Non-communicable airway disease and air pollution in three African Countries: Benin, Cameroon and The Gambia.

BACKGROUND: Air pollution exposure can increase the risk of development and exacerbation of chronic airway disease (CAD). We set out to assess CAD patients in Benin, Cameroon and The Gambia and to compare their measured exposures to air pollution. METHODOLOGY: We recruited patients with a diagnosis of CAD from four clinics in the three countries. We collected epidemiological, spirometric and home air pollution data. RESULTS: Of the 98 adults recruited, 56 were men; the mean age was 51.6 years (standard deviation ±17.5). Most (69%) patients resided in cities and ever smoking was highest in Cameroon (23.0%). Cough, wheeze and shortness of breath were reported across the countries. A diagnosis of asthma was present in 74.0%; 16.3% had chronic obstructive pulmonary disease and 4.1% had chronic bronchitis. Prevalence of airflow obstruction was respectively 77.1%, 54.0% and 64.0% in Benin, Cameroon, and Gambia. Across the sites, 18.0% reported >5 exacerbations. The median home particulate matter less than 2.5 µm in diameter (PM2.5) was respectively 13.0 µg/m3, 5.0 µg/m3 and 4.4 µg/m3. The median home carbon monoxide (CO) exposures were respectively 1.6 parts per million (ppm), 0.3 ppm and 0.4 ppm. Home PM2.5 differed significantly between the three countries (P < 0.001) while home CO did not. CONCLUSION: Based on these results, preventive programmes should focus on ensuring proper spirometric diagnosis, good disease control and reduction in air pollution exposure.

CONTEXTE: L'exposition à la pollution de l'air peut accroître le risque de développement et d'aggravation des maladies chroniques des voies respiratoires (CAD). Nous avons entrepris d'évaluer les patients atteints de CAD au Bénin, au Cameroun et en Gambie et de comparer les niveaux d'exposition à la pollution de l'air qu'ils ont subis. MÉTHODOLOGIE: Nous avons sélectionné des patients ayant reçu un diagnostic de CAD dans quatre cliniques de ces trois pays. Nous avons collecté des informations épidémiologiques, des mesures spirométriques ainsi que des données sur la pollution de l'air à leur domicile. RÉSULTATS: En total, 98 individus adultes ont été sélectionnés pour cette étude. Parmi eux, 56 étaient de sexe masculin. L'âge moyen de ces participants était de 51,6 ans, avec un écart-type de ±17,5. La majorité des patients (69%) résidaient en milieu urbain, tandis que le taux de tabagisme le plus élevé était observé au Cameroun (23,0%). Les symptômes de toux, de respiration sifflante et d'essoufflement ont été rapportés dans tous les pays. Parmi les patients, 74% ont reçu un diagnostic d'asthme, 16,3% souffraient de maladie pulmonaire obstructive chronique et 4,1% de bronchite chronique. L'obstruction des voies respiratoires était présente respectivement chez 77,1%, 54,0% et 64,0% des cas au Bénin, au Cameroun et en Gambie. Sur l'ensemble des sites, 18,0% ont signalé plus de cinq exacerbations. La médiane des PM2.5 à domicile était de 13,0 µg/m3, 5,0 µg/m3 et 4,4 µg/m3, respectivement. Les expositions médianes au monoxyde de carbone (CO) à domicile étaient de 1,6 ppm, 0,3 ppm et 0,4 ppm respectivement. Les PM2,5 à domicile présentaient des différences significatives entre les trois pays (P < 0,001), contrairement au CO à domicile. CONCLUSION: En se basant sur ces résultats, il est recommandé que les programmes de prévention se focalisent sur un dépistage spirométrique adéquat, une gestion efficace de la maladie et une diminution de l'exposition à la pollution atmosphérique.

Household carbon monoxide (CO) concentrations in a large African city: An unquantified public health burden?

