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Oxygen in Metabolic Dysfunction and Its Therapeutic Relevance

Significance: In recent years, a number of studies have shown altered oxygen partial pressure at a tissue level in metabolic disorders, and some researchers have considered oxygen to be a (macro) nutrient. Oxygen availability may be compromised in obesity and several other metabolism-related pathological conditions, including sleep apnea-hypopnea syndrome, the metabolic syndrome (which is a set of

Metabolomics Profiling of Patients With A-β+ Ketosis-Prone Diabetes During Diabetic Ketoacidosis

When stable and near-normoglycemic, patients with "A-β+" ketosis-prone diabetes (KPD) manifest accelerated leucine catabolism and blunted ketone oxidation, which may underlie their proclivity to develop diabetic ketoacidosis (DKA). To understand metabolic derangements in A-β+ KPD patients during DKA, we compared serum metabolomics profiles of adults during acute hyperglycemic crises, without (n =

The Outcome of Critically Ill COVID-19 Patients Is Linked to Thromboinflammation Dominated by the Kallikrein/Kinin System

An important manifestation of severe COVID-19 is the ARDS-like lung injury that is associated with vascular endothelialitis, thrombosis, and angiogenesis. The intravascular innate immune system (IIIS), including the complement, contact, coagulation, and fibrinolysis systems, which is crucial for recognizing and eliminating microorganisms and debris in the body, is likely to be involved in the path

Treatment of patients with Graves’ disease in Sweden compared to international surveys of an ‘index patient’

Introduction: The treatment strategies for a 42-year-old female index patient with moderate Graves’ disease (GD) vary according to several international surveys. The important question whether surveys of treatment preferences in theoretical patient cases also match how real patients are treated has not yet been addressed. Materials and Methods: From a Swedish cohort of 1186 GD patients (TT-12 coho

The combined impact of ankle–brachial index and transcutaneous oxygen pressure on mortality in patients with type 2 diabetes and foot ulcers

Aims: A diabetic foot ulcer (DFU) is associated with increased cardiovascular risk and mortality, independently of ulcer etiology (ischemic, neuro-ischemic or neuropathic). Ankle–brachial index (ABI) is the most commonly used test when diagnosing peripheral macrovascular disease and is a well-known marker for increased cardiovascular risk. Transcutaneous oxygen pressure (TcPO2) is considered to be

Predicting Type 1 Diabetes Onset using Novel Survival Analysis with Biomarker Ontology

Type 1 diabetes (T1D) is a chronic autoimmune disease that affects about 1 in 300 children and up to 1 in 100 adults during their life-time1. Improvements in early prediction of T1D onset may help prevent diagnosis for diabetic ketoacidosis, a serious complication often associated with a missed or delayed T1D diagnosis. In addition to genetic factors, progression to T1D is strongly associated with

Adherence to oral glucose tolerance testing in children in stage 1 of type 1 diabetes : The TEDDY study

Objective: To examine adherence to the oral glucose tolerance test (OGTT) in multiple islet autoantibody children in stage 1 of developing type 1 diabetes (T1D). Methods: Children are followed from birth in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Completion of an OGTT is recommended every 6 months in children ≥3 years of age who are multiple islet autoantibody positi

FS-GBDT : identification multicancer-risk module via a feature selection algorithm by integrating Fisher score and GBDT

Cancer is a highly heterogeneous disease caused by dysregulation in different cell types and tissues. However, different cancers may share common mechanisms. It is critical to identify decisive genes involved in the development and progression of cancer, and joint analysis of multiple cancers may help to discover overlapping mechanisms among different cancers. In this study, we proposed a fusion f

Migrant Middle Eastern women with gestational diabetes seven years after delivery-positive long-term development of beliefs about health and illness shown in follow-up interviews

Aim: No previous studies have been found focusing on the long-term development of beliefs about health, illness and healthcare in migrant women with gestational diabetes mellitus (GDM). The aim of this study was to explore this and the influence on health-related behaviour (i.e. self-care and care seeking) in migrant women from the Middle East living in Sweden seven years after delivery. Backgroun

Dangerous Proteins and Where to Find Them- Structural and functional studies of bacterial and viral proteins interacting with human immune receptors in health and disease

