A Case of a Giant Siliconoma Mimicking Localized Breast Cancer.

Silicone gel-filled breast implants are widely used for breast augmentation and reconstruction after mastectomy. However, there are some known complications associated with silicone implants: Leakage and migration of silicone particles from the implant cause a granulomatous reaction. Granulomas may present as masses with features of malignancy on breast MRI.

NLRP3 inflammasome-induced pyroptosis and serum ASC specks are increased in patients with cardiogenic shock.

Cardiogenic shock (CS) is characterized by impaired cardiac function, very high mortality, and limited treatment options. The proinflammatory signaling during different phases of CS is incompletely understood. We collected serum and plasma ( = 44) as well as freshly isolated peripheral blood mononuclear cells (PBMCs, = 7) of patients with CS complicating acute myocardial infarction on admission and after revascularization (24, 48, and 72 h) and of healthy controls (serum and plasma, = 75; PBMCs, = 12).

Novel Long Noncoding RNA Affects Monocyte Subtypes, Reducing Inflammation and Promoting Vascular Healing.

Background: Activation of the immune system contributes to cardiovascular diseases. The role of human-specific long noncoding RNAs in cardioimmunology is poorly understood.

Methods: Single-cell sequencing in peripheral blood mononuclear cells revealed a novel human-specific long noncoding RNA called (heart failure-associated transcript 4).

Structure-Activity Relationship Studies of Aryl Sulfoxides as Reversible Monoacylglycerol Lipase Inhibitors.

Monoacylglycerol lipase (MAGL) is the key enzyme for the hydrolysis of endocannabinoid 2-arachidonoylglycerol (2-AG). The central role of MAGL in the metabolism of 2-AG makes it an attractive therapeutic target for a variety of disorders, including inflammation-induced tissue injury, pain, multiple sclerosis, and cancer. Previously, we reported , an aryl sulfoxide, as a peripherally restricted, covalent reversible MAGL inhibitor that reduced neuropathic pain and inflammation in preclinical models.

Discovery of isoquinoline sulfonamides as allosteric gyrase inhibitors with activity against fluoroquinolone-resistant bacteria.

Bacteria have evolved resistance to nearly all known antibacterials, emphasizing the need to identify antibiotics that operate via novel mechanisms. Here we report a class of allosteric inhibitors of DNA gyrase with antibacterial activity against fluoroquinolone-resistant clinical isolates of Escherichia coli. Screening of a small-molecule library revealed an initial isoquinoline sulfonamide hit, which was optimized via medicinal chemistry efforts to afford the more potent antibacterial LEI-800.

Monocytes as Targets for Immunomodulation by Regional Citrate Anticoagulation.

Immune alterations in end-stage renal patients receiving hemodialysis are complex and predispose patients to infections. Anticoagulation may also play an immunomodulatory role in addition to the accumulation of uremic toxins and the effects of the dialysis procedure. Accordingly, it has been recently shown that the infection rate increases in patients under regional citrate anticoagulation (RCA) compared with systemic heparin anticoagulation (SHA).

Female-to-Male Chest Surgery in Transgender Patients: A Comparison Between 2 Different Techniques and a Satisfaction Study in a Single Center.

Background: Gender dysphoria is a distress caused by a mismatch between gender identity and the sex assigned at birth. About 0.5% of the population suffer from gender dysphoria, which represents 25 million people worldwide.

Membrane-bound Interleukin-1α mediates leukocyte adhesion during atherogenesis.

Introduction: The interleukin-1 (IL-1) family and the NLR family pyrin domain-containing 3 (NLRP3) inflammasome contribute to atherogenesis but the underlying mechanisms are incompletely understood. Unlike IL-1β, IL-1α is not dependent on the NLRP3 inflammasome to exert its pro-inflammatory effects. Here, a non-genetic model was applied to characterize the role of IL-1α, IL-1β, and NLRP3 for the pathogenesis of atherosclerosis.

Increased Expression of Anaphylatoxin C5a-Receptor-1 in Neutrophils and Natural Killer Cells of Preterm Infants.

