Pareto-optimal reversed-phase chromatography separation of three insulin variants with a solubility constraint.

With the shift of focus of the regulatory bodies, from fixed process conditions towards flexible ones based on process understanding, model-based optimization is becoming an important tool for process development within the biopharmaceutical industry. In this paper, a multi-objective optimization study of separation of three insulin variants by reversed-phase chromatography (RPC) is presented. The decision variables were the load factor, the concentrations of ethanol and KCl in the eluent, and the cut points for the product pooling.

Effects on Subclinical Heart Failure in Type 2 Diabetic Subjects on Liraglutide Treatment vs. Glimepiride Both in Combination with Metformin: A Randomized Open Parallel-Group Study.

Objective: We aimed to investigate the effect of liraglutide treatment on heart function in type 2 diabetes (T2D) patients with subclinical heart failure.

Methods: Randomized open parallel-group trial. 62 T2D patients (45 male) with subclinical heart failure were randomized to either once daily liraglutide 1.

Design of two-column batch-to-batch recirculation to enhance performance in ion-exchange chromatography.

Preparative liquid chromatography is a separation technique widely used in the manufacturing of fine chemicals and pharmaceuticals. A major drawback of traditional single-column batch chromatography step is the trade-off between product purity and process performance. Recirculation of impure product can be utilized to make the trade-off more favorable.

The transcriptional coregulator is a target gene for the Wilms' tumor gene 1 protein (WT1) in leukemic cells.

The Wilms' tumor gene 1 () is recurrently mutated in acute myeloid leukemia. Mutations and high expression of associate with a poor prognosis. In mice, WT1 cooperates with the () fusion gene in the induction of acute leukemia, further emphasizing a role for WT1 in leukemia development.

Polyamine concentration is increased in thoracic ascending aorta of patients with bicuspid aortic valve.

Polyamines are cationic molecules synthesized via a highly regulated pathway, obtained from the diet or produced by the gut microbiota. They are involved in general molecular and cellular phenomena that play a role also in vascular disease. Bicuspid aortic valve (BAV) is a congenital malformation associated to a greater risk of thoracic ascending aorta (TAA) aneurysm, whose pathogenesis is not yet well understood.

Redox-sensitive reversible self-assembly of amino acid-naphthalene diimide conjugates.

Peptide and low molecular weight amino acid-based materials that self-assemble in response to environmental triggers are highly desirable candidates in forming functional materials with tunable biophysical properties. In this paper, we explore redox-sensitive self-assembly of cationic phenylalanine derivatives conjugated to naphthalene diimide (NDI). Self-assembly of the cationic Phe-NDI conjugates into nanofibrils was induced in aqueous solvent at high ionic strength.

Dispersion of TiO nanoparticles improves burn wound healing and tissue regeneration through specific interaction with blood serum proteins.

Burn wounds are one of the most important causes of mortality and especially morbidity around the world. Burn wound healing and skin tissue regeneration remain thus one of the most important challenges facing the mankind. In the present study we have addressed this challenge, applying a solution-stabilized dispersion TiO nanoparticles, hypothesizing that their ability to adsorb proteins will render them a strong capacity in inducing body fluid coagulation and create a protective hybrid material coating.

Implementation and evaluation of the Norwegian Ullevaal model as a cardiac rehabilitation model in primary care.

Purpose: To describe the Norwegian Ullevaal model, customised for cardiac patients in primary care, and to evaluate the feasibility of the model through patient outcomes after the 12 week outpatient cardiac rehabilitation programme.

Materials And Methods: A descriptive interventional cohort study with pre-post design. Patients referred to cardiac rehabilitation (n = 273) were enrolled.

Long-Term Results of High-Intensity Exercise-Based Cardiac Rehabilitation in Revascularized Patients for Symptomatic Coronary Artery Disease.

Exercise capacity is a strong predictor of survival rate in patients with and without coronary artery disease. Exercise-based cardiac rehabilitation (CR) with improvements in the peak oxygen uptake (VO) of 3.5 ml/kg/min or more has been shown to be beneficial in earlier observational studies.

A Case of Migraine With Aura Resolving on Warfarin But Not on Apixaban.

Several case reports have associated anticoagulants such as heparin and vitamin K antagonists with reduced symptoms in migraine, but no data exist for direct acting oral factor Xa inhibitors. We report the case of a 55-year-old female who experienced complete remission of migraine with aura for 12 years while on warfarin, with return of symptoms within 3 weeks of switching to apixaban, and resolution of symptoms once again within days of warfarin resumption. Our case suggests that anticoagulation alone is not sufficient to improve migraine symptoms.

Characterizing gastrointestinal stromal tumors and evaluating neoadjuvant imatinib by sequencing of endoscopic ultrasound-biopsies.

Aim: To evaluate endoscopic ultrasound (EUS)-guided biopsies for the pretreatment characterization of gastrointestinal stromal tumors (GIST) to personalize the management of patients.

Methods: All patients with lesions suspected to be GIST who were referred for EUS-sampling at a tertiary Swedish center were eligible for inclusion 2006-2015. During the observational study phase (2006-2011), routine fine-needle-aspiration (EUS-FNA) was performed.

Apolipoprotein A-I attenuates LL-37-induced endothelial cell cytotoxicity.

The human cathelicidin peptide LL-37 has antimicrobial and anti-biofilm functions, but LL-37 may also damage the host by triggering inflammation and exerting a cytotoxic effect, thereby reducing host cell viability. Human plasma mitigates LL-37-induced host cell cytotoxicity but the underlying mechanisms are not completely understood. Apolipoprotein A-I (ApoA-I) is a plasma protein endowed with atheroprotective effects.

