Structural Modifications of the Brain in Acclimatization to High-Altitude

Adaptive changes in respiratory and cardiovascular responses at high altitude (HA) have been well clarified. However, the central mechanisms underlying HA acclimatization remain unclear. Using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) with fractional anisotropy (FA) calculation, we investigated 28 Han immigrant residents (17–22 yr) born and raised at HA of 2616–4200 m in Qinghai-Tibetan Plateau for at least 17 years and who currently attended college at sea-level (SL). Their family migrated from SL to HA 2–3 generations ago and has resided at HA ever since. Control subjects were matched SL residents. HA residents (vs. SL) showed decreased grey matter volume in the bilateral anterior insula, right anterior cingulate cortex, bilateral prefrontal cortex, left precentral cortex, and right lingual cortex. HA residents (vs. SL) had significantly higher FA mainly in the bilateral anterior limb of internal capsule, bilateral superior and inferior longitudinal fasciculus, corpus callosum, bilateral superior corona radiata, bilateral anterior external capsule, right posterior cingulum, and right corticospinal tract. Higher FA values in those regions were associated with decreased or unchanged radial diffusivity coinciding with no change of longitudinal diffusivity in HA vs. SL group. Conversely, HA residents had lower FA in the left optic radiation and left superior longitudinal fasciculus. Our data demonstrates that HA acclimatization is associated with brain structural modifications, including the loss of regional cortical grey matter accompanied by changes in the white matter, which may underlie the physiological adaptation of residents at HA

Aging Skin: Nourishing from the Inside Out, Effects of Good Versus Poor Nitrogen Intake on Skin Health and Healing

Skin is the outermost defense organ which protects us from the environment, constituting around 8 % of an adult’s body weight. Healthy skin contains one-eighth of the body’s total proteins. The balance of turnover and synthesis of skin proteins is primarily dependent on the availability of sufficient nitrogen-containing substrates, namely, amino acids, essential for protein metabolism in any other tissue and body organs. The turnover of skin proteins has been shown to be rapid, and the mobilization of amino acids at the expense of skin proteins is relevant in experimental models of protein malnutrition. As a result, alterations in nutritional status should be suspected, diagnosed, and eventually treated for any skin lesions. Protein malnutrition has a dramatic prevalence in patients aged >70 or more, independent of the reason for hospitalization. The quality of nutrition and content of essential amino acids are strictly connected to skin health and integrity of its protein components. Collagen fiber deposition is highly and rapidly influenced by alterations in the essential to nonessential amino acid ratios. The most relevant nutritional factor of skin health is the prevalence of essential amino acids

Cerebrovascular reactivity among native-raised high altitude residents: an fMRI study

Background: The impact of long term residence on high altitude (HA) on human brain has raised concern among researchers in recent years. This study investigated the cerebrovascular reactivity among native-born high altitude (HA) residents as compared to native sea level (SL) residents. The two groups were matched on the ancestral line, ages, gender ratios, and education levels. A visual cue guided maximum inspiration task with brief breath holding was performed by all the subjects while Blood-Oxygenation-Level-Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) data were acquired from them

Tim-3 Negatively Regulates IL-12 Expression by Monocytes in HCV Infection

T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) is a newly identified negative immunomodulator that is up-regulated on dysfunctional T cells during viral infections. The expression and function of Tim-3 on human innate immune responses during HCV infection, however, remains poorly characterized. In this study, we report that Tim-3 is constitutively expressed on human resting CD14+ monocyte/macrophages (M/MØ) and functions as a cap to block IL-12, a key pro-inflammatory cytokine linking innate and adaptive immune responses. Tim-3 expression is significantly reduced and IL-12 expression increased upon stimulation with Toll-like receptor 4 (TLR4) ligand - lipopolysaccharide (LPS) and TLR7/8 ligand - R848. Notably, Tim-3 is over-expressed on un-stimulated as well as TLR-stimulated M/MØ, which is inversely associated with the diminished IL-12 expression in chronically HCV-infected individuals when compared to healthy subjects. Up-regulation of Tim-3 and inhibition of IL-12 are also observed in M/MØ incubated with HCV-expressing hepatocytes, as well as in primary M/MØ or monocytic THP-1 cells incubated with HCV core protein, an effect that mimics the function of complement C1q and is reversible by blocking the HCV core/gC1qR interaction. Importantly, blockade of Tim-3 signaling significantly rescues HCV-mediated inhibition of IL-12, which is primarily expressed by Tim-3 negative M/MØ. Tim-3 blockade reduces HCV core-mediated expression of the negative immunoregulators PD-1 and SOCS-1 and increases STAT-1 phosphorylation. Conversely, blocking PD-1 or silencing SOCS-1 gene expression also decreases Tim-3 expression and enhances IL-12 secretion and STAT-1 phosphorylation. These findings suggest that Tim-3 plays a crucial role in negative regulation of innate immune responses, through crosstalk with PD-1 and SOCS-1 and limiting STAT-1 phosphorylation, and may be a novel target for immunotherapy to HCV infection

Neuropsychological Correlates of Cystic Fibrosis in Patients 5 to 8 Years Old

Intellectual, academic, and neuropsychological tests were administered to 20 children with cystic fibrosis (CF). Results were compared to test results from 20 controls matched for gender, age, and socioeconomic status. No differences between the groups were found. For children with CF, Verbal IQ, sensory-perceptual skills, and incidental learning correlated (rs = .39-.67) with Shwachman criteria of disease severity, with significant positive relations with the Growth and Nutrition measure, an index of the severity of the disease. Processing of tactile-perceptual information may be particularly vulnerable to disease severity. This study provides more information than previously available on the neuropsychological status of young children with CF, and it offers some hypotheses regarding the relation between disease severity and neuropsychological function.published_or_final_versio