Prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) in a middle-aged population with overweight and normal liver enzymes, and diagnostic accuracy of noninvasive proxies.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing at an alarming rate. Elevated liver enzymes are a primary reason to refer patients for further testing. However, liver enzymes within the normal range do not exclude the presence of MASLD. We examined the prevalence of MASLD in a middle-aged population with overweight and normal liver enzymes. In addition, we examined the accuracy of 4 sets of noninvasive proxies for MASLD. We included 1017 participants from the Netherlands epidemiology of obesity cohort study with body mass index ≥25 kg/m2 and liver enzymes (asparate aminotransferase, alanine aminotransferase, gamma-glutamyltranspeptidase) within normal range. The diagnostic accuracy of biomarker scores (fatty liver index, liver fat score [LFS], STEATO-ELSA, and hepatic steatosis index) was determined against elevated hepatic triglyceride content measured by 1proton magnetic resonance spectroscopy. Participants (mean age 56 years, 49% women), had a median body mass index of 29.6 kg/m2 and a median hepatic triglyceride content of 4.4%. MASLD was present in 42% of participants and was more common in men than women, with respectively 47% and 36% being affected. The LFS showed the highest accuracy with an area under the curve of 0.72. We identified metabolic syndrome as the prime predictor for MASLD with an odds ratio of 2.95 (95% confidence interval 2.20-3.98). The prevalence of MASLD in middle-aged men and women with overweight and liver enzymes within the normal range is over 40%. LFS showed the highest accuracy to detect MASLD, but, overall, biomarker scores performed relatively poor. The presence of metabolic syndrome was the prime predictor of MASLD.

Blood lead concentrations in exposed forecourt attendants and taxi drivers in parts of South Africa.

BACKGROUND: Leaded fuel was banned in South Africa in 2006, in order to improve human health and reduce environmental pollution. Lead (Pb) has been suggested to contribute to the development of neurodegenerative disorders, and the role of respiratory exposure to Pb from petrol fumes should not be neglected in this context. In addition to Pb, petrol contains various harmful chemicals including other neurotoxic metals and hydrocarbons. OBJECTIVES AND METHODS: Here, we investigated concentrations of Pb and other metals in blood from petrol station forecourt attendants (n = 38), taxi drivers (n = 21), and unexposed controls (n = 36). Taxi drivers and forecourt attendants were divided into three groups each, based on number of years worked. A questionnaire was designed to investigate the health status of the participants. Blood samples were collected by medical professionals and analyzed for metal concentrations by ICP-MS. RESULTS: A positive correlation between number of years worked and Pb blood concentrations was found. The highest Pb concentration (60.2 µg/L) was observed in a forecourt attendant who had worked 11-20 years, and the average Pb concentration in this group (24.5 µg/L) was significantly (p < 0.05) higher than in forecourt attendants who had worked 2-5 years (10.4 µg/L). Some individuals had elevated concentrations of manganese, arsenic, cadmium, chromium and cobalt, yet not significantly elevated at the group level. The blood levels of arsenic appeared to be related to smoking. Mood swings, dizziness, headaches and tiredness were reported by the workers. CONCLUSION: Blood Pb concentrations in petrol station forecourt attendants and taxi drivers exposed to leaded petrol are elevated and correlate to exposure time. A health monitoring program should be erected for all individuals working in these industries, and preventive measures should be implemented to eliminate metal exposure from petrol.

