Lancet neurology
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Translation of successful target and compound validation studies into clinically effective therapies is a major challenge, with potential for costly clinical trial failures. This situation holds true for the epilepsies-complex diseases with different causes and symptoms. Although the availability of predictive animal models has led to the development of effective antiseizure therapies that are routinely used in clinical practice, showing that translation can be successful, several important unmet therapeutic needs still exist. ⋯ No treatment can prevent the development of epilepsy in at-risk patients or cure patients with epilepsy. And no specific treatment for epilepsy-associated comorbidities exists. To meet these demands, a redesign of translational approaches is urgently needed.
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Being overweight or obese, as measured with body-mass index or central adiposity (waist circumference), and the trajectory of body-mass index over the life course have been associated with brain atrophy, white matter changes, disturbances of blood-brain barrier integrity, and risk of all-cause late-onset dementia and Alzheimer's disease. This observation leads us to question what it is about body-mass index that is associated with health of the brain and dementia risk. ⋯ Hundreds of adipokines have been identified, creating a complexity that is a challenge to simplify. Nonetheless, adipokines are being investigated in association with clinical dementia outcomes, and with imaging-based measures of brain volume, structure, and function in human beings and in preclinical models of clinical dementia.
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Allodynia (pain due to a stimulus that does not usually provoke pain) and hyperalgesia (increased pain from a stimulus that usually provokes pain) are prominent symptoms in patients with neuropathic pain. Both are seen in various peripheral neuropathies and central pain disorders, and affect 15-50% of patients with neuropathic pain. ⋯ Pain intensity and relief are important measures in clinical pain studies, but might be insufficient to capture the complexity of the pain experience. Better understanding of allodynia and hyperalgesia might provide clues to the underlying pathophysiology of neuropathic pain and, as such, they represent new or additional endpoints in pain trials.
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Observational Study
Prevalence of sleep deficiency and use of hypnotic drugs in astronauts before, during, and after spaceflight: an observational study.
Sleep deprivation and fatigue are common subjective complaints among astronauts. Previous studies of sleep and hypnotic drug use in space have been limited to post-flight subjective survey data or in-flight objective data collection from a small number of crew members. We aimed to characterise representative sleep patterns of astronauts on both short-duration and long-duration spaceflight missions. ⋯ The National Aeronautics and Space Administration.