Best and Worst in Health and Healthcare – July & August 2016




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The northern hemisphere’s summer is ending and that is definitely bad news. The good news is that this was not a silly season in health and healthcare research.

Here’s the best and worst news of the summer.

The best

Drug repurposing screening reveals possible candidates for anti-Zika therapy

Developing a new drug is a long process, but the Zika virus outbreak has created a global health emergency and a pressing need for therapies that is incompatible with the timings of drug development. This led to a major study published in Nature Medicine in which over 6,000 compounds were screened for possible drug repurposing, including approved drugs, clinical trial drug candidates and pharmacologically active compounds. This screening allowed the identification of compounds that were able to inhibit Zika infection, suppress the effects of infection in neurons, or inhibit viral replication. Furthermore, combination treatments using neuroprotective and antiviral compounds showed a potentiation of a protective effect from Zika-induced cell death in human neuronal cell progenitors and glial cells. Besides allowing a fast identification of potential anti-Zika therapies, these results also highlight the efficacy of this screening strategy. Maybe drug repurposing screenings should be a more common procedure.

Docosahexaenoic acid (DHA) in post stroke management

Omega-3 fatty acids are known to have many beneficial effects. It has been suggested that their neuroprotective effects may be useful in post stroke therapy. To test this hypothesis, a study published in PLoS One used emulsions of docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) to treat mice with stroke-like brain injury. It was found that treatment with DHA was able to reduce oxidative damage and improve short- and long-term neurological outcomes. This effect was associated with an accumulation of DHA in brain mitochondria and DHA-derived bioactive metabolites in brain tissue that led to prolonged neuroprotection. Maybe diet can hold the answer to post stroke management.

A new opioid drug with less side-effects

Opioids such as morphine or oxycodone are highly effective pain killers but they have an extensive list of side-effects, including addiction and fatal respiratory depression. Finding a molecule that could have a similar efficacy without the side-effects could be a great discovery. A new study published in Nature therefore aimed at identifying molecules that could selectively act on opioid receptors with similar analgesic effects to current opioid drugs but without inducing respiratory depression. A computational analysis of over 3 million molecules was performed in order to determine which molecules could potentially bind to the mu-opioid-receptor. From all the compounds analyzed, one stood out: it is called PZM21 and it was shown to be an effective analgesic while being devoid of many of the side effects of current opioids.

Brain-machine interface therapies effective in paraplegic patients

There may be a new promising therapy for paraplegic patients. A study published in Scientific Reports tested the use of brain-machine interface training for rehabilitation of chronic spinal cord injured paraplegics. The training paradigm combined immersive virtual reality training, enriched visual-tactile feedback, and walking with two EEG-controlled robotic actuators, including a custom-designed lower limb exoskeleton capable of delivering tactile feedback to subjects. After 12 months of training, all the participants showed neurological improvements in sensation and regained voluntary motor control in muscles below the spinal cord injury level, which was associated with a marked improvement in walking. Half of the patients were even upgraded to an incomplete paraplegia classification. This was an impressive recovery that shows the tremendous potential of brain-machine interface therapies.

Exercise improves cognition in schizophrenia patients

Cognitive deficits are common among people with schizophrenia. Given the known cognitive benefits of exercise, it is possible that it may be helpful in counterbalancing the cognitive effects of schizophrenia. To evaluate this hypothesis, a meta-analysis of all controlled trials investigating the cognitive outcomes of exercise interventions in schizophrenia was conducted. The results were published in the Schizophrenia Bulletin and showed that exercise significantly improved cognition, including working memory, social cognition, and attention/vigilance. Interventions which were supervised by physical activity professionals were shown to be more effective. This study thereby indicates that regular exercise can be beneficial and have therapeutic potential for individuals with schizophrenia.

The worst

Traumatic brain injury increases the risk of neurodegenerative changes later in life  

According to a new study published in JAMA Neurology, traumatic brain injury can increase the likelihood of developing neurodegenerative disorders later in life. This work compiled data from other studies to include a total of 7130 participants. A history of traumatic brain injury with loss of consciousness was compared with the incidence of dementia, Alzheimer’s disease, Pakinson’s disease, mild cognitive impairment, and neuropathologic outcomes such as neurofibrillary tangles, neuritic plaques, microinfarcts, cystic infarcts, Lewy bodies, and hippocampal sclerosis. Data indicated that traumatic brain injury with loss of consciousness is associated with an increased risk for Lewy body accumulation, progression of parkinsonism, and Parkinson’s disease. No association was found with dementia, Alzheimer’s disease, neuritic plaques, or neurofibrillary tangles.

