Prognostic relevance of CD163 immune cells in patients with metastatic breast cancer.

Metastatic breast cancer (MBC) is generally considered an incurable disease and even though new treatments are available, the median survival is approximately three years. The introduction of immune therapies for MBC highlights the importance of the immune system in cancer progression and treatment. CD163 anti-inflammatory myeloid cells, including tumor associated macrophages (TAMs), are known to be of relevance in early breast cancer but their role in MBC is not yet established.

ProSAAS is preferentially up-regulated during homeostatic scaling and reduces amyloid plaque burden in the 5xFAD mouse hippocampus.

The accumulation of β-amyloid in Alzheimer's disease greatly impacts neuronal health and synaptic function. To maintain network stability in the face of altered synaptic activity, neurons engage a feedback mechanism termed homeostatic scaling; however, this process is thought to be disrupted during disease progression. Previous proteomics studies have shown that one of the most highly regulated proteins in cell culture models of homeostatic scaling is the small secretory chaperone proSAAS.

Overlooked by the obstetric gaze - how women with persistent health problems due to severe perineal trauma experience encounters with healthcare services: a qualitative study.

Background: During the first year postpartum, about 25 per cent of Swedish women with severe perineal trauma (SPT), i.e., a third- or fourth-degree perineal laceration at childbirth, are unsatisfied with their healthcare contacts.

ProSAAS is Preferentially Secreted from Neurons During Homeostatic Scaling and Reduces Amyloid Plaque Size in the 5xFAD Mouse Hippocampus.

The accumulation of β-amyloid in Alzheimer's disease greatly impacts neuronal health and synaptic function. To maintain network stability in the face of altered synaptic activity, neurons engage a feedback mechanism termed homeostatic scaling; however, this process is thought to be disrupted during disease progression. Previous proteomics studies have shown that one of the most highly regulated proteins in cell culture models of homeostatic scaling is the small secretory chaperone proSAAS.

Comorbidities in childhood atopic dermatitis: A population-based study.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease that is associated with allergic comorbidities. However, studies examining comorbidities in childhood AD are incomplete, which may contribute to suboptimal care.

Objective: The objective was to compare the risk of developing different allergic and non-allergic comorbidities among children with AD to that of a matched non-AD reference cohort in Sweden.

SERCA2 regulates proinsulin processing and processing enzyme maturation in pancreatic beta cells.

Aims/hypothesis: Increased circulating levels of incompletely processed insulin (i.e. proinsulin) are observed clinically in type 1 and type 2 diabetes.

Negotiating the ambiguity of an (in)authentic working life: a grounded theory study into severe perineal trauma.

Background: In Sweden, persistent physical and psychological health problems occur in about three in ten women who sustain severe perineal trauma (SPT) during childbirth. As most Swedish women work outside the home, the question of if and how SPT-related morbidity influences working life needs exploration. This study aims to qualitatively explore how women with persistent SPT-related morbidities experience and conceptualise their problems concerning working life.

Regional and clinical guidelines for prevention and care of obstetric anal sphincter injuries - A critical frame analysis.

Objective: Policy documents govern how the prevention and care of obstetric anal sphincter injuries (OASIS) are implemented. Thus, in the absence of Swedish national guidelines on OASIS, differing views may be visible in the regional and local policy documents. Therefore, we aimed to analyse regional and local policies, guidelines, and care programs on the prevention of OASIS and care for OASIS-affected women in a Swedish context by applying a critical frame analysis inspired by Verloo.

Design, synthesis, and characterization of novel fluorogenic substrates of the proprotein convertases furin, PC1/3, PC2, PC5/6, and PC7.

Proprotein convertases (PCs) are involved in the pathogenesis of various diseases, making them promising drug targets. Most assays for PCs have been performed with few standard substrates, regardless of differences in cleavage efficiencies. Derived from studies on substrate-analogue inhibitors, 11 novel substrates were synthesized and characterized with five PCs.

Persistence With Biologic Treatments in Psoriasis: A Structured Literature Review of Studies Using Administrative Database and Clinical Registry Data.

Background: Psoriasis is a chronic, autoimmune-mediated inflammatory disorder. Drug persistence is a composite measure of effectiveness, safety, and treatment satisfaction, often estimated using data from administrative databases and clinical registries. Persistence rates calculated from these two data sources appear to be systematically different.

"It's all about time and timing": nursing staffs' experiences with an agile development process, from its initial requirements to the deployment of its outcome of ICT solutions to support discharge planning.

Background: Agile projects are statistically more likely to succeed then waterfall projects. The overall aim of this study was to explore the nursing staffs' experiences with an agile development process, from its initial requirements to the deployment of its outcome of ICT solutions aimed at supporting discharge planning.

Methods: An explorative design with quantitative and qualitative methods was used.

Sequestration of TDP-43 Aggregates by Cytoplasmic Expression of the proSAAS Chaperone.

As neurons age, protein homeostasis becomes less efficient, resulting in misfolding and aggregation. Chaperone proteins perform vital functions in the maintenance of cellular proteostasis, and chaperone-based therapies that promote sequestration of toxic aggregates may prove useful in blocking the development of neurodegenerative disease. We previously demonstrated that proSAAS, a small secreted neuronal protein, exhibits potent chaperone activity against protein aggregation in vitro and blocks the cytotoxic effects of amyloid and synuclein oligomers in cell culture systems.

