Deep Proteome Coverage of Microglia Using a Streamlined Data-Independent Acquisition-Based Proteomic Workflow: Method Consideration for a Phenotypically Diverse Cell Type.

As the primary innate immune cells of the brain, microglia play a key role in various homeostatic and disease-related processes. To carry out their numerous functions, microglia adopt a wide range of phenotypic states. The proteomic landscape represents a more accurate molecular representation of these phenotypes; however, microglia present unique challenges for proteomic analysis.

Inflammatory Risk Factors for Chronic Subdural Hematoma in a Nationwide Cohort.

Background: The discovery of biomarkers in chronic subdural haematomas (CSDH) suggests that inflammation is part of CSDH pathophysiology. It is unknown whether inflammation reflects an independent CSDH driver or haematoma degeneration. This knowledge holds a potential target for anti-inflammatory treatment in patients at risk of CSDH.

Ischaemic cardiotoxicity of aromatase inhibitors in postmenopausal patients with early breast cancer in Denmark: a cohort study of real-world data.

Background: For aromatase inhibitor treatment (AIT) in breast cancer, there is an unresolved concern about ischaemic cardiotoxicity. We investigated the association between AIT and ischaemic cardiotoxicity in a prospective cohort of female patients with early breast cancer who received contemporary treatment in Denmark.

Methods: In this prospective cohort study in Denmark, we identified postmenopausal patients of any age diagnosed with breast cancer as recorded in the nationwide Danish Breast Cancer Cooperative Group (DBCG) clinical database between Jan 1, 2009, and Dec 31, 2020, and linked them to other nationwide registries.

A semi-automated workflow for DIA-based global discovery to pathway-driven PRM analysis.

Targeted proteomics, which includes parallel reaction monitoring (PRM), is typically utilized for more precise detection and quantitation of key proteins and/or pathways derived from complex discovery proteomics datasets. Initial discovery-based analysis using data independent acquisition (DIA) can obtain deep proteome coverage with low data missingness while targeted PRM assays can provide additional benefits in further eliminating missing data and optimizing measurement precision. However, PRM method development from bioinformatic predictions can be tedious and time-consuming because of the DIA output complexity.

Fkbp5 gene deletion: Circadian rhythm profile and brain proteomics in aged mice.

FKBP51, also known as FK506-binding protein 51, is a molecular chaperone and scaffolding protein with significant roles in regulating hormone signaling and responding to stress. Genetic variants in FKBP5, which encodes FKBP51, have been implicated in a growing number of neuropsychiatric disorders, which has spurred efforts to target FKBP51 therapeutically. However, the molecular mechanisms and sub-anatomical regions influenced by FKBP51 in these disorders are not fully understood.

A Simplified Method for Comprehensive Capture of the Proteome.

is a major human pathogen causing myriad infections in both community and healthcare settings. Although well studied, a comprehensive exploration of its dynamic and adaptive proteome is still somewhat lacking. Herein, we employed streamlined liquid- and gas-phase fractionation with PASEF analysis on a TIMS-TOF instrument to expand coverage and explore the dark proteome.

Low-density lipoprotein cholesterol response to statins according to comorbidities and co-medications: A population-based study.

Background: The response of low-density lipoprotein cholesterol (LDL-C) to statin therapy is variable, and may be affected by the presence of co-morbid conditions or the use of concomitant medications. Systematic variation in the response to statins based on these factors could affect the selection of the statin treatment regimen in population subgroups. We investigated whether common comorbidities and co-medications had clinically important effects on statin responses in individual patients.

A pilot study exploring time- and dose-dependent DNA damage and chromosomal instability caused by benzo[a]pyrene in two urothelial cell types.

Environmental and occupational exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with adverse health effects in humans. Uncertainty exists regarding the causation of urinary bladder cancer by benzo[a]pyrene (B[a]P) due to a lack of sufficient data. In this work, we focused on in-vitro DNA damage and the formation of micronuclei and chromosomal aberrations as predictors of cancer risk, applying a wide range of dosages and time periods to quantify the onset, intensity, and duration of the response.

Post-migration HIV acquisition: A systematic review and meta-analysis.

Migrants in Europe face a disproportionate burden of HIV infection; however, it remains unclear if this can be prevented through public health interventions in host countries. We undertake a systematic review and meta-analysis to estimate post-migration HIV acquisition (PMHA) as a proportion of all HIV cases in European migrants. MEDLINE, EMBASE, Global Health, HMIC, and Cochrane Library were searched with terms capturing 'HIV', 'migration', and 'Europe'.

The effectiveness of pollen allergen immunotherapy on allergic rhinitis over 18 years: A national cohort study in Denmark.

Background: Because long-term effectiveness of pollen allergen immune therapy (AIT) for allergic rhinitis (AR) is not well-described, we studied effectiveness over 18 years in Denmark.

Methods: A register-based cohort study using data on filled prescriptions, 1995-2016, Denmark. In a cohort of 1.

Effectiveness of low-density lipoprotein cholesterol reduction with lipid lowering therapy for secondary prevention amongst older individuals: a nationwide cohort study.

Background: Data about the clinical benefit from initial low-density lipoprotein cholesterol (LDL-C) reduction with lipid lowering treatment for secondary prevention and risk of major vascular events amongst older as compared with younger individuals treated during routine clinical care are limited. We investigated this in a nationwide cohort.

