Biofilm formation of Flavobacterium psychrophilum on various substrates

The ability of Flavobacterium psychrophilum to adhere to and form biofilms on different types of materials used on rainbow trout (Oncorhynchus mykiss) farms was evaluated in this study. F. psychrophilum NCIMB 1947T, was inoculated onto a variety of different surfaces, including stainless steel, plastic, glass, wood, and zinc pyrithione encapsulated antibacterial plastic. The samples were then cultured in a humidified chamber or transferred into fish tanks containing either (1) freshwater or (2) filtered lake water. The formation of biofilms was quantified by fluorescent microscopy. F. psychrophilum formed biofilms on all of the surfaces tested; however, the adherence of the bacterium to the antibacterial plastic was much lower than the attachment observed on the other surfaces, illustrating the bacteriostatic properties of this material for F. psychrophilum. Moreover, bacterial numbers were greater on the surfaces maintained in lake water compared with those maintained in freshwater. The mineral composition of the lake water may have been responsible for the increased bacterial adherence observed between the two types of water. Treatment of the water, regular cleaning of equipment and the use of antimicrobial material to house the fish may help reduce biofilm formation by F. psychrophilum in fish farming systems

Glucocerebrosidase expression patterns in the non-human primate brain

Glucocerebrosidase (GCase) is a lysosomal enzyme encoded by the GBA1 gene. Mutations in GBA1 gene lead to Gaucher’s disease, the most prevalent lysosomal storage disorder. GBA1 mutations reduce GCase activity, therefore promoting the aggregation of alphasynuclein, a common neuropathological finding underlying Parkinson’s disease (PD) and dementia with Lewy bodies. However, it is also worth noting that a direct link between GBA1 mutations and alpha-synuclein aggregation indicating cause and effect is still lacking, with limited experimental evidence to date. Bearing in mind that a number of strategies increasing GCase expression for the treatment of PD are currently under development, here we sought to analyze the baseline expression of GCase in the brain of Macaca fascicularis, which has often been considered as the gold-standard animal model of PD. Although as with other lysosomal enzymes, GCase is expected to be ubiquitously expressed, here a number of regional variations have been consistently found, together with several specific neurochemical phenotypes expressing very high levels of GCase. In this regard, the most enriched expression of GCase was constantly found in cholinergic neurons from the nucleus basalis of Meynert, dopaminergic cells in the substantia nigra pars compacta, serotoninergic neurons from the raphe nuclei, as well as in noradrenergic neurons located in the locus ceruleus. Moreover, it is also worth noting that moderate levels of expression were also found in a number of areas within the paleocortex and archicortex, such as the entorhinal cortex and the hippocampal formation, respectively

Risk of ischaemic heart disease and acute myocardial infarction in a Spanish population: observational prospective study in a primary-care setting

BACKGROUND: Ischaemic heart disease is a global priority of health-care policy, because of its social repercussions and its impact on the health-care system. Yet there is little information on coronary morbidity in Spain and on the effect of the principal risk factors on risk of coronary heart disease. The objective of this study is to describe the epidemiology of coronary disease (incidence, mortality and its association with cardiovascular risk factors) using the information gathered by primary care practitioners on cardiovascular health of their population. METHODS: A prospective study was designed. Eight primary-care centres participated, each contributing to the constitution of the cohort with the entire population covered by the centre. A total of 6124 men and women aged over 25 years and free of cardiovascular disease agreed to participate and were thus enrolled and followed-up, with all fatal and non-fatal coronary disease episodes being registered during a 5-year period. Repeated measurements were collected on smoking, blood pressure, weight and height, serum total cholesterol, high-density and low-density lipoproteins and fasting glucose. Rates were calculated for acute myocardial infarction and ischaemic heart disease. Associations between cardiovascular risk factors and coronary disease-free survival were evaluated using Kaplan-Meier and Cox regression analyses. RESULTS: Mean age at recruitment was 51.6 ± 15, with 24% of patients being over 65. At baseline, 74% of patients were overweight, serum cholesterol over 240 was present in 35% of patients, arterial hypertension in 37%, and basal glucose over 126 in 11%. Thirty-four percent of men and 13% of women were current smokers. During follow-up, 155 first episodes of coronary disease were detected, which yielded age-adjusted rates of 362 and 191 per 100,000 person-years in men and women respectively. Disease-free survival was associated with all risk factors in univariate analyses. After multivariate adjustments, age, male gender, smoking, high total cholesterol, high HDL/LDL ratio, diabetes and overweight remained strongly associated with risk. Relative risks for hypertension in women and for diabetes in men did not reach statistical significance. CONCLUSION: Despite high prevalence of vascular risk factors, incidence rates were lower than those reported for other countries and other periods, but similar to those reported in the few population-based studies in Spain. Effect measures of vascular risk factors were mainly as reported worldwide and support the hypothesis that protective factors not considered in this study must exist as to explain low rates. This study shows the feasibility of conducting epidemiological cohort studies in primary-care settings

