Shear-Sensing by C-Reactive Protein: Linking Aortic Stenosis and Inflammation.

Background: CRP (C-reactive protein) is a prototypical acute phase reactant. Upon dissociation of the pentameric isoform (pCRP [pentameric CRP]) into its monomeric subunits (mCRP [monomeric CRP]), it exhibits prothrombotic and proinflammatory activity. Pathophysiological shear rates as observed in aortic valve stenosis (AS) can influence protein conformation and function as observed with vWF (von Willebrand factor).

Efficacy and safety of ligelizumab in adults and adolescents with chronic spontaneous urticaria: results of two phase 3 randomised controlled trials.

Background: Many patients with chronic spontaneous urticaria (CSU) do not achieve complete control of their symptoms with current available treatments. In a dose-finding phase 2b study, ligelizumab improved urticaria symptoms in patients with H1-antihistamine (H1-AH) refractory CSU. Here, we report the efficacy and safety outcomes from two ligelizumab phase 3 studies.

Low-Cost High-Throughput Genotyping for Diagnosing Familial Hypercholesterolemia.

Background: Familial hypercholesterolemia (FH) is a common but underdiagnosed genetic disorder characterized by high low-density lipoprotein cholesterol levels and premature cardiovascular disease. Current sequencing methods to diagnose FH are expensive and time-consuming. In this study, we evaluated the accuracy of a low-cost, high-throughput genotyping array for diagnosing FH.

Perspective on the current state of the LRRK2 field.

Almost 2 decades after linking LRRK2 to Parkinson's disease, a vibrant research field has developed around the study of this gene and its protein product. Recent studies have begun to elucidate molecular structures of LRRK2 and its complexes, and our understanding of LRRK2 has continued to grow, affirming decisions made years ago to therapeutically target this enzyme for PD. Markers of LRRK2 activity, with potential to monitor disease progression or treatment efficacy, are also under development.

Activated Coagulation FXII: A Unique Target for In Vivo Molecular Imaging.

Background: Current clinical imaging of thromboembolic diseases often relies on indirect detection of thrombi, which may delay diagnosis and ultimately the institution of beneficial, potentially lifesaving treatment. Therefore, the development of targeting tools that facilitate the rapid, specific, and direct imaging of thrombi using molecular imaging is highly sought after. One potential molecular target is FXIIa (factor XIIa), which initiates the intrinsic coagulation pathway but also activates the kallikrein-kinin system, thereby initiating coagulation and inflammatory/immune responses.

Bisphenol-A release from thermoplastic clear aligner materials: A systematic review.

Aim: The aim of the present study was to undertake a systematic review of the available evidence on the release of bisphenol-A (BPA) from thermoplastic materials used in the fabrication of clear aligners (CA).

Methods: Electronic databases, such as MEDLINE (via PubMed), Google Scholar, Scopus, Cochrane Library, Web of Science, OpenGrey, and the U.S.

How effective is maxillary expansion as an interceptive treatment in individuals with palatally displaced canines? A systematic review and meta-analysis.

Background: The objective was to provide a synthesis of the existing literature on the effectiveness of maxillary expansion in intercepting palatally displaced canines (PDCs).

Methods: Studies that evaluated the effectiveness of maxillary expansion in subjects with PDCs in the mixed dentition period were included. The following electronic databases were searched until November 30, 2021: MEDLINE (via PubMed), Scopus, Google Scholar, Web of Science, and Cochrane library.

Are clear aligners environment friendly?

Clear aligner therapy has revolutionized orthodontic care delivery over the last 2 decades. With the increase in demand for clear aligner therapy, there is a concern about the plastic burden on the environment. Hence, we initiated research to investigate its environmental impact.

Elevated circulating follistatin associates with an increased risk of type 2 diabetes.

The hepatokine follistatin is elevated in patients with type 2 diabetes (T2D) and promotes hyperglycemia in mice. Here we explore the relationship of plasma follistatin levels with incident T2D and mechanisms involved. Adjusted hazard ratio (HR) per standard deviation (SD) increase in follistatin levels for T2D is 1.

What has changed in orthodontic patient care between the two surges of the COVID-19 pandemic? A thematic analysis.

Background And Aim: The coronavirus disease 2019 (COVID-19) has brought new challenges to every specialty and orthodontics is no exception. Currently, there seems no way other than to mitigate the risk and proceed with routine orthodontic treatment. The aim of the present study was to conduct a qualitative inquiry into the coping strategies, perceptions and anticipations of orthodontic patients and the challenges faced by orthodontists.

