have all high impact but low manageability. Managing these drivers needs to be done in a longer time perspective, e.g., by developing long-term policies and exchange of ideas.


Assuntos
Mudança Climática , Inundações , Cidades , Meio Ambiente , Urbanização
4.
Opt Express ; 26(26): 33930-33941, 2018 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-30650824

RESUMO

X-ray phase-contrast imaging allows for non-invasive analysis in low-absorbing materials, such as soft tissue. Its application in medical or materials science has yet to be realized on a wider scale due to the requirements on the X-ray source, demanding high flux and small source size. Laser wakefield accelerators generate betatron X-rays fulfilling these criteria and can be suitable sources for phase-contrast imaging. In this work, we present the first phase-contrast images obtained by using ionization injection-based laser wakefield acceleration, which results in a higher photon yield and smoother X-ray beam profile compared to self-injection. A peak photon yield of 1.9 × 1011 ph/sr and a source size of 3 µm were estimated. Furthermore, the current laser parameters produce an X-ray spectrum mainly in the soft X-ray range, in which laser-plasma based phase-contrast imaging had yet to be studied. The phase-contrast images of a Chrysopa lacewing resolve features on the order of 4 µm. These images are further used for a tomographic reconstruction and a volume rendering, showing details on the order of tens of µm.

5.
Eur J Neurol ; 25(11): 1326-1332, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29924461

RESUMO

BACKGROUND AND PURPOSE: External counterpulsation improves cerebral perfusion velocity in acute stroke and may stimulate collateral artery growth. However, whether (non-acute) at-risk patients with high-grade carotid artery disease may benefit from counterpulsation needs to be validated. METHODS: Twenty-eight patients (71 ± 6.5 years, five women) with asymptomatic unilateral chronic severe internal carotid artery stenosis (>70%) or occlusion were randomized to receive 20 min active counterpulsation followed by sham treatment or vice versa. Cerebral blood flow velocity (CBFV) (measured bilaterally by transcranial middle cerebral artery Doppler), tissue oxygenation index (TOI) (measured over the bilateral prefrontal cortex by near-infrared spectroscopy) and cerebral hemodynamic parameters, such as relative pulse slope index (RPSI), were monitored. RESULTS: Ipsilateral mean CBFV (ΔVmean +3.5 ± 1.2 cm/s) and tissue oxygenation (ΔTOI +2.86 ± 0.8) increased significantly during active counterpulsation compared to baseline, whilst the sham had little effect (ΔVmean +1.13 ± 1.1 cm/s; ΔTOI +1.25 ± 0.65). On contralateral sides, neither counterpulsation nor sham control had any effect on either parameter. During counterpulsation, early dynamic changes in ΔRPSI of the ipsilateral CBFV signal predicted improved tissue oxygenation during counterpulsation (odds ratio 1.179, 95% confidence interval 1.01-1.51), whilst baseline cerebrovascular reactivity to hypercapnia failed to show an association. CONCLUSIONS: In patients with high-grade carotid disease, ipsilateral cerebral oxygenation and blood flow velocity are increased by counterpulsation. This is a necessary condition for the stimulation of regenerative collateral artery growth and thus a therapeutic concept for the prevention of cerebral ischaemia. This study provides a rationale for further clinical investigations on the long-term effects of counterpulsation on cerebral hemodynamics and collateral growth.


Assuntos
Circulação Cerebrovascular/fisiologia , Transtornos Cerebrovasculares/terapia , Contrapulsação , Idoso , Velocidade do Fluxo Sanguíneo/fisiologia , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/fisiopatologia , Feminino , Hemodinâmica/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/diagnóstico por imagem , Ultrassonografia Doppler Transcraniana
6.
Pediatr Nephrol ; 33(4): 639-649, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29196979