Interleukin-1 receptor antagonist, interleukin-2 receptor alpha subunit and amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: To clarify the causal associations of interleukin-1 receptor antagonist (IL-1ra) and interleukin-2 receptor alpha subunit (IL-2rα) with the risk of amyotrophic lateral sclerosis (ALS). METHODS: A two-sample Mendelian randomization study design was employed. Single-nucleotide polymorphisms associated with IL-1ra (n = 2) and IL-2rα (n = 1) at the genome-wide significance level were used as unbiased instrumental variables. Summary-level data for ALS were obtained from Project MinE, an international collaboration consortium with 12 577 ALS cases and 23 475 controls of European descent. RESULTS: Genetic predisposition to higher levels of IL-1ra was significantly associated with lower odds of ALS. For a 1-SD increase of circulating IL-1ra levels, the odds ratio of ALS was 0.64 (95% confidence intervals, 0.46-0.88; P = 0.005). There was a borderline inverse association between IL-2rα levels and ALS (odds ratio, 0.91; 95% confidence intervals, 0.83-1.00; P = 0.058). CONCLUSIONS: Interleukin-1 receptor antagonist levels were inversely associated with ALS, suggesting that interleukin-1 inhibitors may lower the risk of this always fatal disease. The role of IL-2rα levels in ALS needs further verification in causal inference studies with larger sample sizes.

Unique Access to u-Channel Physics: Exclusive Backward-Angle Omega Meson Electroproduction.

Backward-angle meson electroproduction above the resonance region, which was previously ignored, is anticipated to offer unique access to the three quark plus sea component of the nucleon wave function. In this Letter, we present the first complete separation of the four electromagnetic structure functions above the resonance region in exclusive ω electroproduction off the proton, ep→e^{'}pω, at central Q^{2} values of 1.60, 2.45 GeV^{2}, at W=2.21 GeV. The results of our pioneering -u≈-u_{min} study demonstrate the existence of a unanticipated backward-angle cross section peak and the feasibility of full L/T/LT/TT separations in this never explored kinematic territory. At Q^{2}=2.45 GeV^{2}, the observed dominance of σ_{T} over σ_{L}, is qualitatively consistent with the collinear QCD description in the near-backward regime, in which the scattering amplitude factorizes into a hard subprocess amplitude and baryon to meson transition distribution amplitudes: universal nonperturbative objects only accessible through backward-angle kinematics.

Effectiveness of a combined exercise training and home-based walking programme on physical activity compared with standard medical care in moderate COPD: a randomised controlled trial.

OBJECTIVE: To estimate the effectiveness of a 10-week combined exercise training and home-based walking programme on daily physical activity (PA) compared with standard medical care in patients with moderate chronic obstructive pulmonary disease (COPD). DESIGN: Randomised controlled trial. SETTING: Primary care physiotherapy. PARTICIPANTS: Consecutive patients with stable COPD at Gold Stage II with a score of two or more on the Medical Research Council Dyspnoea Scale. INTERVENTION: Ten-week combined exercise training and home-based walking programme compared with standard medical care. MAIN OUTCOMES: At baseline and after 10 weeks, daily PA was evaluated by accelerometry using three levels of intensity and expressed as metabolic equivalent of task. In addition, daily activities (Physical Activity Scale for the Elderly), functional exercise capacity (6-minute Walk Test), health-related quality of life (Chronic Respiratory Questionnaire) and exercise self-efficacy (Exercise Self-Regulatory Efficacy Scale) were measured. RESULTS: Fifty-two patients {34 females; mean age 70.2 [standard deviation (SD) 9.5] years; mean forced expiratory volume in 1second 67% (SD 9.2) of predicted} were randomised. PA, adjusted for baseline differences, increased significantly in the intervention group compared with the control group, by 26.1minutes/day [95% confidence interval (CI) 7.3 to 44.9]. The increase in functional capacity between groups was clinically relevant (34.0m, 95% CI 2.3 to 65.6) in favour of the intervention group. CONCLUSIONS: A combined exercise training and home-based walking programme in primary care physiotherapy improved PA in patients with moderate COPD. Clinical trial registration number NL24766.018.08.

Hair as an indicator of the body content of polonium in humans: preliminary results from study of five male volunteers.

