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Patients should contact their GP or prescribing clinician if they experience: Severe or persistent cramps that do not respond to simple measures or significantly impact daily activities and sleep quality Frequent cramping occurring multiple times daily or nightly Associated symptoms such as muscle weakness, numbness, tingling, or changes in sensation, which may indicate neurological involvement Visible muscle changes including swelling, redness, tenderness, or asymmetry between legs Signs of dehydration such as dizziness, reduced urine output, dark urine, or confusion These features may indicate underlying conditions requiring investigation, such as significant electrolyte disturbances, peripheral neuropathy (particularly relevant in diabetes), peripheral arterial disease, or, rarely, more serious muscle disorders
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Furthermore, the paper explores how these regulatory mechanisms affect NRF2s roles in oxidative stress, inflammation, and cell death, identifying novel therapeutic targets and strategies