RESUMO

OBJECTIVE: Recent clinical studies have suggested an increased risk of elevated arterial pressure in patients with hydronephrosis. Animals with experimentally induced hydronephrosis develop hypertension, which is correlated to the degree of obstruction and increased oxidative stress. In this prospective study we investigated changes in arterial pressure, oxidative stress, and nitric oxide (NO) homeostasis following correction of hydronephrosis. METHODS: Ambulatory arterial pressure (24 h) was monitored in pediatric patients with hydronephrosis (n = 15) before and after surgical correction, and the measurements were compared with arterial pressure measurements in two control groups, i.e. healthy controls (n = 8) and operated controls (n = 8). Markers of oxidative stress and NO homeostasis were analyzed in matched urine and plasma samples. RESULTS: The preoperative mean arterial pressure was significantly higher in hydronephrotic patients [83 mmHg; 95% confidence interval (CI) 80-88 mmHg] than in healthy controls (74 mmHg; 95% CI 68-80 mmHg; p < 0.05), and surgical correction of ureteral obstruction reduced arterial pressure (76 mmHg; 95% CI 74-79 mmHg; p < 0.05). Markers of oxidative stress (i.e., 11-dehydroTXB2, PGF2α, 8-iso-PGF2α, 8,12-iso-iPF2α-VI) were significantly increased (p < 0.05) in patients with hydronephrosis compared with both control groups, and these were reduced following surgery (p < 0.05). Interestingly, there was a trend for increased NO synthase activity and signaling in hydronephrosis, which may indicate compensatory mechanism(s). CONCLUSION: This study demonstrates increased arterial pressure and oxidative stress in children with hydronephrosis compared with healthy controls, which can be restored to normal levels by surgical correction of the obstruction. Once reference data on ambulatory blood pressure in this young age group become available, we hope cut-off values can be defined for deciding whether or not to correct hydronephrosis surgically.


Assuntos
Pressão Arterial/fisiologia , Biomarcadores/metabolismo , Hidronefrose/cirurgia , Óxido Nítrico/metabolismo , Estresse Oxidativo/fisiologia , Monitorização Ambulatorial da Pressão Arterial/métodos , Criança , Pré-Escolar , Feminino , Homeostase/fisiologia , Humanos , Hidronefrose/fisiopatologia , Hipertensão/etiologia , Hipertensão/cirurgia , Lactente , Rim/fisiopatologia , Testes de Função Renal/métodos , Masculino , Estudos Prospectivos , Procedimentos Cirúrgicos Urológicos/métodos
7.
Am J Physiol Renal Physiol ; 313(4): F864-F873, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28679594

RESUMO

Via developmental programming, prenatal perturbations, such as exposure to glucocorticoids and maternal malnutrition alter kidney development and contribute to the development of hypertension. To examine the possibility that alterations in tubuloglomerular feedback (TGF) contribute to the development of hypertension in offspring following maternal dexamethasone treatment (Dex) in early gestation, studies were conducted in fetal sheep and lambs. Pregnant ewes were infused with dexamethasone (0.48 mg/h) at 26-28 days gestation. No differences were observed in mean arterial pressure, glomerular filtration rate. or electrolyte excretion rates between the Dex and Untreated fetuses or lambs. Gestational exposure to Dex markedly enhanced TGF sensitivity, as the turning point in Dex-treated fetuses was significantly lower (12.9 ± 0.9 nl/min; P < 0.05) compared with Untreated fetuses (17.0 ± 1.0 nl/min). This resetting of TGF sensitivity persisted after birth (P < 0.01). TGF reactivity did not differ between the groups in fetuses or lambs. In response to nitric oxide inhibition, TGF sensitivity increased (the turning point decreased) and reactivity increased in Untreated fetuses and lambs, but these effects were blunted in the Dex-treated fetuses and lambs. Our data suggest that an altered TGF response may be an underlying renal mechanism contributing to the development of hypertension in the Dex model of fetal programming. The lower tonic level of NO production in these dexamethasone-exposed offspring may contribute to the development of hypertension as adults.


Assuntos
Dexametasona/toxicidade , Glucocorticoides/toxicidade , Hipertensão/induzido quimicamente , Rim/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Animais , Feminino , Indazóis , Testes de Função Renal , NG-Nitroarginina Metil Éster , Óxido Nítrico/metabolismo , Gravidez , Punções , Ovinos
8.
Nature ; 469(7328): 68-71, 2011 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-21179086

