C-Reactive protein level and left ventricular mass are associated with acute cellular rejection after heart transplant

OBJECTIVES: Acute cellular rejection (ACR) remains a major complication of heart transplant (HT). The gold standard for its diagnosis is endomyocardial biopsy (EMB), whereas the role of non-invasive biomarkers for detecting ACR is unclear. This study aimed to identify non-invasive biomarkers for the diagnosis of ACR in patients undergoing HT and presenting with normal left ventricular function. METHODS: We evaluated patients who underwent HT at a single center between January 2010 and June 2019. Patients were enrolled after HT, and those with left ventricular (LV) systolic dysfunction before EMB were excluded. We included only the results of the first EMB performed at least 30 days after HT (median, 90 days). Troponin, B-type natriuretic peptide (BNP), and C-reactive protein (CRP) levels were measured and echocardiography was performed up to 7 days before EMB. ACR was defined as International Society for Heart and Lung Transplantation grade 2R or 3R on EMB. We performed logistic regression analysis to identify the non-invasive predictors of ACR (2R or 3R) and evaluated the accuracy of each using area under the receiver operator characteristic curve analysis. RESULTS: We analyzed 72 patients after HT (51.31±13.63 years; 25 [34.7%] women); of them, 9 (12.5%) developed ACR. Based on multivariate logistic regression analysis, we performed forward stepwise selection (entry criteria, p<0.05). The only independent predictors that remained in the model were CRP level and LV mass index. The optimal cut-off point for CRP level was ≥15.9 mg/L (odds ratio [OR], 11.7; p=0.007) and that for LV mass index was ≥111 g/m2 (OR, 13.6; p=0.003). The area under the receiver operating characteristic curve derived from this model was 0.87 (95% confidence interval [CI], 0.75-0.99), with sensitivity of 85.7% (95% CI, 42.1%-99.6%), specificity of 78.4% (95% CI, 64.7%-88.7%), positive predictive value of 35.3% (95% CI, 14.3%-61.7%), and negative predictive value of 97.6% (95% CI, 87.1%-99.9%). CONCLUSIONS: Among patients undergoing HT, CRP level and LV mass were directly associated with ACR, but troponin and BNP levels were not

Quantum degeneracy in atomic point contacts revealed by chemical force and conductance

Quantum degeneracy is an important concept in quantum mechanics with large implications to many processes in condensed matter. Here, we show the consequences of electron energy level degeneracy on the conductance and the chemical force between two bodies at the atomic scale. We propose a novel way in which a scanning probe microscope can detect the presence of degenerate states in atomic-sized contacts even at room temperature. The tunneling conductance G and chemical binding force F between two bodies both tend to decay exponentially with distance in a certain distance range, usually maintaining direct proportionality G∝F. However, we show that a square relation G∝F2 arises as a consequence of quantum degeneracy between the interacting frontier states of the scanning tip and a surface atom. We demonstrate this phenomenon on the Si(111)-(7×7) surface reconstruction where the Si adatom possesses a strongly localized dangling-bond state at the Fermi levelThis work was supported by Grants-in-Aid for Scientific Research (Grants No. 22221006, No. 24360016, No. 24651116, No. 22760028, and No. 25106002) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT), Funding Program for Next Generation World-Leading Researchers. P. J. and M. O. acknowledge the financial support of GAAV M100101207. M.O. acknowledges the support provided by the Czech Science Foundation (GAČR) under Project No. P204/11/P578. R. P. and P. P. acknowledge Projects No. MAT2011-23627, No. CSD2010-00024, No. PLE2009-0061 (MINECO, Spain), and CAM S2009/ MAT-1467. P. P. was supported by the Ramón y Cajal Program (MINECO, Spain

Caos e Fractais

Neste artigo, trabalharemos principalmente com a família quadrática Q_c(x) = x^2 + c, onde o valor real c é denominado parâmetro da família. Desenvolveremos uma teoria para compreendermos o comportamento das possíveis órbitas de um sistema. Em seguida introduziremos a noção de caos, apresentando as condições para que um sistema dinâmico seja considerado caótico. Por fim, apresentaremos também uma breve introdução a teoria dos fractais

