Circulating collagen breakdown products as a biomarker for presence and instability of human intracranial aneurysms.

Introduction: There is an unmet need for improved detection of intracranial aneurysms (IAs) and distinction between stable and unstable (high rupture risk) IAs. Within the IA wall, synthesis and degradation of type I collagen as the main molecular constituent balance each other to maintain IA stability. We hypothesized that collagen breakdown products could serve as molecular markers for IA presence and instability.

Risk-Based Approach for Defining Retest Dates for Active Pharmaceutical Ingredients and Excipients.

Drug substances and excipients must be stored in recommended storage conditions and should comply with their specifications during the retest period for their use in the manufacture of drug products. The ICH (International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use) and WHO (World Health Organization) regulatory guidelines mandate that after the retest period, the drug substances must be retested for compliance with the specification and then used immediately in the manufacture of the finished product. Although these substances can be retested multiple times, an emphasis is placed on immediate use following a retest and compliance with standards.

Osteocalcin improves testicular morphology but does not ameliorate testosterone synthesis signaling in azoospermic mice.

Objective: Osteocalcin (OCN) influences spermatogenesis in conjunction with testosterone and estrogen. OCN facilitates the secretion of testosterone by engaging with G protein-coupled receptor class C group 6 member A (GPRC6A) on Leydig cells and with androgen receptors on Sertoli cells.

Methods: Adult mice were assigned to the following groups: control; sham I, which received dimethyl sulfoxide for 5 weeks followed by phosphate-buffered saline for 1 month; azoospermia, which was treated with busulfan (40 mg/kg); sham II, which consisted of azoospermic animals that received phosphate-buffered saline for 1 month beginning at the 5-week mark; and the experimental group, which included azoospermic mice treated with OCN (3 ng/g/day) for 1 month.

Sertoli Cell-Conditioned Medium Induces Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells to Male Germ-Like Cells in Busulfan-Induced Azoospermic Mouse Model.

Non-obstructive azoospermia is a severe form of male infertility, with limited effective treatments. Bone marrow mesenchymal stem cells (BMSCs) can differentiate to different cell lines; therefore, transplantation of these cells is used for treatment of several diseases. Since these cells require induction factors to differentiate into germ cells, we co-transplanted bone marrow stem cells (BMSCs) with Sertoli cell-conditioned medium (SCCM) into the testis of azoospermic mice.

Pentoxifylline promotes spermatogenesis via upregulation of the Nrf2-ARE signalling pathway in a mouse model of germ-cell apoptosis induced by testicular torsion-detorsion.

Context: Testicular torsion-detorsion results in loss of germ cells and infertility. Pentoxifylline has been shown to prevent tissue damage.

Aims: To determine the effect of pentoxifylline on germ cell survival in torsion-detorsion induced apoptosis Methods: Twenty male mice were divided into four groups of five animals each: Control, T1 (Torsion-detorsion+single dose 100mg/kg Pentoxifylline/IP), T2 (Torsion-detorsion+daily 20mg/kg pentoxifylline/IP for 2weeks, and T/D (Torsion-detorsion only).

The genes road: impact of migration on newborn screening and health amid the COVID-19 pandemic in the Eastern Mediterranean region.

Nearly two-thirds of migrants residing in camps in Europe are women and children. Many of these children, being born on the way without essential newborns screening, are at some point admitted to pediatric wards in asylum countries. With hospitals overwhelmed with COVID-19 cases, taking appropriate care of newborns becomes a considerable burden.

Acid sensing ion channels in rat cerebral arteries: Probing the expression pattern and vasomotor activity.

Aims: The recent identification of acid sensing ion channels (ASICs) in vascular beds suggests their possible involvement in modulating vasomotor tone. Therefore, we investigated the gene expression profiles of ASIC subtypes in the middle cerebral artery (MCA) of Wistar rats and the functional implication of ASICs in acidosis-induced relaxation as well as maintenance of resting tension.

Main Methods: Real time PCR was employed to study the pattern of ASIC mRNA expression in the MCA wall in comparison with (i) matching brain tissue samples and (ii) arteries cultured for 24 h and 48 h.

Engendering a conducive environment for university students with physical disabilities: assessing availability of assistive facilities in Nigeria.

Purpose: This study assessed awareness and availability of assistive facilities in a Nigerian public university.

