Alzheimer's dementia (AD) is the most common major neurocognitive impairment and the fifth leading cause of death in older adults in the United States. The diagnosis is clinical; however, laboratory tests and imaging frequently rule out secondary causes of dementia. Unfortunately, the treatment available for AD does not reverse dementia, but it may help improve the symptoms and slow the progression of the disease. The conventional treatment -acetylcholinesterase inhibitor (AChEI) therapy and N-methyl-D-aspartate (NMDA) receptor antagonist -is considered to enhance executive function, overall cognition, and activities of daily living. AChEIs such as donepezil, rivastigmine, and galantamine are approved for mild-to-moderate dementia. Furthermore, memantine, an NMDA receptor antagonist, is authorized for moderate-to-severe dementia. Aducanumab, the newest drug available, is an amyloid-beta (Aβ) monoclonal antibody approved only for mild AD. Treatment with either AChEIs or memantine is more cost-effective than aducanumab and the best supportive care. Aducanumab has particular recommendations with strict monitoring and several adverse effects, including amyloid-related imaging abnormalities. The most common adverse effects of AChEIs and memantine include gastrointestinal symptoms, dizziness, confusion, and headaches. Therefore, monitoring should be performed periodically at the clinician's discretion for clinical response and tolerability of medication. Conventional therapies are only for symptom management but are still beneficial to patients and caregivers. Unfortunately, at this time, aducanumab's risks outweigh the benefits with a questionable approval process by the Food and Drug Administration (FDA). However, given the potential disease-modifying capabilities of aducanumab, other disease-modifying options may become available by possibly reducing inflammation, preventing Aβ plaques from clumping, or keeping tau proteins from tangling.

Oxidative DNA damage can lead to cancer, and as enzymatic DNA repair systems become compromised during the aging process, the role of exogenous antioxidants becomes more critical. Here, we examined whether such non-enzymatic DNA repair can be effected by the common cellular antioxidant glutathione, investigating both permanent DNA damage products and the guanine radical intermediates that form them, using the flash-quench technique to carry out the one-electron oxidation of guanine. In gel-shift assays, the presence of reduced glutathione at physiological (millimolar) concentrations strongly inhibits oxidative DNA–protein cross-linking. In contrast, the oxidized glutathione dimer affords only a minimal amount of protection, even at elevated pH where there is more of the strongly reducing thiolate form. In flash photolysis experiments, the formation and decay of the guanine neutral radical were monitored at 510 nm. Transient absorption measurements with a guanine-rich 22-mer DNA duplex on the millisecond time scale show that the yield of this long-lived signal is significantly diminished in the presence of reduced glutathione, suggesting a reduction process that is fast relative to the measurement. Indeed, transient absorption experiments carried out on faster time scales show that the microsecond decay of the guanine radical signal is visibly faster with glutathione present. Glutathione is perhaps best known as an electron source in enzymatic reactions, to maintain cysteines in reduced states in proteins and to deactivate reactive oxygen species. However, these results show that another important task for glutathione may be to directly intercept DNA radicals before permanent DNA damage can occur.

Purpose of Review Myocardial infarction with nonobstructive coronary arteries (MINOCA) is defined as acute myocardial infarction (MI) with angiographically no obstructive coronary artery disease or stenosis ≤ 50%. MINOCA is diagnostically challenging and complex, making it difficult to manage effectively. This condition accounts for 6–8% of all MI and poses an increased risk of morbidity and mortality after diagnosis. Prompt recognition and targeted management are essential to improve outcomes and our understanding of this condition, but this process is not yet standardized. This article offers a comprehensive review of MINOCA, delving deep into its unique clinical profile, invasive and noninvasive diagnostic strategies for evaluating MINOCA in light of the lack of widespread availability for comprehensive testing, and current evidence surrounding targeted therapies for patients with MINOCA. Recent Findings MINOCA is not uncommon and requires comprehensive assessment using various imaging modalities to evaluate it further. Summary MINOCA is a heterogenous working diagnosis that requires thoughtful approach to diagnose the underlying disease responsible for MINOCA further.

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