HRFlexToT: A High Dynamic Range ASIC for Time-of-Flight Positron Emission Tomography

Time-of-Flight positron emission tomography scanners demand fast and efficient photo sensors and scintillators coupled to fast readout electronics. This article presents the high resolution flexible Time-over-Threshold (HRFlexToT), a 16-channel application-specific-integrated circuit for silicon photomultipliers (SiPM) anode readout manufactured using XFAB 0.18- \mu \text{m} CMOS technology. The main features of the HRFlexToT are a linear Time-over-Threshold with an extended dynamic range (10 bits) for energy measurement, low power consumption (≈ 3.5 mW/ch), and an excellent timing response. The experimental measurements show an energy linearity error of ≈ 3% and an energy resolution of about 12% at 511 keV. Single-photon time resolution measurements performed using an Fondazione Bruno Kessler (FBK) SiPM NUV-HD ( 4 \times 4 mm2 pixel, 40- \mu \text{m} cell) and a Hamamatsu SiPM S13360-3050CS are around 142 and 167 ps full width at half maximum (FWHM), respectively. Coincidence time resolution (CTR) measurements with small cross-section pixelated crystals (LSO:Ce,Ca 0.4%, 2 \times 2 \times 5 mm3) coupled to the same Hamamatsu S13360-3050CS and FBK NUV-HD sensors yield a CTR of 117 ps and 119 ps, respectively. Measurements performed with a large cross-section monolithic crystal (LFS crystal measuring 25 \times 25 \times 20 mm3) and a Hamamatsu SiPM array S13361-6050NE-04 show a CTR of 324 ps FWHM after time-walk and time-skew correction

COPD Clinical Control: predictors and long-term follow-up of the CHAIN cohort

CHAIN Study Investigators.[Background] Control in COPD is a dynamic concept that can reflect changes in patients’ clinical status that may have prognostic implications, but there is no information about changes in control status and its long-term consequences.[Methods] We classified 798 patients with COPD from the CHAIN cohort as controlled/uncontrolled at baseline and over 5 years. We describe the changes in control status in patients over long-term follow-up and analyze the factors that were associated with longitudinal control patterns and related survival using the Cox hazard analysis.[Results] 134 patients (16.8%) were considered persistently controlled, 248 (31.1%) persistently uncontrolled and 416 (52.1%) changed control status during follow-up. The variables significantly associated with persistent control were not requiring triple therapy at baseline and having a better quality of life. Annual changes in outcomes (health status, psychological status, airflow limitation) did not differ in patients, regardless of clinical control status. All-cause mortality was lower in persistently controlled patients (5.5% versus 19.1%, p = 0.001). The hazard ratio for all-cause mortality was 2.274 (95% CI 1.394–3.708; p = 0.001). Regarding pharmacological treatment, triple inhaled therapy was the most common option in persistently uncontrolled patients (72.2%). Patients with persistent disease control more frequently used bronchodilators for monotherapy (53%) at recruitment, although by the end of the follow-up period, 20% had scaled up their treatment, with triple therapy being the most frequent therapeutic pattern.[Conclusions] The evaluation of COPD control status provides relevant prognostic information on survival. There is important variability in clinical control status and only a small proportion of the patients had persistently good control. Changes in the treatment pattern may be relevant in the longitudinal pattern of COPD clinical control. Further studies in other populations should validate our results.[Trial registration] Clinical Trials.gov: identifier NCT01122758.This study has been funded by AstraZeneca.Peer reviewe

The combined use of cross-section analysis and other stratigraphic recording systems in the cleaning of two panel paintings from the fifteenth- and sixteenth-century

Cross sections are frequently used in the stratigraphic study of pictorial structures. Thanks to cross sections, it is possible to study and record original and non-original strata that may provide important information regarding the artist's technique and later restoration processes. This information helps conservators design different strategies in processes such as cleaning. However, it is often in cleaning where the advantages and limitations of cross sections become obvious. When dealing with a complex structure, cross sections may not be enough to record in a comprehensive and accurate manner all the strata removed during cleaning. In some cases, the conservator may obtain during cleaning a great amount of stratigraphic information that is not visible in the cross sections. Therefore, it may be necessary to resort to other recording systems, such as the stratigraphic unit recording sheet and the stratigraphic diagram, which are frequently used in archaeological stratigraphy. This article demonstrates how cross-section analysis was combined with stratigraphic study during the cleaning of two panel paintings to gain an improved understanding of their complicated layer structure.Barros García, JM.; Reina De La Torre, A.; Pérez Marín, E. (2014). The combined use of cross-section analysis and other stratigraphic recording systems in the cleaning of two panel paintings from the fifteenth- and sixteenth-century. Studies in Conservation. 60(4):245-252. doi:10.1179/2047058414Y.0000000128S24525260

