Galectin inhibitors and nanoparticles as a novel therapeutic strategy for glioblastoma multiforme.

Over the past two decades, the gold standard of glioblastoma multiforme (GBM) treatment is unchanged and adjunctive therapy has offered little to prolong both quality and quantity of life. To improve pharmacotherapy for GBM, galectins are being studied provided their positive correlation with the malignancy and disease severity. Despite the use of galectin inhibitors and literature displaying the ability of the lectin proteins to decrease tumor burden and decrease mortality within various malignancies, galectin inhibitors have not been studied for GBM therapy. Interestingly, anti-galectin siRNA delivered in nanoparticle capsules, assisting in blood brain barrier penetrance, is well studied for GBM, and has demonstrated a remarkable ability to attenuate both galectin and tumor count. Provided that the two therapies have an analogous anti-galectin effect, it is hypothesized that galectin inhibitors encapsuled within nanoparticles will likely have a similar anti-galectin effect in GBM cells and further correlate to a repressed tumor burden.

Single-Stage Titanium Mesh Cranioplasty for the Treatment of Depressed Skull Fractures.

BACKGROUND: Historically, depressed skull fractures that warranted surgery were treated in 2 stages: the first stage involved debridement and craniectomy, followed by the second stage of delayed cranioplasty. More recently, single-stage autologous cranioplasty has been proven to be safe. However, there is a paucity of literature regarding single-stage titanium mesh cranioplasty when autologous repair is not possible. METHODS: A retrospective review identified 22 patients who underwent single-stage titanium mesh cranioplasty for the acute treatment of comminuted depressed skull fractures. Fracture location, fracture etiology, timing of surgery, neurologic complications, infection, and cosmetic deformity were recorded. Average follow-up was 9 months. RESULTS: The mean age of the patients was 34 years (range: 3-77); 83% were male. Seventeen (77%) involved the frontal bone, with 7 (32%) involving the frontal sinus. Eighteen (82%) had open defects at presentation. Sixteen (73%) were neurologically normal. Average time from presentation to repair was 11 hours (range: 1-28 hours). There were no neurologic worsening, seizures, or infections postoperatively. Antibiotic prophylaxis was prescribed in 13 cases (57%). One patient required revision surgery for persistent cosmetic deformity. CONCLUSIONS: Autologous cranioplasty for depressed skull fractures is not always possible especially in cases of significant comminution. From our case series, single-stage titanium mesh cranioplasty appears to be a safe option.

PAD Inhibitors as a Potential Treatment for SARS-CoV-2 Immunothrombosis.

Since the discovery of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, the virus's dynamicity has resulted in the evolution of various variants, including the delta variant and the more novel mu variant. With a multitude of mutant strains posing as challenges to vaccine efficacy, it is critical that researchers embrace the development of pharmacotherapeutics specific to SARS-CoV-2 pathophysiology. Neutrophil extracellular traps and their constituents, including citrullinated histones, display a linear connection with thrombotic manifestations in COVID-19 patients. Peptidylarginine deiminases (PADs) are a group of enzymes involved in the modification of histone arginine residues by citrullination, allowing for the formation of NETs. PAD inhibitors, specifically PAD-4 inhibitors, offer extensive pharmacotherapeutic potential across a broad range of inflammatory diseases such as COVID-19, through mediating NETs formation. Although numerous PAD-4 inhibitors exist, current literature has not explored the depth of utilizing these inhibitors clinically to treat thrombotic complications in COVID-19 patients. This review article offers the clinical significance of PAD-4 inhibitors in reducing thrombotic complications across various inflammatory disorders like COVID-19 and suggests that these inhibitors may be valuable in treating the origin of SARS-CoV-2 immunothrombosis.

Development and initial validation of the urban adolescent hope scale.

OBJECTIVE: Hope is an important component to adolescents' mental health and well-being. While much study and theory have explored hope, few examine the idea within contextualized factors such as locale. Even fewer have sought to measure hope for urban adolescents. The Urban Adolescent Hope Scale (UAHS) was developed to measure hope in a contextualized manner as guided by previous qualitative inquiry. This study aims to establish initial validation for the UAHS. METHOD: Using findings from qualitative inquiry, a 24-item proposed measure of hope for urban adolescents was developed. Experts in various fields were consulted to provide face and content validity. The instrument was then given at school-wide needs assessment at an urban Midwestern high school. RESULTS: Using a confirmatory factor analysis, fit indices (RMSEA, TLI, CFI, and SRMR) and measures of internal consistency indicated a reliable five-factor structure of hope consisted of Spirituality (α = .936), Personal Agency (α = .930), The Basics (α = .936), Education (α = .921), and Caring Connections (α = .875). CONCLUSION: The findings from this study indicate the UAHS has initial validity and reliability to be used as a measure of hope for urban adolescents. Future implications for research and practice are provided.