RESUMO

Shell structure and magic numbers in atomic nuclei were generally explained by pioneering work that introduced a strong spin-orbit interaction to the nuclear shell model potential. However, knowledge of nuclear forces and the mechanisms governing the structure of nuclei, in particular far from stability, is still incomplete. In nuclei with equal neutron and proton numbers (N = Z), enhanced correlations arise between neutrons and protons (two distinct types of fermions) that occupy orbitals with the same quantum numbers. Such correlations have been predicted to favour an unusual type of nuclear superfluidity, termed isoscalar neutron-proton pairing, in addition to normal isovector pairing. Despite many experimental efforts, these predictions have not been confirmed. Here we report the experimental observation of excited states in the N = Z = 46 nucleus (92)Pd. Gamma rays emitted following the (58)Ni((36)Ar,2n)(92)Pd fusion-evaporation reaction were identified using a combination of state-of-the-art high-resolution γ-ray, charged-particle and neutron detector systems. Our results reveal evidence for a spin-aligned, isoscalar neutron-proton coupling scheme, different from the previous prediction. We suggest that this coupling scheme replaces normal superfluidity (characterized by seniority coupling) in the ground and low-lying excited states of the heaviest N = Z nuclei. Such strong, isoscalar neutron-proton correlations would have a considerable impact on the nuclear level structure and possibly influence the dynamics of rapid proton capture in stellar nucleosynthesis.

9.
J Fish Biol ; 90(6): 2462-2469, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28393360

RESUMO

Accelerometer technology was used to evaluate behaviours in the teleost ambush predator pike Esox lucius foraging on crucian carp Carassius carassius. Automated rule-based estimates of prey-size determined handling time were obtained and are compared with video-recorded behaviours. Solutions to tag attachment and the limitations imposed by battery-time and data-logging capacities are evaluated.


Assuntos
Carpas/fisiologia , Esocidae/fisiologia , Comportamento Predatório , Animais , Cadeia Alimentar , Telemetria/métodos
10.
Am J Physiol Renal Physiol ; 310(1): F43-56, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26538440

RESUMO

Hydronephrosis is associated with the development of salt-sensitive hypertension. Studies have suggested that increased sympathetic nerve activity and oxidative stress play important roles in hypertension and the modulation of salt sensitivity. The present study primarily aimed to examine the role of renal sympathetic nerve activity in the development of hypertension in rats with hydronephrosis. In addition, we aimed to investigate if NADPH oxidase (NOX) function could be affected by renal denervation. Partial unilateral ureteral obstruction (PUUO) was created in 3-wk-old rats to induce hydronephrosis. Sham surgery or renal denervation was performed at the same time. Blood pressure was measured during normal, high-, and low-salt diets. The renal excretion pattern, NOX activity, and expression as well as components of the renin-angiotensin-aldosterone system were characterized after treatment with the normal salt diet. On the normal salt diet, rats in the PUUO group had elevated blood pressure compared with control rats (115 ± 3 vs. 87 ± 1 mmHg, P < 0.05) and displayed increased urine production and lower urine osmolality. The blood pressure change in response to salt loading (salt sensitivity) was more pronounced in the PUUO group compared with the control group (15 ± 2 vs. 5 ± 1 mmHg, P < 0.05). Renal denervation in PUUO rats attenuated both hypertension (97 ± 3 mmHg) and salt sensitivity (5 ± 1 mmHg, P < 0.05) and normalized the renal excretion pattern, whereas the degree of renal fibrosis and inflammation was not changed. NOX activity and expression as well as renin and ANG II type 1A receptor expression were increased in the renal cortex from PUUO rats and normalized by denervation. Plasma Na(+) and K(+) levels were elevated in PUUO rats and normalized after renal denervation. Finally, denervation in PUUO rats was also associated with reduced NOX expression, superoxide production, and fibrosis in the heart. In conclusion, renal denervation attenuates hypertension and restores the renal excretion pattern, which is associated with reduced renal NOX and components of the renin-angiotensin-aldosterone system. This study emphasizes a link between renal nerves, the development of hypertension, and modulation of NOX function.


Assuntos
Pressão Sanguínea , Hidronefrose/enzimologia , Hipertensão/cirurgia , Rim/enzimologia , Rim/inervação , NADPH Oxidases/metabolismo , Estresse Oxidativo , Simpatectomia/métodos , Animais , Biomarcadores/sangue , Biomarcadores/urina , Modelos Animais de Doenças , Fibrose , Frequência Cardíaca , Hidronefrose/etiologia , Hidronefrose/genética , Hidronefrose/fisiopatologia , Hipertensão/enzimologia , Hipertensão/etnologia , Hipertensão/genética , Hipertensão/fisiopatologia , Rim/patologia , Masculino , Miocárdio/enzimologia , Miocárdio/patologia , NADPH Oxidases/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Eliminação Renal , Sistema Renina-Angiotensina , Cloreto de Sódio na Dieta , Obstrução Ureteral/complicações
11.
Acta Anaesthesiol Scand ; 60(2): 166-76, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26373922

