Limb shaking transient ischemic attack secondary to innominate artery stenosis.

Limb shaking transient ischemic attack is a rare disease manifestation typically caused by carotid stenosis but rarely caused by flow-limiting lesions involving more proximal vasculature. We demonstrate a case of limb shaking transient ischemic attack secondary to innominate stenosis in a 69-year-old woman who presented after a left leg shaking spell that caused her to fall and fracture her ipsilateral tibia. She did not experience changes in mentation and did not show any evidence of a postictal period.

The transcription factor C/EBPβ promotes vascular endothelial growth factor A expression and neural stem cell expansion.

The bZIP transcription factor CCAAT-enhancer-binding protein β (C/EBPβ) exhibits neurogenic, neuritogenic, and pro-survival effects in the central nervous system. Here, we show that C/EBPβ regulates neural stem cell (NSC) expansion and vascular endothelial growth factor A (VEGF-A) level by acting on a C/EBPβ-responsive element within the Vegf-a promoter. As predicted, C/EBPβ depletion reduced VEGF-A production, NSC number, and average neurosphere size in proliferating cultures.

Corticosteroid Treatment Prevents Lipopolysaccharide-Induced Increase of ACE2 and Reduces Fibrin Degradation Products in Bronchoalveolar Lavage Fluid.

The assessment of systemic corticosteroid effects on intrapulmonary disease biomarkers is challenging. This retrospective evaluation of a human endotoxemia model quantified ACE2 and fibrin degradation product (FDP) concentrations in bronchoalveolar lavage fluid (BALF) samples from a randomized, double-blind, placebo-controlled study (NCT01714427). Twenty-four healthy volunteers received either 2 × 40 mg intravenous dexamethasone or placebo.

Screening and Confirmatory Testing for SARS-CoV-2 Antibodies: Comparison of Health and Non-Health Workers in a Nationwide Healthcare Organization in Central Europe.

Despite being located close to the European epicenter of the COVID-19 pandemic in Italy, Austria has managed to control the first wave. In Austria, the largest health insurance fund covers 7 million people and has 12,000 employees, including 3700 healthcare workers (HCW). For patient and staff safety, transmission control measures were implemented and mass testing of employees for SARS-CoV-2 antibodies was conducted.

Fractal-Based Analysis of Bone Microstructure in Crohn's Disease: A Pilot Study.

Crohn's disease (CD) is associated with bone loss and increased fracture risk. TX-Analyzer™ is a new fractal-based technique to evaluate bone microarchitecture based on conventional radiographs. The aim of the present study was to evaluate the TX-Analyzer™ of the thoracic and lumbar spine in CD patients and healthy controls (CO) and to correlate the parameters to standard imaging techniques.

Phosphorylation within the bipartite NLS alters the localization and toxicity of the ER stress response factor DDIT3/CHOP.

Regulated nuclear-cytoplasmic trafficking is a well-established mechanism utilized by cells to regulate adaptive and maladaptive responses to acute oxidant stress. Commonly associated with endoplasmic reticulum stress, the bZIP transcription factor CCAAT/enhancer-binding protein homologous protein (CHOP/DDIT3) mediates the cellular response to redox stress with effects on cellular growth, differentiation, and survival. We show through functional analyses that CHOP contains a conserved, compound pat4/bipartite nuclear localization signal within the basic DNA-binding domain.

Inflammatory Bowel Disease: A Nationwide Study of Hip Fracture and Mortality Risk After Hip Fracture.

Background And Aims: With rising rates of inflammatory bowel diseases [IBD] in older adults, management of comorbidities such as osteoporosis is becoming increasingly important. Hip fracture [HF] is the most serious consequence of low bone mineral quality and is associated with excess risk of mortality. For older IBD patients, there are only limited data available.

Randomized, Double-Blind, Placebo-Controlled, Single-Ascending-Dose Study of the Penetration of a Monoclonal Antibody Combination (ASN100) Targeting Cytotoxins in the Lung Epithelial Lining Fluid of Healthy Volunteers.

