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Background and objective: Infection after transrectal prostate biopsy (TPBx) is a well-known risk. A comprehensive investigation of risk factors may identify measures for safe TPBx as an alternative to a change in biopsy route. The aim of this study was to identify risk factors for infection after TPBx. Methods: We included all outpatient TPBx cases in Region Kronoberg, Sweden, from January 2010 to December 2019. The primary outcome was post-TPBx infection, defined as prescription of antibiotics indicated for urinary tract infection (UTI) or inpatient care for infection within 30 d. We analysed the following factors in relation to post-TPBx infection: age, diabetes mellitus, prostate cancer diagnosed at index biopsy, previous prostate biopsy, two or more biopsies in the past 24 mo, a positive urine culture, two or more negative urine cultures (UCs) in the past 24 mo, antibiotic treatment grouped as four types, and medication for benign prostatic hyperplasia (BPH). Logistic regression was used to calculate odds ratios (ORs). Key findings and limitations: Of 5788 TPBx procedures in 4040 patients, 405 (7.0%) led to an infection and 170 (2.9%) to inpatient care for infection. Risk factors for post-TPBx infection (ORs 1.5-2.5) were diabetes mellitus, antibiotic treatment for a UTI, fluoroquinolone treatment, and a positive urine culture. Weaker risk factors (ORs 1.3-1.5) were non-UTI antibiotic treatment, BPH medication, and negative UCs before TPBx. Conclusions and clinical implications: Our results confirm that diabetes mellitus and previous UTI are risk factors for infection after TPBx. Lower urinary tract symptoms and treatment with any kind of antibiotic were associated with infection, which has not been previously reported. Patient summary: In a large population-based study from Sweden, we investigated which clinical factors increase the risk of an infection after transrectal prostate biopsy. Our results confirm that diabetes and a previous urinary tract infection are risk factors. We also found two new factors associated with the risk of infection after biopsy: lower urinary tract symptoms and any antibiotic treatment.
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Both high serum insulin-like growth factor-binding protein-1 (s-IGFBP-1) and insulin resistance (IR) are associated with poor functional outcome poststroke, whereas overweight body mass index (BMI; 25-30) is related to fewer deaths and favorable functional outcome in a phenomenon labeled "the obesity paradox". Furthermore, IGFBP-1 is inversely related to BMI, in contrast to the linear relation between IR and BMI. Here, we investigated s-IGFBP-1 and IR concerning BMI and 7-year poststroke functional outcome. We included 451 stroke patients from the Sahlgrenska Study on Ischemic Stroke (SAHLSIS) with baseline measurements of s-IGFBP1, homeostasis model assessment of IR (HOMA-IR), BMI (categories: normal-weight (8.5-25), overweight (25-30), and obesity (>30)), and high-sensitivity C-reactive protein (hs-CRP) as a measure of general inflammation. Associations with poor functional outcome (modified Rankin scale [mRS] score: 3-6) after 7 years were evaluated using multivariable binary logistic regression, with overweight as reference due to the nonlinear relationship. Both normal-weight (odds-ratio [OR] 2.32, 95% confidence interval [CI] 1.30-4.14) and obese (OR 2.25, 95% CI 1.08-4.71) patients had an increased risk of poor functional outcome, driven by deaths only in the normal-weight. In normal-weight, s-IGFBP-1 modestly attenuated (8.3%) this association. In the obese, the association was instead attenuated by HOMA-IR (22.4%) and hs-CRP (10.4%). Thus, a nonlinear relation between BMI and poor 7-year functional outcome was differently attenuated in the normal-weight and the obese.