Methods: Study was conducted in Obafemi Awolowo University (OAU), Ile Ife Nigeria using a mixed methods approach. Fifty two students with disability (SWD) were interviewed with a semistructured, self-administered questionnaire.

The dynamic excitation of a granular chain: Contact mechanics finite element analysis and experimental validation.

There is currently interest in transmitting acoustic signals along granular chains to produce waveforms of relevance to biomedical ultrasound applications. The study of such a transduction mechanism is greatly aided by the use of validated theoretical models. In view of this, a finite element analysis is presented in this paper.

The Effect of Boundary Conditions on Resonant Ultrasonic Spherical Chains.

The response of a resonant chain of spheres to changes in holder material and precompression is studied at ultrasonic frequencies. The system is found to be very sensitive to these parameters, with the creation of impulsive waveforms from a narrow bandwidth input seen only for certain chain lengths and holder materials. In addition, careful experiments were performed using known amounts of precompression force, using a calibrated stylus arrangement.

Analysis of solitary wave impulses in granular chains using ultrasonic excitation.

The propagation of broad bandwidth solitary wave impulses, generated within granular chains by narrow bandwidth ultrasonic excitation, is studied in detail. Theoretical predictions are compared to experimental results. It is demonstrated that the observed effects result from a sum of a solitary wave traveling out from the source with a wave that reflects from the far end of the chain.

Ultrasonic propagation in finite-length granular chains.

A narrowband ultrasound source has been used to generate solitary wave impulses in finite-length chains of spheres. Once the input signal is of sufficient amplitude, both harmonics and sub-harmonics of the input frequency can be generated as non-linear normal modes of the system, allowing a train of impulses to be established from a sinusoidal input. The characteristics of the response have been studied as a function of the physical properties of the chain, the input waveform and the level of static pre-compression.

Quantification of mRNA using real-time PCR and Western blot analysis of MAPK events in chondrocyte/agarose constructs.

In vitro models of chondrocyte mechanobiology have been used to compare the intracellular signalling pathways altered in normal and osteoarthritis-affected cartilage. However, differences in the model system and type of loading configuration have led to complicated pathways. This chapter is a follow-on of previous studies from our group utilising 3D agarose as a physiological model to study mechanotransduction pathways.

Dynamic compression alters NFkappaB activation and IkappaB-alpha expression in IL-1beta-stimulated chondrocyte/agarose constructs.

Objective And Design: Determine the effect of IL-1beta and dynamic compression on NFkappaB activation and IkappaB-alpha gene expression in chondrocyte/agarose constructs.

Methods: Constructs were cultured under free-swelling conditions or subjected to dynamic compression for up to 360 min with IL-1beta and/or PDTC (inhibits NFkappaB activation). Nuclear translocation of NFkappaB-p65 was analysed by immunofluoresence microscopy.

Dynamic compression influences interleukin-1beta-induced nitric oxide and prostaglandin E2 release by articular chondrocytes via alterations in iNOS and COX-2 expression.

Interleukin-1beta (IL-1beta) induces the release of nitric oxide (.NO) and prostaglandin E2 (PGE2) by chondrocytes and this effect can be reversed with the application of dynamic compression. Previous studies have indicated that integrins may play a role.

The effects of direct current stimulation on isolated chondrocytes seeded in 3D agarose constructs.

Endogenous electrical activity has been detected in articular cartilage. It has previously been suggested that the associated electrical currents and potentials are important to the mechanotransduction processes in cartilage. The present study investigates the effects of direct current on cell proliferation and matrix synthesis, using the well established 3D chondrocyte--agarose model system.

Dynamic compression counteracts IL-1beta induced inducible nitric oxide synthase and cyclo-oxygenase-2 expression in chondrocyte/agarose constructs.

Background: Nitric oxide and prostaglandin E2 (PGE2play pivotal roles in both the pathogenesis of osteoarthritis and catabolic processes in articular cartilage. These mediators are influenced by both IL-1beta and mechanical loading, and involve alterations in the inducible nitric oxide synthase (iNOS) and cyclo-oxygenase (COX)-2 enzymes. To identify the specific interactions that are activated by both types of stimuli, we examined the effects of dynamic compression on levels of expression of iNOS and COX-2 and involvement of the p38 mitogen-activated protein kinase (MAPK) pathway.