Reduced lysosomal acid lipase activity: A new marker of liver disease severity across the clinical continuum of non-alcoholic fatty liver disease?

Lysosomal acid lipase (LAL) plays a key role in intracellular lipid metabolism. Reduced LAL activity promotes increased multi-organ lysosomal cholesterol ester storage, as observed in two recessive autosomal genetic diseases, Wolman disease and Cholesterol ester storage disease. Severe liver steatosis and accelerated liver fibrosis are common features in patients with genetic LAL deficiency. By contrast, few reliable data are available on the modulation of LAL activity in vivo and on the epigenetic and metabolic factors capable of regulating its activity in subjects without homozygous mutations of the Lipase A gene. In the last few years, a less severe and non-genetic reduction of LAL activity was reported in children and adults with non-alcoholic fatty liver disease (NAFLD), suggesting a possible role of LAL reduction in the pathogenesis and progression of the disease. Patients with NAFLD show a significant, progressive reduction of LAL activity from simple steatosis to non-alcoholic steatohepatitis and cryptogenic cirrhosis. Among cirrhosis of different etiologies, those with cryptogenic cirrhosis show the most significant reductions of LAL activity. These findings suggest that the modulation of LAL activity may become a possible new therapeutic target for patients with more advanced forms of NAFLD. Moreover, the measurement of LAL activity may represent a possible new marker of disease severity in this clinical setting

Solid CO_2 in low-mass young stellar objects: Comparison between Spitzer and laboratory spectra

Context. Solid interstellar CO_2 is an abundant component of ice dust mantles. Its ubiquity towards quiescent molecular clouds, as well as protostellar envelopes, has recently been confirmed by the IRS (InfraRed Spectrograph) aboard the Spitzer Space Telescope. Although it has been shown that CO_2 cannot be efficiently formed in the gas phase, the CO_2 surface formation pathway is still unclear. To date several CO_2 surface formation mechanisms induced by energetic (e.g., UV photolysis and cosmic ray irradiation) and non-energetic (e.g., cold atom addition) input have been proposed. Aims. Our aim is to investigate the contribution of cosmic ray irradiation to the formation of CO_2 in different regions of the interstellar medium (ISM). To achieve this goal we compared quantitatively laboratory data with the CO_2 bending mode band profile observed towards several young stellar objects (YSOs) and a field star by the Spitzer Space Telescope. Methods. All the experiments presented here were performed at the Laboratory for Experimental Astrophysics in Catania (Italy). The interstellar relevant samples were all irradiated with fast ions (30−200 keV) and subsequently annealed in a stainless steel high vacuum chamber (P < 10^(-7) mbar). Chemical and structural modifications of the ice samples were monitored by means of infrared spectroscopy. Laboratory spectra were then used to fit some thirty observational spectra. Results. A qualitative analysis shows that a good fit can be obtained with a minimum of two components. The choice of the laboratory components is based on the chemical-physical condition of each source. A quantitative analysis of the sources with known visual extinction (A_V) and methanol abundances highlights that the solid carbon dioxide can be efficiently and abundantly formed after ion irradiation of interstellar ices in all the selected YSOs in a time compatible with cloud lifetimes (3 × 10^7 years). Only in the case of field stars can the expected CO_2 column density formed upon energetic input not explain the observed abundances. This result, to be confirmed along the line of sight to different quiescent clouds, gives an indirect indication that CO_2 can also be formed in an early cloud stage through surface reactions induced by non-energetic mechanisms. In a later stage, when ices are exposed to higher UV and cosmic ray doses, the CO_2 total abundance is strongly affected by energetic formation mechanisms. Conclusions. Our results indicate that energetic processing of icy grain mantles significantly contribute to the formation of solid phase interstellar CO_2

Long-term prediction of adherence to continuous positive air pressure therapy for the treatment of moderate/severe obstructive sleep apnea syndrome