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Índice de Massa Corporal , Inflamação , Resistência à Insulina , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina , Humanos , Feminino , Masculino , Idoso , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Inflamação/metabolismo , Inflamação/sangue , Pessoa de Meia-Idade , Obesidade/metabolismo , Obesidade/complicações , Obesidade/sangue , Acidente Vascular Cerebral/metabolismo , Proteína C-Reativa/metabolismo , Biomarcadores/sangue , Sobrepeso/metabolismo , Sobrepeso/sangue , Peptídeos Semelhantes à InsulinaRESUMO
BACKGROUND: Previous research found that healthcare professionals had low preparedness for palliative care. Thus, it is necessary to explore healthcare professionals' self-efficacy. The Swedish Self-Efficacy in Palliative Care Scale (SEPC-SE) evaluates readiness in communication, patient management and multidisciplinary teamwork; however, it should be tested on a larger population. Furthermore, the constructs of the SEPC-SE should be compared to that of the original SEPC. AIM: This study aimed to evaluate the consensus between the construct validity and reliability of the SEPC and the translated and adapted SEPC-SE. Furthermore, it aimed to describe and compare the self-efficacy of nurses and physicians in hospitals and explore the associated factors. METHODS: The nurses (n = 288) and physicians (n = 104) completed the SEPC-SE. Factor analysis with Cronbach's alpha evaluated validity and reliability, and an analysis using the Mann-Whitney U test compared self-efficacy and multiple linear regression-associated factors. RESULTS: The SEPC-SE revealed three factors with high reliability. Education or experience in specialised palliative care was minor, especially for nurses. Self-efficacy was highest in patient management (nurses, median [md] = 74.57, physicians md = 81.71, p = 0.010) and communication (nurses md = 69.88, physicians md = 77.00, p = 0.141) and lowest in multidisciplinary teamwork (nurses md = 52.44, physicians md = 62.88, p = 0.001). The strongest associations with self-efficacy were education at work and advanced homecare experiences. In addition, there were significant associations between years in the profession, male sex, physicians and university education. CONCLUSION: The SEPC-SE is valid and reliable for measuring self-efficacy. Nurses had lower self-efficacy than physicians. Physicians were associated with higher self-efficacy and had more education and experience in palliative care settings, which may explain their levels of self-efficacy.
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Cuidados Paliativos , Autoeficácia , Humanos , Suécia , Estudos Transversais , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Médicos/psicologia , Reprodutibilidade dos Testes , Inquéritos e Questionários , Enfermeiras e Enfermeiros/psicologiaRESUMO
We introduce a general, variational scheme for systematic approximation of a given Kohn-Sham free-energy functional by partitioning the density matrix into distinct spectral domains, each of which may be spanned by an independent diagonal representation without requirement of mutual orthogonality. It is shown that by generalizing the entropic contribution to the free energy to allow for independent representations in each spectral domain, the free energy becomes an upper bound to the exact (unpartitioned) Kohn-Sham free energy, attaining this limit as the representations approach Kohn-Sham eigenfunctions. A numerical procedure is devised for calculation of the generalized entropy associated with spectral partitioning of the density matrix. The result is a powerful framework for Kohn-Sham calculations of systems whose occupied subspaces span multiple energy regimes. As a case in point, we apply the proposed framework to warm- and hot-dense matter described by finite-temperature density functional theory, where at high energies the density matrix is represented by that of the free-electron gas, while at low energies it is variationally optimized. We derive expressions for the spectral-partitioned Kohn-Sham Hamiltonian, atomic forces, and macroscopic stresses within the projector-augmented wave (PAW) and the norm-conserving pseudopotential methods. It is demonstrated that at high temperatures, spectral partitioning facilitates accurate calculations at dramatically reduced computational cost. Moreover, as temperature is increased, fewer exact Kohn-Sham states are required for a given accuracy, leading to further reductions in computational cost. Finally, it is shown that standard multiprojector expansions of electronic orbitals within atomic spheres in the PAW method lack sufficient completeness at high temperatures. Spectral partitioning provides a systematic solution for this fundamental problem.
