Fabrication and characterization of multi-layered coaxial agar-based electrospun biocomposite mat, novel replacement for transdermal patches.

In the performed study, a novel fabrication of agar-based nanofibers was electrospun in an asymmetric bilayer dressing for biomedical transdermal patches. The optimal parameters for the fabrication of agar-based nanofibers after optimization were a feed rate of 10 μL/min, a 7 cm collector-to-nozzle distance, a 15 kV applied voltage, and a 700-rpm rotating collector speed. Coaxial nanofibers, as a second asymmetric layer, were produced using polyvinyl alcohol (PVA) with cephalexin hydrate, an antibacterial drug, as the core and agar-PCL as the sheath.

Multifunctional 58S Bioactive Glass/Silver/Cerium Oxide-Based Biocomposites with Effective Antibacterial, Cytocompatibility, and Mechanical Properties.

58S bioactive glass (BG) has effective biocompatibility and bioresorbable properties for bone tissue engineering; however, it has limitations regarding antibacterial, antioxidant, and mechanical properties. Therefore, we have developed BG biocomposites by reinforcing 58S BG with silver and ceria nanoparticles, which showed effective bactericidal properties by forming inhibited zones of 2.13 mm (against ) and 1.

3D-Printed Multifunctional Ag/CeO/ZnO Reinforced Hydroxyapatite-Based Scaffolds with Effective Antibacterial and Mechanical Properties.

Conventional three-dimensional (3D)-printed hydroxyapatite (HA)-based constructs have limited utility in bone tissue engineering due to their poor mechanical properties, elevated risk of microbial infection, and limited pore interconnectivity. 3D printing of complex multiple components to fabricate fully interconnected scaffolds is a challenging task; here, in this work, we have developed a procedure for fabrication of printable ink for complex systems containing multinanomaterials, i.e.

Network pharmacology-based anti-colorectal cancer activity of piperlonguminine in the ethanolic root extract of Piper longum L.

Colorectal cancer (CRC) has the second highest incidence and fatality rates of any malignancy, at 10.2 and 9.2%, respectively.

Assessment of Leptin Levels and Their Correlation With the Severity of Obstructive Sleep Apnea Syndrome: A Case-Control Study.

Background Obstructive sleep apnea (OSA) is characterized by a combination of structural issues in the upper airway and imbalances in the respiratory control system. While numerous studies have linked OSA with obesity, it remains uncertain whether leptin, a hormone associated with fat, plays a role in the functional and anatomical defects that lead to OSA. Therefore, the aim of this study was to investigate whether leptin levels could be used as a predictor of OSA syndrome (OSAS).

A comprehensive regulatory and industry review of modeling and simulation practices in oncology clinical drug development.

Exposure-response (E-R) analyses are an integral component in the development of oncology products. Characterizing the relationship between drug exposure metrics and response allows the sponsor to use modeling and simulation to address both internal and external drug development questions (e.g.

Multi-length scale strengthening and cytocompatibility of ultra high molecular weight polyethylene bio-composites by functionalized carbon nanotube and hydroxyapatite reinforcement.

The mechanical properties, such as hardness and elastic modulus, of ultra-high molecular weight polyethylene (UHMWPE) composites for acetabular cup liner are improved by adding hydroxyapatite (HAp) and carbon nanotubes (CNT). However, the weak adhesion of HAp (H) and CNT (C) with UHMWPE (U) limits the enhancement of mechanical properties. Thus, the surface of these reinforcements is silane-treated to improve the adhesion with polymer via Si-O and C=O bonds, as evidenced from spectroscopy techniques.

Opportunities and Challenges of Disease Progression Modeling in Drug Development - An IQ Perspective.

Disease progression modeling (DPM) represents an important model-informed drug development framework. The scientific communities support the use of DPM to accelerate and increase efficiency in drug development. This article summarizes International Consortium for Innovation & Quality (IQ) in Pharmaceutical Development mediated survey conducted across multiple biopharmaceutical companies on challenges and opportunities for DPM.

Multifunctional Hydroxyapatite Composites for Orthopedic Applications: A Review.

Being a bioactive material, hydroxyapatite (HAp) is regarded as one of the most attractive ceramic biomaterials for bone and hard-tissue replacement and regeneration. Despite its substantial biocompatibility, osteoconductivity, and compositional similarity to that of bone, the employment of HAp is still limited in orthopedic applications due to its poor mechanical (low fracture toughness and bending strength) and antibacterial properties. These significant challenges lead to the notion of developing novel HAp-based composites via different fabrication routes.

Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study.

Background: CARTITUDE-1 aimed to assess the safety and clinical activity of ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor T-cell therapy with two B-cell maturation antigen-targeting single-domain antibodies, in patients with relapsed or refractory multiple myeloma with poor prognosis.

Methods: This single-arm, open-label, phase 1b/2 study done at 16 centres in the USA enrolled patients aged 18 years or older with a diagnosis of multiple myeloma and an Eastern Cooperative Oncology Group performance status score of 0 or 1, who received 3 or more previous lines of therapy or were double-refractory to a proteasome inhibitor and an immunomodulatory drug, and had received a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody. A single cilta-cel infusion (target dose 0·75 × 10 CAR-positive viable T cells per kg) was administered 5-7 days after start of lymphodepletion.