Padrões de controle de crises em pacientes com epilepsia de lobo temporal com ou sem esclerose hipocampal

Objective Patients with mesial temporal lobe epilepsy (MTLE) may present unstable pattern of seizures. We aimed to evaluate the occurrence of relapse-remitting seizures in MTLE with (MTLE-HS) and without (MTLE-NL) hippocampal sclerosis. Method We evaluated 172 patients with MTLE-HS (122) or MTLE-NL (50). Relapse-remitting pattern was defined as periods longer than two years of seizure-freedom intercalated with seizure recurrence. Infrequent seizures was considered as up to three seizures per year and frequent seizures as any period of seizures higher than that. Results Thirty-seven (30%) MTLE-HS and 18 (36%) MTLE-NL patients had relapse-remitting pattern (X2, p = 0.470). This was more common in those with infrequent seizures (X2, p < 0.001). Twelve MTLE-HS and one MTLE-NL patients had prolonged seizure remission between the first and second decade of life (X2, p = 0.06). Conclusion Similar proportion of MTLE-HS or MTLE-NL patients present relapse-remitting seizures and this occurs more often in those with infrequent seizures.Patients with mesial temporal lobe epilepsy (MTLE) may present unstable pattern of seizures. We aimed to evaluate the occurrence of relapse-remitting seizures in MTLE with (MTLE-HS) and without (MTLE-NL) hippocampal sclerosis. Method: We evaluated 172 pat7327982FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO2005/56578-4; 2009/54552-9SEM INFORMAÇÃOPacientes com epilepsia do lobo temporal mesial (ELTM) podem apresentar padrão instável de crises epilépticas. Nosso objetivo foi avaliar ocorrência de crises remitente-recorrentes em ELTM com (ELTM-EH) e sem (ELTM-NL) esclerose hipocampal. Método: Ava

Evolução da epilepsia de lobo temporal mesial familiar

OBJECTIVE: To analyze seizure outcome in individuals with familial mesial temporal lobe epilepsy (FMTLE). METHOD: We followed prospectively 64 individuals with FMTLE and 37 asymptomatic individuals belonging to 28 families. RESULTS: Patients with FMTLE had a mean follow up was 93.4 ± 15.8 months. At baseline they were divided in benign (n = 29), remission (n = 28) and refractory (n = 7). At last follow up visit 41.4% patients with benign FMTLE remained classified as benign, 20.7% became refractory and 37.9% were in remission. In the subgroup of FMTLE in remission 21 75% remained without seizures; 21.4% were classified as benign FMTLE, and one died (3.6%) from cause unrelated to epilepsy. All refractory patients remained refractory. From the asymptomatic group, 10.8% became symptomatic (FMTLE). The mean follow up was 76.0 ± 21.2 months. CONCLUSION: Prospective follow up of more than 7 years in patients with FMTLE revealed that it is unlikely to achieve seizure control in those with refractory seizures. Patients with diagnose of more benign forms of FMTLE for more than one year are likely to either remit or remain under well controlled seizures. The majority of patients who had achieved seizure remission remained seizure-free and none became refractory. Asymptomatic individuals had a greater probability to have seizures compared to the general population in a 6 year period of follow up.OBJETIVOS: Analisar a evolução de famílias com epilepsia de lobo temporal mesial familiar (ELTMF). METODOLOGIA: Seguimento prospectivo de 64 pacientes com ELTMF e 37 membros assintomáticos pertencente a 28 famílias. RESULTADOS: A média de seguimento dos pacientes com ELTMF foi de 93,4 ± 15,8 meses. Na avaliação inicial os pacientes foram divididos em benignos (n = 29), remissão (n = 28) e refratários (n = 7). Na última visita disponível, 41,4% dos pacientes com ELTMF benigna permaneceram classificados como benignos, 20,7% tornaram-se refratários e 37,9% entraram em remissão. No grupo em remissão, 75% permaneceram livres de crise, 21,4% foram classificados como benignos e um faleceu (3,6%) de causa não relacionada à epilepsia. Todos pacientes refratários permaneceram refratários. Em relação aos assintomáticos 10,8% evoluíram com crises. A média de seguimento dos assintomáticos foi de 76,0 ± 21,2 meses. CONCLUSÃO: O seguimento prospectivo de mais de 7 anos de pacientes com ELTMF revelou que é improvável ocorrer controle de crises no grupo refratário. No grupo benigno é muito provável que estes indivíduos entrem em remissão ou permaneçam com evolução benigna. A maioria dos pacientes do grupo em remissão permaneceu em remissão e nenhum se tornou refratário. Em relação aos assintomáticos a probabilidade de apresentar uma crise no decorrer de aproximadamente 6 anos foi maior que o observado na população geral.111113Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Age-Related Maximum Heart Rate Among Ischemic and Nonischemic Heart Failure Patients Receiving beta-Blockade Therapy

