Effectiveness of janus kinase inhibitors in relapsing giant cell arteritis in real-world clinical practice and review of the literature.

Background: A substantial proportion of patients with giant cell arteritis (GCA) relapse despite standard therapy with glucocorticoids, methotrexate and tocilizumab. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway is involved in the pathogenesis of GCA and JAK inhibitors (JAKi) could be a therapeutic alternative. We evaluated the effectiveness of JAKi in relapsing GCA patients in a real-world setting and reviewed available literature.

Results of prophylactic simple fasciocutaneous advancement in the initial management of acute ankle fractures with high risk of operative wound complication.

Unlabelled: Ankle fracture is the third most prevalent fracture in older adults. Wound dehiscence is the most frequent complication. Our objective is to determine the operative wound complication rate in patients with unstable ankle fracture in whom a prophylactic simple fasciocutaneous advancement was used.

Specific MRP4 Inhibitor Ceefourin-1 Enhances Apoptosis Induced by 6-Mercaptopurine in Jurkat Leukemic Cells, but Not in Normal Lymphoblast Cell Line CRL-1991.

: The multidrug resistance protein 4 (MRP4) is a member of the ABC transporter, which has been extensively related to many types of cancer including leukemia. MRP4 overexpression and activity over the efflux of some chemotherapeutic drugs are the main causes of chemoresistance. 6-mercaptopurine (6-MP) is a chemotherapeutic drug widely used in the consolidation and maintenance phases of leukemia treatment.

Complex FFA1 receptor (in)dependent modulation of calcium signaling by free fatty acids.

The expression of free fatty acid 1 receptors (FFA1R), activated by long chain fatty acids in human pancreatic β-cells and enhancing glucose-stimulated insulin secretion are an attractive target to treat type 2 diabetes. Yet several clinical studies with synthetic FFA1R agonists had to be discontinued due to cytotoxicity and/or so-called "liver concerns". It is not clear whether these obstructions are FFA1R dependent.

Forming Habits, Overcoming Obstacles, and Setting Realistic Goals: A Qualitative Study of Physical Activity Maintenance Among Latinas.

Background: The impact of physical activity interventions for Latina women can be enhanced by identifying and implementing strategies to achieve long-term physical activity maintenance. Physical activity promotion research has mainly focused on physical activity initiation and we know little regarding individual, interpersonal, or environmental factors that influence maintenance of physical activity. This study aimed to qualitatively explore and understand factors associated with maintenance and non-maintenance of physical activity among Latinas.

Study of Endogen Substrates, Drug Substrates and Inhibitors Binding Conformations on MRP4 and Its Variants by Molecular Docking and Molecular Dynamics.

Multidrug resistance protein-4 (MRP4) belongs to the ABC transporter superfamily and promotes the transport of xenobiotics including drugs. A non-synonymous single nucleotide polymorphisms (nsSNPs) in the ABCC4 gene can promote changes in the structure and function of MRP4. In this work, the interaction of certain endogen substrates, drug substrates, and inhibitors with wild type-MRP4 (WT-MRP4) and its variants G187W and Y556C were studied to determine differences in the intermolecular interactions and affinity related to SNPs using protein threading modeling, molecular docking, all-atom, coarse grained, and umbrella sampling molecular dynamics simulations (AA-MDS and CG-MDS, respectively).

WinMLR, a software program for the simultaneous determination of several components in mixtures using multilinear regression analysis.

The program WinMLR has been developed for the quantification of mixtures of several components by making a multilinear regression treatment of experimental data to a linear combination of standard signals. Data may be obtained with any multichannel detector having more measuring channels than components to be resolved. For a correct resolution, a linear relationship between the signal of every channel and the component concentration is required.

Inactivation of helminth eggs in an electro-Fenton reactor: Towards full electrochemical disinfection of human waste using activated carbon.

The disinfection of helminth eggs and Escherichia coli contaminated aqueous solutions, was studied using an electro-Fenton reactor equipped with a polarized activated carbon (AC) packed bed and two chambers loaded with cation exchange resins. Experiments using different arrangements and operation conditions, revealed that effective elimination of Escherichia coli takes place in all electrochemical disinfection tests. For the more resistant helminth eggs however, adsorption, electro-oxidation and electro-Fenton experiments showed retention within the reactor and pathogen inactivation values of 0, 16, and 25%, respectively.