Natural Course of the Diffusing Capacity of the Lungs for Carbon Monoxide in COPD: Importance of Sex

[Background] The value of the single-breath diffusing capacity of the lungs for carbon monoxide (Dlco) relates to outcomes for patients with COPD. However, little is known about the natural course of Dlco over time, intersubject variability, and factors that may influence Dlco progression.[Research Question] What is the natural course of Dlco in patients with COPD over time, and which other factors, including sex differences, could influence this progression?[Study Design and Methods] We phenotyped 602 smokers (women, 33%), of whom 506 (84%) had COPD and 96 (16%) had no airflow limitation. Lung function, including Dlco, was monitored annually over 5 years. A random coefficients model was used to evaluate Dlco changes over time.[Results] The mean (± SE) yearly decline in Dlco % in patients with COPD was 1.34% ± 0.015%/y. This was steeper compared with non-COPD control subjects (0.04% ± 0.032%/y; P = .004). Sixteen percent of the patients with COPD, vs 4.3% of the control subjects, had a statistically significant Dlco % slope annual decline (4.14%/y). At baseline, women with COPD had lower Dlco values (11.37% ± 2.27%; P < .001) in spite of a higher FEV1 % than men. Compared with men, women with COPD had a steeper Dlco annual decline of 0.89% ± 0.42%/y (P = .039).[Interpretation] Patients with COPD have an accelerated decline in Dlco compared with smokers without the disease. However, the decline is slow, and a testing interval of 3 to 4 years may be clinically informative. The lower and more rapid decline in Dlco values in women, compared with men, suggests a differential impact of sex in gas exchange function.[Trial Registry] ClinicalTrials.gov; No.: NCT01122758; URL: www.clinicaltrials.govThis study was funded in part by an unrestricted grant from AstraZeneca, and also by the COPD Research Program of the Spanish Respiratory Society (PII de EPOC of SEPAR).Peer reviewe

STARD1 promotes NASH-driven HCC by sustaining the generation of bile acids through the alternative mitochondrial pathway

Background & Aims Besides their physiological role in bile formation and fat digestion, bile acids (BAs) synthesised from cholesterol in hepatocytes act as signalling molecules that modulate hepatocellular carcinoma (HCC). Trafficking of cholesterol to mitochondria through steroidogenic acute regulatory protein 1 (STARD1) is the rate-limiting step in the alternative pathway of BA generation, the physiological relevance of which is not well understood. Moreover, the specific contribution of the STARD1-dependent BA synthesis pathway to HCC has not been previously explored. Methods STARD1 expression was analyzed in a cohort of human non-alcoholic steatohepatitis (NASH)-derived HCC specimens. Experimental NASH-driven HCC models included MUP-uPA mice fed a high-fat high-cholesterol (HFHC) diet and diethylnitrosamine (DEN) treatment in wild-type (WT) mice fed a HFHC diet. Molecular species of BAs and oxysterols were analyzed by mass spectrometry. Effects of NASH-derived BA profiles were investigated in tumour-initiated stem-like cells (TICs) and primary mouse hepatocytes (PMHs). Results Patients with NASH-associated HCC exhibited increased hepatic expression of STARD1 and an enhanced BA pool. Using NASH-driven HCC models, STARD1 overexpression in WT mice increased liver tumour multiplicity, whereas hepatocyte-specific STARD1 deletion (Stard1ΔHep) in WT or MUP-uPA mice reduced tumour burden. These findings mirrored the levels of unconjugated primary BAs, β-muricholic acid and cholic acid, and their tauroconjugates in STARD1-overexpressing and Stard1ΔHep mice. Incubation of TICs or PMHs with a mix of BAs mimicking this profile stimulated expression of genes involved in pluripotency, stemness and inflammation. Conclusions The study reveals a previously unrecognised role of STARD1 in HCC pathogenesis, wherein it promotes the synthesis of primary BAs through the mitochondrial pathway, the products of which act in TICs to stimulate self-renewal, stemness and inflammation. Lay summary Effective therapy for hepatocellular carcinoma (HCC) is limited because of our incomplete understanding of its pathogenesis. The contribution of the alternative pathway of bile acid (BA) synthesis to HCC development is unknown. We uncover a key role for steroidogenic acute regulatory protein 1 (STARD1) in non-alcoholic steatohepatitis-driven HCC, wherein it stimulates the generation of BAs in the mitochondrial acidic pathway, the products of which stimulate hepatocyte pluripotency and self-renewal, as well as inflammation.We acknowledge support from grants PID2019-111669RB-100, SAF2017-85877R and SAF2015-73579-JIN from Plan Nacional de I+D funded by the Agencia Estatal de Investigación (AEI), the Fondo Europeo de Desarrollo Regional (FEDER) and CIBEREHD; the center grant P50AA011999 Southern California Research Center for ALPD and Cirrhosis funded by NIAAA / NIH; as well as support from AGAUR of the Generalitat de Catalunya SGR-2017-1112, European Cooperation in Science & Technology (COST) ACTION CA17112 Prospective European Drug-Induced Liver Injury Network, the ‘ER stress-mitochondrial cholesterol axis in obesity-associated insulin resistance and comorbidities’-Ayudas FUNDACION BBVA and the Red Nacional 2018-102799-T de Enfermedades Metabólicas y Cáncer, and Project 201916/31 "Contribution of mitochondrial oxysterol and bile acid metabolism to liver carcinogenesis" 2019 by Fundació Marato TV3. We also acknowledge the support from the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain (PI16/00598, co-funded by European Regional Development Fund / European Social Fund, ‘Investing in your future’) and Centro Internacional sobre el Envejecimiento (OLD-HEPAMARKER, 0348_CIE_6_E), Spain. We also acknowledge support from R01 CA2344128 and U01 AA022614 grants to M.K.Peer reviewe

