Age-associated functional healing of musculoskeletal trauma through regenerative engineering and rehabilitation.

Traumatic musculoskeletal injuries that lead to volumetric muscle loss (VML) are challenged by irreparable soft tissue damage, impaired regenerative ability, and reduced muscle function. Regenerative rehabilitation strategies involving the pairing of engineered therapeutics with exercise have guided considerable advances in the functional repair of skeletal muscle following VML. However, few studies evaluate the efficacy of regenerative rehabilitation across the lifespan.

Effects of in utero delta-9-tetrahydrocannabinol (THC) exposure on fetal and infant musculoskeletal development in a preclinical nonhuman primate model.

The endocannabinoid system (ECS) plays a major role in the maintenance of bodily homeostasis and adaptive response to external insults. It has been shown to regulate crucial physiological processes and behaviors, spanning nervous functions, anxiety, cognition, and pain sensation. Due to this broad activity, the ECS has been explored as a potential therapeutic target in the treatment of select diseases.

Murine Progeria Model Exhibits Delayed Fracture Healing with Dysregulated Local Immune Response.

Background: Bone fracture is one of the most globally prevalent injuries, with an estimated 189 million bone fractures occurring annually. Delayed union or nonunion occurs in up to 15% of fractures and involves the interruption or complete failure of bone continuity following fracture. Preclinical testing is essential to support the translation of novel strategies to promote improved fracture repair treatment, but there is a paucity of small animal models that recapitulate clinical attributes associated with delayed fracture healing.

Clinical validation of CFDG as a marker associated with senescence and osteoarthritic phenotypes.

Chronic conditions associated with aging have proven difficult to prevent or treat. Senescence is a cell fate defined by loss of proliferative capacity and the development of a pro-inflammatory senescence-associated secretory phenotype comprised of cytokines/chemokines, proteases, and other factors that promotes age-related diseases. Specifically, an increase in senescent peripheral blood mononuclear cells (PBMCs), including T cells, is associated with conditions like frailty, rheumatoid arthritis, and bone loss.

Evaluating the Morphology of Unique Superficial Fissured Cartilage Lesions at the Femoral Head-Neck Junction in Patients with Femoroacetabular Impingement Syndrome.

Background: While an association between femoroacetabular impingement (FAI) and osteoarthritis (OA) has been reported, the mechanistic differences and transition between the 2 conditions is not fully understood. In FAI, cartilage lesions at the femoral head-neck junction can sometimes be visualized during hip arthroscopy.

Purpose/hypothesis: The purpose of this study was to describe a unique dimpled pattern of superficial fissured cartilage lesions on the femoral head-neck junction at impingement site in patients with FAI syndrome (FAIS) and to evaluate the clinical, histological, and genetic phenotype of this cartilage.

A Systemic and Local Comparison of Senescence in an Acute Anterior Cruciate Ligament Injury-A Pilot Case Series.

Background: Senescence, a characteristic of cellular aging and inflammation, has been linked to the acceleration of osteoarthritis. The purpose of this study is to prospectively identify, measure, and compare senescent profiles in synovial fluid and peripheral blood in patients with an acute knee injury within 48 h.

Methods: Seven subjects, aged 18-60 years, with an acute ACL tear with effusion were prospectively enrolled.

Encapsulation of β-NGF in injectable microrods for localized delivery accelerates endochondral fracture repair.

Currently, there are no non-surgical FDA-approved biological approaches to accelerate fracture repair. Injectable therapies designed to stimulate bone healing represent an exciting alternative to surgically implanted biologics, however, the translation of effective osteoinductive therapies remains challenging due to the need for safe and effective drug delivery. Hydrogel-based microparticle platforms may be a clinically relevant solution to create controlled and localized drug delivery to treat bone fractures.

Mechanical strain drives exosome production, function, and miRNA cargo in C2C12 muscle progenitor cells.