Glutamic Acid Increased Methotrexate Polyglutamation and Cytotoxicity in a CCRF-SB Acute Lymphoblastic Leukemia Cell Line.

: Acute lymphoblastic leukemia (ALL) is the most common type of cancer in childhood. The majority of patients respond to treatment, but those with resistant phenotypes suffer relapse or death. The antifolate methotrexate (MTX) is the most commonly used drug against ALL due to its efficacy.

Predictive capacity of baseline hyperreflective dots on the intravitreal dexamethasone implant (Ozurdex®) outcomes in diabetic macular edema: a multicenter study.

Purpose: The purpose of this study is to evaluate the predictive capacity of the baseline hyperreflective dots (HRDs) on the functional and anatomical response in patients with diabetic macular edema (DME). Additionally, we assessed the impact of the intravitreal dexamethasone (DEX) implant on the functional and anatomic outcomes.

Methods: Retrospective, multicenter study.

Cypate and Cypate-Glucosamine as Near-Infrared Fluorescent Probes for In Vivo Tumor Imaging.

Near-infrared (NIR) imaging is a promising technique for use as a noninvasive and sensitive diagnostic tool. Although the NIR fluorescently labeled glucose analog glucosamine (cypate-glucosamine) has applications in preclinical imaging, the transport pathways and fate of this probe in tissues remain unaddressed. Here, we have synthesized and characterized cypate and cypate-glucosamine conjugate (cy-2-glu), and investigated the probable transport pathways of these probes in vitro and in vivo.

Essential Role of Endothelial MCPIP in Vascular Integrity and Post-Ischemic Remodeling.

MCP-1-induced protein (MCPIP, also known as Zc3h12a or Regnase-1), a newly identified suppressor of cytokine signaling, is expressed in endothelial cells (ECs). To investigate the role of endothelial MCPIP in vascular homeostasis and function, we deleted the MCPIP gene specifically in ECs using the Cre-LoxP system. EC-specific MCPIP deletion resulted in systemic inflammation, increased vessel permeability, edema, thrombus formation, and premature death in mice.

Types and factors affecting injury rates of mechanical contractors.

Background: In the United States, about 38,000 cases of nonfatal workplace injuries were reported in 2015, in the category of 'mechanical work' (plumbing, heating, and air conditioning); this is nearly identical to the number of cases reported under 'building construction'.

Objective: This paper analyzes the types and rates of injuries and illnesses of mechanical contractors of southern Nevada, including the nature of the injuries and illnesses, body parts affected by injuries, causes of injuries, and factors affecting the injury rates.

Methods: To obtain data, a survey consisting of questions regarding the number of injuries and types of injuries was conducted with 31 mechanical contractors of southern Nevada involved in plumbing, piping, heating, refrigeration, and air conditioning.

Determining the presence of chemicals with suspected endocrine activity in drinking water from the Madrid region (Spain) and assessment of their estrogenic, androgenic and thyroidal activities.

Endocrine disruptors (EDs) are natural or man-made chemicals that can affect the health of organisms by interfering with their normal hormonal functions. Many of these substances can cause their effects at very low doses and, considering the key role played by the endocrine system on development, organisms in early phases of growth (foetal, childhood, puberty) are especially sensitive to the action of EDs. In addition, when combined, they can show additive, antagonistic and synergistic activities.

B cell phenotypes in patients with rheumatoid arthritis relapsing after rituximab: expression of B cell-activating factor-binding receptors on B cell subsets.

Serum levels of B cell-activating factor (BAFF) rise following rituximab (RTX) therapy in patients with rheumatoid arthritis (RA). Initiation of naive B cell return to the periphery and autoreactive B cell expansion leading to relapse after RTX may therefore be linked to interactions between BAFF and BAFF-binding receptors (BBR). Relationships between serum BAFF and BBR expression [(BAFFR, calcium signal modulating cyclophilic ligand interactor (TACI) and B cell maturation antigen (BCMA)] were determined on B cell subsets, defined using immunoglobulin (Ig)D/CD38.

Increased C-reactive protein plasma levels are not involved in the onset of post-operative atrial fibrillation.

