Estudio clínico y genético en carcinoma basocelular esporádico y asociado a Síndrome de Gorlin

[ES] El carcinoma basocelular (CBC) es el tumor más común en la población caucásica y constituye aproximadamente el 80% de los cánceres cutáneos no melanoma. Existen dos formas fundamentales de presentación: esporádica y asociada a genodermatosis, destacando el siíndrome de gorlin en este último grupo. En la patogenia molecular del carcinoma basocelular destacan las mutaciones en el gen PTCH1, que se encuentra involucrado en la vía de señalización sonic hedhehog. El objetivo de esta tesis doctoral es analizar las características clínicas y moleculares pacientes con carcinomas basocelulares esporádicos y con síndrome de Gorlin y de los tumores que desarrollan estos enfermos. Para llevar a cabo este proyecto se obtienen muestras de sangre periférica y de tumor de cada paciente para el estudio genético. Las muestras se procesan y se obtiene en ADN, que posteriormente se analiza. Primeramente se realiza estudio del gen PTCH1 mediante PCR y secuenciación directa. Posteriormente, se efectúa un estudio con CGH-array en las muestras tumorales, para identificar posibles regiones cromosómicas alteradas además de la región en la que está mapeada PTCH1. Se obtienen datos clínicos a partir de las historias clínicas de los pacientes y se revisan las muestras histológicas de los tumores. Se indentifican mutaciones patogénicas en PTCH1 con una frecuencia similar a la publicada en la literatura médica. Además, se localizan varias regiones cromsómicas alteradas con alta frecuencia en los dos tipos de pacientes

Síndrome de Gorlin

[ES]El síndrome de Gorlin es una enfermedad infrecuente de herencia autosómica dominante producida por mutaciones en genes de la vía de señalización Sonic Hedgehog, entre los que destaca PTCH1. Se caracteriza por el desarrollo de múltiples carcinomas basocelulares en edades tempranas, que pueden ir asociados a otras manifestaciones cutáneas como pits palmoplantares, o a manifestaciones extracutáneas, entre las que destacan los queratoquistes odontogénicos y el meduloblastoma. El papel del dermatólogo es importante en la sospecha de este síndrome, pero suele ser necesario un equipo multidisciplinar en el diagnóstico, seguimiento y en el tratamiento de estos pacientes. El tratamiento dermatológico puede ser complicado debido al alto número de carcinomas basocelulares y a su extensión. En los últimos años se han desarrollado nuevos fármacos que inhiben la vía Sonic Hedgehog y parecen prometedores para estos pacientes, aunque su eficacia está limitada por los efectos secundarios y la creación de resistencias.[EN]Gorlin syndrome is a rare autosomal dominant disease caused by mutations in the sonic hedgehog signaling pathway. Of particular importance is the PTCH1 gene. The disease is characterized by the development of multiple basal cell carcinomas at young ages. These tumors may present with other skin manifestations such as palmoplantar pits and with extracutaneous manifestations such as odontogenic keratocysts and medulloblastoma. Although the dermatologist may be key for recognizing clinical suspicion of the syndrome, a multidisciplinary team is usually necessary for diagnosis, treatment, and follow-up. Skin treatment may be complicated due to the large number of basal cell carcinomas and the extent of involvement

Designing ICTs for Users with Mild Cognitive Impairment: A Usability Study

Background: Research has supported the cost-effectiveness of cognitive training tools enhanced by information and communication technologies (ICT) in several populations, including individuals with mild cognitive impairment (MCI) and age-related cognitive decline. The implementation of ICTs in this population, however, is sometimes challenging to their cognitive and age characteristics. Ultimately, this might compromise the effectiveness of ICT-enhanced therapies in this population. The aim of this study is to test the usability and acceptability of a European project prototype for elderly care, in an attempt to explore the ICT design needs of users with MCI. Methods: Participants were 28 individuals aged 58-95 years and with a diagnosis of MCI. Results: The results showed a low perception of peripheral elements and the need to place main interaction elements in the centre of the screen. The correlation between the general level of autonomy (daily life activities) and the ICT autonomy level was significant and positive. The speed of audio help had a significant impact on performance. Conclusion: The present work contributes to the literature on ICT usability needs of users with MCI. Some usability recommendations for designing interfaces for this type of user are provided in the text

Brief Acceptance and Commitment Therapy for Fibromyalgia: Feasibility and Effectiveness of a Replicated Single-Case Design

