Change in fatigue in patients with ulcerative colitis or Crohn's disease initiating biologic therapy.

Background: Fatigue is common among patients with inflammatory bowel diseases (IBDs) and is associated with decreased quality of life (QoL).

Aims: Describe fatigue evolution and identify factors associated with fatigue outcomes in patients with ulcerative colitis (UC) or Crohn's disease (CD) initiating biologic treatment.

Methods: Data from adult Belgian patients with UC or CD enrolled in a prospective real-world study were utilized.

Association of real life postural transitions kinematics with fatigue in neurodegenerative and immune diseases.

Fatigue is prevalent in immune-mediated inflammatory and neurodegenerative diseases, yet its assessment relies largely on patient-reported outcomes, which capture perception but not fluctuations over time. Wearable sensors, like inertial measurement units (IMUs), offer a way to monitor daily activities and evaluate functional capacity. This study investigates the relationship between sit-to-stand and stand-to-sit transitions and self-reported physical and mental fatigue in participants with Parkinson's, Huntington's, rheumatoid arthritis, systemic lupus erythematosus, primary Sjögren's syndrome and inflammatory bowel disease.

Evaluation of walking activity and gait to identify physical and mental fatigue in neurodegenerative and immune disorders: preliminary insights from the IDEA-FAST feasibility study.

Background: Many individuals with neurodegenerative (NDD) and immune-mediated inflammatory disorders (IMID) experience debilitating fatigue. Currently, assessments of fatigue rely on patient reported outcomes (PROs), which are subjective and prone to recall biases. Wearable devices, however, provide objective and reliable estimates of gait, an essential component of health, and may present objective evidence of fatigue.

Fatigue-Related Changes of Daily Function: Most Promising Measures for the Digital Age.

Background: Fatigue is a prominent symptom in many diseases and is strongly associated with impaired daily function. The measurement of daily function is currently almost always done with questionnaires, which are subjective and imprecise. With the recent advances of digital wearable technologies, novel approaches to evaluate daily function quantitatively and objectively in real-life conditions are increasingly possible.

Identification of Fatigue and Sleepiness in Immune and Neurodegenerative Disorders from Measures of Real-World Gait Variability.

Current assessments of fatigue and sleepiness rely on patient reported outcomes (PROs), which are subjective and prone to recall bias. The current study investigated the use of gait variability in the "real world" to identify patient fatigue and daytime sleepiness. Inertial measurement units were worn on the lower backs of 159 participants (117 with six different immune and neurodegenerative disorders and 42 healthy controls) for up to 20 days, whom completed regular PROs.

Assessing fatigue and sleep in chronic diseases using physiological signals from wearables: A pilot study.

Problems with fatigue and sleep are highly prevalent in patients with chronic diseases and often rated among the most disabling symptoms, impairing their activities of daily living and the health-related quality of life (HRQoL). Currently, they are evaluated primarily Patient Reported Outcomes (PROs), which can suffer from recall biases and have limited sensitivity to temporal variations. Objective measurements from wearable sensors allow to reliably quantify disease state, changes in the HRQoL, and evaluate therapeutic outcomes.

Improving fatigue in multiple sclerosis by smartphone-supported energy management: The MS TeleCoach feasibility study.

Background: Fatigue is a frequently occurring, often disabling symptom in MS with no single effective treatment. In current fatigue management interventions, personalized, real-time follow-up is often lacking. The objective of the study is to assess the feasibility of the MS TeleCoach, a novel intervention offering telemonitoring of fatigue and telecoaching of physical activity and energy management in persons with MS (pwMS) over a 12-week period.

Do general practitioners and psychiatrists agree about defining cure from depression? The DEsCRIBE™ survey.

Background: This study aimed to document the outcome dimensions that physicians see as important in defining cure from depression. The study also aimed to analyse physicians' attitudes about depression and to find out whether they affect their prescribing practices and/or the outcome dimensions that they view as important in defining cure.

Methods: A 51-item questionnaire based on six validated scales was used to rate the importance of several depression outcome dimensions.

Amyloid, presenilins, and Alzheimer's disease.

The regulated intramembrane proteolysis of the amyloid precursor protein (APP) that results in the generation of a toxic 40 to 42 amino acid fragment, Abeta, and a C-terminal intracellular fragment stands central in the pathogenesis of Alzheimer's disease. The fibrillar Abeta peptide is extracellularly deposited in plaques in the amygdala, the hippocampus, and the neocortex of affected individuals. The APP intracellular fragment binds to transcription factors and is translocated to the nucleus, where it influences transcription.

gamma-Secretase activity requires the presenilin-dependent trafficking of nicastrin through the Golgi apparatus but not its complex glycosylation.

Nicastrin and presenilin are two major components of the gamma-secretase complex, which executes the intramembrane proteolysis of type I integral membrane proteins such as the amyloid precursor protein (APP) and Notch. Nicastrin is synthesized in fibroblasts and neurons as an endoglycosidase-H-sensitive glycosylated precursor protein (immature nicastrin) and is then modified by complex glycosylation in the Golgi apparatus and by sialylation in the trans-Golgi network (mature nicastrin). These modifications are not observed with exogenously overexpressed nicastrin.