Poor sleep increases inflammation

Good sleep is essential for good health. Since sleep disturbances have been associated with an increased risk of inflammatory diseases, a systematic review and meta-analysis published in Biological Psychiatry aimed at assessing the evidence linking sleep disturbance, sleep duration, and inflammation in adult humans. It was found that sleep disturbance and long sleep duration, but not short sleep duration, are associated with increases in markers of systemic inflammation. Increased systemic inflammation has been associated with a number of disorders, including neurological and metabolic disorders; it also plays an important role in aging. This study therefore reinforces the notion that poor sleep can contribute to the development of various pathologies.

What happens when we stop exercising?

There is extensive evidence showing how exercise is great for health, including brain health. But what happens to the brain when we stop exercising? One answer to this question was recently published in Frontiers in Aging Neuroscience. The effects of 10 days of detraining on physically fit older adults was assessed and it was shown that the interruption of regular exercise induced a decrease in resting cerebral blood flow in eight gray matter brain regions, including the hippocampus. A decreased cerebral blood flow can have a significant negative impact on cognitive functions. This study indicates that the beneficial effects of exercise may rely on the maintenance of regular physical activity throughout life.

The effect of lead on brain development

Lead is a toxic heavy metal that can affect brain development in children. However, little was known about the mechanisms of lead neurotoxicity in children. A study published in Environmental Health Perspectives assessed the effect of lead on neural stem cells aiming at linking changes in those cells to neurodevelopmental outcomes in children who were exposed to lead. It was shown that lead exposure significantly alters the expression of 19 genes, including genes associated with oxidative stress response and neuroprotection. By interfering with the expression of these genes, lead can have a significant impact on cognitive development, explaining the neurodevelopmental deficits observed in children exposed to lead.

Calcium supplementation may increase the risk of dementia

Recently, the use of calcium supplements has been questioned due to possible detrimental effects on health. A study published in Neurology therefore aimed to determine if calcium supplementation may be associated with the development of dementia in women. The study followed dementia-free women aged 70–92 years for five years. Data showed that calcium supplementation was associated with the development of dementia in women with a history of stroke or presence of white matter lesions, but not in groups without these conditions. Although further studies may be needed to validate these findings, this indicates that calcium supplementation may increase the risk of developing dementia in elderly women with cerebrovascular disease.

References

Alfini AJ, et al (2016). Hippocampal and Cerebral Blood Flow after Exercise Cessation in Master Athletes. Front Aging Neurosci, 8:184. doi: 10.3389/fnagi.2016.00184

Crane PK, et al (2016). Association of Traumatic Brain Injury With Late-Life Neurodegenerative Conditions and Neuropathologic Findings. JAMA Neurol [Epub ahead of print]. doi: 10.1001/jamaneurol.2016.1948

Donati AR, et al (2016). Long-Term Training with a Brain-Machine Interface-Based Gait Protocol Induces Partial Neurological Recovery in Paraplegic Patients. Sci Rep, 6:30383. doi: 10.1038/srep30383

Firth J, et al (2016). Aerobic Exercise Improves Cognitive Functioning in People With Schizophrenia: A Systematic Review and Meta-Analysis. Schizophr Bull [Epub ahead of print]. doi: 10.1093/schbul/sbw115

Irwin MR, et al (2016). Sleep Disturbance, Sleep Duration, and Inflammation: A Systematic Review and Meta-Analysis of Cohort Studies and Experimental Sleep Deprivation. Biol Psychiatry, 80(1):40-52. doi: 10.1016/j.biopsych.2015.05.014

Kern J, et al (2016). Calcium supplementation and risk of dementia in women with cerebrovascular disease. Neurology [Epub ahead of print]. doi: 10.1212/WNL.0000000000003111

Manglik A, et al (2016). Structure-based discovery of opioid analgesics with reduced side effects. Nature, 17:1-6. doi: 10.1038/nature19112

Mayurasakorn K, et al (2016). DHA but Not EPA Emulsions Preserve Neurological and Mitochondrial Function after Brain Hypoxia-Ischemia in Neonatal Mice. PLoS One, 11(8):e0160870. doi: 10.1371/journal.pone.0160870

Wagner PJ, et al (2016). In Vitro Effects of Lead on Gene Expression in Neural Stem Cells and Associations between Upregulated Genes and Cognitive Scores in Children. Environ Health Perspect, [Epub ahead of print]. doi: 10.1289/EHP265

Xu M, et al (2016). Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen. Nat Med [Epub ahead of print] doi: 10.1038/nm.4184

Image via WikiImages / Pixabay.

Sara Adaes, PhD

Sara Adaes, PhD, has been a researcher in neuroscience for over a decade. She studied biochemistry and did her first research studies in neuropharmacology. She has since been investigating the neurobiological mechanisms of pain at the Faculty of Medicine of the University of Porto, in Portugal. Follow her on Twitter @saradaes
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