Human Islet Expression Levels of Prostaglandin E Synthetic Enzymes, But Not Prostaglandin EP3 Receptor, Are Positively Correlated with Markers of β-Cell Function and Mass in Nondiabetic Obesity.

Elevated islet production of prostaglandin E (PGE), an arachidonic acid metabolite, and expression of prostaglandin E receptor subtype EP3 (EP3) are well-known contributors to the β-cell dysfunction of type 2 diabetes (T2D). Yet, many of the same pathophysiological conditions exist in obesity, and little is known about how the PGE production and signaling pathway influences nondiabetic β-cell function. In this work, plasma arachidonic acid and PGE metabolite levels were quantified in a cohort of nondiabetic and T2D human subjects to identify their relationship with glycemic control, obesity, and systemic inflammation.

Noninvasive, longitudinal imaging-based analysis of body adipose tissue and water composition in a melanoma mouse model and in immune checkpoint inhibitor-treated metastatic melanoma patients.

Background: As cancer cachexia (CC) is associated with cancer progression, early identification would be beneficial. The aim of this study was to establish a workflow for automated MRI-based segmentation of visceral (VAT) and subcutaneous adipose tissue (SCAT) and lean tissue water (LTW) in a B16 melanoma animal model, monitor diseases progression and transfer the protocol to human melanoma patients for therapy assessment.

Methods: For in vivo monitoring of CC B16 melanoma-bearing and healthy mice underwent longitudinal three-point DIXON MRI (days 3, 12, 17 after subcutaneous tumor inoculation).

Genomewide Association Study of Severe Covid-19 with Respiratory Failure.

Background: There is considerable variation in disease behavior among patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19). Genomewide association analysis may allow for the identification of potential genetic factors involved in the development of Covid-19.

Methods: We conducted a genomewide association study involving 1980 patients with Covid-19 and severe disease (defined as respiratory failure) at seven hospitals in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe.

The identification and function of a Netrin-1 mutation in a pedigree with premature atherosclerosis.

Background And Aims: Neuroimmune guidance cues have been shown to play a role in atherosclerosis, but their exact role in human pathophysiology is largely unknown. In the current study, we investigated the role of a c.1769G > T variant in Netrin-1 in (premature) atherosclerosis.

Role of β-glucosidase 2 in aberrant glycosphingolipid metabolism: model of glucocerebrosidase deficiency in zebrafish.

β-glucosidases [GBA1 (glucocerebrosidase) and GBA2] are ubiquitous essential enzymes. Lysosomal GBA1 and cytosol-facing GBA2 degrade glucosylceramide (GlcCer); GBA1 deficiency causes Gaucher disease, a lysosomal storage disorder characterized by lysosomal accumulation of GlcCer, which is partly converted to glucosylsphingosine (GlcSph). GBA1 and GBA2 also may transfer glucose from GlcCer to cholesterol, yielding glucosylated cholesterol (GlcChol).

Patients who underwent total hip or knee arthroplasty are more physically active than the general Dutch population.

Total hip arthroplasty (THA) and total knee arthroplasty (TKA) bring relief of pain and functional disability to patients with end-stage osteoarthritis, and however, the literature on their impact on patients' level of physical activity (PA) is scarce. Cross-sectional study in patients who underwent THA/TKA surgery in the preceding 6-22 months and a random sample of persons aged >40 years from the Dutch general population, participating in a national survey. PA in minutes per week (min/week) and adherence to the Dutch recommendation for PA (NNGB yes/no) were measured by the short questionnaire to assess health-enhancing PA.

Genetic Variation in the 11β-hydroxysteroid-dehydrogenase 1 Gene Determines NAFLD and Visceral Obesity.

Context/objective: Acute pharmacological inhibition of 11β-hydroxysteroid-dehydrogenase 1 (11β-HSD1), which converts cortisone into the much more potent cortisol in peripheral tissues, results in reduction of total, visceral, and liver fat but not insulin resistance. We now investigated whether lifelong alterations of 11β-HSD1 activity similarly affect these cardiometabolic risk parameters by studying single-nucleotide polymorphisms (SNPs) in the 11β-HSD1-coding gene (HSD11B1).

Design/methods: Liver fat content was measured by H-magnetic resonance spectroscopy and total and visceral fat mass by H-magnetic resonance tomography in 327 subjects.

Exploring associations between exposure to sexy online self-presentations and adolescents' sexual attitudes and behavior.

Previous research suggests that adolescents' social network site use is related to their sexual development. However, the associations between adolescents' exposure to sexy self-presentations of others on social network sites and their sexual attitudes and experience have not yet been empirically supported. This study investigated reciprocal longitudinal relationships between adolescents' exposure to others' sexy self-presentations on social network sites and their sexual attitudes (i.