Objective. Overall, the literature on the effectiveness of psychological treatments in general and those for fibromyalgia in particular has been dominated by research designs that focus on large groups and explore changes on average, so the treatment impact at the individual level remains unclear. In this quasi-experimental, replicated single-case design, we will test the feasibility and effectiveness of a brief acceptance and committed therapy intervention using ecological momentary assessment supported by technology. Methods. The sample comprised 7 patients (3 in the individual condition and 4 in the group condition) who received a brief, 5-week psychological treatment. Patient evolution was assessed one week prior to treatment onset and during the whole study with a smartphone app. Because ecological momentary assessment and the use of an app are not frequent practices in routine care, we also evaluated the feasibility of this assessment methodology (i.e., compliance with the app). Change was investigated with a nonoverlap of all pairs index. Outcomes were pain interference with sleep and social activities, fatigue, sadness, and pain intensity. Results. Patient change was not uniform across outcomes. Four patients (two in each condition) showed relatively moderate levels of change (approximately 60% nonoverlap in several outcomes). The remaining patients showed more modest improvements which affected a reduced number of outcomes. Based on nonoverlapping indices, there was no clear evidence in favor of any treatment format. Conclusions. An alternative design to large-scale trials, one that focuses on the individual change, exists and it can be implemented in pain research. The use of technology (e.g., smartphones) simplifies such designs by facilitating ecological momentary assessment. Based on our findings showing that changes were not homogeneous across patients or outcomes, more single-case designs and patient-centered analyses (e.g., responder and moderation analyses) are required

An internet-delivered Cognitive-Behavioral Therapy (iCBT) for Prolonged Grief Disorder (PGD) in adults: A multiple-baseline single-case experimental design study

The death of a loved one has physical, psychological, and social consequences. Between 9.8 and 21.5 % of people who lose a loved one develop Prolonged Grief Disorder (PGD). Internet- and computer-based interventions (i.e., Internet-delivered Cognitive-Behavioral Therapy, iCBT) are cost-effective and scalable alternatives that make it possible to reach more people with PGD. The main goal of the present investigation was to examine the effect and feasibility (usability and satisfaction) of an iCBT (GROw program) for adults with PGD. A secondary objective was to detect adherence to the app (Emotional Monitor) used to measure daily grief symptoms. The study had a single-case multiple-baseline AB design with six participants. The GROw program is organized sequentially in eight modules, and it is based on the dual-process model of coping with bereavement. Evaluations included a pre-to-post treatment assessment of depression, grief symptoms, and typical grief beliefs, along with daily measures of symptom frequency and intensity on the Emotional Monitor App. Treatment opinions and adherence to the App were also collected. Efficacy data were calculated using a Nonoverlap of All Pairs (NAP) analysis and Reliable Change Index (RCI). The mean age of the sample was 29.5 years (SD = 8.19). Two participants dropped out of the study. Adherence to the App varied across patients (4.8 % -77.8 %). Most participants (75 %) showed a clinically significant change (recovered) in depression, and 50 % obtained a clinically significant improvement (recovered) in symptoms of loss and typical beliefs in complicated grief. The participants reported high usability and satisfaction with the treatment content and format. In sum, the GROw program was very well accepted and generally feasible, and it has strong potential for treating PGD. The results support scaling up the treatment by using more complex designs with larger samples (i.e., randomized controlled trials comparing GROw with active conditions

Telemonitoring in chronic pain management using smartphone apps: a randomized controlled trial comparing usual assessment against app-based monitoring with and without clinical alarms

Abstract: Background. The usefulness of mHealth in helping to target face-to-face interventions for chronic pain more effectively remains unclear. In the present study, we aim to test whether the Pain Monitor mobile phone application (app) is well accepted by clinicians, and can help improve existent medical treatments for patients with chronic musculoskeletal pain. Regarding this last goal, we compared three treatment conditions, namely usual treatment, usual treatment with an app without alarms and usual treatment with an app with alarms. All treatments lasted one month. The three treatments were compared for all outcomes, i.e., pain severity and interference, fatigue, depressed mood, anxiety and anger. Methods. In this randomized controlled trial, the usual monitoring method (i.e., onsite; n = 44) was compared with daily ecological momentary assessment using the Pain Monitor app¿both with (n = 43) and without alarms (n = 45). Alarms were sent to the clinicians in the presence of pre-established undesired clinical events and could be used to make treatment adjustments throughout the one-month study. Results. With the exception of anger, clinically significant changes (CSC; 30% improvement) were greater in the app + alarm condition across outcomes (e.g., 43.6% of patients experienced a CSC in depressed mood in the app + alarm condition, which occurred in less than 29% of patients in the other groups). The clinicians were willing to use the app, especially the version with alarms. Conclusions. The use of apps may have some benefits in individual health care, especially when using alarms to tailor treatments

