Plos One
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Multiple sclerosis (MS) is characterized by demyelinating and degenerative processes within the central nervous system. Unlike conventional MRI,new advanced imaging techniques improve pathological specificity and better highlight the relationship between anatomical damage and clinical impairment. ⋯ Selective GM atrophy and widespread WM tracts damage are associated with functional impairment of upper-limb motion and cognition. The combined analysis of volumetric and DTI data may help to better understand structural alterations underlying physical and cognitive dysfunction in MS.
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A frameshift mutation of ubiquitin called ubiquitin(+1) (UBB(+1)) was found in the aging and Alzheimer's disease brains and thought to be associated with neuronal dysfuction and degeneration. Even though ubiquitylation has been known to regulate vital cellular functions mainly through proteasome-dependent degradation of polyubiquitinated substrates, proteolysis-independent roles of ubiquitylation have emerged as key mechanisms in various signaling cascades. In this study, we have investigated the effect of UBB(+1) on proinflammatory signaling such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in human astrocytes. ⋯ Ectopic expression of UBB(+1) suppressed TNF-α- and IL-1β-induced activation of NF-κB and JNK signaling pathway. Furthermore, we have demonstrated that polyubiquitylation of TRAFs and subsequent phosphorylation of TAK1 were significantly inhibited by stable expression of UBB(+1). Collectively, these results suggest that UBB(+1) may affect proinflammatory signaling in the central nervous system via inhibitory mechanisms of ubiquitin-dependent signaling in human astrocytes.
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The relative contributions of genetics and environment to asthma in Hispanics or to asthma in children younger than 3 years are not well understood. ⋯ Our longitudinal study in Puerto Rican twins demonstrates a changing contribution of shared environmental effects to liability for physician-diagnosed asthma and asthma medication use between ages 1 and 3 years. Early-life environmental tobacco smoke reduction could markedly reduce asthma morbidity in young Puerto Rican children.
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Increasing numbers of survivors of preterm birth are growing into adulthood today. Long-term health-effects of prematurity are still poorly understood, but include increased risk for diabetes, obesity and cardiovascular diseases in adult life. To test if reduced physical fitness may be a link in the causal chain of preterm birth and diseases in later life, the association of preterm birth and adult exercise capacity was investigated. The hypothesis was that preterm birth contributes independently of other risk factors to lower physical fitness in adulthood. ⋯ Being born preterm as well as being born small for gestational age predicts low exercise capacity in otherwise healthy young men. The effect size of being born preterm equal or exceed that of other known risk factors for unfitness in adults, such as low parental education and overweight.
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The role of pretreatment dynamic contrast-enhanced perfusion MR imaging (DCE-PWI) and diffusion-weighted MR imaging (DWI) in predicting the treatment response of oropharyngeal or hypopharyngeal squamous cell carcinoma (OHSCC) to chemoradiation remains unclear. We prospectively investigated the ability of pharmacokinetic parameters derived from pretreatment DCE-PWI and DWI to predict the local control of OHSCC patients treated with chemoradiation. Between August, 2010 and March, 2012, patients with untreated OHSCC scheduled for chemoradiation were eligible for this prospective study. ⋯ When the local control and local failure groups were compared, significant differences were observed in K (trans) and the tumor location (P = 0.01 and P = 0.04, respectively). In the multivariable analysis, only K (trans) was statistically significant (P = 0.04). Our results suggest that pretreatment K (trans) may help predict the local control in OHSCC patients treated with chemoradiation.