The radionuclide (210)Po is of importance from a radiation protection view and has properties that cause special problems when attempting to determine the body content in humans. Estimates have traditionally been made from either urine and/or fecal samples, which require a time-consuming radiochemical preparation before alpha spectrometric determination. In order to find a more simple and less labor intensive method hair has been used as a bioindicator and investigated in this study. The relationship between intake and excretion in hair has been estimated in five volunteers who ingested radioactive polonium ((209)Po as a bio-tracer for (210)Po) in well determined quantities. Four of the volunteers were given 5-10 Bq (209)Po in a single intake (acute intake) and one volunteer has ingested a daily intake of 58.7 mBq (209)Po for a period of 180 d. Human hair was found to reflect the daily clearance of ingested polonium peaking at 0.001-0.01% d(-1) of the ingested amount, thereafter decreasing mono-exponentially, corresponding to a biological half-time of 10-20 days. For the case of protracted intake a mono-exponential build-up was observed with a half-time of 40 ± 5 d. In addition, after cessation of intake, a short-term component (74%) with a biological half-time of 16 ± 4 d, and a long-term component (26%) with a half-time of 93 ± 53 d were observed. It is concluded that hair can be used to detect not only the amount of ingested polonium but also whether the intake was protracted or acute.

Development of knowledge tests for multi-disciplinary emergency training: a review and an example.

BACKGROUND: The literature is sparse on written test development in a post-graduate multi-disciplinary setting. Developing and evaluating knowledge tests for use in multi-disciplinary post-graduate training is challenging. The objective of this study was to describe the process of developing and evaluating a multiple-choice question (MCQ) test for use in a multi-disciplinary training program in obstetric-anesthesia emergencies. METHODS: A multi-disciplinary working committee with 12 members representing six professional healthcare groups and another 28 participants were involved. Recurrent revisions of the MCQ items were undertaken followed by a statistical analysis. The MCQ items were developed stepwise, including decisions on aims and content, followed by testing for face and content validity, construct validity, item-total correlation, and reliability. RESULTS: To obtain acceptable content validity, 40 out of originally 50 items were included in the final MCQ test. The MCQ test was able to distinguish between levels of competence, and good construct validity was indicated by a significant difference in the mean score between consultants and first-year trainees, as well as between first-year trainees and medical and midwifery students. Evaluation of the item-total correlation analysis in the 40 items set revealed that 11 items needed re-evaluation, four of which addressed content issues in local clinical guidelines. A Cronbach's alpha of 0.83 for reliability was found, which is acceptable. CONCLUSION: Content and construct validity and reliability were acceptable. The presented template for the development of this MCQ test could be useful to others when developing knowledge tests and may enhance the overall quality of test development.

South African Menopause Society revised consensus position statement on menopausal hormone therapy, 2014.

The South African Menopause Society (SAMS) consensus position statement on menopausal hormone therapy (HT) 2014 is a revision of the SAMS Council consensus statement on menopausal HT published in the SAMJ in May 2007. Information presented in the previous statement has been re-evaluated and new evidence has been incorporated. While the recommendations pertaining to HT remain similar to those in the previous statement, the 2014 revision includes a wider range of clinical benefits for HT, the inclusion of non-hormonal alternatives such as selective serotonin reuptake inhibitors and serotonin noradrenaline reuptake inhibitors for the management of vasomotor symptoms, and an appraisal of bioidentical hormones and complementary medicines used for treatment of menopausal symptoms. New preparations that are likely to be more commonly used in the future are also mentioned. The revised statement emphasises that commencing HT during the 'therapeutic window of opportunity' maximises the benefit-to-risk profile of therapy in symptomatic menopausal women.

CYP7B1: novel mutations and magnetic resonance spectroscopy abnormalities in hereditary spastic paraplegia type 5A.

