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The circulating dihydrotestosterone/testosterone ratio is increased by gut microbial 5α-reductase activity in females

Background: Dihydrotestosterone (DHT), the most potent ligand to the androgen receptor, is synthesised from testosterone (T) by 5α-reductase type 1 and 2. While type 1 is expressed in several non-reproductive tissues in both sexes, men also express high levels of the high-affinity type 2 isoform in reproductive tissues; yet women have a higher circulating DHT to T (DHT/T) ratio than men. We hypoth

Associations between physical activity and CVD-related metabolomic and proteomic biomarkers

Aim Habitual physical activity (PA) affects metabolism and homeostasis in various tissues and organs. However, detailed knowledge of associations between PA and cardiovascular disease (CVD) risk markers is limited. We sought to identify associations between accelerometer-assessed PA classes and 183 proteomic and 154 metabolomic CVD-related biomarkers. Method We utilized cross-sectional data from t

Addressing fatty tissue in quantitative susceptibility mapping of human knee cartilage

Objective: To evaluate the effects of excluding fatty tissue in QSM of human knee cartilage. Materials and methods: Gradient echo images from 18 knee-healthy volunteers were acquired, from which chemical shift corrected field perturbation maps were calculated. Based on these, QSM maps were reconstructed using morphology enabled dipole inversion and one of three masking alternatives: (1) excluding

Genomic editing of metformin efficacy-associated genetic variants in SLC47A1 does not alter SLC47A1 expression

Several pharmacogenetics studies have identified an association between a greater metformin-dependent reduction in HbA1c levels and the minor A allele at rs2289669 in intron 10 of SLC47A1, encoding multidrug and toxin extrusion 1 (MATE1), a presumed metformin transporter. It is currently unknown if the rs2289669 locus is a cis-eQTL, which would validate its role as predictor of metformin efficacy.

Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-ba

Dopamine Cell Therapy : From Cell Replacement to Circuitry Repair

Cell therapy for Parkinson's disease (PD) is aimed to replace the degenerated midbrain dopamine (mDA) neurons and restore DA neurotransmission in the denervated forebrain targets. A limitation of the intrastriatal grafting approach, which is currently used in clinical trials, is that the mDA neurons are implanted into the target area, in most cases the putamen, and not in the ventral midbrain wher

Pre- and Postoperative Circulating IGF-I, IGFBP-3, and IGFBP-7 Levels in Relation to Endocrine Treatment and Breast Cancer Recurrence : A Nested Case-Control Study

Insulin-like growth factor-I (IGF-I) and its binding proteins (BPs) have been associated with breast cancer risk, especially high IGF-I concentrations and the biologically active fraction estimated as the IGF-I/IGFBP-3 molar ratio. The relation of circulating IGF-I and IGFBP-3 concentrations with risk of breast cancer recurrence has been less documented. In addition a new member to a sub-group of

Replication study reveals miR-483-5p as an important target in prevention of cardiometabolic disease

BackgroundAlterations in levels of circulating micro-RNAs might reflect within organ signaling or subclinical tissue injury that is linked to risk of diabetes and cardiovascular risk. We previously found that serum levels of miR-483-5p is correlated with cardiometabolic risk factors and incidence of cardiometabolic disease in a case–control sample from the populations-based Malmö Diet and Cancer S

Cardiovascular risk factors and autonomic indices in relation to fatal and non-fatal coronary events

OBJECTIVE: Mortality caused by coronary artery disease has markedly decreased in recent years. However, a substantial proportion of patients suffering a coronary event (CE) die within the first day, most of them out of hospital. We aimed to investigate how established cardiovascular (CV) risk factors and CV autonomic indices associate with fatal versus non-fatal CEs in the population.METHODS: 33 0

Associations Between Endometriosis and Gut Microbiota

The gut microbiota has been associated with many diseases, including endometriosis. However, very few studies have been conducted on this topic in human. This study aimed to investigate the association between endometriosis and gut microbiota. Women with endometriosis (N=66) were identified at the Department of Gynaecology and each patient was matched with three controls (N=198) from the general p