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Insulin-like growth factor-binding protein-1 (IGFBP-1) regulates insulin-like growth factor-I (IGF-I) bioactivity, and is a central player in normal growth, metabolism, and stroke recovery. However, the role of serum IGFBP-1 (s-IGFBP-1) after ischemic stroke is unclear. We determined whether s-IGFBP-1 is predictive of poststroke outcome. The study population comprised patients (n = 470) and controls (n = 471) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Functional outcome was evaluated after 3 months, 2, and 7 years using the modified Rankin Scale (mRS). Survival was followed for a minimum of 7 years or until death. S-IGFBP-1 was increased after 3 months (p < 0.01), but not in the acute phase after stroke, compared with the controls. Higher acute s-IGFBP-1 was associated with poor functional outcome (mRS score > 2) after 7 years [fully adjusted odds ratio (OR) per log increase 2.9, 95% confidence interval (CI): 1.4-5.9]. Moreover, higher s-IGFBP-1 after 3 months was associated with a risk of poor functional outcome after 2 and 7 years (fully adjusted: OR 3.4, 95% CI: 1.4-8.5 and OR 5.7, 95% CI: 2.5-12.8, respectively) and with increased mortality risk (fully adjusted: HR 2.0, 95% CI: 1.1-3.7). Thus, high acute s-IGFBP-1 was only associated with poor functional outcome after 7 years, whereas s-IGFBP-1 after 3 months was an independent predictor of poor long-term functional outcome and poststroke mortality.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/complicações , Isquemia Encefálica/complicações , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina , Fatores de Risco , Acidente Vascular Cerebral/complicaçõesRESUMO
Background: Infectious complications after a transrectal prostate biopsy may be severe. In Sweden, a routine culture prior to all prostate biopsies was introduced to enable targeted antimicrobial prophylaxis and reduce postbiopsy infections. Objective: To investigate whether a clinical routine with a urine culture prior to a prostate biopsy and targeted prophylactic antibiotic therapy reduces postbiopsy infections. Design setting and participants: In 2015, a site-specific antimicrobial stewardship programme with a urine culture prior to a prostate biopsy was initiated in Region Kronoberg. To evaluate this routine, we designed a population-based register study including all men who had an outpatient prostate biopsy in 2015-2019 and a control period including all men who had a biopsy in 2010-2014, when a urinary culture was obtained only on clinical suspicion. Outcome measurements and statistical analysis: The primary outcome was infectious complications within 10 d and the secondary outcome was a change in antibiotic prophylactic treatment. An infectious complication was defined as prescription of antibiotics for urinary tract infections or admission to hospital for urinary tract infections or sepsis after a biopsy. Results and limitations: The urine culture period included 2971 prostate biopsy procedures, of which 2684 (90%) were preceded by a urine culture. The control period included 2818 procedures, of which 135 (4.8%) were preceded by a urine culture. Infectious complications were slightly more common during the urine culture period (5.0%) than during the control period (4.3%, p = 0.17), as was inpatient care for infections (3.5% vs 2.2%, p = 0.002). The routine identified 5.4% men with asymptomatic bacteriuria. Despite targeted antibiotic treatment (1.5% received a nonfluoroquinolone treatment), the rate of infectious complications (6.3%) was similar to that in the control period. Conclusions: Prebiopsy urine culture did not lead to fewer postbiopsy infections. Other measures are needed to reduce infectious complications after a prostate biopsy. Patient summary: In this report, we evaluated a routine with urine culture prior to a transrectal prostate biopsy and found that it did not lead to fewer infectious complications.
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Insulin-like growth factor-II (IGF-II) regulates prenatal brain development, but the role in adult brain function and injury is unclear. Here, we determined whether serum levels of IGF-II (s-IGF-II) are associated with mortality and functional outcome after ischemic stroke (IS). The study population comprised ischemic stroke cases (n = 492) and controls (n = 514) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Functional outcome was evaluated after 3 months and 2 years using the modified Rankin Scale (mRS), and additionally, survival was followed at a minimum of 7 years or until death. S-IGF-II levels were higher in IS cases both in the acute phase and at 3-month follow-up compared to controls (p < 0.05 and p < 0.01, respectively). The lowest quintile of acute s-IGF-II was, compared to the four higher quintiles, associated with an increased risk of post-stroke mortality (median follow-up 10.6 years, crude hazard ratio (HR) 2.34, 95% confidence interval (CI) 1.56-3.49, and fully adjusted HR 1.64, 95% CI 1.02-2.61). In contrast, crude associations with poor functional outcome (mRS 3-6) lost significance after full adjustment for covariates. In conclusion, s-IGF-II was higher in IS cases than in controls, and low acute s-IGF-II was an independent risk marker of increased mortality.
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Microstructural evolution is a key aspect of understanding and exploiting the processing-structure-property relationship of materials. Modeling microstructure evolution usually relies on coarse-grained simulations with evolution principles described by partial differential equations (PDEs). Here we demonstrate that convolutional recurrent neural networks can learn the underlying physical rules and replace PDE-based simulations in the prediction of microstructure phenomena. Neural nets are trained by self-supervised learning with image sequences from simulations of several common processes, including plane-wave propagation, grain growth, spinodal decomposition, and dendritic crystal growth. The trained networks can accurately predict both short-term local dynamics and long-term statistical properties of microstructures assessed herein and are capable of extrapolating beyond the training datasets in spatiotemporal domains and configurational and parametric spaces. Such a data-driven approach offers significant advantages over PDE-based simulations in time-stepping efficiency and offers a useful alternative, especially when the material parameters or governing PDEs are not well determined.