Evidence that the beta-catenin nuclear translocation assay allows for measuring presenilin 1 dysfunction.

Background: Mutations in the presenilin (PSEN) genes are responsible for the majority of early-onset Alzheimer disease (AD) cases. PSEN1 is a component of a high molecular weight, endoplasmic reticulum, membrane-bound protein complex, including beta-catenin. Pathogenic PSEN1 mutations were demonstrated to have an effect on beta-catenin and glycogen synthase kinase-3beta(GSK-3beta), two members of the wingless Wnt pathway.

Molecular genetics of Alzheimer's disease: what have we learned?

Alzheimer's disease (AD), by far the most common form of dementia in the elderly, is clinically characterized by gradual, progressive loss in cognitive functioning and changes in personality, ultimately leading to death. It is now well established that genetic factors play an important role in AD. So far, three genes have been identified in which mutations cause autosomal-dominant AD: the amyloid precursor protein (APP) gene on chromosome 21, the presenilin 1 (PSEN1) gene on chromosome 14, and the homologous presenilin 2 (PSEN2) gene on chromosome 1.

Binding partners of Alzheimer's disease proteins: are they physiologically relevant?

Protein-protein interactions are a molecular basis for the structural and functional organization within cells. They are mediated by a growing number of protein modules that bind peptide targets. Alterations in binding affinities can have serious consequences for some essential cellular processes.

Genetic association of the presenilin-1 regulatory region with early-onset Alzheimer's disease in a population-based sample.

Genetic association has been reported between a di-allelic polymorphism in intron 8 of presenilin-1 (PSEN1) and Alzheimer's disease (AD) in some studies but not in others. In a population-based series of 102 patients with early onset AD and 118 community controls we examined whether polymorphisms in linkage disequilibrium with intron8 of PSEN1 may explain the association. In addition to the intron 8 polymorphism (P = 0.

Alzheimer's disease associated presenilin 1 interacts with HC5 and ZETA, subunits of the catalytic 20S proteasome.

Proteolytic processing and degradation tightly regulate the amount of stable, functional presenilin 1 (PSEN1) in the cell. The approximately 46-kDa PSEN1 holoprotein is cleaved into a approximately 30-kDa N-terminal fragment (NTF) and a approximately 20-kDa C-terminal fragment (CTF) by an unknown protease. The fragments are stabilized in a high molecular weight complex and nonincorporated fragments and excess holoprotein are degraded by the 26S proteasome.

Identification of caspases that cleave presenilin-1 and presenilin-2. Five presenilin-1 (PS1) mutations do not alter the sensitivity of PS1 to caspases.

Mutations in the presenilin (PS) genes PSI and PS2 are involved in Alzheimer's disease (AD). Recently, apoptosis-associated cleavage of PS proteins was identified. Here we demonstrate that PS1 as well as PS2 are substrates for different members of the caspase protein family.

Molecular genetic analysis of familial early-onset Alzheimer's disease linked to chromosome 14q24.3.

Genetic linkage studies have indicated that chromosome 14q24.3 harbours a major locus for early-onset (onset age <65 years) Alzheimer's disease (AD3). Positional cloning efforts have identified a novel gene S182 or presenilin 1 as the AD3 gene.

Mutation analysis of the chromosome 14q24.3 dihydrolipoyl succinyltransferase (DLST) gene in patients with early-onset Alzheimer disease.

Linkage analysis studies have indicated that the chromosome band 14q24.3 harbours a major gene for familial early-onset Alzheimer's disease (AD). Recently we localized the chromosome 14 AD gene (AD3) in the 6.

The role of endoscopic retrograde cholangiopancreatography: sphincterotomy versus common bile duct exploration as a primary technique in the management of choledocholithiasis.

253 patients underwent diagnostic or therapeutic intervention for a presumed diagnosis of choledocholithiasis. In 104 (mean age, 60 years) the diagnosis was confirmed by endoscopic retrograde cholangiopancreatography (ERCP) or common bile duct exploration (CBDE). Of this group, 70 patients first underwent a total of 102 attempts at endoscopic sphincterotomy (ERCP-S).

Molecular cloning and expression of cDNA for human antileukoprotease from cervix uterus.

We have isolated cDNA clones for the human antileukoprotease HUSI-I, an elastase inhibitor, from a library, containing cDNA inserts made from human cervix uterus. A library of 10 000 recombinants was screened using a mixture of 16 different oligodeoxyribonucleotides which correspond to amino acids 79-84 and one 20mer oligodeoxyribonucleotide corresponding to amino acids 19-26. Two overlapping cDNA clones, containing the entire coding sequence and part of the 5'- and 3'-untranslated region, were isolated.

5-Substituents in the uridine moiety and their effect on the conformation of ApU-type dinucleoside phosphates.

The ApU analogues ApT, Apcl5U, Apbr5U, Apa5U and Apno5(2)U were synthesized with the aid of ribonuclease U2 starting from 2',3'-cyclic Ap and the respective uridine derivatives. For these compounds the ultraviolet data, the difference spectra, the hypochromism and the temperature dependence of the CD spectra are reported. The dimerisation shifts of the pyrimidine protons which were obtained from the 100 MHz PMR spectra confirm the optical results.