Mesenchymal stem cells (MSCs) have been proven to promote tissue repair. However, concerns related to their clinical application and regulatory hurdles remain. Recent data has demonstrated the proregenerative secretome of MSCs can result in similar effects in the absence of the cells themselves.

Wireless Measurements Using Electrical Impedance Spectroscopy to Monitor Fracture Healing.

There is an unmet need for improved, clinically relevant methods to longitudinally quantify bone healing during fracture care. Here we develop a smart bone plate to wirelessly monitor healing utilizing electrical impedance spectroscopy (EIS) to provide real-time data on tissue composition within the fracture callus. To validate our technology, we created a 1-mm rabbit tibial defect and fixed the bone with a standard veterinary plate modified with a custom-designed housing that included two impedance sensors capable of wireless transmission.

Lateral semi-circular canal asymmetry in females with idiopathic scoliosis.

Purpose: Adolescent idiopathic scoliosis (AIS) is a three-dimensional spinal structural deformity that occurs in otherwise normal individuals. Although curve progression and severity vary amongst individuals, AIS can lead to significant cosmetic and functional deformity. AIS etiology has been determined to be genetic, however, exact genetic and biological processes underlying this disorder remain unknown.

Polyacrylamide Hydrogels Produce Hydrogen Peroxide from Osmotic Swelling in Aqueous Media.

This work demonstrates that hydrogen peroxide (HO) is generated in weak polyacrylamide hydrogels due to mechanochemical reactions to osmotic swelling. Hydrogels are important tools and materials for many biomedical applications, particularly for growth of stem cells. However, swollen gels are under constant tension, which makes their individual chains susceptible to mechanochemical bond breakage.

Social media in nurse education: Utilization and E-professionalism.

Objective: To explore faculty and student utilization of social media and its professional implications in nurse education.

Methods: A descriptive study. Five hundred six Bachelor of Nursing students, 112 Practical Nursing students and 74 faculty members were invited to complete a questionnaire of 28 questions relating to social media.

[Melatonin as a marker of the grade of cardiac disorders during cachexia development in oncological patients of different ages].

We have examined 103 patients at the age from 28 to 78 with the newly diagnosed oncological disease at stages II-IV before the beginning of anticancer treatment. The identification of the signs of the cachexia syndrome and its stage (pre-cachexia, cachexia) were carried out in the accordance with the CASCO criteria (2011) and taking into the account the age of the patients. The cardiovascular infringements were found to be comorbid to the oncological disease significantly more often in patients with signs of cachexia syndrome on the pre-cachexia stage and the total index of cardiovascular disorders in oncological patients increases with the severity of cachexia.

Same-visit HIV testing in Trinidad and Tobago.

Background: The Ministry of Health (hereafter, Ministry) of Trinidad and Tobago is responsible for delivery of all health services in the country. The Ministry takes responsibility for direct delivery of care in the public sector and has initiated a process whereby those seeking HIV test results could obtain confidential reports during a single-visit to a testing location. The Ministry requested technical assistance with this process from the Caribbean Epidemiology Centre (CAREC).

Estrogen prevents sustained COLO-205 human colon cancer cell growth by inducing apoptosis, decreasing c-myb protein, and decreasing transcription of the anti-apoptotic protein bcl-2.

The proto-oncogene c-myb is overexpressed in human colon cancer cells. c-myb is known to be affected by estrogen in some breast cancers and leukemias. However, the mechanism of c-myb regulation via estrogen in colon cancer requires further investigation.

Minimal residual disease is a significant predictor of treatment failure in non T-lineage adult acute lymphoblastic leukaemia: final results of the international trial UKALL XII/ECOG2993.

The predictive value of molecular minimal residual disease (MRD) monitoring using polymerase chain reaction amplification of clone-specific immunoglobulin or T-cell Receptor rearrangements was analysed in 161 patients with non T-lineage Philadelphia-negative acute lymphoblastic leukaemia (ALL) participating in the UK arm of the international ALL trial UKALL XII/Eastern Cooperative Oncology Group (ECOG) 2993. MRD positivity (> or =10(-4)) in patients treated with chemotherapy alone was associated with significantly shorter relapse-free survival (RFS) at several time-points during the first year of therapy. MRD status best discriminated outcome after phase 2 induction, when the relative risk of relapse was 8.