UNLABELLED: The SPG5A subtype of Hereditary Spastic Paraplegia (HSP) is a rare autosomal recessive neurodegenerative disorder caused by mutations in the CYP7B1 gene, which encodes a steroid cytochrome P450 7α-hydroxylase. This enzyme provides the primary metabolic route for neurosteroids. Clinically, SPG5A has been characterized as a pure form of HSP with a variable age of onset, but recently a broader spectrum of phenotypes has been described. OBJECTIVE: This study characterizes four unrelated SPG5A patients through clinical evaluation. METHODS: The investigations included blood biochemistry, electrophysiology, brain MRI and MR spectroscopy. RESULTS: One patient had saccadic pursuit eye movements in addition to a pure HSP phenotype. Motor evoked potential (MEP) examinations revealed prolonged central conduction time. MRI of the brain showed white matter hyperintensities (WMH) in one patient. MRS showed elevated mI/Cr ratio in white matter in two patients; in the one patient with WMH and in one patient with normal MRI. Four novel mutations were identified; one frameshift (c.509 delT p.L170fs), one premature stop codon (c.334 C>T p.R112X), one amino acid changing (c.440 G>A p.G147D) and one duplication (c.945_947 dupGGC p.A316AA). CONCLUSION: SPG5A could be characterized as a predominantly pure HSP. MRS showing elevated mI/Cr ratio in the white matter may be indicative of SPG5A.

Activation of old carbon by erosion of coastal and subsea permafrost in Arctic Siberia.

The future trajectory of greenhouse gas concentrations depends on interactions between climate and the biogeosphere. Thawing of Arctic permafrost could release significant amounts of carbon into the atmosphere in this century. Ancient Ice Complex deposits outcropping along the ~7,000-kilometre-long coastline of the East Siberian Arctic Shelf (ESAS), and associated shallow subsea permafrost, are two large pools of permafrost carbon, yet their vulnerabilities towards thawing and decomposition are largely unknown. Recent Arctic warming is stronger than has been predicted by several degrees, and is particularly pronounced over the coastal ESAS region. There is thus a pressing need to improve our understanding of the links between permafrost carbon and climate in this relatively inaccessible region. Here we show that extensive release of carbon from these Ice Complex deposits dominates (57 ± 2 per cent) the sedimentary carbon budget of the ESAS, the world's largest continental shelf, overwhelming the marine and topsoil terrestrial components. Inverse modelling of the dual-carbon isotope composition of organic carbon accumulating in ESAS surface sediments, using Monte Carlo simulations to account for uncertainties, suggests that 44 ± 10 teragrams of old carbon is activated annually from Ice Complex permafrost, an order of magnitude more than has been suggested by previous studies. We estimate that about two-thirds (66 ± 16 per cent) of this old carbon escapes to the atmosphere as carbon dioxide, with the remainder being re-buried in shelf sediments. Thermal collapse and erosion of these carbon-rich Pleistocene coastline and seafloor deposits may accelerate with Arctic amplification of climate warming.

Inclusion body myositis in Alzheimer's disease.

BACKGROUND: The prevalence of Alzheimer's disease is increasing. Could findings of similar deposits in brain and muscle tissue explain this increase? The purpose of this report is to illustrate that Alzheimer's disease and inclusion body myositis may share a common aetiology. RESULTS: We present a case where Alzheimer's disease and inclusion body myositis coexist in the same patient. Amyloid-beta deposition and the presence of phosphorylated tau protein have been noted in brain tissue and in muscle biopsy from patients with these disorders. METHODS: Electrophysiological methods are needed for proper diagnosis of this brain and muscle disorder. Recent data on deposit structures in both conditions may indicate an environmental aetiology for Alzheimer's disease and inclusion body myositis. CONCLUSION: By combining electrophysiological methods with muscle biopsy in cases of Alzheimer's disease, the possible aetiological connection between simultaneous affection of both muscle and brain in this condition can be established.

Levels and transfer of 210Po and 210Pb in Nordic terrestrial ecosystems.