RESUMO

BACKGROUND: Postoperative pain may lead to delayed mobilization, persisting pain, and psychosocial distress. There are no simple and reliable techniques for prediction of postoperative pain. This study was designed to evaluate if pain induced by venous cannulation or propofol injection can be used to predict postoperative pain. METHODS: This prospective study included 180 patients scheduled for laparoscopic cholecystectomy. Pain intensity associated with peripheral venous cannulation and administration of propofol preoperatively and pain intensity, and use of opioid postoperatively was recorded. RESULTS: Patients scoring cannulation-induced pain intensity > 2.0 VAS units were given postoperative opioid more often (65% vs. 36%; P < 0.001), earlier (12 min vs. 90 min; P < 0.001), and in higher doses (4.8 mg vs. 0 mg; P < 0.001), and also reported higher levels of postoperative pain intensity (5.8 vs. 2.9 VAS units; P < 0.001). There were also significant (P < 0.01) correlations with postoperative pain intensity (rs = 0.24), time to opioid administration (rs = -0.26), and total dose of opioid (rs = 0.25). Propofol-induced pain intensity correlated significantly (P < 0.05) with postoperative pain intensity (rs = 0.19). CONCLUSION: Pain intensity associated with venous cannulation and propofol infusion can easily be evaluated at bedside before surgery without specific equipment or training. Patients scoring > 2.0 VAS units on venous cannulation were found to have 3.4 times higher risk of postoperative pain after laparoscopic cholecystectomy. Low pain intensity associated with venous cannulation and propofol infusion indicate lower risk of postoperative pain.


Assuntos
Anestésicos Intravenosos/administração & dosagem , Cateterismo Periférico/efeitos adversos , Medição da Dor , Dor Pós-Operatória/diagnóstico , Propofol/administração & dosagem , Adulto , Idoso , Anestésicos Intravenosos/efeitos adversos , Colecistectomia Laparoscópica , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Propofol/efeitos adversos , Estudos Prospectivos
12.
Diabetologia ; 58(7): 1610-20, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25835725

RESUMO

AIMS/HYPOTHESIS: Adenosine is an important regulator of metabolism; however, the role of the A1 receptor during ageing and obesity is unclear. The aim of this study was to investigate the effects of A1 signalling in modulating metabolic function during ageing. METHODS: Age-matched young and aged A 1 (also known as Adora1)-knockout (A1(-/-)) and wild-type (A1(+/+)) mice were used. Metabolic regulation was evaluated by body composition, and glucose and insulin tolerance tests. Isolated islets and islet arterioles were used to detect islet endocrine and vascular function. Oxidative stress and inflammation status were measured in metabolic organs and systemically. RESULTS: Advanced age was associated with both reduced glucose clearance and insulin sensitivity, as well as increased visceral adipose tissue (VAT) in A1(+/+) compared with A1(-/-) mice. Islet morphology and insulin content were similar between genotypes, but relative changes in in vitro insulin release following glucose stimulation were reduced in aged A1(+/+) compared with A1(-/-) mice. Islet arteriolar responses to angiotensin II were stronger in aged A1(+/+) mice, this being associated with increased NADPH oxidase activity. Ageing resulted in multiple changes in A1(+/+) compared with A1(-/-) mice, including enhanced NADPH oxidase-derived O2(-) formation and NADPH oxidase isoform 2 (Nox2) protein expression in pancreas and VAT; elevated levels of circulating insulin, leptin and proinflammatory cytokines (TNF-α, IL-1ß, IL-6 and IL-12); and accumulation of CD4(+) T cells in VAT. This was associated with impaired insulin signalling in VAT from aged A1(+/+) mice. CONCLUSIONS/INTERPRETATION: These studies emphasise that A1 receptors regulate metabolism and islet endocrine and vascular functions during ageing, including via the modulation of oxidative stress and inflammatory responses, among other things.