BACKGROUND: Continuous positive airway pressure (CPAP) therapy is a highly effective treatment for obstructive sleep apnea syndrome (OSAS). However, poor adherence is a limiting factor, and a significant proportion of patients are unable to tolerate CPAP. The aim of this study was to determine predictors of long-term non-compliance with CPAP. METHODS: CPAP treatment was prescribed to all consecutive patients with moderate or severe OSAS (AHI ≥15 events/h) (n = 295) who underwent a full-night CPAP titration study at home between February 1, 2002 and December 1, 2016. Adherence was defined as CPAP use for at least 4 h per night and five days per week. Subjects had periodical follow-up visits including clinical and biochemical evaluation and assessment of adherence to CPAP. RESULTS: Median follow-up observation was 74.8 (24.2/110.9) months. The percentage of OSAS patients adhering to CPAP was 41.4% (42.3% in males and 37.0% in females), and prevalence was significantly higher in severe OSAS than in moderate (51.8% vs. 22.1%; p &lt; 0.001; respectively). At multivariate analysis, lower severity of OSAS (HR = 0.66; CI 95 0.46-0.94) p &lt; 0.023), cigarette smoking (HR = 1.72; CI 95 1.13-2.61); p = 0.011), and previous cardiovascular events (HR = 1.95; CI 95 1.03-3.70; p = 0.04) were the only independent predictors of long-term non-adherence to CPAP after controlling for age, gender, and metabolic syndrome. CONCLUSIONS: In our cohort of patients with moderate/severe OSAS who were prescribed CPAP therapy, long-term compliance to treatment was present in less than half of the patients. Adherence was positively associated with OSAS severity and negatively associated with cigarette smoking and previous cardiovascular events at baseline

High Resolution 4.7 um Keck/NIRSPEC Spectra of Protostars. I: Ices and Infalling Gas in the Disk of L1489 IRS

We explore the infrared M band (4.7 um) spectrum of the class I protostar L1489 IRS in the Taurus Molecular Cloud. This is the highest resolution wide coverage spectrum at this wavelength of a low mass protostar observed to date (R=25,000; Dv=12 km/s). Many narrow absorption lines of gas phase 12CO, 13CO, and C18O are detected, as well as a prominent band of solid 12CO. The gas phase 12CO lines have red shifted absorption wings (up to 100 km/s), likely originating from warm disk material falling toward the central object. The isotopes and the 12CO line wings are successfully fitted with a contracting disk model of this evolutionary transitional object (Hogerheijde 2001). This shows that the inward motions seen in millimeter wave emission lines continue to within ~0.1 AU from the star. The colder parts of the disk are traced by the prominent CO ice band. The band profile results from CO in 'polar' ices (CO mixed with H2O), and CO in 'apolar' ices. At the high spectral resolution, the 'apolar' component is, for the first time, resolved into two distinct components, likely due to pure CO and CO mixed with CO2, O2 and/or N2. The ices have probably experienced thermal processing in the upper disk layer traced by our pencil absorption beam: much of the volatile 'apolar' ices has evaporated and the depletion factor of CO onto grains is remarkably low (~7%). This study shows that high spectral resolution 4.7 um observations provide important and unique information on the dynamics and structure of protostellar disks and the evolution of ices in these disks.Comment: 11 pages, 6 figures Scheduled to appear in ApJ 568 n2, 1 April 200

Overstocking dairy cows during the dry period affects dehydroepiandrosterone and cortisol secretion