Methods: Individuals aged ≥ 50 years with a first-time hospitalisation for a cardiovascular event (index event, including acute coronary syndrome, non-haemorrhagic stroke, transient ischaemic attack and coronary revascularisation), 1 January 2008 to 31 October 2018, who subsequently used lipid lowering treatment, and had an LDL-C measurement before and after the event were included.

Cumulative Incidence of Thiazide-Induced Hyponatremia : A Population-Based Cohort Study.

Background: According to drug labels, the frequency of thiazide-induced hyponatremia is unknown or uncommon to very rare (that is, <1 in 10 000 to <1 in 100), but the exact burden remains unclear.

Objective: To estimate the increase in the cumulative incidence of hyponatremia using thiazide diuretics compared with nonthiazide antihypertensive drugs in routine clinical practice.

Design: Population and register-based cohort study using target trial emulation.

Assessing household lifestyle exposures from consumer purchases, the My Purchases cohort.

Consumer purchase data (CPD) is a promising instrument to assess the impact of purchases on health, but is limited by the need for manual scanning, a lack of access to data from multiple retailers, and limited information on product data and health outcomes. Here we describe the My Purchases cohort, a web-app enabled, prospective collection of CPD, covering several large retail chains in Denmark, that enables linkage to health outcomes. The cohort included 459 participants as of July 03, 2023.

Time trends in preeclampsia and gestational diabetes in Denmark and Alberta, Canada, 2005-2018-A population-based cohort study.

Introduction: Preeclampsia and gestational diabetes mellitus share risk factors such as obesity and increased maternal age, which have become more prevalent in recent decades. We examined changes in the prevalence of preeclampsia and gestational diabetes between 2005 and 2018 in Denmark and Alberta, Canada, and investigated whether the observed trends can be explained by changes in maternal age, parity, multiple pregnancy, comorbidity, and body mass index (BMI) over time.

Material And Methods: This study was a register-based cohort study conducted using data from the Danish National Health Registers and the provincial health registers of Alberta, Canada.

LDL-C Reduction With Lipid-Lowering Therapy for Primary Prevention of Major Vascular Events Among Older Individuals.

Background: Reducing low-density lipoprotein (LDL) cholesterol with lipid-lowering therapy has consistently been shown to lower the risk of cardiovascular disease in primary prevention trials where the majority of individuals are aged <70 years. For older individuals, however, evidence is less clear.

Objectives: In this study, the authors sought to compare the clinical effectiveness of lowering LDL cholesterol by means of lipid-lowering therapy for primary prevention of cardiovascular disease among older and younger individuals in a Danish nationwide cohort.

Reference ranges for third-trimester maternal cardiovascular function parameters measured in normotensive pregnant women using a non-invasive cardiac output monitor: A study based on data from the prospective PEACH cohort study.

Objective: We defined reference ranges for maternal cardiac output, systemic vascular resistance, and stroke volume measured in the third trimester of pregnancy using the Ultrasound Cardiac Output Monitor 1A.

Design: Based on data from the prospective PEACH (PreEclampsia, Angiogenesis, Cardiac dysfunction and Hypertension) cohort study.

Setting: Rigshospitalet and Hvidovre Hospital, Denmark.

Association Between Age and Low-Density Lipoprotein Cholesterol Response to Statins : A Danish Nationwide Cohort Study.

Background: There is large patient-to-patient variability in the low-density lipoprotein cholesterol (LDL-C) response to statin treatment. The reduction in LDL-C may depend on the age of the patient treated-particularly in older adults, who have been substantially underrepresented in randomized controlled trials.

Objective: To investigate the association between age and the LDL-C reduction by statins.

Normative Echocardiographic Left Ventricular Parameters and Reference Intervals in Infants.

Background: In pediatric echocardiography, reference intervals are required to distinguish normal variation from pathology. Left ventricular (LV) parameters are particularly important predictors of clinical outcome. However, data from healthy newborns are limited, and current reference intervals provide an inadequate approximation of normal reference ranges.

Non-surgical treatment of mild to moderate peri-implantitis with an oscillating chitosan brush or a titanium curette-12-month follow-up of a multicenter randomized clinical trial.

Objectives: To study clinical and radiographic outcomes after non-surgical treatment of peri-implantitis using either an oscillating chitosan brush (OCB) or titanium curette (TC) and to observe changes in clinical signs of inflammation after repeated treatment.

Methods: Thirty-nine patients with dental implants (n = 39) presented with radiographic bone level (RBL) of 2-4 mm, bleeding index (BI) ≥ 2, and probing pocket depth (PPD) ≥ 4 mm were randomly assigned to mechanical debridement with OCB (test) or TC (control). Treatment was performed at baseline and repeated at 3, 6, and 9 months in cases with > 1 implant site with BI ≥ 1 and PPD≥4 mm.

Deregulated expression of the 14q32 miRNA cluster in clear cell renal cancer cells.

Clear cell renal cell carcinomas (ccRCC) are characterized by arm-wide chromosomal alterations. Loss at 14q is associated with disease aggressiveness in ccRCC, which responds poorly to chemotherapeutics. The 14q locus contains one of the largest miRNA clusters in the human genome; however, little is known about the contribution of these miRNAs to ccRCC pathogenesis.