Care pathways in atopic dermatitis: a retrospective population-based cohort study.

Background: Atopic dermatitis (AD) is a complex disease with variations in severity and healthcare utilization. Examining patient pathways through analyses of longitudinal patient data provides an opportunity to describe real-world clinical patient care and evaluate healthcare access and treatment.

Objective: To describe longitudinal care pathways including health care management, treatment patterns and disease progression (by proxy measures) in patients with AD.

The G209R mutant mouse as a model for human PCSK1 polyendocrinopathy.

PCSK1 encodes an enzyme required for prohormone maturation into bioactive peptides. A striking number of SNPs and rare mutations in PCSK1 are associated with a range of clinical phenotypes. Infants bearing two copies of a catalytically inactivating mutation, such as G209R, exhibit life-threatening chronic diarrhea and subsequently develop systemic endocrinopathies.

Validation of Patient Identification Algorithms for Atopic Dermatitis Using Healthcare Databases.

Introduction: The use of real-world data offers a possibility to perform large-scale epidemiological studies in actual clinical settings. Despite their many advantages, administrative databases were not designed to be used in research, and the validation of diagnoses and treatments in administrative databases is needed. The primary objective of this study was to validate an existing algorithm based on dispensed prescriptions and diagnoses of skin conditions to identify pediatric patients with atopic dermatitis (AD), using a diagnosis of AD in primary care as a gold standard.

Obesity, POMC, and POMC-processing Enzymes: Surprising Results From Animal Models.

Peptides derived from proopiomelanocortin (POMC) are well-established neuropeptides and peptide hormones that perform multiple functions, including regulation of body weight. In humans and some animals, these peptides include α- and β-melanocyte-stimulating hormone (MSH). In certain rodent species, no β-MSH is produced from POMC because of a change in the cleavage site.

Mice lacking PC1/3 expression in POMC-expressing cells do not develop obesity.

Pro-opiomelanocortin (POMC) neurons form an integral part of the central melanocortin system regulating food intake and energy expenditure. Genetic and pharmacological studies have revealed that defects in POMC synthesis, processing, and receptor signaling lead to obesity. It is well established that POMC is extensively processed by a series of enzymes, including prohormone convertases PC1/3 and PC2, and that genetic insufficiency of both PC1/3 and POMC is strongly associated with obesity risk.

Corrigendum to: Persistence of biologic treatments in psoriatic arthritis: a population-based study in Sweden.

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A protease protection assay for the detection of internalized alpha-synuclein pre-formed fibrils.

Alpha-synuclein pre-formed fibrils (PFFs) represent a promising model system for the study of cellular processes underlying cell-to-cell transmission of alpha-synuclein proteopathic aggregates. However, the ability to differentiate the fate of internalized PFFs from those which remain in the extracellular environment remains limited due to the propensity for PFFs to adhere to the cell surface. Removal of PFFs requires repeated washing and/or specific quenching of extracellular fluorescent PFF signals.

A novel economic framework to assess the cost-effectiveness of bone-forming agents in the prevention of fractures in patients with osteoporosis.

Unlabelled: A novel cost-effectiveness model framework was developed to incorporate the elevated fracture risk associated with a recent fracture and to allow sequential osteoporosis therapies to be evaluated. Treating patients with severe osteoporosis after a recent fracture with a bone-forming agent followed by antiresorptive therapy can be cost-effective compared with antiresorptive therapy alone. Incorporating these novel technical attributes in economic evaluations can support appropriate policy and reimbursement decision-making.

Cost-effectiveness of romosozumab for the treatment of postmenopausal women with severe osteoporosis at high risk of fracture in Sweden.

Unlabelled: Romosozumab is a novel bone-building drug that reduces fracture risk. This health economic analysis indicates that sequential romosozumab-to-alendronate can be a cost-effective treatment option for postmenopausal women with severe osteoporosis at high risk of fracture.

Purpose: To estimate the cost-effectiveness of sequential treatment with romosozumab followed by alendronate ("romosozumab-to-alendronate") compared with alendronate alone in patients with severe osteoporosis at high risk of fracture in Sweden.

Mouse Models of Human Proprotein Convertase Insufficiency.

The kexin-like proprotein convertases perform the initial proteolytic cleavages that ultimately generate a variety of different mature peptide and proteins, ranging from brain neuropeptides to endocrine peptide hormones, to structural proteins, among others. In this review, we present a general introduction to proprotein convertase structure and biochemistry, followed by a comprehensive discussion of each member of the kexin-like subfamily of proprotein convertases. We summarize current knowledge of human proprotein convertase insufficiency syndromes, including genome-wide analyses of convertase polymorphisms, and compare these to convertase null and mutant mouse models.

Secreted Chaperones in Neurodegeneration.

Protein homeostasis, or proteostasis, is a combination of cellular processes that govern protein quality control, namely, protein translation, folding, processing, and degradation. Disruptions in these processes can lead to protein misfolding and aggregation. Proteostatic disruption can lead to cellular changes such as endoplasmic reticulum or oxidative stress; organelle dysfunction; and, if continued, to cell death.