Auxiliary activation of the complement system and its importance for the pathophysiology of clinical conditions.

Activation and regulation of the cascade systems of the blood (the complement system, the coagulation/contact activation/kallikrein system, and the fibrinolytic system) occurs via activation of zymogen molecules to specific active proteolytic enzymes. Despite the fact that the generated proteases are all present together in the blood, under physiological conditions, the activity of the generated proteases is controlled by endogenous protease inhibitors. Consequently, there is remarkable little crosstalk between the different systems in the fluid phase.

Modulating Supramolecular Peptide Hydrogel Viscoelasticity Using Biomolecular Recognition.

Self-assembled peptide-based hydrogels are emerging materials that have been exploited for wound healing, drug delivery, tissue engineering, and other applications. In comparison to synthetic polymer hydrogels, supramolecular peptide-based gels have advantages in biocompatibility, biodegradability, and ease of synthesis and modification. Modification of the emergent viscoelasticity of peptide hydrogels in a stimulus responsive fashion is a longstanding goal in the development of next-generation materials.

High clinical impact and diagnostic accuracy of EUS-guided biopsy sampling of subepithelial lesions: a prospective, comparative study.

Background: In a tertiary center setting we aimed to study the diagnostic accuracy and clinical impact of EUS-guided biopsy sampling (EUS-FNB) with a reverse bevel needle compared with that of fine needle aspiration (EUS-FNA) in the work-up of subepithelial lesions (SEL).

Methods: All patients presenting with SELs referred for EUS-guided sampling were prospectively included in 2012-2015. After randomization of the first pass modality, dual sampling with both EUS-FNB and EUS-FNA was performed in each lesion.

Auditory brainstem response (ABR) profiling tests as diagnostic support for schizophrenia and adult attention-deficit hyperactivity disorder (ADHD).

Objective: To evaluate the performances of two auditory brainstem response (ABR) profiling tests as potential biomarkers and diagnostic support for schizophrenia and adult attention-deficit hyperactivity disorder (ADHD), respectively, in an investigator-initiated blinded study design.

Method: Male and female patients with schizophrenia (n=26) and adult ADHD (n=24) meeting Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM IV) diagnostic criteria and healthy controls (n=58) comprised the analysis set (n=108) of the total number of study participants (n=119). Coded sets of randomized ABR recordings were analysed by an independent party blinded to clinical diagnoses before a joint code-breaking session.

Absence of conformational change in complement factor 3 and factor XII adsorbed to acrylate polymers is related to a high degree of polymer backbone flexibility.

In previous investigations, the authors have examined the adsorption of albumin, immunoglobulin, and fibrinogen to a series of acrylate polymers with different backbone and side-group flexibility. The authors showed that protein adsorption to acrylates with high flexibility, such as poly(lauryl methacrylate) (PLMA), tends to preserve native conformation. In the present study, the authors have continued this work by examining the conformational changes that occur during the binding of complement factor 3 (C3) and coagulation factor XII (FXII).

Identification of sequence variants influencing immunoglobulin levels.

Immunoglobulins are the effector molecules of the adaptive humoral immune system. In a genome-wide association study of 19,219 individuals, we found 38 new variants and replicated 5 known variants associating with IgA, IgG or IgM levels or with composite immunoglobulin traits, accounted for by 32 loci. Variants at these loci also affect the risk of autoimmune diseases and blood malignancies and influence blood cell development.

The link between morphology and complement in ocular disease.

The complement system is a vital component of the immune-priveliged human eye that is always active at a low-grade level, preventing harmful intraocular injuries caused by accumulation of turnover products and controlling pathogens to preserve eye homeostasis and vision. The complement system is a double-edged sword that is essential for protection but may also become harmful and contribute to eye pathology. Here, we review the evidence for the involvement of complement system dysregulation in age-related macular degeneration, glaucoma, uveitis, and neuromyelitis optica, highlighting the relationship between morphogical changes and complement system protein expression and regulation in these diseases.

Display of functional proteins on supramolecular peptide nanofibrils using a split-protein strategy.

The display of functional proteins on self-assembled peptide nanofibrils is challenging since the steric bulk of proteins attached to simple self-assembling peptides often impedes incorporation into nanofibrils. Herein is described a split-protein strategy to tether functional proteins to preassembled peptide nanofibrils. In this strategy, a short affinity motif peptide derived from a split protein system is appended to a self-assembly motif (the amphipathic Ac-(FKFE)-NH peptide) to form an affinity-assembly fusion peptide.

Secretory leukocyte protease inhibitor regulates human periodontal ligament cell production of pro-inflammatory cytokines.

Objective: Regulation of immune-like cell properties of periodontal ligament (PDL) cells is not understood. We investigate the importance of secretory leukocyte protease inhibitor (SLPI) for production of pro-inflammatory cytokines in human PDL cells.

Materials And Methods: PDL cells were isolated from teeth extracted for orthodontic reasons.

Self-Assembly, Hydrogelation, and Nanotube Formation by Cation-Modified Phenylalanine Derivatives.

Fluorenylmethoxycarbonyl-protected phenylalanine (Fmoc-Phe) derivatives are a privileged class of molecule that spontaneously self-assemble into hydrogel fibril networks. Fmoc-Phe-derived hydrogels are typically formed by dilution of the hydrogelator from an organic cosolvent into water, by dissolution of the hydrogelator under basic aqueous conditions followed by adjustment of the pH with acid, or by other external triggering forces, including sonication and heating. These conditions complicate biological applications of these hydrogels.