Age-associated alterations in cholesterol homeostasis: evidence from a cross-sectional study in a Northern Italy population.

BACKGROUND: The modifications of cholesterol metabolism associated with aging are ill-defined. The objective of this study was to define age-associated alterations of the different metabolic pathways controlling cholesterol homeostasis by analyzing circulating sterols. METHODS: We analyzed serum samples collected from 201 adult (75 male, 126 female) subjects within the epidemiological MICOL study (Multicentrica Italiana Colelitiasi). The age range was 38-79 years; 103 had evidence of gallstones. The concentrations of the different sterols, recognized as markers of the main pathways of cholesterol homeostasis, were analyzed by gas chromatography-mass spectrometry, including lathosterol (synthesis), campesterol and sitosterol (absorption), and 7α-hydroxy-4-cholesten-3-one (degradation to bile acids). RESULTS: A significant direct correlation was detected between age and cholesterol levels (r =0.34, P<0.01). The lathosterol/cholesterol ratio was lower in older age quartiles (P<0.05 by analysis of variance), with an inverse correlation between the lathosterol/cholesterol ratio and age (r=-0.32, P<0.01). Such correlation was particularly evident in females. The campesterol/cholesterol and sitosterol/cholesterol ratios were inversely correlated with aging in control, but not in gallstone patients. The levels of 7α-hydroxy-4-cholesten-3-one were not correlated with age. CONCLUSION: These data show a reduction of cholesterol synthesis with aging which is associated with increased circulating cholesterol levels. The finding might be related to a reduced metabolic need for cholesterol in advancing age, leading to a downregulation of the main mechanisms of cholesterol intake in the liver. A different age-related behavior was observed in gallstone-free versus gallstone patients regarding cholesterol absorption. The possible implications in terms of the pharmacological management of hypercholesterolemia in the elderly remain to be defined

Epidemiology of Herpes Simplex Virus Infection in Pregnancy: A Pilot Study:

Herpes simplex virus (HSV) infection is one of the most common sexually transmitted viral diseases worldwide. HSV type 2 causes most genital herpes and HSV type 1 is usually transmitted via non-sexual contacts. We studied 109 pregnant women between January 2007 and December 2008, in relation to their age, condom use, number of sexual partners, age at first intercourse, parity and smoking habits. The aim of this study is to evaluate the prevalence of HSV cervical infection and HSV co-infection with other genital microorganisms associated with poor neonatal outcome. Our results show that of the 109 outpatients enrolled, 30% were HSV1 and/or HSV2 positive, of whom 30% were infected with both HSV1 and HSV2, 18% were infected with HSV1 alone and 52% with HSV2 alone. A significant association between HSV1 and HSV2 infection was found, and the prevalence of HSV2 infection in women infected with HSV1 was 63%. The prevalence of HSV1/2 varied in the presence of other vaginal microorganisms but a statistical significant association was not found. This pilot study is probably too small to obtain statistically significant results. Nevertheless, using these observed results, we calculated that about 530 patients with comparable features should be enrolled to detect an increase of 50% in HSV infection due to the presence of other genital infections and potential risk factors

Age-related changes in bile acid synthesis and hepatic nuclear receptor expression

BACKGROUND:Recent data highlighted the role of nuclear receptors in the transcriptional regulation of the limiting enzyme of bile acid synthesis, cholesterol 7alpha-hydroxylase, in cellular and animal models. This study was designed to analyze the effects of age on cholesterol 7alpha-hydroxylase and related nuclear receptor expression in human livers.DESIGN:Surgical liver biopsies were obtained in 23 patients requiring operation on the gastrointestinal tract. mRNA levels of cholesterol 7alpha-hydroxylase and related nuclear receptors and co-activators were assayed by quantitative real-time RT-PCR. Serum levels of 7alpha-hydroxy-4-cholesten-3-one, a marker of bile acid synthesis, were assayed by gas-liquid chromatography:mass spectrometry.RESULTS:Ageing was inversely correlated with serum 7alpha-hydroxy-4-cholesten-3-one and with cholesterol 7alpha-hydroxylase mRNA levels (r = -0.44 and r = -0.45 on a semi-log scale, respectively, P < 0.05). Among different nuclear factors, cholesterol 7alpha-hydroxylase mRNA best correlated with hepatocyte nuclear factor-4 (r = 0.55 on a log scale, P < 0.05); hepatocyte nuclear factor-4 levels were also inversely correlated with age (r = -0.64 on a semi-log scale, P < 0.05). Age was inversely correlated with serum insulin-like growth factor-I levels, which were directly correlated with hepatocyte nuclear factor-4 and cholesterol 7alpha-hydroxylase expression. No suppressive effect of short heterodimer partner expression on cholesterol 7alpha-hydroxylase was observed.CONCLUSIONS:Ageing associates with reduced bile acid synthesis, possibly related to decreased hepatic expression of hepatocyte nuclear factor-4 and consequently of cholesterol 7alpha-hydroxylase. Age-related modifications of the growth hormone/insulin-like growth factor axis might play a role. These findings may help to elucidate the pathophysiology of age-related modifications of cholesterol metabolism

