Treating Cardiovascular Disease in the Inflammatory Setting of Rheumatoid Arthritis: An Ongoing Challenge.

Despite progress in treating rheumatoid arthritis, this autoimmune disorder confers an increased risk of developing cardiovascular disease (CVD). Widely used screening protocols and current clinical guidelines are inadequate for the early detection of CVD in persons with rheumatoid arthritis. Traditional CVD risk factors alone cannot be applied because they underestimate CVD risk in rheumatoid arthritis, missing the window of opportunity for prompt intervention to decrease morbidity and mortality. The lipid profile is insufficient to assess CVD risk. This review delves into the connection between systemic inflammation in rheumatoid arthritis and the premature onset of CVD. The shared inflammatory and immunologic pathways between the two diseases that result in subclinical atherosclerosis and disrupted cholesterol homeostasis are examined. The treatment armamentarium for rheumatoid arthritis is summarized, with a particular focus on each medication's cardiovascular effect, as well as the mechanism of action, risk-benefit profile, safety, and cost. A clinical approach to CVD screening and treatment for rheumatoid arthritis patients is proposed based on the available evidence. The mortality gap between rheumatoid arthritis and non-rheumatoid arthritis populations due to premature CVD represents an urgent research need in the fields of cardiology and rheumatology. Future research areas, including risk assessment tools and novel immunotherapeutic targets, are highlighted.

Fibrosis in Chronic Kidney Disease: Pathophysiology and Therapeutic Targets.

Chronic kidney disease (CKD) is a slowly progressive condition characterized by decreased kidney function, tubular injury, oxidative stress, and inflammation. CKD is a leading global health burden that is asymptomatic in early stages but can ultimately cause kidney failure. Its etiology is complex and involves dysregulated signaling pathways that lead to fibrosis. Transforming growth factor (TGF)-ß is a central mediator in promoting transdifferentiation of polarized renal tubular epithelial cells into mesenchymal cells, resulting in irreversible kidney injury. While current therapies are limited, the search for more effective diagnostic and treatment modalities is intensive. Although biopsy with histology is the most accurate method of diagnosis and staging, imaging techniques such as diffusion-weighted magnetic resonance imaging and shear wave elastography ultrasound are less invasive ways to stage fibrosis. Current therapies such as renin-angiotensin blockers, mineralocorticoid receptor antagonists, and sodium/glucose cotransporter 2 inhibitors aim to delay progression. Newer antifibrotic agents that suppress the downstream inflammatory mediators involved in the fibrotic process are in clinical trials, and potential therapeutic targets that interfere with TGF-ß signaling are being explored. Small interfering RNAs and stem cell-based therapeutics are also being evaluated. Further research and clinical studies are necessary in order to avoid dialysis and kidney transplantation.

Therapeutic Potential of P110 Peptide: New Insights into Treatment of Alzheimer's Disease.

Mitochondrial degeneration in various neurodegenerative diseases, specifically in Alzheimer's disease, involves excessive mitochondrial fission and reduced fusion, leading to cell damage. P110 is a seven-amino acid peptide that restores mitochondrial dynamics by acting as an inhibitor of mitochondrial fission. However, the role of P110 as a neuroprotective agent in AD remains unclear. Therefore, we performed cell culture studies to evaluate the neuroprotective effect of P110 on amyloid-ß accumulation and mitochondrial functioning. Human SH-SY5Y neuronal cells were incubated with 1 µM and 10 µM of P110, and Real-Time PCR and Western blot analysis were done to quantify the expression of genes pertaining to AD and neuronal health. Exposure of SH-SY5Y cells to P110 significantly increased APP mRNA levels at 1 µM, while BACE1 mRNA levels were increased at both 1 µM and 10 µM. However, protein levels of both APP and BACE1 were significantly reduced at 10 µM of P110. Further, P110 treatment significantly increased ADAM10 and Klotho protein levels at 10 µM. In addition, P110 exposure significantly increased active mitochondria and reduced ROS in live SH-SY5Y cells at both 1 µM and 10 µM concentrations. Taken together, our results indicate that P110 might be useful in attenuating amyloid-ß generation and improving neuronal health by maintaining mitochondrial function in neurons.