Assuntos
Inflamação/genética , Estresse Oxidativo/genética , Receptor A1 de Adenosina/genética , Tecido Adiposo/metabolismo , Envelhecimento/metabolismo , Angiotensina II/farmacologia , Animais , Composição Corporal/genética , Linfócitos T CD4-Positivos/metabolismo , Citocinas/metabolismo , Feminino , Intolerância à Glucose/genética , Insulina/metabolismo , Resistência à Insulina , Ilhotas Pancreáticas/irrigação sanguínea , Masculino , Glicoproteínas de Membrana/metabolismo , Metabolismo/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NADPH Oxidase 2 , NADPH Oxidases/metabolismo , Fluxo Sanguíneo Regional/fisiologia , Transdução de Sinais/genética
13.
J Intern Med ; 278(6): 645-59, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26096600

RESUMO

Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.


Assuntos
Doenças Cardiovasculares , Doença Pulmonar Obstrutiva Crônica , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/terapia , Feminino , Técnicas Genéticas , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteômica/métodos , Saúde Pública/métodos , Saúde Pública/estatística & dados numéricos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/terapia , Fatores de Risco , Fatores Socioeconômicos , Suécia/epidemiologia
14.
Mol Psychiatry ; 19(6): 733-41, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23877834

RESUMO

Selective serotonin reuptake inhibitors, tricyclic antidepressants, various psychoactive drugs, as well as endogenous steroids and cannabinoid-like compounds are metabolized by the polymorphic cytochrome P450 2C19 (CYP2C19). Absence of this enzyme has been recently shown to associate with lower levels of depressive symptoms in human subjects. To investigate endogenous functions of CYP2C19 and its potential role in brain function, we have used a transgenic mouse model carrying the human CYP2C19 gene. Here, CYP2C19 was expressed in the developing fetal, but not adult brain and was associated with altered fetal brain morphology, where mice homozygous for the CYP2C19 transgenic insert had severely underdeveloped hippocampus and complete callosal agenesis and high neonatal lethality. CYP2C19 expression was also found in human fetal brain. In adult hemizygous mice we observed besides decreased hippocampal volume, an altered neuronal composition in the hippocampal dentate gyrus. Reduced hippocampal volumes have been reported in several psychiatric disorders, supporting the relevance of this model. Here we found that adult hemizygous CYP2C19 transgenic mice demonstrate behavior indicative of increased stress and anxiety based on four different tests. We hypothesize that expression of the CYP2C19 enzyme prenatally may affect brain development by metabolizing endogenous compounds influencing this development. Furthermore, CYP2C19 polymorphism may have a role in interindividual susceptibility for psychiatric disorders.


Assuntos
Transtornos de Ansiedade/patologia , Transtornos de Ansiedade/fisiopatologia , Encéfalo/patologia , Encéfalo/fisiopatologia , Citocromo P-450 CYP2C19/metabolismo , Animais , Hidrocarboneto de Aril Hidroxilases/genética , Hidrocarboneto de Aril Hidroxilases/metabolismo , Comportamento Animal/fisiologia , Encéfalo/crescimento & desenvolvimento , Corticosterona/sangue , Citocromo P-450 CYP2C19/genética , Feminino , Hipocampo/crescimento & desenvolvimento , Hipocampo/patologia , Hipocampo/fisiopatologia , Humanos , Interneurônios/fisiologia , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurônios/patologia , Neurônios/fisiologia , Tamanho do Órgão , Proteínas Proto-Oncogênicas c-fos/metabolismo , RNA Mensageiro/metabolismo , Estresse Psicológico/fisiopatologia
15.
Eur J Neurol ; 22(4): 717-24, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25648859

RESUMO

BACKGROUND AND PURPOSE: Brain tumors represent a rare and relatively uncharacterized tumor type in Lynch syndrome. METHODS: The national Danish Hereditary Nonpolyposis Colorectal Cancer Register was utilized to estimate the cumulative life-time risk for brain tumors in Lynch syndrome, and the mismatch repair (MMR) status in all tumors available was evaluated. RESULTS: Primary brain tumors developed in 41/288 families at a median age of 41.5 (range 2-73) years. Biallelic MMR gene mutations were linked to brain tumor development in childhood. The risk of brain tumors was significantly higher (2.5%) in MSH2 gene mutation carriers compared to patients with mutations in MLH1 or MSH6. Glioblastomas predominated (56%), followed by astrocytomas (22%) and oligodendrogliomas (9%). MMR status was assessed in 10 tumors, eight of which showed MMR defects. None of these tumors showed immunohistochemical staining suggestive of the IDH1 R132H mutation. CONCLUSION: In Lynch syndrome brain tumors occurred in 14% of the families with significantly higher risks for individuals with MSH2 gene mutations and development of childhood brain tumors in individuals with constitutional MMR defects.


