Metabolism of low-density lipoproteins by cultured hepatocytes from normal and homozygous familial hypercholesterolemic subjects

The profoundly elevated concentrations of low-density lipoproteins (LDL) present in homozygous familial hypercholesterolemia lead to symptomatic cardiovascular disease and death by early adulthood. Studies conducted in nonhepatic tissues demonstrated defective cellular recognition and metabolism of LDL in these patients. Since mammalian liver removes at least half of the LDL in the circulation, the metabolism of LDL by cultured hepatocytes isolated from familial hypercholesterolemic homozygotes was compared to hepatcytes from normal individuals. Fibroblast studies demonstrated that the familial hypercholesterolemic subjects studied were LDL receptor-negative (less than 1% normal receptor activity) and LDL receptor-de fective (18% normal receptor activity). Cholesterol-depleted hepatocytes from normal subjects bound and internalized 125I-labeled LDL (Bmax = 2.2 μg LDL/mg cell protein). Preincubation of normal hepatocytes with 200 μg/ml LDL reduced binding and internalization by approx. 40%. In contrast, 125I-labeled LDL binding and internalization by receptor-negative familial hypercholesterolemic hepatocytes was unaffected by cholesterol loading and considerably lower than normal. This residual LDL uptake could not be ascribed to fluid phase endocytosis as determined by [14C]sucrose uptake. The residual LDL binding by familial hypercholesterolemia hepatocytes led to a small increase in hepatocyte cholesterol content which was relatively ineffective in reducing hepatocyte 3-hydroxy-3-methylglutaryl-CoA reductase activity. Receptordefective familial hypercholesterolemia hepatocytes retained some degree of regulatable 125I-labeled LDL uptake, but LDL uptake did not lead to normal hepatocyte cholesterol content or 3-hydroxy-3-methylglutaryl-CoA reductase activity. These combined results indicate that the LDL receptor abnormality present in familial hypercholesterolemia fibroblasts reflects deranged hepatocyte LDL recognition and metabolism. In addition, a low-affinity, nonsaturable uptake process for LDL is present in human liver which does not efficiently modulate hepatocyte cholesterol content or synthesis. © 1986

Chemochromic Pd-V2O5 Sensors for Passive Hydrogen Detection in Nuclear Containments

The ability to detect and monitor hydrogen gas efficiently in process and storage facilities, handling nuclear material, is crucial to ensuring their safety. The accumulation of hydrogen gas, above the lower flammable limit (LFL), in a nuclear waste containment is a concern since it creates the potential for a hydrogen-air explosion to occur, which could lead to a loss of containment and result in the uncontrolled release of radioactive material into the surrounding environment. The events that took place at Fukushima Daiichi Nuclear Power Plant highlighted the vulnerability of conventional hydrogen detection to extreme events, where power may be lost. In the present work, chemochromic hydrogen sensors have been fabricated, using transition metal oxide thin films, to provide eye-readable detection systems that would be resilient to plant power failure. Vanadium oxide (V2O5) films were prepared on quartz glass substrates by sol-gel deposition and sensitized with a palladium (Pd) catalyst, deposited by electron beam evaporation. When exposed to hydrogen, the Pd catalyst dissociates H2 to H atoms, which diffuse into the V(V)2O5 forming a hydrogen-vanadium metal bronze, H2V(III)2O5, resulting in a noticeable colour change from orange to dark green. To assess their viability for nuclear safety applications, these sensors have been irradiated to total doses between 5 and 250 kGy using a Co-60 gamma isotope irradiator. The results suggest that gamma irradiation, at the levels examined, has an effect on the initial colour of the V2O5 and Pd-V2O5 thin films with decreased transmittance above 540 nm. The orange starting colour darkened and developed a green tone, with the degree of colour change depending on the applied total dose. Changes in surface morphology and characteristics have been examined by using Scanning Electron Microscopy (SEM) and Raman spectroscopy. High level (250 kGy) gamma radiation exposure begins to produce surface degradation on V2O5 thin films; however this behaviour is not observed for films that are also coated with palladium. Chemochromic properties of both un-irradiated and irradiated Pd-V2O5 thin films were determined by examining their optical transmittance, using UV-vis spectroscopy, under exposure to a 4% H2-N2 gas mixture. Exposure to gamma radiation has been found to have negligible effect upon colour change behaviour after 30 minutes exposure to hydrogen gas. The results suggest that the thin film V2O5 sensitised with Pd is a plausible technique for application in the monitoring of hydrogen gas in low-level gamma radiation environments