Identification of Smith–Magenis syndrome cases through an experimental evaluation of machine learning methods

This research work introduces a novel, nonintrusive method for the automatic identification of Smith–Magenis syndrome, traditionally studied through genetic markers. The method utilizes cepstral peak prominence and various machine learning techniques, relying on a single metric computed by the research group. The performance of these techniques is evaluated across two case studies, each employing a unique data preprocessing approach. A proprietary data “windowing” technique is also developed to derive a more representative dataset. To address class imbalance in the dataset, the synthetic minority oversampling technique (SMOTE) is applied for data augmentation. The application of these preprocessing techniques has yielded promising results from a limited initial dataset. The study concludes that the k-nearest neighbors and linear discriminant analysis perform best, and that cepstral peak prominence is a promising measure for identifying Smith–Magenis syndrome

Chiral Single-Molecule Potentiometers Based on Stapled ortho- Oligo(phenylene)ethynylenes

We report on the chemical design of chiral molecular junctions with stress-dependent conductance, whose helicity is maintained during the stretching of a single molecule junction due to the stapling of both ends of the inner helix. In the reported compounds, different conductive pathways are observed, with clearly different conductance values and plateau-length distributions, attributed to different conformations of the helical structures. The large chiro-optical responses and the potential use of these molecules as unimolecular spin filters have been theoretically proved using state-of-the-art Density Functional Theory (DFT) calculations, including a fully ab-initio estimation of the CISS-originating spin polarization which is done, for the first time, for a realistic molecular system

Evidence of the high prevalence of neurological disorders in nonsyndromic X-linked recessive ichthyosis: a retrospective case series

[Background]: X-linked recessive ichthyosis (XLI) is a relatively common type of ichthyosis caused by a deficiency in the steroid sulfatase (STS) enzyme. It is the only type of ichthyosis that can be both syndromic and nonsyndromic. Typical clinical features include dark-brown scale of variable size favouring the extensor surfaces of the extremities.[Objectives]: To characterize clinically nonsyndromic XLI, with a particular focus on extracutaneous manifestations.[Methods]: This was a multicentre retrospective review of clinical findings from a case series of patients with a clinical and genetic diagnosis of XLI.[Results]: We identified 30 patients with XLI belonging to 25 different families carrying a deletion in the STS locus. All patients had dark scales of variable size on the extensor surfaces of the extremities. Lack of flexural involvement and pruritus were common but inconsistent findings, whereas palmoplantar hyperlinearity was absent in all but one patient. A history of orchiopexy was present in 10% and thus was more common than expected vs. the general population (3%). Neurological disorders including epilepsy (13%) and attention deficit hyperactivity disorder (ADHD; 30%) were over-represented in patients with XLI.[Conclusions]: This was a retrospective study with a limited number of patients. In the absence of confirmatory genetic testing and family history of the disease, dark-brown scale of the extensor surfaces and the absence of palmoplantar hyperlinearity appear to be the most reliable clinical findings supporting a diagnosis of XLI. Dermatologists should be aware of the high prevalence of ADHD and epilepsy in patients with nonsyndromic XLI

Corpus y construcciones: perspectivas hispánicas

Los trabajos que integran este volumen constituyen una muestra significativa de las aportaciones actuales de la lingüística de corpus en el ámbito hispánico. La primera parte está dedicada al análisis de fenómenos gramaticales con datos de corpus. La segunda se centra en el diseño y elaboración de corpus textuales de diverso tipo, con especial atención a las posibilidades de recuperación y explotación de los datos que contienen. En ambos bloques se pone de manifiesto la variedad de recursos y métodos de análisis propiciados por el desarrollo de corpus tanto del español como de otras lenguas (gallego, portugués, alemán). Varios capítulos muestran la necesidad de un enfoque plurilingüe, bien para dar cuenta de fenómenos de variación y cambio en situaciones de contacto, bien para desarrollar recursos lingüísticos para la enseñanza de lenguas extranjeras o para la traducción. La autoría plural de la obra configura un panorama diverso y estimulante de las posibilidades que ofrece la lingüística de corpus para profundizar en el conocimiento de las lenguas.Axencia Galega de Innovación, ref. nº ED431B 2017/3