Assuntos
Astrocitoma/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/genética , Oligodendroglioma/epidemiologia , Sistema de Registros , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Comorbidade , Dinamarca/epidemiologia , Feminino , Glioblastoma/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
AIDS Behav ; 19(5): 821-31, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25432878

RESUMO

The use of antiretroviral therapy to prevent HIV transmission is now advocated in many settings, yet little research has documented the views of people with HIV. Semi-structured interviews were conducted in Australia between 2012 and 2014 with 27 HIV-positive people not using treatment at the time of interview. Thematic analysis of views on treatment-as-prevention found that while many participants recognised potential prevention benefits, only a minority was in support of initiating treatment solely to achieve those benefits. A range of uncertain or critical views were expressed regarding who would benefit, risk reduction, and changing treatment norms. Participants resisted responsibility narratives that implied treatment should be used for the public good, in favour of making considered decisions about their preferred approach to managing HIV. Engaging communities in dialogue and debate regarding the risks and benefits of treatment will be critical if this new prevention strategy is to engender public trust.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/prevenção & controle , Comportamento de Redução do Risco , Adulto , Idoso , Austrália , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gravidez , Pesquisa Qualitativa , Análise de Regressão
17.
J Wound Care ; 24(5): 204, 206-10, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25970757

RESUMO

OBJECTIVE: To compare a superabsorbent polymer dressing (DryMax Extra; DME), an antibacterial absorbent polymer dressing (Sorbact absorption dressing; SB) and an antibacterial superabsorbent polymer dressing (Sorbion Sachet S; SSS) activity against Pseudomonas aeruginosa biofilms. METHOD: A 3D acellular synthetic soft tissue (ASST) allowing biofilm formation, was prepared and inoculated with Pseudomonas aeruginosa, before the application of dressings. The dressings DME, with and without a silver net, and two benchmark dressings SB and SSS were tested. After 24 hours' incubation, qualitative assessment by visual screening of the soft tissue and bacterial burden assessment in the dressings and acellular soft tissue model were performed. RESULTS: DME combined with a silver net gave a distinct and wide colourless zone of inhibition while partial zones of inhibition were seen for DME, SSS and SB. Compared with the tissues exposed to the other dressings, those exposed to SB and the bacterial control appeared green and opaque. In descending order, the most visual growth was seen in bacterial control, followed by SB, SSS, and DME. The bacterial load was equivalent for all dressings without an antimicrobial substance in both ASST (around log 10) and dressing (around log 11). The bacterial load for DME combined with a silver net, in comparison to DME alone was significantly reduced, with log 3.6 in dressings and log 4.2 in ASST. CONCLUSION: The removal of bacteria by DME was equivalent to SB and SSS. Furthermore, DME limited the production of the green colour, indicative of Pyocyanin. If extrapolated to a wound, the ability of DME to absorb Pseudomonas aeruginosa and limit Pyocyanin levels in the wound might lead to reduced virulence.


Assuntos
Derme Acelular/microbiologia , Bandagens/microbiologia , Biofilmes/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Antibacterianos/uso terapêutico , Carga Bacteriana , Humanos , Polímeros , Pseudomonas aeruginosa/patogenicidade , Piocianina , Compostos de Prata/farmacologia , Virulência
18.
Nano Lett ; 14(2): 541-6, 2014 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-24387246

RESUMO

The modified phonon dispersion is of importance for understanding the origin of the reduced heat conductivity in nanowires. We have measured the phonon dispersion for 50 nm diameter InSb (111) nanowires using time-resolved X-ray diffraction. By comparing the sound speed of the bulk (3880 m/s) and that of a classical thin rod (3600 m/s) to our measurement (2880 m/s), we conclude that the origin of the reduced sound speed and thereby to the reduced heat conductivity is that the C44 elastic constant is reduced by 35% compared to the bulk material.