Safety and efficacy of talacotuzumab plus decitabine or decitabine alone in patients with acute myeloid leukemia not eligible for chemotherapy: results from a multicenter, randomized, phase 2/3 study.

Talacotuzumab, a humanized anti-CD123 monoclonal antibody, was evaluated in combination with decitabine in elderly patients with acute myeloid leukemia (AML) not eligible for intensive chemotherapy. A multicenter, phase 2/3 study was initiated to determine the recommended phase 2 dose (RP2D) of talacotuzumab (Part A) followed by an open-label, randomized comparison of talacotuzumab in combination with decitabine versus decitabine alone to assess achievement of complete response (CR) and overall survival (OS) in Part B. Ten patients were enrolled in Part A and 316 in Part B; the results presented here are based on a database lock on January 25, 2018.

Blinatumomab Pharmacodynamics and Exposure-Response Relationships in Relapsed/Refractory Acute Lymphoblastic Leukemia.

We evaluated blinatumomab pharmacokinetics, pharmacodynamics (CD3+ T-cell, CD19+ B-cell, and cytokine levels), and their associations with efficacy or safety in relapsed/refractory acute lymphoblastic leukemia. Blinatumomab pharmacokinetics (continuous intravenous infusion) from a phase 2 study (n = 189; NCT01466179) were assessed noncompartmentally. Associations between steady-state concentration (C ) and efficacy (complete remission [CR] or CR with partial hematologic recovery [CRh]) or safety (cytokine release syndrome [CRS] and neurologic events [NEs]) were evaluated with statistical models.

A Phase I, First-in-Human Study of AMG 780, an Angiopoietin-1 and -2 Inhibitor, in Patients with Advanced Solid Tumors.

Purpose: To assess the toxicity, pharmacokinetics, tumor vascular response, tumor response, and pharmacodynamics of AMG 780, a mAb designed to inhibit the interaction between angiopoietin-1 and -2 and the Tie2 receptor.

Experimental Design: This was a phase I dose-escalation study of patients with advanced solid tumors refractory to standard treatment without previous antiangiogenic treatment. AMG 780 was administered by intravenous infusion every 2 weeks in doses from 0.

Attitude toward mouthguard utilization among North Indian school children.

Objectives: The present study was designed to evaluate the attitude toward mouthguard utilization among 8-11-year-old athletically active schoolchildren in Ludhiana, Punjab, India.

Materials And Methods: A cross-sectional survey was conducted among 2,000 schoolchildren aged 8-11 years of both the sexes, attending private schools in Ludhiana, Punjab, India. Children were questioned about their perceptions regarding the protective role of mouthguards and the reasons behind not using mouthguards.

Role of platelet-rich plasma in combination with alloplastic bone substitute in regeneration of osseous defects.

Introduction: Bone grafts are frequently used for the treatment of bone defects, but can cause postoperative complications, and sometimes a sufficient quantity of bone is not available. Hence, synthetic biomaterials have been used as an alternative to autogenous bone grafts. Recent clinical reports suggest that application of autologous blood plasma enriched with platelets can enhance the formation of new bone.

von Willebrand factor self-association on platelet GpIbalpha under hydrodynamic shear: effect on shear-induced platelet activation.

The function of the mechanosensitive, multimeric blood protein von Willebrand factor (VWF) is dependent on its size. We tested the hypothesis that VWF may self-associate on the platelet glycoprotein Ibα (GpIbα) receptor under hydrodynamic shear. Consistent with this proposition, whereas Alexa-488-conjugated VWF (VWF-488) bound platelets at modest levels, addition of unlabeled VWF enhanced the extent of VWF-488 binding.

Application of fluorescence spectroscopy to quantify shear-induced protein conformation change.

Rapid and robust methods are required to quantify the effect of hydrodynamic shear on protein conformation change. We evaluated such strategies in this work and found that the binding of the fluorescent probe 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid (bis-ANS) to hydrophobic pockets in the blood protein von Willebrand factor (VWF) is enhanced upon the application of fluid shear to the isolated protein. Significant structural changes were observed when the protein was sheared at shear rates >or= 6000/s for approximately 3.

Fluid shear induces conformation change in human blood protein von Willebrand factor in solution.

Many of the physiological functions of von Willebrand Factor (VWF), including its binding interaction with blood platelets, are regulated by the magnitude of applied fluid/hydrodynamic stress. We applied two complementary strategies to study the effect of fluid forces on the solution structure of VWF. First, small-angle neutron scattering was used to measure protein conformation changes in response to laminar shear rates (G) up to 3000/s.

Solution structure of human von Willebrand factor studied using small angle neutron scattering.

von Willebrand factor (VWF) binding to platelets under high fluid shear is an important step regulating atherothrombosis. We applied light and small angle neutron scattering to study the solution structure of human VWF multimers and protomer. Results suggest that these proteins resemble prolate ellipsoids with radius of gyration (R(g)) of approximately 75 and approximately 30 nm for multimer and protomer, respectively.