Carbon monoxide (CO) is a poisonous gas produced by incomplete combustion of carbon-based fuels that is linked to mortality and morbidity. Household air pollution from burning fuels on poorly ventilated stoves can lead to high concentrations of CO in homes. There are few datasets available on household concentrations of CO in urban areas of sub-Saharan African countries. CO was measured every minute over 24 h in a sample of homes in Nairobi, Kenya. Data on household characteristics were gathered by questionnaire. Metrics of exposure were summarised and analysis of temporal changes in concentration was performed. Continuous 24-h data were available from 138 homes. The mean (SD), median (IQR) and maximum 24-h CO concentration was 4.9 (6.4), 2.8 (1.0-6.3) and 44 ppm, respectively. 50% of homes had detectable CO concentrations for 847 min (14h07m) or longer during the 24-h period, and 9% of homes would have activated a CO-alarm operating to European specifications. An association between a metric of total CO exposure and self-reported exposure to vapours >15 h per week was identified, however this were not statistically significant after adjustment for the multiple comparisons performed. Mean concentrations were broadly similar in homes from a more affluent area and an informal settlement. A model of typical exposure suggests that cooking is likely to be responsible for approximately 60% of the CO exposure of Nairobi schoolchildren. Household CO concentrations are substantial in Nairobi, Kenya, despite most homes using gas or liquid fuels. Concentrations tend to be highest during the evening, probably associated with periods of cooking. Household air pollution from cooking is the main source of CO exposure of Nairobi schoolchildren. The public health impacts of long-term CO exposure in cities in sub-Saharan Africa may be considerable and should be studied further.

Repeatability and reproducibility of cardiac manganese-enhanced magnetic resonance imaging.

Manganese-enhanced magnetic resonance imaging can provide a surrogate measure of myocardial calcium handling. Its repeatability and reproducibility are currently unknown. Sixty-eight participants: 20 healthy volunteers, 20 with acute myocardial infarction, 18 with hypertrophic and 10 with non-ischemic dilated cardiomyopathy underwent manganese-enhanced magnetic resonance imaging. Ten healthy volunteers were re-scanned at 3 months. Native T1 values and myocardial manganese uptake were assessed for intra and inter-observer repeatability. Scan-rescan reproducibility was assessed in ten healthy volunteers. Intra-observer and inter-observer correlation was excellent in healthy volunteers for mean native T1 mapping [Lin's correlation coefficient (LCC) 0.97 and 0.97 respectively] and myocardial manganese uptake (LCC: 0.99 and 0.96 respectively). Scan-rescan correlation for native T1 and myocardial manganese uptake was also excellent. Similarly, intra-observer correlations for native T1 and myocardial manganese uptake in patients with acute myocardial infarction (LCC: 0.97 and 0.97 respectively), hypertrophic (LCC: 0.98 and 0.97 respectively) and dilated cardiomyopathy (LCC: 0.99 and 0.95 respectively) were excellent. Limits of agreement were broader in patients with dilated cardiomyopathy. Manganese-enhanced magnetic resonance imaging has high repeatability and reproducibility in healthy myocardium and high repeatability in diseased myocardium. However, further study is needed to establish robustness in pathologies with diffuse myocardial fibrosis.

Measurement of SARS-CoV-2 in air and on surfaces in Scottish hospitals.

BACKGROUND: There are still uncertainties in our knowledge of the amount of SARS-CoV-2 virus present in the environment - where it can be found, and potential exposure determinants - limiting our ability to effectively model and compare interventions for risk management. AIM: This study measured SARS-CoV-2 in three hospitals in Scotland on surfaces and in air, alongside ventilation and patient care activities. METHODS: Air sampling at 200 L/min for 20 min and surface sampling were performed in two wards designated to treat COVID-19-positive patients and two non-COVID-19 wards across three hospitals in November and December 2020. FINDINGS: Detectable samples of SARS-CoV-2 were found in COVID-19 treatment wards but not in non-COVID-19 wards. Most samples were below assay detection limits, but maximum concentrations reached 1.7×103 genomic copies/m3 in air and 1.9×104 copies per surface swab (3.2×102 copies/cm2 for surface loading). The estimated geometric mean air concentration (geometric standard deviation) across all hospitals was 0.41 (71) genomic copies/m3 and the corresponding values for surface contamination were 2.9 (29) copies/swab. SARS-CoV-2 RNA was found in non-patient areas (patient/visitor waiting rooms and personal protective equipment changing areas) associated with COVID-19 treatment wards. CONCLUSION: Non-patient areas of the hospital may pose risks for infection transmission and further attention should be paid to these areas. Standardization of sampling methods will improve understanding of levels of environmental contamination. The pandemic has demonstrated a need to review and act upon the challenges of older hospital buildings meeting current ventilation guidance.

