Dropout from cognitive behavioural treatment in a case of bulimia nervosa: The role of the therapeutic alliance

Despite the refinement of the cognitive treatment for eating disorders, relatively high dropout rates represent a major problem for therapists and researchers. This study investigated the case of a patient with a diagnosis of bulimia nervosa, who dropped out of outpatient CBT after 28 weekly sessions. In addition to standard clinical outcome assessment, we examined how patient's psychological functioning and therapeutic alliance changed across sessions by applying observer-rating scales to the therapy transcripts. Although the patient reported some improvement at the six-month retest, observer ratings showed persistence of impaired functioning and frequent ruptures in the patient-therapist relationship throughout the treatment. We concluded that a thorough examination of the therapy process might help to understand the factors that lead to premature treatment termination

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Encephalopathies with intracranial calcification in children: clinical and genetic characterization

Abstract Background We present a group of patients affected by a paediatric onset genetic encephalopathy with cerebral calcification of unknown aetiology studied with Next Generation Sequencing (NGS) genetic analyses. Methods We collected all clinical and radiological data. DNA samples were tested by means of a customized gene panel including fifty-nine genes associated with known genetic diseases with cerebral calcification. Results We collected a series of fifty patients. All patients displayed complex and heterogeneous phenotypes mostly including developmental delay and pyramidal signs and less frequently movement disorder and epilepsy. Signs of cerebellar and peripheral nervous system involvement were occasionally present. The most frequent MRI abnormality, beside calcification, was the presence of white matter alterations; calcification was localized in basal ganglia and cerebral white matter in the majority of cases. Sixteen out of fifty patients tested positive for mutations in one of the fifty-nine genes analyzed. In fourteen cases the analyses led to a definite genetic diagnosis while results were controversial in the remaining two. Conclusions Genetic encephalopathies with cerebral calcification are usually associated to complex phenotypes. In our series, a molecular diagnosis was achieved in 32% of cases, suggesting that the molecular bases of a large number of disorders are still to be elucidated. Our results confirm that cerebral calcification is a good criterion to collect homogeneous groups of patients to be studied by exome or whole genome sequencing; only a very close collaboration between clinicians, neuroradiologists and geneticists can provide better results from these new generation molecular techniques

Encephalopathies with intracranial calcification in children: Clinical and genetic characterization

none42noBackground: We present a group of patients affected by a paediatric onset genetic encephalopathy with cerebral calcification of unknown aetiology studied with Next Generation Sequencing (NGS) genetic analyses. Methods: We collected all clinical and radiological data. DNA samples were tested by means of a customized gene panel including fifty-nine genes associated with known genetic diseases with cerebral calcification. Results: We collected a series of fifty patients. All patients displayed complex and heterogeneous phenotypes mostly including developmental delay and pyramidal signs and less frequently movement disorder and epilepsy. Signs of cerebellar and peripheral nervous system involvement were occasionally present. The most frequent MRI abnormality, beside calcification, was the presence of white matter alterations; calcification was localized in basal ganglia and cerebral white matter in the majority of cases. Sixteen out of fifty patients tested positive for mutations in one of the fifty-nine genes analyzed. In fourteen cases the analyses led to a definite genetic diagnosis while results were controversial in the remaining two. Conclusions: Genetic encephalopathies with cerebral calcification are usually associated to complex phenotypes. In our series, a molecular diagnosis was achieved in 32% of cases, suggesting that the molecular bases of a large number of disorders are still to be elucidated. Our results confirm that cerebral calcification is a good criterion to collect homogeneous groups of patients to be studied by exome or whole genome sequencing; only a very close collaboration between clinicians, neuroradiologists and geneticists can provide better results from these new generation molecular techniques.noneTonduti D.; Panteghini C.; Pichiecchio A.; Decio A.; Carecchio M.; Reale C.; Moroni I.; Nardocci N.; Campistol J.; Garcia-Cazorla A.; Perez Duenas B.; Zorzi G.; Ardissone A.; Granata T.; Freri E.; Zibordi F.; Ragona F.; D'Arrigo S.; Saletti V.; Esposito S.; Pantaleoni C.; Riva D.; De Giorgis V.; Cereda C.; Valente M.L.; Sproviero D.; Poo Arguelles M.P.; Estupina C.F.; Sans Fito A.M.; Martorell Sampol L.; Del Mar O'Callaghan Gordo M.; Ortez Gonzalez C.I.; Gonzalez Alvarez V.; Garcia-Segarra N.; Fusco C.; Bertini E.; Diodato D.; Fazzi E.; Galli J.; Chiapparini L.; Garavaglia B.; Orcesi S.Tonduti, D.; Panteghini, C.; Pichiecchio, A.; Decio, A.; Carecchio, M.; Reale, C.; Moroni, I.; Nardocci, N.; Campistol, J.; Garcia-Cazorla, A.; Perez Duenas, B.; Zorzi, G.; Ardissone, A.; Granata, T.; Freri, E.; Zibordi, F.; Ragona, F.; D'Arrigo, S.; Saletti, V.; Esposito, S.; Pantaleoni, C.; Riva, D.; De Giorgis, V.; Cereda, C.; Valente, M. L.; Sproviero, D.; Poo Arguelles, M. P.; Estupina, C. F.; Sans Fito, A. M.; Martorell Sampol, L.; Del Mar O'Callaghan Gordo, M.; Ortez Gonzalez, C. I.; Gonzalez Alvarez, V.; Garcia-Segarra, N.; Fusco, C.; Bertini, E.; Diodato, D.; Fazzi, E.; Galli, J.; Chiapparini, L.; Garavaglia, B.; Orcesi, S

Imagens em trânsito: as virgens de Luján e Sumampa e os circuitos coloniais na América Meridional na primeira metade do século XVII

This article seeks to analyze the materiality and part of the trajectory of two seventeenth-century terracotta statuettes - one of Nossa Senhora da Conceição and another of Nossa Senhora da Consolação - who respectively became the Virgin of Luján, patron of Argentina, and Virgen of Sumampa. Both are understood here as intertwined in the various networks and connections between the Portuguese and Spanish America in the contiguous areas of South America in the first half of the seventeenth century. In the text, we discuss a possible "Paulista" origin of these images which, in addition to an apparent coincidence, attests that the great "Peruvian space," articulated by Potosí, also included distinct regions of Portuguese America. Ii is in this expanded space marked by the traffic of people, goods and objects linked to the networks of smuggling that we follow the paths of these two images, trying to visualize how they got peculiar meanings in different contexts and environments.Neste artigo busca-se analisar a materialidade e parte da trajetória de duas imagens seiscentistas em terracota - uma de Nossa Senhora da Conceição e outra de Nossa Senhora da Consolação - que se tornaram, respectivamente, a Virgen de Luján, padroeira da Argentina, e a Virgen de Sumampa. Ambas são compreendidas aqui como entrelaçadas nas variadas redes e conexões estabelecidas entre a América portuguesa e espanhola, nos espaços contíguos da América Meridional na primeira metade do século XVII. No texto, discute-se uma possível procedência "paulista" dessas imagens, o que, para além de uma aparente casualidade, atesta como o grande "espaço peruano", articulado por Potosí, incluía também distintas regiões da América portuguesa. É nesse espaço ampliado, marcado pelo tráfego de pessoas, mercadorias e objetos atrelados às redes comerciais de contrabando, que acompanhamos os percursos dessas duas imagens, buscando visualizar como elas ganharam sentidos peculiares em ambientes e contextos diversos