Characterising the performance of hydrogen sensitive coatings for nuclear safety applications

The detection of hydrogen gas is essential in ensuring the safety of nuclear plants. However, events at Fukushima Daiichi NPP highlighted the vulnerability of conventional detection systems to extreme events, where power may be lost. Herein, chemochromic hydrogen sensors have been fabricated using transition metal oxide thin films, sensitised with a palladium catalyst, to provide passive hydrogen detection systems that would be resilient to any plant power failures. To assess their viability for nuclear safety applications, these sensors have been gamma-irradiated to four total doses (0, 5, 20, 50 kGy) using a Co-60 gamma radioisotope. Optical properties of both un-irradiated and irradiated samples were investigated to compare the effect of increased radiation dose on the sensors resultant colour change. The results suggest that gamma irradiation, at the levels examined (>5 kGy), has a significant effect on the initial colour of the thin films and has a negative effect on the hydrogen sensing abilities

Review of parameterisation and a novel database (LiionDB) for continuum Li-ion battery models

The Doyle–Fuller–Newman (DFN) framework is the most popular physics-based continuum-level description of the chemical and dynamical internal processes within operating lithium-ion-battery cells. With sufficient flexibility to model a wide range of battery designs and chemistries, the framework provides an effective balance between detail, needed to capture key microscopic mechanisms, and simplicity, needed to solve the governing equations at a relatively modest computational expense. Nevertheless, implementation requires values of numerous model parameters, whose ranges of applicability, estimation, and validation pose challenges. This article provides a critical review of the methods to measure or infer parameters for use within the isothermal DFN framework, discusses their advantages or disadvantages, and clarifies limitations attached to their practical application. Accompanying this discussion we provide a searchable database, available at www.liiondb.com, which aggregates many parameters and state functions for the standard DFN model that have been reported in the literature

Very Cold Gas and Dark Matter

We have recently proposed a new candidate for baryonic dark matter: very cold molecular gas, in near-isothermal equilibrium with the cosmic background radiation at 2.73 K. The cold gas, of quasi-primordial abundances, is condensed in a fractal structure, resembling the hierarchical structure of the detected interstellar medium. We present some perspectives of detecting this very cold gas, either directly or indirectly. The H$_2$ molecule has an "ultrafine" structure, due to the interaction between the rotation-induced magnetic moment and the nuclear spins. But the lines fall in the km domain, and are very weak. The best opportunity might be the UV absorption of H$_2$ in front of quasars. The unexpected cold dust component, revealed by the COBE/FIRAS submillimetric results, could also be due to this very cold H$_2$ gas, through collision-induced radiation, or solid H$_2$ grains or snowflakes. The $\gamma$-ray distribution, much more radially extended than the supernovae at the origin of cosmic rays acceleration, also points towards and extended gas distribution.Comment: 16 pages, Latex pages, crckapb macro, 3 postscript figures, uuencoded compressed tar file. To be published in the proceeedings of the "Dust-Morphology" conference, Johannesburg, 22-26 January, 1996, D. Block (ed.), (Kluwer Dordrecht

Healthcare use for acute gastrointestinal illness in two Inuit communities: Rigolet and Iqaluit, Canada

