Diagnosing dementia: No easy job

<p>Abstract</p> <p>Background</p> <p>From both clinical experience and research we learned that in complex progressive disorders such as dementia, diagnosis includes multiple steps, each with their own clinical and research characteristics.</p> <p>Discussion</p> <p>Diagnosing starts with a trigger phase in which the GP gradually realizes that dementia may be emerging. This is followed by a disease-oriented diagnosis and subsequently a care -oriented diagnosis. In parallel the GP should consider the consequences of this process for the caregiver and the interaction between both. As soon as a comprehensive diagnosis and care plan are available, monitoring follows.</p> <p>Summary</p> <p>We propose to split the diagnostic process into four diagnostic steps, followed by a monitoring phase. We recommend to include these steps when designing studies on screening, diagnosis and monitoring of patients with dementia and their families.</p

Planck pre-launch status: The optical system

Planck is a scientific satellite that represents the next milestone in space-based research related to the cosmic microwave background, and in many other astrophysical fields. Planck was launched on 14 May of 2009 and is now operational. The uncertainty in the optical response of its detectors is a key factor allowing Planck to achieve its scientific objectives. More than a decade of analysis and measurements have gone into achieving the required performances. In this paper, we describe the main aspects of the Planck optics that are relevant to science, and the estimated in-flight performance, based on the knowledge available at the time of launch. We also briefly describe the impact of the major systematic effects of optical origin, and the concept of in-flight optical calibration. Detailed discussions of related areas are provided in accompanying papers

An extraterrestrial trigger for the Early Cretaceous massive volcanism? Evidence from the paleo-Tethys Ocean

The Early Cretaceous Greater Ontong Java Event in the Pacific Ocean may have covered ca. 1% of the Earth's surface with volcanism. It has puzzled scientists trying to explain its origin by several mechanisms possible on Earth, leading others to propose an extraterrestrial trigger to explain this event. A large oceanic extraterrestrial impact causing such voluminous volcanism may have traces of its distal ejecta in sedimentary rocks around the basin, including the paleo-Tethys Ocean which was then contiguous with the Pacific Ocean. The contemporaneous marine sequence at central Italy, containing the sedimentary expression of a global oceanic anoxic event (OAE1a), may have recorded such ocurrence as indicated by two stratigraphic intervals with 187Os/188Os indicative of meteoritic influence. Here we show, for the first time, that platinum group element abundances and inter-element ratios in this paleo-Tethyan marine sequence provide no evidence for an extraterrestrial trigger for the Early Cretaceous massive volcanism

Digenic inheritance involving a muscle-specific protein kinase and the giant titin protein causes a skeletal muscle myopathy

\ua9 The Author(s) 2024.In digenic inheritance, pathogenic variants in two genes must be inherited together to cause disease. Only very few examples of digenic inheritance have been described in the neuromuscular disease field. Here we show that predicted deleterious variants in SRPK3, encoding the X-linked serine/argenine protein kinase 3, lead to a progressive early onset skeletal muscle myopathy only when in combination with heterozygous variants in the TTN gene. The co-occurrence of predicted deleterious SRPK3/TTN variants was not seen among 76,702 healthy male individuals, and statistical modeling strongly supported digenic inheritance as the best-fitting model. Furthermore, double-mutant zebrafish (srpk3−/−; ttn.1+/−) replicated the myopathic phenotype and showed myofibrillar disorganization. Transcriptome data suggest that the interaction of srpk3 and ttn.1 in zebrafish occurs at a post-transcriptional level. We propose that digenic inheritance of deleterious changes impacting both the protein kinase SRPK3 and the giant muscle protein titin causes a skeletal myopathy and might serve as a model for other genetic diseases

Digenic inheritance involving a muscle-specific protein kinase and the giant titin protein causes a skeletal muscle myopathy.

In digenic inheritance, pathogenic variants in two genes must be inherited together to cause disease. Only very few examples of digenic inheritance have been described in the neuromuscular disease field. Here we show that predicted deleterious variants in SRPK3, encoding the X-linked serine/argenine protein kinase 3, lead to a progressive early onset skeletal muscle myopathy only when in combination with heterozygous variants in the TTN gene. The co-occurrence of predicted deleterious SRPK3/TTN variants was not seen among 76,702 healthy male individuals, and statistical modeling strongly supported digenic inheritance as the best-fitting model. Furthermore, double-mutant zebrafish (srpk3-/-; ttn.1+/-) replicated the myopathic phenotype and showed myofibrillar disorganization. Transcriptome data suggest that the interaction of srpk3 and ttn.1 in zebrafish occurs at a post-transcriptional level. We propose that digenic inheritance of deleterious changes impacting both the protein kinase SRPK3 and the giant muscle protein titin causes a skeletal myopathy and might serve as a model for other genetic diseases

Quantifying activity changes of neuromuscular patients using the ACTIVLIM questionnaire: a 5-years longitudinal study

info:eu-repo/semantics/publishe