19.
Am J Physiol Endocrinol Metab ; 307(8): E653-63, 2014 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-25139049

RESUMO

Pancreatic islet blood perfusion varies according to the needs for insulin secretion. We examined the effects of blood lipids on pancreatic islet blood flow in anesthetized rats. Acute administration of Intralipid to anesthetized rats increased both triglycerides and free fatty acids, associated with a simultaneous increase in total pancreatic and islet blood flow. A preceding abdominal vagotomy markedly potentiated this and led acutely to a 10-fold increase in islet blood flow associated with a similar increase in serum insulin concentrations. The islet blood flow and serum insulin response could be largely prevented by pretreatment with propranolol and the selective ß3-adrenergic inhibitor SR-59230A. The nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester prevented the blood flow increase but was less effective in reducing serum insulin. Increased islet blood flow after Intralipid administration was also seen in islet and whole pancreas transplanted rats, i.e., models with different degrees of chronic islet denervation, but the effect was not as pronounced. In isolated vascularly perfused single islets Intralipid dilated islet arterioles, but this was not affected by SR-59230A. Both the sympathetic and parasympathetic nervous system are important for the coordination of islet blood flow and insulin release during hyperlipidemia, with a previously unknown role for ß3-adrenoceptors.


Assuntos
Hiperlipidemias/fisiopatologia , Insulina/metabolismo , Ilhotas Pancreáticas/irrigação sanguínea , Receptores Adrenérgicos beta 3/metabolismo , Fluxo Sanguíneo Regional , Regulação para Cima , Nervo Vago/fisiopatologia , Antagonistas de Receptores Adrenérgicos beta 3/farmacologia , Animais , Emulsões/efeitos adversos , Ácidos Graxos não Esterificados/sangue , Ácidos Graxos não Esterificados/metabolismo , Hiperlipidemias/sangue , Hiperlipidemias/etiologia , Hiperlipidemias/metabolismo , Insulina/sangue , Secreção de Insulina , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/inervação , Ilhotas Pancreáticas/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Pâncreas/irrigação sanguínea , Pâncreas/efeitos dos fármacos , Pâncreas/inervação , Pâncreas/metabolismo , Perfusão , Fosfolipídeos/efeitos adversos , Propanolaminas/farmacologia , Ratos Endogâmicos WF , Receptores Adrenérgicos beta 3/química , Fluxo Sanguíneo Regional/efeitos dos fármacos , Óleo de Soja/efeitos adversos , Triglicerídeos/sangue , Triglicerídeos/metabolismo , Regulação para Cima/efeitos dos fármacos , Vagotomia Troncular , Nervo Vago/efeitos dos fármacos , Nervo Vago/cirurgia
20.
J Intern Med ; 275(2): 127-33, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24010553

RESUMO

BACKGROUND: It is well established that subjects with moderately elevated plasma levels of C-reactive protein (CRP) have an increased risk of development of cardiovascular events. As atherosclerosis is a disease characterized by chronic arterial inflammation, it is possible that moderate increases in CRP level reflect the presence of plaque inflammation. To investigate this possibility, we compared plasma levels of hsCRP the day before carotid endarterectomy with the degree of inflammation in the excised plaque tissue. METHODS: Luminex immunoassays were used to determine the levels of IL-6, IL-10, monocyte chemoattractant protein-1 and tumour necrosis factor-α (TNF-α) in plasma and in homogenized plaque tissue from 160 endarterectomy specimens. Plaque sections were stained with antibodies against CD68 to determine the plaque macrophage content. RESULTS: Plasma high-sensitivity (hs)CRP levels were significantly correlated with plasma IL-6 and TNF-α. However, there were no significant associations between plasma hsCRP concentration and plaque cytokine levels or macrophage contents. CONCLUSIONS: The present findings strongly argue against hsCRP as a marker of plaque inflammation. Hence, it is more likely that elevated hsCRP is a sign of a subclinical systemic inflammation and this in turn may contribute to progression of cardiovascular disease.


Assuntos
Proteína C-Reativa/metabolismo , Estenose das Carótidas/sangue , Citocinas/sangue , Inflamação/sangue , Placa Aterosclerótica/sangue , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/metabolismo , Estenose das Carótidas/metabolismo , Estenose das Carótidas/patologia , Quimiocina CCL2/sangue , Citocinas/metabolismo , Feminino , Humanos , Imunoensaio , Interleucina-10/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Fatores de Risco , Fator de Necrose Tumoral alfa/sangue
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