Background: Increased inflammation biomarkers plasma levels, including C-reactive protein (CRP), have been associated with the initiation and perpetuation of atrial fibrillation (AF). However, it is not known whether an increased CRP plasma level, without concomitant inflammation, is sufficient to induce AF. We investigated whether higher CRP plasma levels, determined by the presence of +219G>A CRP gene polymorphism, is associated with an increased risk of post-operative AF.

Atrial Function Assessed by Speckle Tracking Echocardiography Is a Good Predictor of Postoperative Atrial Fibrillation in Elderly Patients.

Objective: Advanced age is an independent predictor of postoperative atrial fibrillation (POAF) in patients undergoing coronary artery bypass surgery. We evaluated whether left atrial (LA) dysfunction assessed by strain contributes to identifying elderly patients prone to POAF.

Methods: Case-control study of 70 subjects undergoing coronary artery bypass surgery.

Transcription factors STAT6 and KLF4 implement macrophage polarization via the dual catalytic powers of MCPIP.

Macrophage polarization plays a critical role in tissue homeostasis, disease pathogenesis, and inflammation and its resolution. IL-4-induced macrophage polarization involves induction of STAT6 and Krüppel-like factor 4 (KLF4), which induce each other and promote M2 polarization. However, how these transcription factors implement M2 polarization is not understood.

Long-term survival with a stentless free-hand Batista pericardial aortic valve prosthesis: A case report.

Introduction: Stented bovine pericardial prosthetic valves are a good option for older patients, except when there is a fragile small aortic annulus, when, if there is no contraindication to anticoagulation, a mechanical prosthesis may be indicated.

Presentation Of Case: We report a 72 year-old man who underwent coronary bypass grafting and aortic valve replacement with a stentless valve fashioned from bovine pericardium using the Batista technique. Despite early sternal infection and dehiscence, and renal and respiratory failure during 15 years follow-up, he remains alive and self-sufficient.

Effect of rituximab on B cell phenotype and serum B cell-activating factor levels in patients with thrombotic thrombocytopenic purpura.

Autoantibodies inhibiting the activity of the metalloproteinase, ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), underlie the pathogenesis of thrombotic thrombocytopenic purpura (TTP). Rituximab (RTX) combined with plasma-exchange (PEX) is an effective treatment in TTP. Patients can remain in remission for extended periods following PEX/RTX, and this is associated with continuing reduction in antibodies to ADAMTS13.

Total serum immunoglobulin levels in patients with RA after multiple B-cell depletion cycles based on rituximab: relationship with B-cell kinetics.

Objective: To investigate whether the incidence of secondary hypogammaglobulinaemia in patients with RA following rituximab was related to patterns of B-cell return and relapse.

Methods: CD19(+) B-cell and serum immunoglobulin (sIg) determinations were done every 2 or 3 months in 137 consecutive patients treated with one or more courses of rituximab-based B-cell depletion therapy. The pattern of B-cell return, either concordant or discordant with relapse, was also recorded.

Clinical evidence of intravitreal triamcinolone acetonide in the management of age-related macular degeneration.

Triamcinolone acetonide (TA) is one of the first pharmacologic compounds evaluated for the treatment of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). The most important effects of TA consist in the stabilisation of the blood-retinal barrier and the down-regulation of inflammation. TA also has anti-angiogenic and anti-fibrotic properties.

Increased levels of oxidative stress, subclinical inflammation, and myocardial fibrosis markers in primary aldosteronism patients.

Background: Patients with primary aldosteronism experience greater left ventricular hypertrophy and a higher frequency of cardiovascular events than do essential hypertensive patients with comparable blood pressure levels. Aldosterone has been correlated with increased oxidative stress, endothelial inflammation, and fibrosis, particularly in patients with heart disease.

Aim: To evaluate oxidative stress, subclinical endothelial inflammation, and myocardial fibrosis markers in patients with primary aldosteronism and essential hypertension.

Systemic vascular cell adhesion molecule-1 predicts the occurrence of post-operative atrial fibrillation.

Background: Post-operative atrial fibrillation occurs in 30% of patients after on-pump heart surgery and is associated to elevated inflammatory markers. We have evaluated if the systemic biomarkers of inflammation and endothelial damage, vascular cell adhesion molecule-1 (VCAM-1) and soluble thrombomodulin may help in identifying patients prone to development of post-operative atrial fibrillation.

Methods: One hundred and forty-four patients in sinus rhythm submitted to elective coronary artery bypass surgery.