The Châtelperronian Neanderthals of Cova Foradada (Calafell, Spain) used imperial eagle phalanges for symbolic purposes

Evidence for the symbolic behavior of Neanderthals in the use of personal ornaments is relatively scarce. Among the few ornaments documented, eagle talons, which were presumably used as pendants, are the most frequently recorded. This phenomenon appears concentrated in a specific area of southern Europe during a span of 80 thousand years. Here, we present the analysis of one eagle pedal phalange recovered from the Châtelperronian layer of Foradada Cave (Spain). Our research broadens the known geographical and temporal range of this symbolic behavior, providing the first documentation of its use among the Iberian populations, as well as of its oldest use in the peninsula. The recurrent appearance of large raptor talons throughout the Middle Paleolithic time frame, including their presence among the last Neanderthal populations, raises the question of the survival of some cultural elements of the Middle Paleolithic into the transitional Middle to Upper Paleolithic assemblages and beyond

Cardiovascular risk estimated after 13 years of follow-up in a low-incidence Mediterranean region with high-prevalence of cardiovascular risk factors

<p>Abstract</p> <p>Background</p> <p>Murcia (south-east Spain) shows increased cardiovascular (CV) morbimortality as compared to other Spanish regions. Our objective was to assess the CV risk associated with major risk factors (RF) among adult population of Murcia.</p> <p>Methods</p> <p>A cohort of 2314 subjects (18-70 years) with full biochemical and questionnaire data was followed-up for 13 years. Incident cases of ischemic heart disease and stroke were identified by record linkage, individual questionnaires and revision of medical records. Relative risks were obtained by multivariate Cox regression stratified by age and sex, and ischemic risk attributable to CVRF was calculated.</p> <p>Results</p> <p>After more than 26276 person-years of follow-up, 57 incident ischemic events (77% men) and 37 stroke cases (62% men) were identified. Independent risk factors of ischemic heart disease (IHD) and all CV events combined, with RR ranging from 1.6 to 2.6, were total serum cholesterol ≥ 240 mg/dl (HR = 2.6, 95%CI:1.3-5.1), blood pressure levels ≥ 140/90 mmHg (HR = 2.6, 95%CI:1.4-4.8), ever tobacco smoking (HR = 2.2; 95%CI:1.1-4.5), and diabetes (HR = 2.0; 95%CI: 1.0-3.8). No increased CV risk was detected for known participants under treatment who showed cholesterol and blood pressure values below the clinical risk threshold. Smoking was significantly associated with stroke. For all events combined, the major risk factors were hypercholesterolemia, hypertension and ever use of tobacco. Despite its high prevalence, obesity was not associated to CV risk. Most of the IHD cases were attributable to smoking (44%), hypertension (38%) and hypercholesterolemia (26%).</p> <p>Conclusions</p> <p>In the Region of Murcia, smoking accounted for the largest proportion of cardiovascular risk, whereas hypertension displaced hypercholesterolemia as the second leading cause of CV disease. Our study deepens in our understanding of the cardiovascular epidemiology in Spanish areas of Mediterranean Europe with relatively high cardiovascular morbimortality, that are poorly represented by the available risk equations.</p