Stressful situations trigger several changes such as the secretion of cortisol and dehydroepiandrosterone (DHEA) from the adrenal cortex, in response to ACTH. The aim of this study was to verify whether overstocking during the dry period (from 21&nbsp;\ub1&nbsp;3 d to the expected calving until calving) affects DHEA and cortisol secretion and behavior in Holstein Friesian cows. Twenty-eight cows were randomly divided into 2 groups (14 animals each), balanced for the number of lactations, body condition score, and expected date of calving. Cows in the far-off phase of the dry period (from 60 to 21 d before the expected calving date) were housed together in a bedded pack. Then, animals from 21&nbsp;\ub1&nbsp;3 d before the expected calving until calving were housed in pens with the same size but under different crowding conditions due to the introduction of heifers (interference animals) into the pen. The control condition (CTR) had 2 animals per pen with 12.0&nbsp;m2 each, whereas the overstocked condition (OS) had 3 interference animals in the same pen with 4.8&nbsp;m2 for each animal. On d 1230&nbsp;\ub1&nbsp;3, 1221&nbsp;\ub1&nbsp;3, 1215&nbsp;\ub1&nbsp;3, 1210&nbsp;\ub1&nbsp;3, and 125&nbsp;\ub1&nbsp;3 before and 10, 20, and 30 after calving, blood samples were collected from each cow for the determination of plasma DHEA and cortisol concentrations by RIA. Rumination time (min/d), activity (steps/h), lying time (min/d), and lying bouts (bouts/d) were individually recorded daily. In both groups, DHEA increased before calving and the concentration declined rapidly after parturition. Overstocking significantly increased DHEA concentration compared with the CTR group at d 1210 (1.79&nbsp;\ub1&nbsp;0.09 vs. 1.24&nbsp;\ub1&nbsp;0.14 pmol/mL), whereas an increase of cortisol was observed at d 1215 (3.64&nbsp;\ub1&nbsp;0.52 vs. 1.64&nbsp;\ub1&nbsp;0.46&nbsp;ng/mL). The OS group showed significantly higher activity (steps/h) compared with the CTR group. Daily lying bouts tended to be higher for the OS group compared with CTR group in the first week of treatment. The overall results of this study documented that overstocking during the dry period was associated with a short-term changes in DHEA and cortisol but these hormonal modifications did not influence cow behavior

Infrared, UV/VIS and Raman Spectroscopy of Comet Wild-2 Samples Returned by the Stardust Mission

Results from the preliminary examination of Stardust samples obtained using various spectroscopic methods will be presented

Evaluation of polygenic determinants of non-alcoholic fatty liver disease (NAFLD) by a candidate genes resequencing strategy

NAFLD is a polygenic condition but the individual and cumulative contribution of identified genes remains to be established. To get additional insight into the genetic architecture of NAFLD, GWAS-identified GCKR, PPP1R3B, NCAN, LYPLAL1 and TM6SF2 genes were resequenced by next generation sequencing in a cohort of 218 NAFLD subjects and 227 controls, where PNPLA3 rs738409 and MBOAT7 rs641738 genotypes were also obtained. A total of 168 sequence variants were detected and 47 were annotated as functional. When all functional variants within each gene were considered, only those in TM6SF2 accumulate in NAFLD subjects compared to controls (P = 0.04). Among individual variants, rs1260326 in GCKR and rs641738 in MBOAT7 (recessive), rs58542926 in TM6SF2 and rs738409 in PNPLA3 (dominant) emerged as associated to NAFLD, with PNPLA3 rs738409 being the strongest predictor (OR 3.12, 95% CI, 1.8-5.5, P 0.28 was associated with a 3-fold increased risk of NAFLD. Interestingly, rs61756425 in PPP1R3B and rs641738 in MBOAT7 genes were predictors of NAFLD severity. Overall, TM6SF2, GCKR, PNPLA3 and MBOAT7 were confirmed to be associated with NAFLD and a score based on these genes was highly predictive of this condition. In addition, PPP1R3B and MBOAT7 might influence NAFLD severity

Novel measurements of refractive index, density and mid-infrared integrated band strengths for solid O2, N2O and NO2: N2O4 mixtures

We present novel measurements of the refractive index, density and integrated band strengths of mid-infrared features of solid N2O at 16 K and of NO2 and N2O4 in two frozen NO2: N2O4 mixtures deposited at 16 and 60 K. The refractive index and density measurements were performed also for frozen O2 deposited at 16 K. In this case, the integrated band strength values could not be determined since O2 is a homonuclear molecule and therefore its fundamental mode is not infrared active. The solid samples were analysed by infrared spectroscopy in the 8000÷800 cm-1 range. The sample thickness was measured by the interference curve obtained using a He-Ne laser operating at 543 nm. The refractive index at this laser wavelength was obtained, by numerical methods, from the measured amplitude of the interference curve. The density values were obtained using the Lorentz-Lorenz relation. Integrated band strength values were then obtained by a linear fit of the integrated band intensities plotted versus column density values. The astrophysical relevance of these novel measurements is briefly discusse