Particulate matter in aerosols produced by two last generation electronic cigarettes: a comparison in a real-world environment.

The design of e-cigarettes (e-cigs) is constantly evolving and the latest models can aerosolize using high-power sub-ohm resistance and hence may produce specific particle concentrations. The aim of this study was to evaluate the aerosol characteristics generated by two different types of electronic cigarette in real-world conditions, such as a sitting room or a small office, in number of particles (particles/cm3). We compared the real time and time-integrated measurements of the aerosol generated by the e-cigarette types Just Fog and JUUL. Real time (10s average) number of particles (particles/cm3) in 8 different aerodynamic sizes was measured using an optical particle counter (OPC) model Profiler 212-2. Tests were conducted with and without a Heating, Ventilating Air Conditioning System (HVACS) in operation, in order to evaluate the efficiency of air filtration. During the vaping sessions the OPC recorded quite significant increases in number of particles/cm3. The JUUL e-cig produced significantly lower emissions than Just Fog with and without the HVACS in operation. The study demonstrates the rapid volatility or change from liquid or semi-liquid to gaseous status of the e-cig aerosols, with half-life in the order of a few seconds (min. 4.6, max 23.9), even without the HVACS in operation. The e-cig aerosol generated by the JUUL proved significantly lower than that generated by the Just Fog, but this reduction may not be sufficient to eliminate or consistently reduce the health risk for vulnerable non e-cig users exposed to it.

Diurnal variability of fine-particulate pollution concentrations: data from 14 low- and middle-income countries.

BACKGROUND: Scientific understanding of indoor air pollution is predominately based on research carried out in cities in high-income countries (HICs). Less is known about how pollutant concentrations change over the course of a typical day in cities in low- and middle-income countries (LMICs).OBJECTIVE: To understand how concentrations of fine particulate matter smaller than 2.5 microns in diameter (PM2.5) change over the course of the day outdoors (across a range of countries) and indoors (using measurements from Dhaka, Bangladesh).DESIGN: Data on PM2.5 concentrations were gathered from 779 households in Dhaka as part of the MCLASS II (Muslim Communities Learning About Second-hand Smoke in Bangladesh) project, and compared to outdoor PM2.5 concentrations to determine the temporal variation in exposure to air pollution. Hourly PM2.5 data from 23 cities in 14 LMICs, as well as London (UK), Paris (France) and New York (NY, USA), were extracted from publicly available sources for comparison.RESULTS: PM2.5 in homes in Dhaka demonstrated a similar temporal pattern to outdoor measurements, with greater concentrations at night than in the afternoon. This pattern was also evident in 19 of 23 LMIC cities.CONCLUSION: PM2.5 concentrations are greater at night than during the afternoon in homes in Dhaka. Diurnal variations in PM2.5 in LMICs is substantial and greater than in London, Paris or New York. This has implications for public health community approaches to health effects of air pollution in LMICs.

'They only smoke in the house when I'm not in': understanding the limited effectiveness of a smoke-free homes intervention.

BACKGROUND: Children's second-hand smoke (SHS) exposure in the home is highest in socio-economically disadvantaged areas. Personalized household air-quality measurements can promote changes in smoking that reduce SHS exposure. The 'First Steps 2 Smoke-free' (FS2SF) intervention is the first to trial this approach delivered as part of health professionals' routine work. This paper reports the findings of qualitative interviews with participants that explored their experiences of the intervention and why outcomes varied. METHODS: 120 women were recruited from the NHS First Steps Programme, which supports disadvantaged mothers. They received either personalized feedback on their home air quality and advice on reducing SHS or standard SHS advice. Qualitative interviews with 15 mothers were analyzed thematically using the Capability, Opportunity, Motivation, Behaviour (COM-B) model. RESULTS: The intervention increased women's capability to change home-smoking behaviour, through increasing awareness and salience of SHS risks to their children, and motivation to act. However, taking effective action was constrained by their limited social and environmental opportunities, including others' smoking in the home. CONCLUSIONS: The FS2SF intervention was ineffective as it was unable to fully address the precarious, complex life circumstances that make creating a smoke-free home particularly difficult for women experiencing intersecting dimensions of disadvantage.