Preterm infants are susceptible to infection and their defense against pathogens relies largely on innate immunity. The role of the complement system for the immunological vulnerability of preterm infants is less understood. Anaphylatoxin C5a and its receptors C5aR1 and -2 are known to be involved in sepsis pathogenesis, with C5aR1 mainly exerting pro-inflammatory effects.

Exploring the epidemiology of mcr genes, genetic context and plasmids in Enterobacteriaceae originating from pigs and humans on farms in Thailand.

Objectives: In veterinary medicine, colistin has been widely used as therapeutic and prophylactic agent, and for growth promotion. However, colistin has been re-introduced into treatment of human MDR bacterial infections. We assessed the characteristics and spread of plasmid-borne colistin resistance among healthy pigs, workers with animal-contact and their household members in Thailand.

The Endothelial Glycocalyx as a Target of Excess Soluble Fms-like Tyrosine Kinase-1.

Soluble fms-like tyrosine kinase-1 (sFlt-1) is a secreted protein that binds heparan sulfate expressed on the endothelial glycocalyx (eGC). In this paper we analyze how excess sFlt-1 causes conformational changes in the eGC, leading to monocyte adhesion, a key event triggering vascular dysfunction. In vitro exposure of primary human umbilical vein endothelial cells to excess sFlt-1 decreased eGC height and increased stiffness as determined by atomic force microscopy (AFM).

Thioguanine is Effective as Maintenance Therapy for Inflammatory Bowel Disease: A Prospective Multicentre Registry Study.

Background And Aims: Thioguanine is a well-tolerated and effective therapy for inflammatory bowel disease [IBD] patients. Prospective effectiveness data are needed to substantiate the role of thioguanine as a maintenance therapy for IBD.

Methods: IBD patients who previously failed azathioprine or mercaptopurine and initiated thioguanine were prospectively followed for 12 months starting when corticosteroid-free clinical remission was achieved (Harvey-Bradshaw Index [HBI] ≤ 4 or Simple Clinical Colitis Activity Index [SCCAI] ≤ 2).

Exposure to Thioguanine During 117 Pregnancies in Women With Inflammatory Bowel Disease.

Background: Safety of thioguanine in pregnant patients with inflammatory bowel disease [IBD] is sparsely recorded. This study was aimed to document the safety of thioguanine during pregnancy and birth.

Methods: In this multicentre case series, IBD patients treated with thioguanine during pregnancy were included.

Validation and update of a prediction model for risk of relapse after cessation of anti-TNF treatment in Crohn's disease.

Background: Anti-tumor necrosis factor (TNF) therapy is effective for the treatment of Crohn's disease. Cessation may be considered in patients with a low risk of relapse. We aimed to externally validate and update our previously developed prediction model to estimate the risk of relapse after cessation of anti-TNF therapy.

Fast Tacrolimus Metabolism Does Not Promote Post-Transplant Diabetes Mellitus after Kidney Transplantation.

Post-transplant diabetes mellitus (PTDM) after kidney transplantation induced by tacrolimus is an important issue. Fast tacrolimus metabolism, which can be estimated by concentration-to-dose (C/D) ratio, is associated with increased nephrotoxicity and unfavorable outcomes after kidney transplantation. Herein, we elucidate whether fast tacrolimus metabolism also increases the risk for PTDM.

VARS2 Depletion Leads to Activation of the Integrated Stress Response and Disruptions in Mitochondrial Fatty Acid Oxidation.

Mutations in mitochondrial aminoacyl-tRNA synthetases (mtARSs) have been reported in patients with mitochondriopathies: most commonly encephalopathy, but also cardiomyopathy. Through a GWAS, we showed possible associations between mitochondrial valyl-tRNA synthetase (VARS2) dysregulations and non-ischemic cardiomyopathy. We aimed to investigate the possible consequences of VARS2 depletion in zebrafish and cultured HEK293A cells.

Increase in antimicrobial resistance in Escherichia coli in food animals between 1980 and 2018 assessed using genomes from public databases.

Background: Next-generation sequencing has considerably increased the number of genomes available in the public domain. However, efforts to use these genomes for surveillance of antimicrobial resistance have thus far been limited and geographically heterogeneous. We inferred global resistance trends in Escherichia coli in food animals using genomes from public databases.