Background. The incidence of self-reported acute gastrointestinal illness (AGI) in Rigolet, Nunatsiavut, and Iqaluit, Nunavut, is higher than reported elsewhere in Canada; as such, understanding AGI-related healthcare use is important for healthcare provision, public health practice and surveillance of AGI. Objectives: This study described symptoms, severity and duration of self-reported AGI in the general population and examined the incidence and factors associated with healthcare utilization for AGI in these 2 Inuit communities. Design: Cross-sectional survey data were analysed using multivariable exact logistic regression to examine factors associated with individuals’ self-reported healthcare and over-the-counter (OTC) medication utilization related to AGI symptoms. Results: In Rigolet, few AGI cases used healthcare services [4.8% (95% CI=1.5-14.4%)]; in Iqaluit, some cases used healthcare services [16.9% (95% CI=11.2-24.7%)]. Missing traditional activities due to AGI (OR=3.8; 95% CI=1.18-12.4) and taking OTC medication for AGI symptoms (OR=3.8; 95% CI=1.2-15.1) were associated with increased odds of using healthcare services in Iqaluit. In both communities, AGI severity and secondary symptoms (extreme tiredness, headache, muscle pains, chills) were significantly associated with increased odds of taking OTC medication. Conclusions: While rates of self-reported AGI were higher in Inuit communities compared to non-Inuit communities in Canada, there were lower rates of AGI-related healthcare use in Inuit communities compared to other regions in Canada. As such, the rates of healthcare use for a given disease can differ between Inuit and non-Inuit communities, and caution should be exercised in making comparisons between Inuit and non-Inuit health outcomes based solely on clinic records and healthcare use

Water quality and health in northern Canada: stored drinking water and acute gastrointestinal illness in Labrador Inuit

One of the highest self-reported incidence rates of acute gastrointestinal illness (AGI) in the global peer-reviewed literature occurs in Inuit communities in the Canadian Arctic. This high incidence of illness could be due, in part, to the consumption of contaminated water, as many northern communities face challenges related to the quality of municipal drinking water. Furthermore, many Inuit store drinking water in containers in the home, which could increase the risk of contamination between source and point-of-use (i.e., water recontamination during storage). To examine this risk, this research characterized drinking water collection and storage practices, identified potential risk factors for water contamination between source and point-of-use, and examined possible associations between drinking water contamination and self-reported AGI in the Inuit community of Rigolet, Canada. The study included a cross-sectional census survey that captured data on types of drinking water used, household practices related to drinking water (e.g., how it was collected and stored), physical characteristics of water storage containers, and self-reported AGI. Additionally, water samples were collected from all identified drinking water containers in homes and analyzed for presence of Escherichia coli and total coliforms. Despite municipally treated tap water being available in all homes, 77.6% of households had alternative sources of drinking water stored in containers, and of these containers, 25.2% tested positive for total coliforms. The use of transfer devices and water dippers (i.e., smaller bowls or measuring cups) for the collection and retrieval of water from containers were both significantly associated with increased odds of total coliform presence in stored water (ORtransfer device = 3.4, 95% CI 1.2–11.7; ORdipper = 13.4, 95% CI 3.8–47.1). Twenty-eight-day period prevalence of self-reported AGI during the month before the survey was 17.2% (95% CI 13.0–22.5), which yielded an annual incidence rate of 2.4 cases per person per year (95% CI 1.8–3.1); no water-related risk factors were significantly associated with AGI. Considering the high prevalence of, and risk factors associated with, indicator bacteria in drinking water stored in containers, potential exposure to waterborne pathogens may be minimized through interventions at the household level

The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients

Background: Preoperative chemoradiotherapy (CRT) followed by surgery is the standard care for locally advanced rectal cancer, but tumour response to CRT and disease outcome are variable. The current study aimed to investigate the effectiveness of plasma telomerase reverse transcriptase (TERT) levels in predicting tumour response and clinical outcome. Methods: 176 rectal cancer patients were included. Plasma samples were collected at baseline (before CRT\ubcT0), 2 weeks after CRT was initiated (T1), post-CRT and before surgery (T2), and 4\u20138 months after surgery (T3) time points. Plasma TERT mRNA levels and total cell-free RNA were determined using real-time PCR. Results: Plasma levels of TERT were significantly lower at T2 (Po0.0001) in responders than in non-responders. Post-CRT TERT levels and the differences between pre- and post-CRT TERT levels independently predicted tumour response, and the prediction model had an area under curve of 0.80 (95% confidence interval (CI) 0.73\u20130.87). Multiple analysis demonstrated that patients with detectable TERT levels at T2 and T3 time points had a risk of disease progression 2.13 (95% CI 1.10\u20134.11)-fold and 4.55 (95% CI 1.48\u201313.95)-fold higher, respectively, than those with undetectable plasma TERT levels. Conclusions: Plasma TERT levels are independent markers of tumour response and are prognostic of disease progression in rectal cancer patients who undergo neoadjuvant therapy