Manganese-enhanced magnetic resonance imaging in dilated cardiomyopathy and hypertrophic cardiomyopathy.

AIMS: The aim of this study is to quantify altered myocardial calcium handling in non-ischaemic cardiomyopathy using magnetic resonance imaging. METHODS AND RESULTS: Patients with dilated cardiomyopathy (n = 10) or hypertrophic cardiomyopathy (n = 17) underwent both gadolinium and manganese contrast-enhanced magnetic resonance imaging and were compared with healthy volunteers (n = 20). Differential manganese uptake (Ki) was assessed using a two-compartment Patlak model. Compared with healthy volunteers, reduction in T1 with manganese-enhanced magnetic resonance imaging was lower in patients with dilated cardiomyopathy [mean reduction 257 ± 45 (21%) vs. 288 ± 34 (26%) ms, P < 0.001], with higher T1 at 40 min (948 ± 57 vs. 834 ± 28 ms, P < 0.0001). In patients with hypertrophic cardiomyopathy, reductions in T1 were less than healthy volunteers [mean reduction 251 ± 86 (18%) and 277 ± 34 (23%) vs. 288 ± 34 (26%) ms, with and without fibrosis respectively, P < 0.001]. Myocardial manganese uptake was modelled, rate of uptake was reduced in both dilated and hypertrophic cardiomyopathy in comparison with healthy volunteers (mean Ki 19 ± 4, 19 ± 3, and 23 ± 4 mL/100 g/min, respectively; P = 0.0068). In patients with dilated cardiomyopathy, manganese uptake rate correlated with left ventricular ejection fraction (r2 = 0.61, P = 0.009). Rate of myocardial manganese uptake demonstrated stepwise reductions across healthy myocardium, hypertrophic cardiomyopathy without fibrosis and hypertrophic cardiomyopathy with fibrosis providing absolute discrimination between the healthy myocardium and fibrosed myocardium (mean Ki 23 ± 4, 19 ± 3, and 13 ± 4 mL/100 g/min, respectively; P < 0.0001). CONCLUSION: The rate of manganese uptake in both dilated and hypertrophic cardiomyopathy provides a measure of altered myocardial calcium handling. This holds major promise for the detection and monitoring of dysfunctional myocardium, with the potential for early intervention and prognostication.

HIV Prevention Method Preferences Within Sexual Partnerships Reported by HIV-Negative MSM and TW in Tijuana, Mexico.

To assess the potential for decreased condom use as pre-exposure prophylaxis (PrEP) is scaled-up in Latin America, we examined HIV prevention method preferences (neither PrEP nor condoms, condoms only, PrEP only, or PrEP with condoms) within 1302 sexual partnerships reported by 397 HIV-negative men who have sex with men (MSM) and transgender women (TW) in Tijuana, Mexico. Using PrEP with condoms (56%) was preferred to using condoms only (24%), using PrEP only (17%), and using neither PrEP nor condoms (3%). Compared to using condoms only, using PrEP only was preferred within primary (adjusted odds ratio [AOR] = 4.13, 95% confidence interval [CI] 1.92, 8.90) and condomless sex practicing (AOR = 6.97, 95% CI 3.92, 12.40) partnerships, suggesting PrEP use may not displace condom use among MSM and TW in Tijuana and other similar settings.

Oral and vaginal HIV pre-exposure prophylaxis product attribute preferences among female sex workers in the Mexico-US border region.