Recent developments regarding environmental impact assessment methodologies for radioactivity have precipitated the need for information on levels of naturally occurring radionuclides within and transfer to wild flora and fauna. The objectives of this study were therefore to determine activity concentrations of the main dose forming radionuclides (210)Po and (210)Pb in biota from terrestrial ecosystems thus providing insight into the behaviour of these radioisotopes. Samples of soil, plants and animals were collected at Dovrefjell, Central Norway and Olkiluoto, Finland. Soil profiles from Dovrefjell exhibited an approximately exponential fall in (210)Pb activity concentrations from elevated levels in humus/surface soils to "supported" levels at depth. Activity concentrations of (210)Po in fauna (invertebrates, mammals, birds) ranged between 2 and 123 Bq kg(-1)d.w. and in plants and lichens between 20 and 138 Bq kg(-1)d.w. The results showed that soil humus is an important reservoir for (210)Po and (210)Pb and that fauna in close contact with this media may also exhibit elevated levels of (210)Po. Concentration ratios appear to have limited applicability with regards to prediction of activity concentrations of (210)Po in invertebrates and vertebrates. Biokinetic models may provide a tool to explore in a more mechanistic way the behaviour of (210)Po in this system.

Aspects on the analysis of 210Po.

There has been little development regarding analysis of polonium (Po) in environmental samples since the 1960 ies. This is due to the straightforward spontaneous deposition of this element on silver (Ag), nickel (Ni) or copper (Cu) without any radiochemical separation. For many years, no radiochemical yield determinant was used and it was generally supposed that the yield was 100% after two depositions. Counting was often done using ZnS scintillation counter coupled to a photomultiplier tube. However, the use of the yield determinants (208)Po and (209)Po and the development of alpha spectrometry showed that the yield was lower. Furthermore, the tendency of Po to volatilize at low temperatures constrains the sample preparation techniques; dry-ashing cannot be used. But during the wet-ashing procedure, there are still some losses. The aim of this study was to evaluate the Po losses during wet-ashing by the use of a double-tracer technique. We have found that the losses were about 30% when open glass beakers were used and about 17% when the samples were digested in microwave oven. When long-necked bottles (Kjeldahl flasks) were used, a loss of about 20% was registered. It has also been observed that (210)Pb to some extent is plating out together with its daughter nuclide Po during the electrochemical deposition. This will result in a systematic error since an unknown amount of supported (210)Po will be produced from the (210)Pb decay depending on the fraction of (210)Pb being deposited on the disc and the waiting time between deposition and measurement of the sample. A further consequence of this is that in the assessment of the (210)Pb content in the sample, very often the remaining liquid is stored after deposition for build-up of (210)Po. Since some (210)Pb is lost on the disc, the result for (210)Pb will be too low. Both these systematic errors give rise to a too high (210)Po/(210)Pb ratio. The fraction of (210)Pb which is plating out has been assessed in this study for different matrices and is about 50-90%. During the measurement by solid state Si-detectors, some Po is evaporated in the vacuum conditions contaminating the detectors. Experiments have here been done by heating the discs after deposition which indicate that less Po is evaporated from Ag than from Ni. The losses from Ag are less than that from the other metals probably due to a deeper penetration into the surface of Po. We conclude that in most aspects, Ag is better to use than the other plating metals.

Outbreak of severe sepsis due to contaminated propofol: lessons to learn.

Nosocomial infections are a frequent concern in healthcare. Despite the available knowledge on nosocomial infections and preventive measures, outbreaks of infections continue to occur. An outbreak of severe sepsis in patients who underwent minor procedures in an operating theatre during two consecutive days is described and analysed in this study. We performed a retrospective cohort study using epidemiological data in order to investigate the source of infection together with microbiological and on-site investigations and interviews. Seven patients met the case definition of postoperative systemic inflammatory response syndrome (SIRS). All other patients operated on over the same period served as controls. Of the risk factors investigated, general anaesthesia and propofol were statistically significant (P=0.003). Klebsiella pneumoniae and Serratia marcescens were cultured from opened vials of propofol, propofol-related devices and from blood cultures from two of the patients. These strains were genotypically indistinguishable. Lapses in aseptic preparation, handling and storage of the propofol were observed, and were the most probable cause of the extrinsic contamination. The daily procedure of handling propofol was not performed according to the manufacturer's recommendations, the main departure being the use of a single-use vial for multiple patients. This study documents the risk of infection due to contaminated propofol and the importance of having written guidelines for its handling.

