Dopa-responsive dystonia and hyperprolactinaemia : a novel association in two sisters

Dopa-Responsive Dystonia (DRD) is a rare hereditary condition of childhood-onset dystonia which responds dramatically to treatment with levodopa. It was first described in 1971 as a "hereditary progressive basal ganglia disease with marked diurnal fluctuation". We describe a novel association between DRD and hyperprolactinaemia occurring in two sisters at the onset of puberty.peer-reviewe

Co-production in community-based substance use disorder treatment services : a scoping review

Purpose of review The personal and social harms from unmanaged substance use disorders (SUD) are substantial. Too few people with SUD are engaged in treatment, partly due to the acceptability and accessibility of services. Co-production – sharing power and decision-making between professionals and people with lived experience (PWLE) – could address barriers to improve uptake and outcomes of SUD treatment. This scoping review examined recent (18 months) literature on co-production in community SUD treatment services. Recent findings Co-production has been used to address barriers to care and co-design new interventions and services, especially for marginalised populations and groups with complex needs. Methods, processes, and the degree of meaningful involvement of PWLE varied across projects. Most work occurred in higher income countries and the impacts on PWLE were rarely explored. Summary Co-production is feasible and can inform the development of more patient-centred SUD treatment services. Projects should be grounded in theory and power differentials in decision-making addressed to ensure equitable and meaningful participation throughout the process. There is a need to explore co-production in the design and evaluation of general SUD treatment, sustainability, impacts on participants, and evaluation of long-term outcomes.Peer reviewe

The religiosity of adolescents and young adults in Malta : tracing trajectories

In a country where almost the totality of the native population is baptized and raised in the Catholic Church, recent surveys have shown several inconsistencies, especially among the young who claim that they do not believe. This study is a follow-up of another one that showed marked differences between the younger generation and older ones regarding the importance of religion in their life. Other surveys gave a similar picture. This study seeks to acquire a deeper understanding of the religiosity of these adolescents and young adults, this time with the use of two validated instruments. The first, the Meaning and Purpose Scales (MAPS), was meant to capture the essence of religion as a meaning-making mode. For the second, since the majority of the participants came from an organized religion, it was worth investigating the reasons why these adolescents were abandoning their religion and where they were going. This was attempted through the administration of the Adolescent Deconversion Scale (ADS). In addition, to detect deconversion-related changes, the participants were asked to undertake the Retrospective Analysis of Religiosity, a graphical method representing their religious development over the years by the plotting of a “religiosity line”. Following a number of contrasts between the test variables and others from the demographic information, a more defined and detailed picture of the religiosity of this segment of the population emerged. The absolute majority of the participants continue to profess their religion, and faith continues to be a major source of meaning in their life. In addition, there is a strong correlation between their personal sense of security and religion and the family, particularly for two-parent families. This study exposed a particular critical point in their religious journey, marking the beginning of a decline in their religion. This also coincides with the major developmental changes that take place during puberty. For the rest, perseverance in the faith journey was very strongly related to having participated for a number of years in a faith group. The family of origin and, later, belonging to a faith group seem to be decisive factors in the transmission and preservation of religiosity. As for those who left religion, the main reasons differed, including existential quests, peer influence, or simply indifference. Most, however, do not seem to have migrated to another religion or sect, and there are signs that many of them might have retained their own personal spirituality privately. Finally, it could be argued that, for some, their religious journey might not be over yet.peer-reviewe

Novel insights by 4D Flow imaging on aortic flow physiology after valve-sparing root replacement with or without neosinuses

This study was undertaken to evaluate the flow dynamics in the aortic root after valve-sparing root replacement with and without neosinuses of Valsalva reconstruction, by exploiting the capability of 4D Flow imaging to measure in vivo blood velocity fields and 3D geometric flow patterns

Fenómenos gramaticales y recursos modalizadores del enunciado en el español culto de Santiago de Chile

No presenta resume

Long-Term Clinical-Pathologic Results of Enzyme Replacement Therapy in Prehypertrophic Fabry Disease Cardiomyopathy