To assess the potential uptake of HIV pre-exposure prophylaxis (PrEP) products among female sex workers (FSWs) vulnerable to HIV infection, we examined the influence of product attributes on willingness to use products among 271 HIV-negative FSWs in Tijuana and Ciudad Juarez, Mexico (2016-2017). Via five-point Likert scale ratings, participants indicated their willingness to use hypothetical products with six attributes: formulation (pill, gel, liquid, or ring), frequency of use (daily, on-demand, or monthly), cost per use (10 or 200 pesos), effectiveness (40% or 80%), side effects (none or mild), and access point (healthcare clinic or non-governmental organization). Conjoint analysis was used to determine the impact of attributes on product ratings and identify preferred product attributes. Multinomial logistic regression was used to identify factors associated with formulation preferences. In both cities, formulation and frequency of use had the greatest impact on ratings. Participants in Ciudad Juarez indicated a strong preference for oral pills, whereas participants in Tijuana indicated roughly equal preferences for oral pills and vaginal gels. Monthly product use was preferred in both cities. Compared to preferring oral pills (38%), preferring vaginal gels (28%) was associated with practicing vaginal lubrication (adjusted odds ratio = 2.08; 95% confidence interval: 1.07-4.04). Oral PrEP may be acceptable to many FSWs in Tijuana and Ciudad Juarez; however, continued development of behaviorally-congruent vaginal PrEP products may also facilitate uptake and ensure sufficient coverage.

Manganese-Enhanced T1 Mapping in the Myocardium of Normal and Infarcted Hearts.

Background: Manganese-enhanced MRI (MEMRI) has the potential to identify viable myocardium and quantify calcium influx and handling. Two distinct manganese contrast media have been developed for clinical application, mangafodipir and EVP1001-1, employing different strategies to mitigate against adverse effects resulting from calcium-channel agonism. Mangafodipir delivers manganese ions as a chelate, and EVP1001-1 coadministers calcium gluconate. Using myocardial T1 mapping, we aimed to explore chelated and nonchelated manganese contrast agents, their mechanism of myocardial uptake, and their application to infarcted hearts. Methods: T1 mapping was performed in healthy adult male Sprague-Dawley rats using a 7T MRI scanner before and after nonchelated (EVP1001-1 or MnCl2 (22 µmol/kg)) or chelated (mangafodipir (22-44 µmol/kg)) manganese-based contrast media in the presence of calcium channel blockade (diltiazem (100-200 µmol/kg/min)) or sodium chloride (0.9%). A second cohort of rats underwent surgery to induce anterior myocardial infarction by permanent coronary artery ligation or sham surgery. Infarcted rats were imaged with standard gadolinium delayed enhancement MRI (DEMRI) with inversion recovery techniques (DEMRI inversion recovery) as well as DEMRI T1 mapping. A subsequent MEMRI scan was performed 48 h later using either nonchelated or chelated manganese and T1 mapping. Finally, animals were culled at 12 weeks, and infarct size was quantified histologically with Masson's trichrome (MTC). Results: Both manganese agents induced concentration-dependent shortening of myocardial T1 values. This was greatest with nonchelated manganese, and could be inhibited by 30-43% with calcium-channel blockade. Manganese imaging successfully delineated the area of myocardial infarction. Indeed, irrespective of the manganese agent, there was good agreement between infarct size on MEMRI T1 mapping and histology (bias 1.4%, 95% CI -14.8 to 17.1 P>0.05). In contrast, DEMRI inversion recovery overestimated infarct size (bias 11.4%, 95% CI -9.1 to 31.8 P=0.002), as did DEMRI T1 mapping (bias 8.2%, 95% CI -10.7 to 27.2 P=0.008). Increased manganese uptake was also observed in the remote myocardium, with remote myocardial ∆T1 inversely correlating with left ventricular ejection fraction after myocardial infarction (r=-0.61, P=0.022). Conclusions: MEMRI causes concentration and calcium channel-dependent myocardial T1 shortening. MEMRI with T1 mapping provides an accurate assessment of infarct size and can also identify changes in calcium handling in the remote myocardium. This technique has potential applications for the assessment of myocardial viability, remodelling, and regeneration.

Extracellular dsRNA induces a type I interferon response mediated via class A scavenger receptors in a novel Chinook salmon derived spleen cell line.