ASN100 is a novel antibody combination of two fully human IgG1(κ) monoclonal antibodies (MAbs), ASN-1 and ASN-2, which neutralize six cytotoxins, alpha-hemolysin (Hla) and five bicomponent leukocidins. We assessed the safety, tolerability, and serum and lung pharmacokinetics of ASN100 in a randomized, double-blind, placebo-controlled single-dose-escalation first-in-human study. Fifty-two healthy volunteers were enrolled and randomized to receive either ASN-1, ASN-2, a combination of both MAbs (ASN100), or a corresponding placebo.

Vascular cell adhesion molecule 1 in patients with severe osteoarthritis of the hip : A prospective cross-sectional study.

Background: Osteoarthritis (OA) of the hip is a frequent and debilitating joint disease. Only few clinical risk factors for hip OA are established and clinically applicable biomarkers to identify patients at risk are still lacking. The glycoprotein vascular cell adhesion molecule 1 (VCAM-1) is expressed by chondrocytes and synovial tissue and was a predictive marker for development of severe large joint OA in a previous study.

Inhibition of complement C1s improves severe hemolytic anemia in cold agglutinin disease: a first-in-human trial.

Cold agglutinin disease is a difficult-to-treat autoimmune hemolytic anemia in which immunoglobulin M antibodies bind to erythrocytes and fix complement, resulting in predominantly extravascular hemolysis. This trial tested the hypothesis that the anti-C1s antibody sutimlimab would ameliorate hemolytic anemia. Ten patients with cold agglutinin disease participated in the phase 1b component of a first-in-human trial.

A Randomized, First-in-Human, Healthy Volunteer Trial of sutimlimab, a Humanized Antibody for the Specific Inhibition of the Classical Complement Pathway.

Aberrant activation of the classical complement pathway is the common underlying pathophysiology of orphan diseases such as bullous pemphigoid, antibody-mediated rejection of organ transplants, cold agglutinin disease, and warm autoimmune hemolytic anemia. Therapeutic options for these complement-mediated disorders are limited and sutimlimab, a humanized monoclonal antibody directed against complement factor C1s, may be potentially useful for inhibition of the classical complement pathway. A phase I, first-in-human, double-blind, randomized, placebo-controlled, dose-escalation trial of single and multiple doses of sutimlimab or placebo was conducted in 64 volunteers to evaluate safety, tolerability, pharmacokinetic, and pharmacodynamic profiles.

Morphine Interaction with Aspirin: a Double-Blind, Crossover Trial in Healthy Volunteers.

Aspirin is a cornerstone in the antiplatelet therapy for acute coronary syndromes. Coadministration of morphine may potentially influence the intestinal absorption, pharmacokinetics, and pharmacodynamics, as seen with P2Y inhibitors. In this trial, healthy volunteers were randomized to receive morphine (5 mg, i.

Single, very low rituximab doses in healthy volunteers - a pilot and a randomized trial: implications for dosing and biosimilarity testing.

There are no  dose-finding trials available for rituximab that could guide dosing in non-malignant diseases. We hypothesized that currently used doses (≥375 mg/m) exceed several hundred-fold the half-maximal effective dose, which is most sensitive for detecting putative differences between biosimilars and important for dose finding. In an open label, exploratory trial healthy volunteers received single infusions of rituximab at doses of 0.

Evaluation of between-, within- and day-to-day variation of coagulation measured by rotational thrombelastometry (ROTEM).

Background And Aims: The aim of this study was to assess the circadian variation and the between- and within-subject variation in 10 healthy subjects over a period of 8 weeks by ROTEM. We further evaluated the influence of elevated body mass index and the effect of low molecular weight heparin and antithrombin on clot formation.

Methods: Citrated blood samples were analysed in the NATEM test system.

Hypophosphatemia, Severe Bone Pain, Gait Disturbance, and Fatigue Fractures After Iron Substitution in Inflammatory Bowel Disease: A Case Report.

Intravenous infusions of different iron formulations are recognized as a cause of hypophosphatemia. Chronic hypophosphatemia can alter bone metabolism and bone material structure. As a consequence, osteomalacia may develop and lead to bone fragility.