Background: The limited ability of enzyme replacement therapy (ERT) in removing globotriaosylceramide from cardiomyocytes is recognized for advanced Fabry disease cardiomyopathy (FDCM). Prehypertrophic FDCM is believed to be cured or stabilized by ERT. However, no pathologic confirmation is available. We report here on the long-term clinical-pathologic impact of ERT on prehypertrophic FDCM. Methods and results: Fifteen patients with Fabry disease with left ventricular maximal wall thickness ≤10.5 mm at cardiac magnetic resonance required endomyocardial biopsy because of angina and ventricular arrhythmias. Endomyocardial biopsy showed coronary small-vessel disease in the angina cohort, and vacuoles in smooth muscle cells and cardiomyocytes ≈20% of the cell surface containing myelin bodies at electron microscopy. Patients received α-agalsidase in 8 cases, and β-agalsidase in 7 cases. Both groups experienced symptom improvement except 1 patients treated with α-agalsidase and 1 treated with β-agalsidase. After ERT administration ranging from 4 to 20 years, all patients had control cardiac magnetic resonance and left ventricular endomyocardial biopsy because of persistence of symptoms or patient inquiry on disease resolution. In 13 asymptomatic patients with FDCM, left ventricular maximal wall thickness and left ventricular mass, cardiomyocyte diameter, vacuole surface/cell surface ratio, and vessels remained unchanged or minimally increased (left ventricular mass increased by <2%) even after 20 years of observation, and storage material was still present at electron microscopy. In 2 symptomatic patients, FDCM progressed, with larger and more engulfed by globotriaosylceramide myocytes being associated with myocardial virus-negative lymphocytic inflammation. Conclusions: ERT stabilizes storage deposits and myocyte dimensions in 87% of patients with prehypertrophic FDCM. Globotriaosylceramide is never completely removed even after long-term treatment. Immune-mediated myocardial inflammation can overlap, limiting ERT activity

Hacia una descripción prosódica del español culto de Santiago de Chile: resultados de una investigación

This article contains the final results of the research project FONDECYT 197/1053 whose aim is to attempt a description of educated Spanish as spoken in Santiago, Chile from a holistic viewpoint that considers the form and function of the prosodic systems at work in the variety under study. In the light of the results obtained from the auditory and acoustic analyses of samples taken from a 25-hour corpus of spoken Spanish, a description of the behaviour of the prosodic subsystems that interact with the segmental system to convey significant differences in meaning is proposed.Este artículo contiene los resultados finales del Proyecto FONDECYT 197/1053 cuyo objetivo es abordar la descripción del habla culta de Santiago de Chile desde una perspectiva holística, que considere con especial atención la forma y función de los sistemas prosódicos según estos se manifiestan en la variedad bajo estudio. A la luz de resultados obtenidos del análisis auditivo y acústico de muestras seleccionadas de habla tomadas de un corpus de 25 horas de duración, se propone una descripción del comportamiento de los subsistemas prosódicos que interactúan con el sistema segmental de la varie- dad bajo estudio para transmitir diferencias de significado distintivo

Risk of Aneurysm Rupture (ROAR) study:protocol for a long-term, longitudinal, UK multicentre study of unruptured intracranial aneurysms

IntroductionUnruptured intracranial aneurysms (UIA) are common in the adult population, but only a relatively small proportion will rupture. It is therefore essential to have accurate estimates of rupture risk to target treatment towards those who stand to benefit and avoid exposing patients to the risks of unnecessary treatment. The best available UIA natural history data are the PHASES study. However, this has never been validated and given the known heterogeneity in the populations, methods and biases of the constituent studies, there is a need to do so. There are also many potential predictors not considered in PHASES that require evaluation, and the estimated rupture risk is largely based on short-term follow-up (mostly 1 year). The aims of this study are to: (1) test the accuracy of PHASES in a UK population, (2) evaluate additional predictors of rupture and (3) assess long-term UIA rupture rates.Methods and analysisThe Risk of Aneurysm Rupture study is a longitudinal multicentre study that will identify patients with known UIA seen in neurosurgery units. Patients will have baseline demographics and aneurysm characteristics collected by their neurosurgery unit and then a single aggregated national cohort will be linked to databases of hospital admissions and deaths to identify all patients who may have subsequently suffered a subarachnoid haemorrhage. All matched admissions and deaths will be checked against medical records to confirm the diagnosis of aneurysmal subarachnoid haemorrhage. The target sample size is 20 000 patients. The primary outcome will be aneurysm rupture resulting in hospital admission or death. Cox regression models will be built to test each of the study’s aims.Ethics and disseminationEthical approval has been given by South Central Hampshire A Research Ethics Committee (21SC0064) and Confidentiality Advisory Group support (21CAG0033) provided under Section 251 of the NHS Act 2006. The results will be disseminated in peer-reviewed journals.Trial registration numberISRCTN17658526.</jats:sec