Deep learning for inverse problems in quantum mechanics

Inverse problems are important in quantum mechanics and involve such questions as finding which potential give a certain spectrum or which arrangement of atoms give certain properties to a molecule or solid. Inverse problems are typically very hard to solve and tend to be very compute intense. We here show that neural networks can easily solve inverse problems in quantum mechanics. It is known tha

Psychometric Properties of the Walking Impact Scale (Walk-12) in Persons with Late Effects of Polio

Background: Many persons with late effects of polio (LEoP) perceive walking limitations in everyday life. A common rating scale to assess walking limitations is the Walking Impact Scale (Walk-12). However, there is limited knowledge about its psychometric properties. Objective: To investigate the psychometric properties of Walk-12 in persons with LEoP. Design: Rasch model analysis of cross-section

Exploring Patient-Specific Cell Replacement Therapy for Parkinson's Disease

Parkinson’s disease (PD) affects over six million people worldwide and is characterised by the progressive loss of dopaminergic (DA) neurons in the substantia nigra, accumulation of pathological alpha-synuclein (αSyn), and inflammation in the brain. This leads to motor impairments including rigidity, akinesia, bradykinesia, resting tremor, and postural instability. Cell replacement therapy aims to

Single-Cell Profiling of Coding and Noncoding Genes in Human Dopamine Neuron Differentiation

Dopaminergic (DA) neurons derived from human pluripotent stem cells (hPSCs) represent a renewable and available source of cells useful for understanding development, developing disease models, and stem-cell therapies for Parkinson's disease (PD). To assess the utility of stem cell cultures as an in vitro model system of human DA neurogenesis, we performed high-throughput transcriptional profiling

A bacterial protease depletes c-MYC and increases survival in mouse models of bladder and colon cancer

Is the oncogene MYC upregulated or hyperactive? In the majority of human cancers, finding agents that target c-MYC has proved difficult. Here we report specific bacterial effector molecules that inhibit cellular MYC (c-MYC) in human cells. We show that uropathogenic Escherichia coli (UPEC) degrade the c-MYC protein and attenuate MYC expression in both human cells and animal tissues. c-MYC protein

Long-Haul Post–COVID-19 Symptoms Presenting as a Variant of Postural Orthostatic Tachycardia Syndrome: The Swedish Experience

Major clinical centers in Sweden have witnessed an inflow of patients with chronic symptoms following initial outpatient care for coronavirus disease-2019 (COVID-19) infection, suggestive of postural orthostatic tachycardia syndrome. This report presents the first case series of 3 Swedish patients diagnosed with postural orthostatic tachycardia syndrome more than 3 months after the primary COVID-2

Cadmium exposure and coronary artery atherosclerosis : A cross-sectional population-based study of swedish middle-aged adults

BACKGROUND: The general population is ubiquitously exposed to the toxic metal cadmium through the diet and smoking. Cadmium exposure is associated with increased morbidity and mortality in myocardial infarction and stroke. Atherosclerosis is the main underlying mechanism of myocardial infarction. However, associations between cadmium and coronary artery atherosclerosis have not been examined. OBJE

Functional and Oncological Outcomes After Open Versus Robot-assisted Laparoscopic Radical Prostatectomy for Localised Prostate Cancer : 8-Year Follow-up

Background: Radical prostatectomy reduces mortality among patients with localised prostate cancer. Evidence on whether different surgical techniques can affect mortality rates is lacking. Objective: To evaluate functional and oncological outcomes 8 yr after robot-assisted laparoscopic prostatectomy (RALP) and open retropubic radical prostatectomy (RRP). Design, setting, and participants: We enroll

Nontypeable haemophilus influenzae P5 binds human C4b-binding protein, promoting serum resistance

Nontypeable Haemophilus influenzae (NTHi) is a Gram-negative human pathogen that causes infections mainly in the upper and lower respiratory tract. The bacterium is associated with bronchitis and exacerbations in patients suffering from chronic obstructive pulmonary disease and frequently causes acute otitis media in preschool children. We have previously demonstrated that the binding of C4b bindi