Realization of nonequilibrium thermodynamic processes using external colored noise

We investigate the dynamics of single microparticles immersed in water that are driven out of equilibrium in the presence of an additional external colored noise. As a case study, we trap a single polystyrene particle in water with optical tweezers and apply an external electric field with flat spectrum but a finite bandwidth of the order of kHz. The intensity of the external noise controls the amplitude of the fluctuations of the position of the particle and therefore of its effective temperature. Here we show, in two different nonequilibrium experiments, that the fluctuations of the work done on the particle obey the Crooks fluctuation theorem at the equilibrium effective temperature, given that the sampling frequency and the noise cutoff frequency are properly chosen

Noninvasive assessment of patients undergoing percutaneous intervention in myocardial infarction

FUNDAMENTO: A reestenose pós-intervenção coronariana percutânea primária permanece um problema de relevância clínica, mesmo com o implante de stents. A capacidade das provas não invasivas para detecção de reestenose não foi totalmente demonstrada. OBJETIVO: Avaliar a habilidade do teste ergométrico (TE) e da cintilografia de perfusão miocárdica (CPM) no diagnóstico de reestenose em pacientes com infarto agudo do miocárdio, e supradenivelamento do segmento ST, submetidos à angioplastia coronariana percutânea primária (ACPP), com implante de stent nas primeiras 12 horas de evolução. MÉTODOS: De Ago/2003-Jan/2006, foram selecionados 64 pacientes (ps) (56,2 ± 10,2 anos, 53 homens) submetidos à ACPP. Apenas ps com fração de ejeção do ventrículo esquerdo > 40,0%, definida por ecocardiograma de repouso, foram incluídos. Teste ergométrico, com as 12 derivações do ECG associadas a precordiais direitas, e CPM foram realizados 6 semanas, 6 meses e um ano após o tratamento. Foi realizada cinecoronariografia no 6º mês. RESULTADOS: Doença uniarterial ocorreu em 46,9% dos ps, sendo a artéria descendente anterior tratada em 48,4%. Reestenose angiográfica ocorreu em 28,8%. Sensibilidade, especificidade, valor preditivo positivo (VPP), valor preditivo negativo (VPN) e acurácia do TE para detecção de reestenose não foram significativos. A adição de derivações precordiais direitas não proporcionou informações adicionais. Sensibilidade, especificidade, VPP, VPN e acurácia da CPM apresentaram correlação com reestenose apenas no 6º mês, considerando-se summed difference score > 2 (p = 0,006) e > 4 (p = 0,014). CONCLUSÃO: O TE não discriminou reestenose. A CPM realizada no 6º mês foi relacionada à reestenose e mostrou-se útil durante a evolução.BACKGROUND: Restenosis after primary percutaneous coronary intervention (PPCI) remains an important clinical problem, even with stent implantation. The ability of noninvasive testing to diagnose restenosis has had only inconsistent demonstration. OBJECTIVE: Our objective was to evaluate the ability of exercise treadmill testing (ETT) and myocardial perfusion imaging (MPI) to diagnose restenosis in patients treated by PPCI within 12 hours of ST-elevation myocardial infarction (STEMI). METHODS: From August 2003 to January 2006, 64 patients (mean age of 56.2±10.2 years, 53 males) were enrolled after PPCI. Only patients with left ventricular ejection fraction (LVEF) > 40%, as assessed by resting transthoracic echocardiography (TTE), were included. ETT with 12-lead ECG monitoring and right precordial leads, as also MPI were performed at 6 weeks, 6 months, and one year after intervention. Coronary angiography was performed at six months. RESULTS: Single-vessel disease was observed in 46.9% of the patients. The left anterior descending coronary artery was treated in 48.4% of the patients. Angiographic restenosis occurred in 28.8%. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of ETT in detecting restenosis were not significant. Right precordial leads did not add information. MPI sensitivity, specificity, PPV, NPV, and accuracy correlated with restenosis only in the 6-month follow-up, both when considering summed difference score >2 (p=0.006) and >4 (p=0.014). CONCLUSION: ETT did not discriminate restenosis in this population. MPI performed at 6 months correlated with restenosis and proved useful during follow-up

Genetic reanalysis of patients with a difference of sex development carrying the NR5A1/SF-1 variant p.Gly146Ala has discovered other likely disease-causing variations.

NR5A1/SF-1 (Steroidogenic factor-1) variants may cause mild to severe differences of sex development (DSD) or may be found in healthy carriers. The NR5A1/SF-1 c.437G>C/p.Gly146Ala variant is common in individuals with a DSD and has been suggested to act as a susceptibility factor for adrenal disease or cryptorchidism. Since the allele frequency is high in the general population, and the functional testing of the p.Gly146Ala variant revealed inconclusive results, the disease-causing effect of this variant has been questioned. However, a role as a disease modifier is still possible given that oligogenic inheritance has been described in patients with NR5A1/SF-1 variants. Therefore, we performed next generation sequencing (NGS) in 13 DSD individuals harboring the NR5A1/SF-1 p.Gly146Ala variant to search for other DSD-causing variants and clarify the function of this variant for the phenotype of the carriers. Panel and whole-exome sequencing was performed, and data were analyzed with a filtering algorithm for detecting variants in NR5A1- and DSD-related genes. The phenotype of the studied individuals ranged from scrotal hypospadias and ambiguous genitalia in 46,XY DSD to opposite sex in both 46,XY and 46,XX. In nine subjects we identified either a clearly pathogenic DSD gene variant (e.g. in AR) or one to four potentially deleterious variants that likely explain the observed phenotype alone (e.g. in FGFR3, CHD7). Our study shows that most individuals carrying the NR5A1/SF-1 p.Gly146Ala variant, harbor at least one other deleterious gene variant which can explain the DSD phenotype. This finding confirms that the NR5A1/SF-1 p.Gly146Ala variant may not contribute to the pathogenesis of DSD and qualifies as a benign polymorphism. Thus, individuals, in whom the NR5A1/SF-1 p.Gly146Ala gene variant has been identified as the underlying genetic cause for their DSD in the past, should be re-evaluated with a NGS method to reveal the real genetic diagnosis

Recessive mutations in the INS gene result in neonatal diabetes through reduced insulin biosynthesis

Heterozygous coding mutations in the INS gene that encodes preproinsulin were recently shown to be an important cause of permanent neonatal diabetes. These dominantly acting mutations prevent normal folding of proinsulin, which leads to beta-cell death through endoplasmic reticulum stress and apoptosis. We now report 10 different recessive INS mutations in 15 probands with neonatal diabetes. Functional studies showed that recessive mutations resulted in diabetes because of decreased insulin biosynthesis through distinct mechanisms, including gene deletion, lack of the translation initiation signal, and altered mRNA stability because of the disruption of a polyadenylation signal. A subset of recessive mutations caused abnormal INS transcription, including the deletion of the C1 and E1 cis regulatory elements, or three different single base-pair substitutions in a CC dinucleotide sequence located between E1 and A1 elements. In keeping with an earlier and more severe beta-cell defect, patients with recessive INS mutations had a lower birth weight (-3.2 SD score vs. -2.0 SD score) and were diagnosed earlier (median 1 week vs. 10 weeks) compared to those with dominant INS mutations. Mutations in the insulin gene can therefore result in neonatal diabetes as a result of two contrasting pathogenic mechanisms. Moreover, the recessively inherited mutations provide a genetic demonstration of the essential role of multiple sequence elements that regulate the biosynthesis of insulin in man

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Track D Social Science, Human Rights and Political Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138414/1/jia218442.pd