Quartz fiber calorimetry

The fundamentals of a new electromagnetic and hadronic sampling calorimetry based on the detection of Cherenkov light generated in quartz optical fibers are presented. Optical fibers transport light only in a selected angular range which results in a non-obvious and absolutely unique characteristic for this new technique: showers of very narrow visible energy. In addition, the technique is characterized by radiation resistance measured in Gigarads and nanosecond signal duration. Combined, these properties make quartz fiber calorimetry a very promising technique for high intensity heavy ion experiments and for the high pseudorapidity regions of high intensity collider experiments. The results of beam tests and simulations are used to illustrate the basic properties and peculiar characteristics of this recent development

Precise mirror alignment and basic performance of the RICH detector of the NA62 experiment at CERN

The Ring Imaging Cherenkov detector is crucial for the identification of charged particles in the NA62 experiment at the CERN SPS. The detector commissioning was completed in 2016 by the precise alignment of mirrors using reconstructed tracks. The alignment procedure and measurement of the basic performance are described. Ring radius resolution, ring centre resolution, single hit resolution and mean number of hits per ring are evaluated for positron tracks. The contribution of the residual mirror misalignment to the performance is calculated.Comment: 13 pages, 10 figure

Natalizumab affects T-cell phenotype in multiple sclerosis: implications for JCV reactivation

The anti-CD49d monoclonal antibody natalizumab is currently an effective therapy against the relapsing-remitting form of multiple sclerosis (RRMS). Natalizumab therapeutic efficacy is limited by the reactivation of the John Cunningham polyomavirus (JCV) and development of progressive multifocal leukoencephalopathy (PML). To correlate natalizumab-induced phenotypic modifications of peripheral blood T-lymphocytes with JCV reactivation, JCV-specific antibodies (serum), JCV-DNA (blood and urine), CD49d expression and relative abundance of peripheral blood T-lymphocyte subsets were longitudinally assessed in 26 natalizumab-treated RRMS patients. Statistical analyses were performed using GraphPad Prism and R. Natalizumab treatment reduced CD49d expression on memory and effector subsets of peripheral blood T-lymphocytes. Moreover, accumulation of peripheral blood CD8+ memory and effector cells was observed after 12 and 24 months of treatment. CD4+ and CD8+ T-lymphocyte immune-activation was increased after 24 months of treatment. Higher percentages of CD8+ effectors were observed in subjects with detectable JCV-DNA. Natalizumab reduces CD49d expression on CD8+ T-lymphocyte memory and effector subsets, limiting their migration to the central nervous system and determining their accumulation in peripheral blood. Impairment of central nervous system immune surveillance and reactivation of latent JCV, can explain the increased risk of PML development in natalizumab-treated RRMS subjects

Light Detection System and Time Resolution of the NA62 RICH

A large RICH detector is used in NA62 to suppress the muon contamination in the charged pion sample by a factor of 100 in the momentum range between 15 and 35 GeV/c. Cherenkov light is collected by 1952 photomultipliers placed at the upstream end. In this paper the characterization of the photomultipliers and the dedicated Frontend and Data Acquisition electronics are described, the time resolution and the light detection efficiency measurement are presented.Comment: 15 pages, 11 figure

Atmospheric Muon Flux at Sea Level, Underground, and Underwater

The vertical sea-level muon spectrum at energies above 1 GeV and the underground/underwater muon intensities at depths up to 18 km w.e. are calculated. The results are particularly collated with a great body of the ground-level, underground, and underwater muon data. In the hadron-cascade calculations, the growth with energy of inelastic cross sections and pion, kaon, and nucleon generation in pion-nucleus collisions are taken into account. For evaluating the prompt muon contribution to the muon flux, we apply two phenomenological approaches to the charm production problem: the recombination quark-parton model and the quark-gluon string model. To solve the muon transport equation at large depths of homogeneous medium, a semi-analytical method is used. The simple fitting formulas describing our numerical results are given. Our analysis shows that, at depths up to 6-7 km w. e., essentially all underground data on the muon intensity correlate with each other and with predicted depth-intensity relation for conventional muons to within 10%. However, the high-energy sea-level data as well as the data at large depths are contradictory and cannot be quantitatively decribed by a single nuclear-cascade model.Comment: 47 pages, REVTeX, 15 EPS figures included; recent experimental data and references added, typos correcte

Measurement of the branching ratio of the decay Ξ0→Σ+μ−νˉμ\Xi^{0}\rightarrow \Sigma^{+} \mu^{-} \bar{\nu}_{\mu}

From the 2002 data taking with a neutral kaon beam extracted from the CERN-SPS, the NA48/1 experiment observed 97 $\Xi^{0}\rightarrow \Sigma^{+} \mu^{-} \bar{\nu}_{\mu}$ candidates with a background contamination of $30.8 \pm 4.2$ events. From this sample, the BR($\Xi^{0}\rightarrow \Sigma^{+} \mu^{-} \bar{\nu}_{\mu}$) is measured to be $(2.17 \pm 0.32_{\mathrm{stat}}\pm 0.17_{\mathrm{syst}})\times10^{-6}$