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Physical activity (PA) and insulin-like growth factor I (IGF-I) have beneficial effects for patients who have suffered an ischemic stroke (stroke). However, the relationship between the levels of PA and IGF-I after stroke has not been explored in detail. We investigated the pre-stroke PA level in relation to the post-stroke serum IGF-I (s-IGF-I) level, at baseline and at 3 months after the index stroke, and calculated the change that occurred between these two time-points (ΔIGF-I). Patients (N = 380; 63.4% males; mean age, 54.7 years) with data on 1-year leisure-time pre-stroke PA and post-stroke s-IGF-I levels were included from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS). Pre-stroke, leisure-time PA was self-reported as PA1-4, with PA1 representing sedentary and PA2-4 indicating progressively higher PA levels. Associations between s-IGF-I and PA were evaluated by multiple linear regressions with PA1 as the reference and adjustments being made for sex, age, history of previous stroke or myocardial infarctions, cardiovascular risk factors, and stroke severity. PA correlated with baseline s-IGF-I and ΔIGF-I, but not with the 3-month s-IGF-I. In the linear regressions, there were corresponding associations that remained as a tendency (baseline s-IGF-I, p = 0.06) or as a significant effect (ΔIGF-I, p = 0.03) after all the adjustments. Specifically, for each unit of PA, ΔIGF-I increased by 9.7 (95% CI 1,1-18.4) ng/mL after full adjustment. This supports the notion that pre-stroke PA is independently related to ΔIGF-I.
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BACKGROUND: The association of serum insulin-like growth factor I (s-IGF-I) with favorable outcome after ischemic stroke (IS) beyond 2 years is unknown. We investigated whether the levels of s-IGF-I 3 months post-stroke were associated with functional recovery up to 7 years after IS, considering also mortality and recurrent strokes. METHODS: Patients (N=324; 65% males; mean age, 55 years) with s-IGF-I levels assessed 3 months after the index IS were included from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). The modified Rankin Scale (mRS) was used to evaluate outcomes at 3 months, 2 and 7 years after IS, and recovery was defined as an improvement, no change, or deterioration in the shifts of mRS score. Baseline stroke severity was determined using the National Institutes of Health Stroke Scale (NIHSS). RESULTS: The mRS score distributions were better in the above-median s-IGF-I group (>146.7 ng/ml). The s-IGF-I level was not associated with recurrent stroke (N=79) or death (N=44), although it correlated with recovery (r=0.12, P=0.035). In the regression analysis, s-IGF-I associated with recovery between 3 months and 7 years (but not between 2 and 7 years). The associations did not withstand adjustment for age and sex. For comparison, the corresponding associations between 3 months and 2 years withstood all adjustments. CONCLUSION: The association for s-IGF-I with long-term post-stroke recovery persists after 7 years, which is also reflected in the mRS score distributions at all time-points. The effects are however modest, and not driven by mortality or recurrent stroke.
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Fator de Crescimento Insulin-Like I/metabolismo , AVC Isquêmico/sangue , AVC Isquêmico/mortalidade , AVC Isquêmico/fisiopatologia , Recuperação de Função Fisiológica/fisiologia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Índice de Gravidade de Doença , Suécia/epidemiologiaRESUMO
BACKGROUND: Insulin resistance (IR) in relation to diabetes is a risk factor for ischemic stroke (IS), whereas less is known about non-diabetic IR and outcome after IS. METHODS: In non-diabetic IS (n = 441) and controls (n = 560) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), IR was investigated in relation to IS severity and functional outcome. IR was evaluated acutely and after 3 months using the Homeostasis model assessment of IR (HOMA-IR). Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS). Functional outcome was evaluated using the modified Rankin Scale (mRS) after 3 months, 2 and 7 years. Associations were evaluated by logistic regression. RESULTS: Higher acute and 3-month HOMA-IR was observed in IS compared to the controls (both p < 0.001) and in severe compared to mild IS (both p < 0.05). High acute HOMA-IR was associated with poor outcome (mRS 3-6) after 3 months and 7 years [crude Odds ratios (ORs), 95% confidence intervals (CIs) 1.50, 1.07-2.11 and 1.59, 1.11-2.30, respectively], but not after 2 years. These associations lost significance after adjustment for all covariates including initial stroke severity. In the largest IS subtype (cryptogenic stroke), acute HOMA-IR was associated with poor outcome after 2 years also after adjustment for age and stroke severity (OR 2.86, 95% CI 1.01-8.12). CONCLUSIONS: In non-diabetic IS patients, HOMA-IR was elevated and related to stroke severity, but after adjustment for IS severity, the associations between HOMR-IR and poor outcome lost significance. This could suggest that elevated IR mostly is a part of the acute IS morbidity. However, in the subgroup of cryptogenic stroke, the associations with poor outcome withstood correction for stroke severity.
