Bone marrow fat content is correlated with hepatic fat content in paediatric non-alcoholic fatty liver disease.

AIM: To investigate the relationship between bone marrow fat content and hepatic fat content in children with known or suspected non-alcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: This was an institutional review board-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant, cross-sectional, prospective analysis of data collected between October 2010 to March 2013 in 125 children with known or suspected NAFLD. Written informed consent was obtained for same-day research magnetic resonance imaging (MRI) of the lumbar spine, liver, and abdominal adiposity. Lumbar spine bone marrow proton density fat fraction (PDFF) and hepatic PDFF were estimated using complex-based MRI (C-MRI) techniques and magnitude-based MRI (M-MRI), respectively. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SCAT) were quantified using high-resolution MRI. All images were acquired by two MRI technologists. Hepatic M-MRI images were analysed by an image analyst; all other images were analysed by a single investigator. The relationship between lumbar spine bone marrow PDFF and hepatic PDFF was assessed with and without adjusting for the presence of covariates using correlation and regression analysis. RESULTS: Lumbar spine bone marrow PDFF was positively associated with hepatic PDFF in children with known or suspected NAFLD prior to adjusting for covariates (r=0.33, p=0.0002). Lumbar spine bone marrow PDFF was positively associated with hepatic PDFF in children with known or suspected NAFLD (r=0.24, p=0.0079) after adjusting for age, sex, body mass index z-score, VAT, and SCAT in a multivariable regression analysis. CONCLUSION: Bone marrow fat content is positively associated with hepatic fat content in children with known or suspected NAFLD. Further research is needed to confirm these results and understand their clinical and biological implications.

Quitting cigarettes completely or switching to smokeless tobacco: do US data replicate the Swedish results?

BACKGROUND: Swedish male smokers are more likely than female smokers to switch to smokeless tobacco (snus) and males' smoking cessation rate is higher than that of females. These results have fuelled international debate over promoting smokeless tobacco for harm reduction. This study examines whether similar results emerge in the United States, one of few other western countries where smokeless tobacco has long been widely available. METHODS: US DATA SOURCE: national sample in Tobacco Use Supplement to Current Population Survey, 2002, with 1-year follow-up in 2003. Analyses included adult self-respondents in this longitudinal sample (n = 15,056). Population-weighted rates of quitting smoking and switching to smokeless tobacco were computed for the 1-year period. RESULTS: Among US men, few current smokers switched to smokeless tobacco (0.3% in 12 months). Few former smokers turned to smokeless tobacco (1.7%). Switching between cigarettes and smokeless tobacco, infrequent among current tobacco users (<4%), was more often from smokeless to smoking. Men quit smokeless tobacco at three times the rate of quitting cigarettes (38.8% vs 11.6%, p<0.001). Overall, US men have no advantage over women in quitting smoking (11.7% vs 12.4%, p = 0.65), even though men are far likelier to use smokeless tobacco. CONCLUSION: The Swedish results are not replicated in the United States. Both male and female US smokers appear to have higher quit rates for smoking than have their Swedish counterparts, despite greater use of smokeless tobacco in Sweden. Promoting smokeless tobacco for harm reduction in countries with ongoing tobacco control programmes may not result in any positive population effect on smoking cessation.

Plasma trace elements and cognitive function in older men and women: the Rancho Bernardo study.

OBJECTIVE: This study examines the sex-specific associations of plasma concentrations of iron, copper, and zinc with cognitive function in older community-dwelling adults. DESIGN: Cross-sectional study. SETTING: 1988-92 follow-up clinic visit. PARTICIPANTS: 602 men and 849 women (average age=75 +/- 8 years) who were community-dwelling and not clinically demented. MEASUREMENTS: Blood samples were assayed for trace elements and 12 cognitive function tests were administered. Sex-specific analyses were adjusted for age, education, alcohol consumption, smoking, exercise, and estrogen use in women. RESULTS: Men and women differed significantly in education and alcohol intake (p's < 0.001), concentrations of plasma iron, copper and zinc (p's < 0.001) and scores on 11 of 12 cognitive function tests (p=0.04 to < 0.001). Regression analyses showed significant inverted U-shaped associations in men; both low and high iron levels were associated with poor performance on total and long-term recall and Serial 7's (p's=0.018, 0.042 and 0.004, respectively) compared to intermediate concentrations. In women, iron and copper concentrations had inverse linear associations with Buschke total, long and short-term recall and Blessed scores (p's < 0.05). Zinc was positively associated with performance on Blessed Items (p=0.008). Analyses comparing cognitive function using categorically defined mineral concentrations yielded similar sex specific results. CONCLUSION: Optimal trace element concentrations may exist for optimal cognitive function in older adults, and these levels may differ by sex and cognitive function domain.

Alzheimer disease without neocortical neurofibrillary tangles: "a second look".