Bacteria and viruses are threats to human that evolved strategies to bypass the immune system and can cause massive damage. Understanding these strategies and elucidating pathogen interacting partners within the human immune system will pave the way for discovery of new medicines and increase human well-being. Superantigens (SAgs) are toxins that induce a massive immune response, causing sever dis

Advances in Type 1 Diabetes Prediction Using Islet Autoantibodies : Beyond a Simple Count

Islet autoantibodies are key markers for the diagnosis of type 1 diabetes. Since their discovery, they have also been recognized for their potential to identify at-risk individuals prior to symptoms. To date, risk prediction using autoantibodies has been based on autoantibody number; it has been robustly shown that nearly all multiple-autoantibody-positive individuals will progress to clinical dis

TRPV1 har viktig roll i hjärnan

The discovery of TRPV1 as a receptor for capsaicin, the pungent ingredient in chili pepper, and noxious heat has triggered immense research on the role of TRP channels as polymodal receptors in sensory neuronal signaling. The rich abundance of TRPV1 in nociceptive primary afferents and its involvement in inflammatory and neuropathic pain encouraged the development of analgesics acting on TRPV1. Ho

Two New Mutations in the CEL Gene Causing Diabetes and Hereditary Pancreatitis : How to Correctly Identify MODY8 Cases

Context: Maturity onset diabetes of the young, type 8 (MODY8) is associated with mutations in the CEL gene, which encodes the digestive enzyme carboxyl ester lipase. Several diabetes cases and families have in recent years been attributed to mutations in CEL without any functional or clinical evidence provided. Objective: To facilitate correct MODY8 diagnostics, we screened 2 cohorts of diabetes p

Alternative translation and retrotranslocation of cytosolic C3 that detects cytoinvasive bacteria

Complement C3 was originally regarded as a serum effector protein, although recent data has emerged suggesting that intracellular C3 can also regulate basic cellular processes. Despite the growing interest in intracellular C3 functions, the mechanism behind its generation has not been demonstrated. In this study we show that C3 can be expressed from an alternative translational start site, resulti

Acute cytokine treatment stimulates glucose uptake and glycolysis in human keratinocytes

During inflammation, cellular glucose uptake and glycolysis are upregulated to meet an increased energy demand. For example, keratinocyte glycolysis is essential for progression of psoriasis. Therefore, understanding the regulation of glucose metabolism in keratinocytes is of importance. Here, we show that the pro-inflammatory cytokines IFNγ and TNF together rapidly induce glucose uptake, glycolys

Metabolic and proteomic signatures of type 2 diabetes subtypes in an Arab population

Type 2 diabetes (T2D) has a heterogeneous etiology influencing its progression, treatment, and complications. A data driven cluster analysis in European individuals with T2D previously identified four subtypes: severe insulin deficient (SIDD), severe insulin resistant (SIRD), mild obesity-related (MOD), and mild age-related (MARD) diabetes. Here, the clustering approach was applied to individuals

How Communicating Polygenic and Clinical Risk for Atherosclerotic Cardiovascular Disease Impacts Health Behavior : an Observational Follow-up Study

Background: Prediction tools that combine polygenic risk scores with clinical factors provide a new opportunity for improved prediction and prevention of atherosclerotic cardiovascular disease, but the clinical utility of polygenic risk score has remained unclear. Methods: We collected a prospective cohort of 7342 individuals (64% women, mean age 56 years) and estimated their 10-year risk for athe

The human TRPA1 intrinsic cold and heat sensitivity involves separate channel structures beyond the N-ARD domain

TRP channels sense temperatures ranging from noxious cold to noxious heat. Whether specialized TRP thermosensor modules exist and how they control channel pore gating is unknown. We studied purified human TRPA1 (hTRPA1) truncated proteins to gain insight into the temperature gating of hTRPA1. In patch-clamp bilayer recordings, ∆1-688 hTRPA1, without the N-terminal ankyrin repeat domain (N-ARD), wa

A Web Portal for Communicating Polygenic Risk Score Results for Health Care Use—The P5 Study

We present a method for communicating personalized genetic risk information to citizens and their physicians using a secure web portal. We apply the method for 3,177 Finnish individuals in the P5 Study where estimates of genetic and absolute risk, based on genetic and clinical risk factors, of future disease are reported to study participants, allowing individuals to participate in managing their