Background: Equations to predict maximum heart rate (HRmax) in heart failure (HF) patients receiving beta-adrenergic blocking (BB) agents do not consider the cause of HF. We determined equations to predict HRmax in patients with ischemic and nonischemic HF receiving BB therapy. Methods and Results: Using treadmill cardiopulmonary exercise testing, we studied HF patients receiving BB therapy being considered for transplantation from 1999 to 2010. Exclusions were pacemaker and/or implantable defibrillator, left ventricle ejection fraction (LVEF) &gt;50%, peak respiratory exchange ratio (RER) &lt;1.00, and Chagas disease. We used linear regression equations to predict HRmax based on age in ischemic and nonischemic patients. We analyzed 278 patients, aged 47 +/- 10 years, with ischemic (n = 75) and nonischemic (n = 203) HF. LVEF was 30.8 +/- 9.4% and 28.6 +/- 8.2% (P = .04), peak VO2 16.9 +/- 4.7 and 16.9 +/- 5.2 mL kg(-1) min(-1) (P = NS), and the HRmax 130.8 +/- 23.3 and 125.3 +/- 25.3 beats/min (P = .051) in ischemic and nonischemic patients, respectively. We devised the equation HRmax = 168 - 0.76 x age (R-2 = 0.095; P = .007) for ischemic HF patients, but there was no significant relationship between age and HRmax in nonischemic HF patients (R-2 = 0.006; P = NS). Conclusions: Our study suggests that equations to estimate HRmax should consider the cause of HF. (J Cardiac Fail 2012;18:831-836)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2006/03910-4]Conselho Nacional de Pesquisa (CNPq) [304733/2008-3, 141272/2012-0

fabH deletion increases DHA productionin Escherichia coli expressing Pfa genes

Background: Some marine bacteria, such as Moritella marina, produce the nutraceutical docosahexaenoic acid (DHA) thanks to a specific enzymatic complex called Pfa synthase. Escherichia coli heterologously expressing the pfa gene cluster from M. marina also produces DHA. The aim of this study was to find genetic or metabolic conditions to increase DHA production in E. coli. Results: First, we analysed the effect of the antibiotic cerulenin, showing that DHA production increased twofold. Then, we tested a series of single gene knockout mutations affecting fatty acid biosynthesis, in order to optimize the synthesis of DHA. The most effective mutant, fabH, showed a threefold increase compared to wild type strain. The combination of cerulenin inhibition and fabH deletion rendered a 6.5-fold improvement compared to control strain. Both strategies seem to have the same mechanism of action, in which fatty acid synthesis via the canonical pathway (fab pathway) is affected in its first catalytic step, which allows the substrates to be used by the heterologous pathway to synthesize DHA. Conclusions: DHA-producing E. coli strain that carries a fabH gene deletion boosts DHA production by tuning down the competing canonical biosynthesis pathway. Our approach can be used for optimization of DHA production in different organisms.Funding: The work in the FdlC and GM laboratories was financed by the Spanish Ministry of Economy, Industry and Competitiveness Grant BFU2014-55534-C2