Despite increased global interest in Chinook salmon aquaculture, little is known of their viral immune defenses. This study describes the establishment and characterization of a continuous cell line derived from Chinook salmon spleen, CHSS, and its use in innate immune studies. Optimal growth was seen at 14-18 °C when grown in Leibovitz's L-15 media with 20% fetal bovine serum. DNA analyses confirmed that CHSS was Chinook salmon and genetically different from the only other available Chinook salmon cell line, CHSE-214. Unlike CHSE-214, CHSS could bind extracellular dsRNA, resulting in the rapid and robust expression of antiviral genes. Receptor/ligand blocking assays confirmed that class A scavenger receptors (SR-A) facilitated dsRNA binding and subsequent gene expression. Although both cell lines expressed three SR-A genes: SCARA3, SCARA4, and SCARA5, only CHSS appeared to have functional cell-surface SR-As for dsRNA. Collectively, CHSS is an excellent cell model to study dsRNA-mediated innate immunity in Chinook salmon.

Multimodality quantitative assessments of myocardial perfusion using dynamic contrast enhanced magnetic resonance and 15O-labelled water positron emission tomography imaging.

Kinetic modelling of myocardial perfusion imaging data allows the absolute quantification of myocardial blood flow (MBF) and can improve the diagnosis and clinical assessment of coronary artery disease (CAD). Positron emission tomography (PET) imaging is considered the reference standard technique for absolute quantification, whilst oxygen-15 (15O)-water has been extensively implemented for MBF quantification. Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) has also been used for MBF quantification and showed comparable diagnostic performance against (15O)-water PET studies. We investigated for the first time the diagnostic performance of two different PET MBF analysis softwares PMOD and Carimas, for obstructive CAD detection against invasive clinical standard methods in 20 patients with known or suspected CAD. Fermi and distributed parameter modelling-derived MBF quantification from DCE-MRI was also compared against (15O)-water PET, in a subgroup of 6 patients. The sensitivity and specificity for PMOD was significantly superior for obstructive CAD detection in both per vessel (0.83, 0.90) and per patient (0.86, 0.75) analysis, against Carimas (0.75, 0.65), (0.81, 0.70), respectively. We showed strong, significant correlations between MR and PET MBF quantifications (r=0.83-0.92). However, DP and PMOD analysis demonstrated comparable and higher haemodynamic differences between obstructive versus (no, minor or non)-obstructive CAD, against Fermi and Carimas analysis. Our MR method assessments against the optimum PET reference standard technique for perfusion analysis showed promising results in per segment level and can support further multi-modality assessments in larger patient cohorts. Further MR against PET assessments may help to determine their comparative diagnostic performance for obstructive CAD detection.

Physical activity levels in urban-based South African learners: A cross-sectional study of 7 348 participants.

BACKGROUND: Establishing profiles of physical activity (PA) is critical in tackling the chronic diseases associated with lack of PA and avoiding healthcare costs. OBJECTIVE: To investigate PA levels in urban-based South African (SA) primary school learners. METHODS: The Physical Activity Questionnaire for Older Children was completed by 7 348 learners (3 867 males and 3 481 females) aged 8 - 14 years, of whom 49% were white, 39% black and 12% from other ethnic groups. Differences in PA levels by ethnic origin and province were determined using an analysis of covariance after adjusting for gender (p<0.05). Bonferroni corrections controlled for multiple comparisons. A fitted regression model examined age-related differences in PA adjusting for province. RESULTS: Of SA learners aged 8 - 14 years, 57% (n=4 224) engaged in moderate levels of PA. Thirty-one percent (n=2 247) did not meet internationally recommended amounts of moderate to vigorous physical activity. Overall, males reported higher PA levels than females (p<0.0001). PA levels declined with age from 11 to 14 years by 14% and 20% in males and females, respectively. Black learners had higher PA levels than white learners (p=0.0039). There were also significant differences in PA levels between the provinces (p<0.0001). CONCLUSION: This study provides evidence of differences in PA levels between gender, age and ethnic groups, and between provinces. A targeted approach to increase PA in high-risk populations in SA is warranted. Increased PA will help reduce the risk of chronic diseases and will contribute to the health of SA's population and the growth of the country's economy.