Prognostic implications of NOTCH1 and FBXW7 mutations in adults with T-cell acute lymphoblastic leukemia treated on the MRC UKALLXII/ECOG E2993 protocol.

Purpose: Notch pathway activation by mutations in either NOTCH1 and/or FBXW7 is one of the most common molecular events in T-cell acute lymphoblastic leukemia (T-ALL) and, in pediatric disease, predicts for favorable outcome. Their prognostic significance in adult T-ALL is unclear. We sought to evaluate the outcome according to mutation status of patients with adult T-ALL treated on the United Kingdom Acute Lymphoblastic Leukaemia XII (UKALLXII)/Eastern Cooperative Oncology Group (ECOG) E2993 protocol.

The JAK2(V617F) tyrosine kinase mutation identifies clinically latent myeloproliferative disorders in patients presenting with hepatic or portal vein thrombosis.

Clinically latent myeloproliferative disorders (MPDs) are important causes of what would otherwise be considered idiopathic hepatic (HVT) or portal vein thrombosis (PVT). They may be difficult to diagnose initially because the peripheral blood count may be normal at the time of thrombosis. A strong association between an activating mutation of the gene encoding one of the Janus kinase family of tyrosine kinases (JAK2(V617F)) and the Philadelphia chromosome-negative MPDs has been identified.

p53-mediated apoptosis of CLL cells: evidence for a transcription-independent mechanism.

The p53 protein plays a key role in securing the apoptotic response of chronic lymphocytic leukemia (CLL) cells to genotoxic agents. Transcriptional induction of proapoptotic proteins including Puma are thought to mediate p53-dependent apoptosis. In contrast, recent studies have identified a novel nontranscriptional mechanism, involving direct binding of p53 to antiapoptotic proteins including Bcl-2 at the mitochondrial surface.

Notch-1 mutations are secondary events in some patients with T-cell acute lymphoblastic leukemia.

Purpose: Activating Notch-1 mutations are frequent in T-cell acute lymphoblastic leukemia (T-ALL), occurring in >50% of patients. In murine models of T-ALL, Notch-1 activation can both directly initiate leukemia and cooperate secondarily to other primary events. Whether acquisition of Notch-1 mutations is an early initiating event or a secondary event in the pathogenesis of human T-ALL is unclear.

Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers.

Highly rearranged and mutated cancer genomes present major challenges in the identification of pathogenetic events driving the neoplastic transformation process. Here we engineered lymphoma-prone mice with chromosomal instability to assess the usefulness of mouse models in cancer gene discovery and the extent of cross-species overlap in cancer-associated copy number aberrations. Along with targeted re-sequencing, our comparative oncogenomic studies identified FBXW7 and PTEN to be commonly deleted both in murine lymphomas and in human T-cell acute lymphoblastic leukaemia/lymphoma (T-ALL).

The sesquiterpene lactone parthenolide induces selective apoptosis of B-chronic lymphocytic leukemia cells in vitro.

We have studied the in vitro actions of the sesquiterpene lactone parthenolide (PTL) on cells isolated from patients with chronic lymphocytic leukemia (CLL). Dye reduction viability assays showed that the median LD(50) for PTL was 6.2 muM (n=78).

Differential expression of CD 180 and IgM by B-cell chronic lymphocytic leukaemia cells using mutated and unmutated immunoglobulin VH genes.

We have studied the surface expression of the Toll-like receptor family member CD 180 on cells from 78 patients with B-chronic lymphocytic leukaemia (B-CLL). B-CLL cells had variable levels of CD 180 expression, but this was always less than that expressed by normal blood B cells and was stable for 24 months. Significantly higher levels of CD 180 were expressed by B-CLL cells with mutated IGVH genes compared with those using unmutated IGVH genes.