Capillaroscopy in 2016 : new perspectives in systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune disorder of unknown etiology characterized by early impairment of the microvascular system. Nailfold microangiopathy and decreased peripheral blood perfusion are typical clinical aspects of SSc. The best method to evaluate vascular injury is nailfold videocapillaroscopy, which detects peripheral capillary morphology, and classifies and scores the abnormalities into different patterns of microangiopathy. Microangiopathy appears to be the best evaluable predictor of the disease development and has been observed to precede the other symptoms by many years. Peripheral blood perfusion is also impaired in SSc, and there are different methods to assess it: laser Doppler and laser speckle techniques, thermography and other emerging techniques

Origins of empathy development in infancy

The current thesis examined the processes involved in the generation of empathy in infancy. This thesis endorses the combination of developmental and cognitive neuroscience techniques for a more comprehensive understanding of empathy. In support of this view, the current work has adopted a multi-method approach in which neuroimaging, psychophysiological and behavioral techniques have been used to examine the cognitive and affective aspects of empathy in infancy. Through a series of experimental studies, this thesis has addressed intertwined yet different aspects of the experience of empathy. Paper 1 investigated individual differences in 8-month-old infants’ neural responses to peers’ emotional non-verbal vocalizations by using event-related potential (ERP) method and parental reports of infants’ temperament. Results showed that infants responded differently to peers’ laughing and crying vocalizations, as indexed by modulations in the N100, P200 and late positive component (LPC). Of special interest, individual differences in negative emotionality were related to amplitude variations in the P200 and LPC components. Paper 2 expands on the previous results by examining frontal asymmetry patterns linked to infants’ affective and behavioral responses to a peer crying and a peer laughing. Eight-month-old infants underwent two assessment sessions on separate days, in which electroencephalography (EEG) and behavioral measures were respectively recorded in each day. EEG analysis showed that distinct neural patterns were related to the observation of a peer laughing and a peer crying, with greater right frontal activation being associated with the observation of a peer crying. Furthermore, correlational analysis suggested a positive relation between left frontal cortical activation and infants’ attempts to approach a peer crying or infants’ attempts to engage with a peer laughing. Following on from it, Paper 3 and 4 investigated potential neurocognitive mechanisms underlying affective and cognitive aspects of empathy. Paper 3 examined the role of motor mimicry and affective evaluation processes in infants’ facial matching responses to others’ emotional facial expressions by measuring spontaneous facial reactions (SFRs). In particular, 4- and 7-month old infants were presented with facial expressions of happiness, anger, and fear. Electromyography (EMG) was used to measure activation in muscles relevant for forming these expressions: zygomaticus major (smiling), corrugator (frowning), and frontalis (forehead raising). Results indicated no selective activation of the facial muscles for the expressions in 4-monthold infants. For 7-month-old infants, evidence for selective facial reactions was found especially for happy faces and fearful faces, while angry faces did not show a clear differential response. Paper 4 goes on to explore the ontogeneis of cognitive aspects of empathy by examining the neural correlates underlying false belief (FB) processing in 15-monthold infants. Using a passive non-verbal FB task, 15-month-old infants were presented with sequences of images depicting a character acting congruently (FBc) or incongruently (FBi) to her false belief about an object’s location, while EEG was continuously recorded. ERPs analysis revealed differences between conditions at frontal locations, as indexed by modulations in the N400 component. Specifically, a more negative N400 waveform was recorded for FBi as compared to FBc trials

Cost-effectiveness of Alzheimer's disease CSF biomarkers and amyloid-PET in early-onset cognitive impairment diagnosis

This study aimed at determining the cost-effectiveness of amyloid-positron emission tomography (PET) compared to Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers (amyloid-?42, total-Tau and phosphorylated-Tau) for the diagnosis of AD in patients with early-onset cognitive impairment. A decision tree model using a national health care perspective was developed to compare the costs and effectiveness associated with Amyloid-PET and AD CSF biomarkers. Available evidence from the literature and primary data from Hospital Clínic de Barcelona were used to inform the model and calculate the efficiency of these diagnostic alternatives. Medical visits and diagnostic procedures were considered and reported in €2020. We calculated the incremental cost-effectiveness ratio to measure the cost per % of correct diagnoses detected and we perform one-way deterministic and probabilistic sensitivity analyses to assess the uncertainty of these results. Compared with AD CSF biomarkers, Amyloid-PET resulted in 7.40% more correctly diagnosed cases of AD, with an incremental total mean cost of €146,854.80 per 100 cases. We found a 50% of probability that Amyloid-PET was cost-effective for a willingness to pay (WTP) of €19,840.39 per correct case detected. Using a WTP of €75,000, the probability that it is cost-effective reached a maximum of 76.9%, thus leading to a conclusion that Amyloid-PET is not a cost-effective technique compared to AD CSF biomarkers, unless the funder is willing to pay a minimum of €19,840.39 to detect one more correct case. Furthermore, obtaining CSF provides simultaneous information on amyloid ? and tau biomarkers and allows other biomarkers to be analyzed at a relatively low cost.© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany

Ion Current Rectification and Long-Range Interference in Conical Silicon Micropores

Fluidic devices exhibiting ion current rectification (ICR), or ionic diodes, are of broad interest for applications including desalination, energy harvesting, and sensing, amongst others. For such applications a large conductance is desirable which can be achieved by simultaneously using thin membranes and wide pores. In this paper we demonstrate ICR in micron sized conical channels in a thin silicon membrane with pore diameters comparable to the membrane thickness but both much larger than the electrolyte screening length. We show that for these pores the entrance resistance is not only key to Ohmic conductance around 0 V, but also for understanding ICR, both of which we measure experimentally and capture within a single analytic theoretical framework. The only fit parameter in this theory is the membrane surface potential, for which we find that it is voltage dependent and its value is excessively large compared to literature. From this we infer that surface charge outside the pore strongly contributes to the observed Ohmic conductance and rectification by a different extent. We experimentally verify this hypothesis in a small array of pores and find that ICR vanishes due to pore-pore interactions mediated through the membrane surface, while Ohmic conductance around 0 V remains unaffected. We find that the pore-pore interaction for ICR is set by a long-ranged decay of the concentration which explains the surprising finding that the ICR vanishes for even a sparsely populated array with a pore-pore spacing as large as 7 $\mu$m.Comment: 30 pages, 6 figures, Supplementary Information: 13 pages, 9 figure

Allele-specific editing ameliorates dominant retinitis pigmentosa in a transgenic mouse model

Retinitis pigmentosa (RP) is a group of progressive retinal degenerations of mostly monogenic inheritance, which cause blindness in about 1:3,500 individuals worldwide. Heterozygous variants in the rhodopsin (RHO) gene are the most common cause of autosomal dominant RP (adRP). Among these, missense variants at C-terminal proline 347, such as p.Pro347Ser, cause severe adRP recurrently in European affected individuals. Here, for the first time, we use CRISPR/Cas9 to selectively target the p.Pro347Ser variant while preserving the wild-type RHO allele in vitro and in a mouse model of adRP. Detailed in vitro, genomic, and biochemical characterization of the rhodopsin C-terminal editing demonstrates a safe downregulation of p.Pro347Ser expression leading to partial recovery of photoreceptor function in a transgenic mouse model treated with adeno-associated viral vectors. This study supports the safety and efficacy of CRISPR/Cas9-mediated allele-specific editing and paves the way for a permanent and precise correction of heterozygous variants in dominantly inherited retinal diseases

Ultrassonografia cardíaca en individus adietes a l'heroína intravenosa assimptomàtics: evidencia de lesions valvulars induïdes per l'adicció

Echocardiograph