Blockade of HLA Antibody-Triggered Classical Complement Activation in Sera From Subjects Dosed With the Anti-C1s Monoclonal Antibody TNT009-Results from a Randomized First-in-Human Phase 1 Trial.

Background: Complement may play a key role in antibody-mediated rejection. A promising therapeutic approach may be classical pathway (CP) inhibition at the level of early component C1.

Methods: In this first-in-human, double-blind, randomized placebo-controlled phase 1 trial, we evaluated the safety and complement inhibitory effect of TNT009, a humanized monoclonal anti-C1s antibody.

Selective glucocorticoid receptor modulation inhibits cytokine responses in a canine model of mild endotoxemia.

Selective glucocorticoid receptor modulators (GRMs) promise to reduce adverse events of glucocorticoids while maintaining anti-inflammatory potency. The present study tested the anti-inflammatory activity of two novel non-steroidal GRMs (GRM1: BI 607812 BS, GRM2: BI 653048 BS*H3PO4) in comparison to prednisolone in a canine model of low dose endotoxemia. This study compared the anti-inflammatory and pharmacokinetic profile of escalating daily oral doses of GRM1 (1, 2.

A Combined NMR and SAXS Analysis of the Partially Folded Cataract-Associated V75D γD-Crystallin.

A cataract is a pathological condition characterized by the clouding of the normally clear eye lens brought about by deposition of crystallin proteins in the lens fiber cells. These protein aggregates reduce visual acuity by scattering or blocking incoming light. Chemical damage to proteins of the crystallin family, accumulated over a lifetime, leads to age-related cataract, whereas inherited mutations are associated with congenital or early-onset cataract.

The use of frozen plasma samples in thromboelastometry.

Thromboelastometry is increasingly used in the clinical and scientific setting. The use of frozen plasma samples may be useful in overcoming certain limitations such as local and timely availability. Whole blood (WB) samples of 20 healthy volunteers were obtained, and plasma was generated.

Dexamethasone inhibits endotoxin-induced coagulopathy in human lungs.

Unlabelled: Essentials Glucocorticoids are associated with an increased risk of thrombosis. Healthy volunteers received dexamethasone or placebo in an endotoxin lung instillation model. Dexamethasone suppressed thrombin generation in bronchoalveolar lavage.

Recombinant human diamine oxidase activity is not inhibited by ethanol, acetaldehyde, disulfiram, diethyldithiocarbamate or cyanamide.

Human diamine oxidase (hDAO, EC 1.4.3.

Dissociation between systemic and pulmonary anti-inflammatory effects of dexamethasone in humans.

Aims: The local pulmonary inflammatory response has a different temporal and qualitative profile compared with the systemic inflammatory response. Although glucocorticoids substantially downregulate the systemic release of acute-phase mediators, it is not clear whether they have comparable inhibitory effects in the human lung compartment. Therefore, we compared the anti-inflammatory effects of a pure glucocorticoid agonist, dexamethasone, on bronchoalveolar lavage and blood cytokine concentrations in response to bronchially instilled endotoxin.

A model comparing how rapidly transfusion of solvent detergent plasma restores clotting factors versus infusion of albumin-saline.

Background: A recent randomized controlled trial demonstrated the bioequivalence between universally applicable and AB0 compatible transfusion plasma in healthy volunteers. There was a limited change in coagulation factor levels and inhibitors before and after plasmapheresis and subsequent plasma transfusion. The aim of this extension trial was to investigate the true capacity of these plasma products to restore baseline levels of coagulation factors and inhibitors after plasma depletion in comparison to haemodilution induced by infusion of albumin solution.

Synaptic proteins in the hippocampus indicative of increased neuronal activity in CA3 in schizophrenia.

Objective: In schizophrenia, hippocampal perfusion is increased and declarative memory function is degraded. Based on an a priori model of hippocampal dysfunction in schizophrenic psychosis, the authors postulated molecular and cellular changes in CA3 consistent with increased NMDA receptor signaling.

Method: Postmortem hippocampal subfield tissue (CA3, CA1) from subjects with schizophrenia and nonpsychiatric comparison subjects was analyzed using Western blotting and Golgi histochemistry to examine the hypothesized outcomes.