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Isquemia Encefálica/metabolismo , Resistência à Insulina , Acidente Vascular Cerebral/metabolismo , Estudos de Casos e Controles , Feminino , Homeostase , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND: Insulin-like growth factor I (IGF-I) has neuroprotective effects in experimental ischemic stroke (IS). However, in patients who have suffered IS, various associations between the levels of serum IGF-I (s-IGF-I) and clinical outcome have been reported, probably reflecting differences in sampling time-points and follow-up periods. Since changes in the levels of post-stroke s-IGF-I have not been extensively explored, we investigated whether decreases in the levels of s-IGF-I between the acute time-point (median, 4 days) and 3 months (ΔIGF-I, further transformed into ΔIGF-I-quintiles, ΔIGF-I-q) are associated with IS severity and outcome. METHODS: In the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) conducted in Gothenburg, Sweden, patients with IS who had s-IGF-I measurements available were included (N = 354; 65% males; mean age, 55 years). Baseline stroke severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) and converted into NIHSS-quintiles (NIHSS-q). Outcomes were assessed using the modified Rankin Scale (mRS) at 3 months and 2 years. RESULTS: In general, the levels of s-IGF-I decreased (positive ΔIGF-I), except for those patients with the most severe NIHSS-q. After correction for sex and age, the 3rd ΔIGF-I-q showed the strongest association to mRS 0-2 [Odds Ratio (OR) 5.11, 95% confidence interval (CI) 2.18-11.9], and after 2 years, the 5th ΔIGF-I-q (OR 3.63, 95% CI 1.40-9.38) showed the strongest association to mRS 0-2. The associations remained significant after multivariate correction for diabetes, smoking, hypertension, and hyperlipidemia after 3 months, but were not significant (p = 0.057) after 2 years. The 3-month associations withstood additional correction for baseline stroke severity (p = 0.035), whereas the 2-year associations were further attenuated (p = 0.31). CONCLUSIONS: Changes in the levels of s-IGF-I are associated primarily with temporally near 3-month outcomes, while associations with long-term 2-year outcomes are weakened and attenuated by other factors. The significance of the change in post-stroke s-IGF-I is compatible with a positive role for IGF-I in IS recovery. However, the exact mechanisms are unknown and probably reflects combinations of multiple peripheral and central actions.
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Isquemia Encefálica/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Acidente Vascular Cerebral/sangue , Isquemia Encefálica/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Acidente Vascular Cerebral/complicações , SuéciaRESUMO
BACKGROUND: Insulin-like growth factor-II (IGF-II) is important for brain development. Although IGF-II is abundant also in adult life, little is known of the role of IGF-II in Alzheimer's disease (AD). OBJECTIVE AND METHODS: This was a cross-sectional study of 60 consecutive patients under primary evaluation of cognitive impairment and 20 healthy controls. The patients had AD dementia or mild cognitive impairment (MCI) diagnosed with AD dementia upon follow-up (nâ=â32), stable MCI (SMCI, nâ=â13), or other dementias (nâ=â15). IGF-II, IGF-binding protein-1 (IGFBP-1), and IGFBP-2 were analyzed in serum and cerebrospinal fluid (CSF). RESULTS: Levels of IGF-II, IGFBP-1, and IGFBP-2 were similar in all groups in the total study population. Gender-specific analyses showed that in men (nâ=â40), CSF IGF-II level was higher in AD compared to SMCI and controls (pâ< â0.01 and pâ< â0.05, respectively). Furthermore, CSF IGFBP-2 level was increased in AD men versus SMCI men (pâ< â0.01) and tended to be increased versus control men (pâ=â0.09). There were no between-group differences in women (nâ=â40). In the total study population (nâ=â80) as well as in men (nâ=â40), CSF levels of IGF-II and IGFBP-2 correlated positively with CSF levels of the AD biomarkers total-tau and phosphorylated tau protein. CONCLUSION: In men, but not women, in the early stages of AD, CSF IGF-II level was elevated, and CSF IGFBP-2 level tended to be increased, compared to healthy controls.
