Plos One
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Randomized Controlled Trial
Effects of naltrexone on pain sensitivity and mood in fibromyalgia: no evidence for endogenous opioid pathophysiology.
The pathophysiological mechanisms underlying fibromyalgia are still unknown, although some evidence points to endogenous opioid dysfunction. We examined how endogenous opioid antagonism affects pain and mood for women with and without fibromyalgia. Ten women with fibromyalgia and ten age- and gender-matched, healthy controls each attended two laboratory sessions. ⋯ Neither group experienced changes in pain sensitivity due to naltrexone administration. Naltrexone did not differentially affect self-reported withdrawal symptoms, or mood, in the fibromyalgia and control groups. Consistent with prior research, there was no evidence found for abnormal endogenous opioid activity in women with fibromyalgia.
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There are 146 million underweight children in the developing world, which contribute to up to half of the world's child deaths. In high burden regions for malnutrition, the treatment of individual children is limited by available resources. Here, we evaluate a large-scale distribution of a nutritional supplement on the prevention of wasting. ⋯ These results demonstrate the potential for distribution of fortified spreads to reduce the incidence of severe wasting in large population of children 6-36 months of age. Although further information is needed on the cost-effectiveness of such distributions, these results highlight the importance of re-evaluating current nutritional strategies and international recommendations for high burden areas of childhood malnutrition.
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Randomized Controlled Trial
A 3-year randomized trial of lifestyle intervention for cardiovascular risk reduction in the primary care setting: the Swedish Björknäs study.
Successfully transferring the findings of expensive and tightly controlled programmes of intensive lifestyle modification to the primary care setting is necessary if such knowledge is to be of clinical utility. The objective of this study was to test whether intensive lifestyle modification, shown previously in tightly-controlled clinical trials to be efficacious for diabetes risk-reduction among high-risk individuals, can reduce cardiovascular risk factor levels in the primary care setting. ⋯ A program of intensive lifestyle modification undertaken in the primary health care setting can favourably influence cardiovascular risk-factor profiles in high-risk individuals.
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Telomerase is an enzyme specialized in maintaining telomere lengths in highly proliferative cells. Loss-of-function mutations cause critical telomere shortening and are associated with the bone marrow failure syndromes dyskeratosis congenita and aplastic anemia and with idiopathic pulmonary fibrosis. Here, we sought to determine the spectrum of clinical manifestations associated with telomerase loss-of-function mutations. ⋯ These results indicate that heterozygous telomerase loss-of-function mutations associate with but are not determinant of a large spectrum of hematologic and liver abnormalities, with the latter sometimes occurring in the absence of marrow failure. Our findings, along with the link between pulmonary fibrosis and telomerase mutations, also suggest a common pathogenic mechanism for fibrotic diseases in which defective telomere repair plays important role.
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Aberrant mitochondrial function appears to play a central role in dopaminergic neuronal loss in Parkinson's disease (PD). 1-methyl-4-phenylpyridinium iodide (MPP(+)), the active metabolite of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), is a selective inhibitor of mitochondrial complex I and is widely used in rodent and cell models to elicit neurochemical alterations associated with PD. Recent findings suggest that Glycogen Synthase Kinase-3beta (GSK-3beta), a critical activator of neuronal apoptosis, is involved in the dopaminergic cell death. In this study, the role of GSK-3beta in modulating MPP(+)-induced mitochondrial dysfunction and neuronal death was examined in vivo, and in two neuronal cell models namely primary cultured and immortalized neurons. ⋯ Inhibition of GSK-3beta activity using well-characterized inhibitors, LiCl and kenpaullone, and RNA interference, prevented MPP(+)-induced cell death by blocking mitochondrial membrane potential changes and subsequent caspase-9 and -3 activation. These results indicate that GSK-3beta is a critical mediator of MPTP/MPP(+)-induced neurotoxicity through its ability to regulate mitochondrial functions. Inhibition of GSK-3beta activity might provide protection against mitochondrial stress-induced cell death.