A double-blind, randomized, multicenter, Italian study of frovatriptan versus rizatriptan for the acute treatment of migraine

The objective of this study was to assess patient satisfaction with acute treatment of migraine with frovatriptan or rizatriptan by preference questionnaire. 148 subjects with a history of migraine with or without aura (IHS 2004 criteria), with at least one migraine attack per month in the preceding 6 months, were enrolled and randomized to frovatriptan 2.5 mg or rizatriptan 10 mg treating 1–3 attacks. The study had a multicenter, randomized, double-blind, cross-over design, with treatment periods lasting <3 months. At the end of the study, patients assigned preference to one of the treatments using a questionnaire with a score from 0 to 5 (primary endpoint). Secondary endpoints were pain-free and pain relief episodes at 2 h, and recurrent and sustained pain-free episodes within 48 h. 104 of the 125 patients (83%, intention-to-treat population) expressed a preference for a triptan. The average preference score was not significantly different between frovatriptan (2.9 ± 1.3) and rizatriptan (3.2 ± 1.1). The rates of pain-free (33% frovatriptan vs. 39% rizatriptan) and pain relief (55 vs. 62%) episodes at 2 h were not significantly different between the two treatments. The rate of recurrent episodes was significantly (p < 0.001) lower under frovatriptan (21 vs. 43% rizatriptan). No significant differences were observed in sustained pain-free episodes (26% frovatriptan vs. 22% rizatriptan). The number of patients with adverse events was not significantly different between rizatriptan (34) and frovatriptan (25, p = NS). The results suggest that frovatriptan has a similar efficacy to rizatriptan, but a more prolonged duration of action

Cell-free stem cell-derived extract formulation for treatment of knee osteoarthritis: study protocol for a preliminary non-randomized, open-label, multi-center feasibility and safety study.

BACKGROUND: Musculoskeletal conditions are highly prevalent, and knee OA is most common. Current treatment modalities have limitations and either fail to solve the underlying pathophysiology or are highly invasive. To address these limitations, attention has focused on the use of biologics. The efficacy of these devices is attributed to presence of growth factors (GFs), cytokines (CKs), and extracellular vesicles (EVs). With this in mind, we formulated a novel cell-free stem cell-derived extract (CCM) from human progenitor endothelial stem cells (hPESCs). A preliminary study demonstrated the presence of essential components of regenerative medicine, namely GFs, CKs, and EVs, including exosomes, in CCM. The proposed study aims to evaluate the safety and efficacy of intraarticular injection of the novel cell-free stem cell-derived extract (CCM) for the treatment of knee OA. METHODS AND ANALYSIS: This is a non-randomized, open-label, multi-center, prospective study in which the safety and efficacy of intraarticular CCM in patients suffering from grade II/III knee OA will be evaluated. Up to 20 patients with grade II/III OA who meet the inclusion and exclusion criteria will be consented and screened to recruit 12 patients to receive treatment. The study will be conducted at up to 2 sites within the USA, and the 12 participants will be followed for 24 months. The study participants will be monitored for adverse reactions and assessed using Numeric Pain Rating Scale (NPRS), Patient-Reported Outcomes Measurement Information System (PROMIS) Score, Knee Injury and Osteoarthritis Outcome Score Jr. (KOOS Jr.), 36-ietm short form survey (SF-36), Single Assessment Numeric Evaluation (SANE), physical exams, plain radiography, and magnetic resonance imaging (MRI) with Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score for improvements in pain, function, satisfaction, and cartilage regeneration. DISCUSSION: This prospective study will provide valuable information into the safety and efficacy of intraarticular administration of cell-free stem cell-derived extract (CCM) in patients suffering with grade II/III knee OA. The outcomes from this initial study of novel CCM will lay the foundation for a larger randomized, placebo-controlled, multi-center clinical trial of intraarticular CCM for symptomatic knee OA. TRIAL REGISTRATION: Registered on July 21, 2021. ClinicalTrials.gov NCT04971798