Exosomes in Cardiovascular Disease: From Mechanism to Therapeutic Target.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally. In recent decades, clinical research has made significant advances, resulting in improved survival and recovery rates for patients with CVD. Despite this progress, there is substantial residual CVD risk and an unmet need for better treatment. The complex and multifaceted pathophysiological mechanisms underlying the development of CVD pose a challenge for researchers seeking effective therapeutic interventions. Consequently, exosomes have emerged as a new focus for CVD research because their role as intercellular communicators gives them the potential to act as noninvasive diagnostic biomarkers and therapeutic nanocarriers. In the heart and vasculature, cell types such as cardiomyocytes, endothelial cells, vascular smooth muscle, cardiac fibroblasts, inflammatory cells, and resident stem cells are involved in cardiac homeostasis via the release of exosomes. Exosomes encapsulate cell-type specific miRNAs, and this miRNA content fluctuates in response to the pathophysiological setting of the heart, indicating that the pathways affected by these differentially expressed miRNAs may be targets for new treatments. This review discusses a number of miRNAs and the evidence that supports their clinical relevance in CVD. The latest technologies in applying exosomal vesicles as cargo delivery vehicles for gene therapy, tissue regeneration, and cell repair are described.

Changes in serial magnetic resonance spectroscopy predict outcome in high-grade glioma during and after postoperative radiotherapy.

AIM: To determine any correlation between magnetic resonance spectroscopy (MRS) pattern of high-grade glioma before, during, and after radiotherapy (RT) with overall survival (OS) and progression-free survival (PFS). PATIENTS AND METHODS: Twenty-six patients prospectively underwent surgery and RT to 60 Gy. MRS was performed before RT, at week 4 of RT, and 2 months post-RT. Normalized and relative metabolite ratios were evaluated. Patients were grouped according to similar evolving MRS patterns and analyzed for differences in OS and PFS. RESULTS: Significant decreases in tumor choline/N-acetyl-aspartate and normalized choline were observed from baseline to post-RT. After a median follow-up of 22.9 months, patients with >40% decrease in normalized choline from week 4 during RT to 2 months post-RT had a significantly worse median OS (9.1 months vs. not reached, p<0.00001) and PFS (5.8 vs. 19.8 months, p=0.0018). CONCLUSION: The change in normalized choline at 2 months post-RT was highly prognostic for PFS and OS. This may allow more individualized response-based treatment.

Unified compaction curve model for tensile strength of tablets made by roller compaction and direct compression.

A model that describes the relationship between roller-compaction conditions and tablet strength is proposed. The model assumes that compaction is cumulative during roller compaction and subsequent granule compaction, and compact strength (ribbon and tablet) is generated irreversibly as if strength is controlled by plastic deformation of primary particles only. Roller-compaction is treated as a compaction step where the macroscopic ribbon strength is subsequently destroyed in milling. This loss in strength is irreversible and tablets compressed from the resulting granulation are weaker than those compressed by direct compression at the same compression force. Roller-compacted ribbons were produced at a range of roll forces for three formulations and subsequently milled and compacted into tablets. Once the total compaction history is taken in account, the compaction behavior of the uncompacted blends and the roller-compacted granules ultimately follow a single master compaction curve--a unified compaction curve (UCC). The model successfully described the compaction behavior of DC grade starch and formulations of lactose monohydrate with 50% or more microcrystalline cellulose, and may be more generally applicable to systems containing significant proportions of any plastically deforming material, including MCC and starch.

Effect of educational preparation on the accuracy of linear growth measurement in pediatric primary care practices: results of a multicenter nursing study.

Consistently monitoring a child's linear growth is one of the least invasive, most sensitive tools to identify normal physiologic functioning and a healthy lifestyle. However, studies, mostly from the United Kingdom, indicate that children are frequently measured incorrectly. Inaccurate linear measurements may result in some children having undetected growth disorders whereas others with normal growth being referred for costly, unwarranted specialty evaluations. This study presents the secondary analysis of a primary study that used a randomized control study design to demonstrate that a didactic educational intervention resulted in significantly more children being measured accurately within eight pediatric practices. The secondary analysis explored the influence of the measurer's educational level on the outcome of accurate linear measurement. Results indicated that RNs were twice as likely as non-RNs to measure children accurately.