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Doença de Alzheimer/líquido cefalorraquidiano , Fator de Crescimento Insulin-Like II/líquido cefalorraquidiano , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/sangue , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Estudos Transversais , Feminino , Seguimentos , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/líquido cefalorraquidiano , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/líquido cefalorraquidiano , Masculino , Fragmentos de Peptídeos/líquido cefalorraquidiano , Fosforilação , Caracteres Sexuais , Proteínas tau/líquido cefalorraquidianoRESUMO
We present and discuss density functional theory calculations of magnetic properties of the family of ferromagnetic compounds, (Fe(1-x)Co(x))(2)B, focusing specifically on the magnetocrystalline anisotropy energy (MAE). Using periodic supercells of various sizes (up to 96 atoms), it is shown that the general qualitative features of the composition dependence of the MAE is in agreement with experimental findings, while our predicted magnitudes are larger than those of experiment. We find that the use of small supercells (6 and 12-atom) favors larger MAE values relative to a statistical sample of configurations constructed with 96-atom supercells. The effect of lattice relaxations is shown to be small. Calculations of the Curie temperature for this alloy are also presented.
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OBJECTIVE: In humans, serum IGF1 (s-IGF1) is associated with outcome after ischemic stroke (IS). Therefore variation at the IGF1 locus could also associate with both IS and s-IGF1. We investigated whether genetic variation at the IGF1 locus is associated with i) s-IGF1, ii) IS occurrence, iii) IS severity, and iv) post-stroke outcome. DESIGN/METHODS: Patients (n=844; 66% males, mean age 56 years) and community controls (n=668) were included from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Post-stroke outcome was evaluated with the modified Rankin Scale at 3 and 24 months after index stroke, and baseline stroke severity with the Scandinavian Stroke Scale. s-IGF1 was determined in patients and after random selection in 40 of the controls. RESULTS: Eleven single nucleotide polymorphisms (SNPs) were selected in the IGF1 gene. In healthy controls the major allele of rs7136446 was associated with higher s-IGF1, whereas in patients no such association was found. No SNP was associated with IS, nor with stroke severity. After multivariate correction for presence of diabetes, smoking, and hypertension, the major allele of rs7136446 was associated with favorable functional outcome 24-months post-stroke (odds ratio 1.46; 95% CI 1.09-1.96). CONCLUSION: Variation in rs7136446 of the IGF1 gene associates with post-stroke outcome in relatively young IS patients. Also, rs7136446 associates with s-IGF1 in controls but not in IS, which indicates that IS perturbs a normal genetic impact on s-IGF1 levels.
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Isquemia Encefálica/complicações , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/sangue , Adulto , Idoso , Alelos , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Índice de Gravidade de Doença , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/genética , Suécia/epidemiologia , Resultado do TratamentoRESUMO
BACKGROUND: Although insulin-like growth factor-I (IGF-I) is of importance for the adult function of the central nervous system (CNS), little is known of the significance of IGF-I in cerebrospinal fluid (CSF) in relation to Alzheimer's disease (AD). METHODS: A cross-sectional study of 60 consecutive patients under primary evaluation of cognitive impairment and 20 healthy controls. The patients had AD dementia or mild cognitive impairment (MCI) diagnosed with AD dementia upon follow-up (n=32), stable MCI (SMCI, n=13), or other dementias (n=15). IGF-I, IGF-binding protein-3 (IGFBP-3), and insulin were measured in serum and CSF. RESULTS: Serum IGF-I level was increased in AD patients and in patients with other dementias compared to healthy controls (P=0.01 and P<0.05, respectively). Serum IGFBP-3 concentration was increased in AD and SMCI patients compared to controls (P=0.001 and P<0.05, respectively). CSF levels of IGF-I and IGFBP-3 as well as serum and CSF levels of insulin were similar in all study groups. In the total study population (n=80), serum levels of IGF-I and IGFBP-3 correlated negatively with CSF ß-amyloid1â42 (Aß1â42) level (r=-0.29, P=0.01 and r=-0.27, P=0.02, respectively) and in the AD patients (n=32), the increased CSF/serum IGF-I ratio correlated positively with the CSF level of phosphorylated tau protein (P-tau; r=0.42, P=0.02). CONCLUSION: Patients with AD as well as other dementias had high levels of IGF-I in serum but not in CSF. In AD patients, the IGF-I system was associated with biomarkers of AD disease status.