Immune-Complex Mimics as a Molecular Platform for Adjuvant-Free Vaccine Delivery

Protein-based vaccine development faces the difficult challenge of finding robust yet non-toxic adjuvants suitable for humans. Here, using a molecular engineering approach, we have developed a molecular platform for generating self-adjuvanting immunogens that do not depend on exogenous adjuvants for induction of immune responses. These are based on the concept of Immune Complex Mimics (ICM), structures that are formed between an oligomeric antigen and a monoclonal antibody (mAb) to that antigen. In this way, the roles of antigens and antibodies within the structure of immune complexes are reversed, so that a single monoclonal antibody, rather than polyclonal sera or expensive mAb cocktails can be used. We tested this approach in the context of Mycobacterium tuberculosis (MTB) infection by linking the highly immunogenic and potentially protective Ag85B with the oligomeric Acr (alpha crystallin, HspX) antigen. When combined with an anti-Acr monoclonal antibody, the fusion protein formed ICM which bound to C1q component of the complement system and were readily taken up by antigen-presenting cells in vitro. ICM induced a strong Th1/Th2 mixed type antibody response, which was comparable to cholera toxin adjuvanted antigen, but only moderate levels of T cell proliferation and IFN-γ secretion. Unfortunately, the systemic administration of ICM did not confer statistically significant protection against intranasal MTB challenge, although a small BCG-boosting effect was observed. We conclude that ICM are capable of inducing strong humoral responses to incorporated antigens and may be a suitable vaccination approach for pathogens other than MTB, where antibody-based immunity may play a more protective role

Mechanical properties of β-HMX

Background: For a full understanding of the mechanical properties of a material, it is essential to understand the defect structures and associated properties and microhardness indentation is a technique that can aid this understanding. Results: The Vickers hardness on (010), {011} and {110} faces lay in the range of 304-363 MPa. The Knoop Hardnesses on the same faces lay in the range 314-482 MPa. From etching of three indented surfaces, the preferred slip planes have been identified as (001) and (101). For a dislocation glide, the most likely configuration for dislocation movement on the (001) planes is (001) [100] (|b| = 0.65 nm) and for the (101) plane as (101) 101~(|b| = 1.084 nm) although (101) [010] (|b| = 1.105 nm) is possible. Tensile testing showed that at a stress value of 2.3 MPa primary twinning occurred and grew with increasing stress. When the stress was relaxed, the twins decreased in size, but did not disappear. The twinning shear strain was calculated to be 0.353 for the (101) twin plane. Conclusions: HMX is considered to be brittle, compared to other secondary explosives. Comparing HMX with a range of organic solids, the values for hardness numbers are similar to those of other brittle systems. Under the conditions developed beneath a pyramidal indenter, dislocation slip plays a major part in accommodating the local deformation stresses. © 2015 Gallagher et al.; licensee Springer

Outcome of Microscopic Incomplete Resection (R1) of Colorectal Liver Metastases in the Era of Neoadjuvant Chemotherapy

Background: Data from patients with colorectal liver metastases (CRLM) who received neoadjuvant chemotherapy before resection were reviewed and evaluated to see whether neoadjuvant chemotherapy influences the predictive outcome of R1 resections (margin is 0 mm) in patients with CRLM. Methods: Between January 2000 and December 2008, all consecutive patients undergoing liver resection for CRLM were analyzed. Patients were divided into those who did and did not receive neoadjuvant chemotherapy. The outcome after R0 (tumor-free margin >0 mm) and R1 (tumor-free margin 0 mm) resection was compared. Results: A total of 264 were eligible for analysis. Median follow-up was 34 months. Patients without chemotherapy showed a significant difference in median disease-free survival (DFS) after R0 or R1 resection: 17 [95% confidence interval (CI) 10-24] months versus 8 (95% CI 4-12) months (P < 0.001), whereas in

Patterns of neonatal hypoxic–ischaemic brain injury

Enormous progress has been made in assessing the neonatal brain, using magnetic resonance imaging (MRI). In this review, we will describe the use of MRI and proton magnetic resonance spectroscopy in detecting different patterns of brain injury in (full-term) human neonates following hypoxic–ischaemic brain injury and indicate the relevance of these findings in predicting neurodevelopmental outcome

Orientation and dynamics of transmembrane peptides: the power of simple models

In this review we discuss recent insights obtained from well-characterized model systems into the factors that determine the orientation and tilt angles of transmembrane peptides in lipid bilayers. We will compare tilt angles of synthetic peptides with those of natural peptides and proteins, and we will discuss how tilt can be modulated by hydrophobic mismatch between the thickness of the bilayer and the length of the membrane spanning part of the peptide or protein. In particular, we will focus on results obtained on tryptophan-flanked model peptides (WALP peptides) as a case study to illustrate possible consequences of hydrophobic mismatch in molecular detail and to highlight the importance of peptide dynamics for the experimental determination of tilt angles. We will conclude with discussing some future prospects and challenges concerning the use of simple peptide/lipid model systems as a tool to understand membrane structure and function