Oxidative stress and antioxidants in cataract development.

PURPOSE OF REVIEW: Oxidative stress plays a central role in cataract pathogenesis, a leading cause of global blindness. This review delves into the role of oxidative stress in cataract development and key biomarkers - glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE) - to clarify their functions and potential applications in predictive diagnostics and therapies. RECENT FINDINGS: Antioxidants serve as pivotal markers in cataract pathogenesis. GSH affects the central lens due to factors such as enzyme depletion and altered connexin expression, impairing GSH diffusion. Age-related oxidative stress may hinder GSH transport via connexin channels or an internal microcirculation system. N-acetylcysteine, a GSH precursor, shows promise in mitigating lens opacity when applied topically. Additionally, SOD, particularly SOD1, correlates with increased cataract development and gel formulations have exhibited protective effects against posterior subscapular cataracts. Lastly, markers of lipid peroxidation, MDA and 4-HNE, have been shown to reflect disease severity. Studies suggest a potential link between 4-HNE and connexin channel modification, possibly contributing to reduced GSH levels. SUMMARY: Oxidative stress is a significant contributor to cataract development, underscoring the importance of antioxidants in diagnosis and treatment. Notably, GSH depletion, SOD decline, and lipid peroxidation markers are pivotal factors in cataract pathogenesis, offering promising avenues for both diagnosis and therapeutic intervention.

Advances in drug therapy and delivery for cataract treatment.

PURPOSE OF REVIEW: Cataract is one of the leading causes of blindness worldwide and surgery is the only available treatment. Pharmacological therapy has emerged as a potential approach to combat the global shortage of surgery due to a lack of access and resources. This review summarizes recent findings in pharmacological treatment and delivery, focusing on drugs that target oxidative stress and the aggregation of crystallins. RECENT FINDINGS: Antioxidants and oxysterols have been shown to improve or reverse lens opacity in cataract models. N-acetylcysteine amide and N-acetylcarnosine are two compounds that have increased bioavailability over their precursors, alleviating the challenges that have come with topical administration. Studies have shown promising results, with topical N-acetylcarnosine clinically decreasing lens opacity. Furthermore, lanosterol, and more recently 5-cholesten-3b,25-diol (VP1-001), have been reported to combat the aggregation of crystallins in vivo and ex vivo . Delivery has improved with the use of nanotechnology, but further research is needed to solidify these compounds' therapeutic effects on cataracts and improve delivery methods to the lens. SUMMARY: Although further research in drug dosage, delivery, and mechanisms will need to be conducted, pharmacologic therapies have provided new strategies and treatments for the reversal of cataracts.

Latency reversal plus natural killer cells diminish HIV reservoir in vivo.

HIV is difficult to eradicate due to the persistence of a long-lived reservoir of latently infected cells. Previous studies have shown that natural killer cells are important to inhibiting HIV infection, but it is unclear whether the administration of natural killer cells can reduce rebound viremia when anti-retroviral therapy is discontinued. Here we show the administration of allogeneic human peripheral blood natural killer cells delays viral rebound following interruption of anti-retroviral therapy in humanized mice infected with HIV-1. Utilizing genetically barcoded virus technology, we show these natural killer cells efficiently reduced viral clones rebounding from latency. Moreover, a kick and kill strategy comprised of the protein kinase C modulator and latency reversing agent SUW133 and allogeneic human peripheral blood natural killer cells during anti-retroviral therapy eliminated the viral reservoir in a subset of mice. Therefore, combinations utilizing latency reversal agents with targeted cellular killing agents may be an effective approach to eradicating the viral reservoir.

Quality improvement time-saving intervention to increase use of a clinical decision support tool to reduce low-value diagnostic imaging in a safety net health system.

IMPORTANCE: Electronic health record (EHR) clinical decision support (CDS) tools can provide evidence-based feedback at the point of care to reduce low-value imaging. Success of these tools has been limited partly due to lack of engagement by busy clinicians. OBJECTIVE: Measure the impact of a time-saving quality improvement intervention to increase engagement with a CDS tool for low back pain imaging ordering. DESIGN, SETTING AND PARTICIPANTS: We conducted a quasi-experimental difference-in-differences analysis at (BLINDED), examining back pain imaging orders from 29 May 2015 to 07 January 2016. The intervention site was (BLINDED) Emergency Medicine/Urgent Care Center (n=5736) and control sites included all other (BLINDED) hospitals and clinics (n=1621). In May 2015, the Department of Health Services installed a CDS tool that triggered a survey when clinicians ordered an imaging test, generating an 'appropriateness score' based on the American College of Radiology guidelines. Clinicians often bypassed the tool, resulting in 'unscored' tests. INTERVENTION: To increase clinician engagement with the tool and decrease the rate of unscored imaging tests, a new policy was implemented at the intervention site on 15 August 2015. If clinicians completed the CDS survey and scored an appropriateness score >3, they could forego a previously mandatory telephone call for pre-imaging utilisation review with the radiology department. MAIN OUTCOMES AND MEASURES: We used EHR data to measure pre-post-intervention differences in: (1) percentage of unscored tests and (2) percentage of tests with high appropriateness scores (>7). RESULTS: Percentage of unscored tests decreased from 69.4% to 10.4% at the intervention site and from 50.6% to 34.8% at the control sites (between-group difference: -23.3%, p<0.001). Percentage of high scoring tests increased from 26.5% to 75.0% at the intervention site and from 17.2% to 22.7% at the control sites (between-group difference: 19%, p<0.001). CONCLUSION: Workflow time-saving interventions may increase physician engagement with CDS tools and have potential to improve practice patterns.