OBJECTIVE: To compare the clinical and pathologic features of plaque only Alzheimer disease (POAD) with plaque and tangle Alzheimer disease (PTAD). METHODS: An autopsy series of 16 patients with POAD and 32 subjects with PTAD on whom extensive antemortem neuropsychological testing was available. Plaques, tangles, and cerebral amyloid angiopathy were examined in the neocortex and hippocampus using thioflavin S staining. In addition, immunocytochemical analysis with AT8 for phosphorylated tau was performed. Midfrontal (MF) synaptic density, MF choline acetyltransferase (ChAT) activity, and apolipoprotein E genotyping were also assessed. RESULTS: Initial neuropsychological test scores and rates of cognitive decline on the Mini-Mental State Examination and Blessed Information-Memory-Concentration were similar between the two groups. However, compared to PTAD, POAD patients tended to deteriorate more slowly on the Mattis Dementia Rating Scale. Furthermore, they were somewhat less impaired on all these measures at last examination. There was an older age at onset and death, and a trend toward a shorter disease duration, in POAD compared to PTAD patients. POAD subjects, by definition, had no neocortical neurofibrillary tangles (NFT) (Braak stages IV or less). In addition, they also had fewer hippocampal NFT, fewer neuritic plaques, and higher mean MF ChAT activity than PTAD subjects. On the other hand, the two groups did not differ significantly in brain weight or MF synaptic density. Although lacking overt tangle formation, the POAD group displayed abnormal phosphorylated tau immunoreactivity in neocortical pyramidal neurons. CONCLUSIONS: Dementing syndromes virtually indistinguishable from each other can, and do, develop in the presence or absence of neocortical NFT. Patients without neocortical NFT are, on average, older at disease onset and death, and show a trend toward a shorter disease duration with somewhat slower deterioration. Although neocortical NFT per se are not obligatory for the development of clinical dementia, more subtle neocortical cytoskeletal tau pathology may contribute to cognitive decline in these subjects.

Cerebrospinal fluid HIV RNA originates from both local CNS and systemic sources.

OBJECTIVE: To identify the sources of HIV virions in CSF by modeling treatment-associated HIV dynamics. BACKGROUND: We postulated a model in which cell-free CSF virions originate from two major sources, namely, systemic non-CNS and CNS tissues, the latter including brain parenchyma and meninges. The model predicted that with initiation of antiretroviral therapy, the acute-phase decline in CSF HIV RNA levels would be controlled by the kinetics of the dominant virion source (systemic versus CNS). Based on prior observations, we hypothesized that the dominant source of CSF virions would shift from systemic to CNS in more advanced disease. METHODS: Three patient groups were studied: Group 1 (n = 5): nondemented, with early HIV disease (CD4+ lymphocytes > or = 400/microL) or pleocytosis (CSF leukocytes > or = 4/microL); Group 2 (n = 5): nondemented, with advanced HIV disease (CD4+ < 400/microL) and no pleocytosis; Group 3 (n = 2): patients with HIV-associated dementia (HAD). All patients began a new, highly active antiretroviral treatment regimen and underwent serial lumbar punctures and phlebotomies. RESULTS: For patients in Group 2, the rate of decline in CSF HIV RNA was slower than in plasma (p < 0.00001). For Group 1, the rate of decline in CSF was not different from plasma (p > 0.25). Patients with HAD showed high CSF HIV RNA after 5 to 6 weeks of treatment despite a 100-fold decrease in plasma HIV RNA. CONCLUSIONS: CSF and plasma HIV dynamics became increasingly independent in advanced HIV disease, and the compartmental discrepancy was largest in HAD. Our findings suggest that viral replication in CNS tissues may constitute a major, independent source of CSF HIV RNA. In patients with HAD, brain parenchyma itself may be the principal CNS tissue source, and CNS-targeted treatment strategies may be required to eradicate this infection.

Nevirapine-resistant human immunodeficiency virus: kinetics of replication and estimated prevalence in untreated patients.

The nonnucleoside reverse transcriptase inhibitor nevirapine rapidly selects for mutant human immunodeficiency virus (HIV) in vivo. The most common mutation occurs at amino acid residue 181 in patients receiving monotherapy. After the initiation of nevirapine therapy, plasma and peripheral blood mononuclear cell samples were collected at frequent intervals and assayed for HIV RNA levels and the proportion of virus containing a mutation at residue 181. HIV RNA levels remained stable for the first 24 h after initiation of therapy and rapidly declined between 1 and 7 days. There was a consistent maximum decrease of 2 log10 HIV RNA copies per ml of plasma (range, 1.96 to 2.43) from baseline after 2 weeks in all monotherapy subjects. The estimated median half-life of HIV RNA was 1.11 days (range, 0.63 to 1.61). After 14 days of therapy, HIV RNA levels began to increase and 181 mutant virus was detected. The estimated doubling time of the emerging virus population ranged from 1.80 to 5.73 days. Viral DNA in peripheral blood mononuclear cells turned over from wild type to the mutant with a mutation at residue 181 significantly more slowly than did HIV RNA in plasma. In two subjects, the calculated prevalence of the 181 mutant virus prior to treatment was 7 and 133 per 10,000 copies of plasma HIV RNA.