HIV seroprevalence and its effect on outcome of moderate to severe burn injuries: A Ugandan experience

\ud \ud HIV infection in a patient with burn injuries complicates the care of both the patient and the treating burn team. This study was conducted to establish the prevalence of HIV among burn patients in our setting and to compare the outcome of these patients who are HIV positive with those who are HIV negative. This was a prospective cohort study involving burn injury patients admitted to Mulago Hospital between November 2005 and February 2006. Patients were stratified into HIV positive (exposed) group and HIV-negative (unexposed) group. Data was collected using a pre-tested coded questionnaire and analyzed using SPSS statistical computer software version 11.5. Of the 130 patients included in the study, 17 (13.1%) patients tested HIV positive and this formed the study (exposed) group. The remaining 113 patients (86.9%) formed the control (unexposed) group. In the HIV positive group, females outnumbered males by a ratio of 1.4:1 and the mean age was 28.4 ± 21.5 years (range 3 months-34 years). 64.7% of HIV positive patients reported to have risk factors for HIV infection. Of these, multiple sexual partners [Odds Ratio 8.44, 95% C.I. (3.87-143.23), P = 0.011] and alcoholism [Odds Ratio 8.34, 95% C.I. (5.76-17.82), P = 0.002] were found to be independently and significantly associated with increased risk to HIV infection. The mean CD4 count for HIV positive and HIV negative patients were 394 ± 328 cells/μL and 912 ± 234 cells/μL respectively which is statistically significant (P = 0.001). There was no difference in the bacteria cultured from the wounds of HIV positive and negative patients (P = 0.322). Patients with clinical signs of sepsis had lower CD4+ counts compared to patients without sepsis (P < 0.001). ). Skin grafting was carried out in 35.3% of HIV negative patients and 29.4% of HIV positive patients with no significant difference in skin graft take and the degree of healed burn on discharge was the same (P = 0.324). There was no significant difference in hospital stay between HIV positive and negative patients (P = 0.674). The overall mortality rate was 11.5%. Using multivariate logistic regression analysis, mortality rate was found to be independently and significantly related to the age of the patient, HIV positive with stigmata of AIDS, CD4 count, inhalation injury, %TBSA and severity of burn (p-value < 0.001). HIV infection is prevalent among burn injury patients in our setting and thus presents an occupational hazard to health care workers who care for these patients. All burn health care workers in this region need to practice universal precautions in order to reduce the risk of exposure to HIV infection and post-exposure prophylaxis should be emphasized. The outcome of burn injury in HIV infected patients is dependent upon multiple variables such as age of the patient, inhalation injury and %TBSA and not the HIV status alone

Invasive pleural malignant mesothelioma with rib destruction and concurrent osteosarcoma in a dog

A 7-year-old Dachshund was clinically examined because of a 10-day history of lameness in the left hind limb. On the basis of radiological and cytological findings, an osteosarcoma of the left acetabular region was suspected. The dog underwent a hemipelvectomy and osteosarcoma was diagnosed by subsequent histopathological examination. An immovable subcutaneous mass was noted on the left chest wall during the physical examination and non-septic neutrophilic inflammation was diagnosed by cytology. Forty days later, the dog showed signs of respiratory distress with an in-diameter increase of the subcutaneous mass up to 4 cm. Thoracic radiography and ultrasonography revealed pleural effusion and a lytic process in the fourth left rib. Furthermore, ultrasound examination revealed a mixed echogenic mobile structure with a diameter of around 2 cm floating within the pleural fluid of the left hemithorax close to the pericardium. The dog underwent surgery for an en bloc resection of the subcutaneous mass together with the fourth rib and the parietal pleura. Moreover, the left altered lung lobe, corresponding to the mobile structure detected by ultrasound, was removed. Based on cytological, histopathological, and immunohistochemical examinations, an invasive epithelioid pleural malignant mesothelioma was diagnosed