Structure-Activity Relationship Studies of Pyrimidine-4-Carboxamides as Inhibitors of -Acylphosphatidylethanolamine Phospholipase D.

-Acylphosphatidylethanolamine phospholipase D (NAPE-PLD) is regarded as the main enzyme responsible for the biosynthesis of -acylethanolamines (NAEs), a family of bioactive lipid mediators. Previously, we reported -(cyclopropylmethyl)-6-(()-3-hydroxypyrrolidin-1-yl)-2-(()-3-phenylpiperidin-1-yl)pyrimidine-4-carboxamide (, ) as the first potent and selective NAPE-PLD inhibitor that decreased NAEs in the brains of freely moving mice and modulated emotional behavior [Mock , 2020, 16, 667-675]. Here, we describe the structure-activity relationship (SAR) of a library of pyrimidine-4-carboxamides as inhibitors of NAPE-PLD that led to the identification of .

Long Noncoding RNA TYKRIL Plays a Role in Pulmonary Hypertension via the p53-mediated Regulation of PDGFRβ.

Long noncoding RNAs (lncRNAs) are emerging as important regulators of diverse biological functions. Their role in pulmonary arterial hypertension (PAH) remains to be explored. To elucidate the role of TYKRIL (tyrosine kinase receptor-inducing lncRNA) as a regulator of p53/ PDGFRβ (platelet-derived growth factor receptor β) signaling pathway and to investigate its role in PAH.

Anti-PCSK9 antibodies inhibit pro-atherogenic mechanisms in APOE*3Leiden.CETP mice.

LDL-cholesterol (LDL-C) is a causal pathogenic factor in atherosclerosis. Monoclonal anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) neutralizing antibodies are novel potent LDL-lowering drugs which reduce cardiovascular events. To characterize their effect on atherogenesis, APOE*3Leiden.

Global geographic trends in antimicrobial resistance: the role of international travel.

Background: Rising antimicrobial resistance (AMR) is a threat to modern medicine, and increasing international mobility facilitates the spread of AMR. Infections with resistant organisms have higher morbidity and mortality, are costlier to treat, result in longer hospital stays and place a greater burden on health systems than infections caused by susceptible organisms. Here we review the role of travel in the international dissemination of AMR and consider actions at the levels of travelers, travel medicine practitioners and policymakers that would mitigate this threat.

Adipogenic Mesenchymal Stem Cells and Hyaluronic Acid as a Cellular Compound for Bone Tissue Engineering.

This study investigates the applicability of adipose mesenchymal stem cells (mADSCs) and hyaluronic acid (HA) as a cellular compound for bone tissue engineering. A critical bone defect was created on each femur of 25 rats in vivo, receiving the following 5 graft treatments: I-Control-defect; II-HA; III-mADSCs; IV-mADSCs+HA; and V-previously osteoinduced mADSCs+HA. Evaluation using microcomputed tomography, histomorphometry, and RT-PCR analysis was performed 23 days after implantation.

The Alkyne Moiety as a Latent Electrophile in Irreversible Covalent Small Molecule Inhibitors of Cathepsin K.

Irreversible covalent inhibitors can have a beneficial pharmacokinetic/pharmacodynamics profile but are still often avoided due to the risk of indiscriminate covalent reactivity and the resulting adverse effects. To overcome this potential liability, we introduced an alkyne moiety as a latent electrophile into small molecule inhibitors of cathepsin K (CatK). Alkyne-based inhibitors do not show indiscriminate thiol reactivity but potently inhibit CatK protease activity by formation of an irreversible covalent bond with the catalytic cysteine residue, confirmed by crystal structure analysis.

Identification and regulation of the long non-coding RNA Heat2 in heart failure.

Aims: Circulating immune cells have a significant impact on progression and outcome of heart failure. Long non-coding RNAs (lncRNAs) comprise novel epigenetic regulators which control cardiovascular diseases and inflammatory disorders. We aimed to identify lncRNAs regulated in circulating immune cells of the blood of heart failure patients.