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Doença de Alzheimer/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Índice de Massa Corporal , Disfunção Cognitiva/sangue , Disfunção Cognitiva/líquido cefalorraquidiano , Estudos Transversais , Demência/sangue , Demência/líquido cefalorraquidiano , Feminino , Humanos , Insulina/sangue , Insulina/líquido cefalorraquidiano , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/líquido cefalorraquidiano , Fator de Crescimento Insulin-Like I/líquido cefalorraquidiano , Fator de Crescimento Insulin-Like I/fisiologia , Masculino , Fragmentos de Peptídeos/líquido cefalorraquidiano , Método Simples-Cego , Relação Cintura-Quadril , Proteínas tau/líquido cefalorraquidianoRESUMO
CONTEXT AND OBJECTIVE: GH has positive cognitive effects when given to GH-IGF-I-deficient patients. GH and IGF-I exert both neuroprotective and regenerative effects on experimental stroke. We investigated whether the endogenous serum IGF-I (s-IGF-I) levels correlated with recovery of functional independence in patients who had suffered an ischemic stroke. SUBJECTS AND METHODS: The s-IGF-I levels were measured in 407 patients (260 males, 147 females) with mean age of 55 (range, 18-69) yr and 40 randomly selected matched controls who were previously included in the Sahlgrenska Academy Study on Ischemic Stroke. Serum samples were collected on two occasions: acutely at 1-10 d (median, 4 d) after stroke and 3 months after the stroke. Recovery after ischemic stroke was evaluated using the modified Rankin scale 3 and 24 months after the stroke, and the Scandinavian Stroke Scale was used for assessments during the acute stage and 3 months after the stroke. RESULTS: The s-IGF-I levels were higher in the acute stage than after 3 months and compared with the controls (P < 0.001 and P < 0.01, respectively), and the s-IGF-I levels were progressively lower in the elderly patients. The levels of s-IGF-I in the acute phase and after 3 months both positively correlated with improvement in the modified Rankin scale scores between 3 and 24 months (P = 0.001; r = 0.174, and P < 0.001; r = 0.24, respectively). CONCLUSION: A high s-IGF-I during the rehabilitation phase of stroke correlates to better recovery of long-term function.
Assuntos
Isquemia Encefálica/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Recuperação de Função Fisiológica/fisiologia , Acidente Vascular Cerebral/sangue , Adolescente , Adulto , Idoso , Isquemia Encefálica/reabilitação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reabilitação do Acidente Vascular Cerebral , Resultado do TratamentoRESUMO
The thermodynamic stabilities of various phases of the nitrides of the platinum-metal elements are systematically studied using density functional theory. It is shown that for the nitrides of Rh, Pd, Ir, and Pt two new crystal structures, in which the metal ions occupy simple tetragonal lattice sites, have lower formation enthalpies at ambient conditions than any previously proposed structures. The region of stability with respect to those structures extends to 17 GPa for PtN2. Calculations show that the PtN2 simple tetragonal structures at this pressure are thermodynamically stable also with respect to phase separation. The fact that the local density and generalized gradient approximations predict different values of the absolute formation enthalpies as well different relative stabilities between simple tetragonal and the pyrite or marcasite structures are further discussed.
RESUMO
We present here a dynamic intensity model calculation of vibronic oscillator strengths for the Cs2NaNdCl6 compound by applying the method of molecular-dynamics simulation (MDS). The force field parameters used for the MDS reproduce the structure and several vibrational frequencies of Cs2NaNdCl6 very well. Both the static-coupling (SC) and dynamic-coupling (DC) mechanisms are taken into account for the intensity parameter calculations, in which the effective point charges and isotropic polarizabilities are optimized with respect to experimental energy levels. A comparison of intensity parameters and vibronic oscillator strengths between the two individual mechanisms indicates that the DC mechanism is operative. The calculated vibronic oscillator strengths for the combined SC and DC mechanism agree quite well with the available experimental values.