Intercomparison of Rn-222 determination from groundwater.

An intercomparison exercise on Rn-222 determination in groundwater was organized between eight Nordic laboratories. The individual laboratory results were in most cases within 20% of the median value and within reported uncertainties. Considering the particular difficulties in preparing, transporting and analyzing Rn-222, being a gaseous radionuclide, the results indicate a high analytical capability among the Nordic laboratories. In order to maintain a high analytical quality, similar intercomparisons will also be needed in the future.

Metabolomic profiling by near-infrared spectroscopy as a tool to assess embryo viability: a novel, non-invasive method for embryo selection.

BACKGROUND: The morphology of an embryo has a limited predictive value for assessing viability and ongoing pregnancy, therefore new selection tools are needed to maintain success rates with single-embryo transfer (SET). In this study, we investigated if metabolomic profiling of biomarkers of embryo culture medium by near-infrared (NIR) spectroscopy has a correlation with ongoing pregnancy in SET. METHODS: A total of 333 patients scheduled for in vitro fertilization (IVF) with SET were included in the study. Embryos were selected for transfer by morphological criteria on Days 2 and 3 of in vitro culture, and left over culture media samples were analyzed by NIR spectroscopy. RESULTS: The NIR spectral analysis produced unique metabolomic profiles that correlated to an embryo's reproductive potential. Resulting relative viability scores between positive and negative pregnancy outcomes were statistically significant (P < 0.03). A logistic regression of factors correlated to pregnancy outcomes showed that maternal age, percent fragmentation and relative viability scores all demonstrated a relationship. The extent of the correlation was determined by accuracy computation, where the accuracy of assessing viable embryos on Day 3 by metabolomic profiling was 53.6% and the accuracy of the morphological selection was 38.5%. In addition, the positive predictive value of metabolomic profiling was 0.365 and the negative predictive value was 0.830. CONCLUSIONS: NIR metabolomic profiling of spent embryo culture media was able to distinguish viable embryos from non-viable embryos for reproduction.

Impact of arbuscular mycorrhizal fungi on uranium accumulation by plants.

Contamination by uranium (U) occurs principally at U mining and processing sites. Uranium can have tremendous environmental consequences, as it is highly toxic to a broad range of organisms and can be dispersed in both terrestrial and aquatic environments. Remediation strategies of U-contaminated soils have included physical and chemical procedures, which may be beneficial, but are costly and can lead to further environmental damage. Phytoremediation has been proposed as a promising alternative, which relies on the capacity of plants and their associated microorganisms to stabilize or extract contaminants from soils. In this paper, we review the role of a group of plant symbiotic fungi, i.e. arbuscular mycorrhizal fungi, which constitute an essential link between the soil and the roots. These fungi participate in U immobilization in soils and within plant roots and they can reduce root-to-shoot translocation of U. However, there is a need to evaluate these observations in terms of their importance for phytostabilization strategies.

Role and influence of mycorrhizal fungi on radiocesium accumulation by plants.

This review summarizes current knowledge on the contribution of mycorrhizal fungi to radiocesium immobilization and plant accumulation. These root symbionts develop extended hyphae in soils and readily contribute to the soil-to-plant transfer of some nutrients. Available data show that ecto-mycorrhizal (ECM) fungi can accumulate high concentration of radiocesium in their extraradical phase while radiocesium uptake and accumulation by arbuscular mycorrhizal (AM) fungi is limited. Yet, both ECM and AM fungi can transport radiocesium to their host plants, but this transport is low. In addition, mycorrhizal fungi could thus either store radiocesium in their intraradical phase or limit its root-to-shoot translocation. The review discusses the impact of soil characteristics, and fungal and plant transporters on radiocesium uptake and accumulation in plants, as well as the potential role of mycorrhizal fungi in phytoremediation strategies.