Utility and cost evaluation of multiparametric magnetic resonance imaging for the assessment of non-alcoholic fatty liver disease.

BACKGROUND: Validated diagnostic tools that are accurate, cost effective and acceptable to patients are required for disease stratification and monitoring in NAFLD. AIMS: To investigate the performance and cost of multiparametric MRI alongside existing biomarkers in the assessment of NAFLD. METHODS: Adult patients undergoing standard of care liver biopsy for NAFLD were prospectively recruited at two UK liver centres and underwent multiparametric MRI, blood sampling and transient elastography withing 2 weeks of liver biopsy. Non-invasive markers were compared to histology as the gold standard. RESULTS: Data were obtained in 50 patients and 6 healthy volunteers. Corrected T1 (cT1) correlated with NAFLD activity score (ρ = 0.514, P < .001). cT1, enhanced liver fibrosis (ELF) test and liver stiffness differentiated patients with simple steatosis and NASH with AUROC (95% CI) of 0.69 (0.50-0.88), 0.87 (0.77-0.79) and 0.82 (0.70-0.94) respectively and healthy volunteers from patients with AUROC (95% CI) of 0.93 (0.86-1.00), 0.81 (0.69-0.92) and 0.89 (0.77-1.00) respectively. For the risk stratification of NAFLD, multiparametric MRI could save £150,218 per 1000 patients compared to biopsy. Multiparametric MRI did not discriminate between individual histological fibrosis stages in this population (P = .068). CONCLUSIONS: Multiparametric MRI accurately identified patients with steatosis, stratifies those with NASH or simple steatosis and reliably excludes clinically significant liver disease with superior negative predictive value (83.3%) to liver stiffness (42.9%) and ELF (57.1%). For the risk stratification of NAFLD, multiparametric MRI was cost effective and, combined with transient elastography, had the lowest cost per correct diagnosis.

Development and use of an Arctic charr cell line to study antiviral responses at extremely low temperatures.

Arctic charr (Salvelinus alpinus) are the northernmost distributed freshwater fish and can grow at water temperatures as low as 0.2 °C. Other teleost species have impaired immune function at temperatures that Arctic charr thrive in, and thus, charr may maintain immune function at these temperatures. In this study, a fibroblastic cell line, named ACBA, derived from the bulbus arteriosus (BA) of Arctic charr was developed for use in immune studies at various temperatures. ACBA has undergone more than forty passages at 18 °C over 3 years, while showing no signs of senescence-associated ß-galactosidase activity and producing nitric oxide. Remarkably, ACBA cells survived and maintained some mitotic activity even at 1 °C for over 3 months. At these low temperatures, ACBA also continued to produce MH class I proteins. After challenge with poly I:C, only antiviral Mx proteins were induced while MH proteins remained constant. When exposed to live viruses, ACBA was shown to permit viral infection and replication of IPNV, VHSV IVa and CSV at 14 °C. Yet at the preferred temperature of 4 °C, only VHSV IVa was shown to replicate within ACBA. This study provides evidence that Arctic charr cells can maintain immune function while also resisting infection with intracellular pathogens at low temperatures.

Brain Development in Fetuses of Mothers with Diabetes: A Case-Control MR Imaging Study.

BACKGROUND AND PURPOSE: Offspring exposed to maternal diabetes are at increased risk of neurocognitive impairment, but its origins are unknown. With MR imaging, we investigated the feasibility of comprehensive assessment of brain metabolism (1H-MRS), microstructure (DWI), and macrostructure (structural MRI) in third-trimester fetuses in women with diabetes and determined normal ranges for the MR imaging parameters measured. MATERIALS AND METHODS: Women with singleton pregnancies with diabetes (n = 26) and healthy controls (n = 26) were recruited prospectively for MR imaging studies between 34 and 38 weeks' gestation. RESULTS: Data suitable for postprocessing were obtained from 79%, 71%, and 46% of women for 1H-MRS, DWI, and structural MRI, respectively. There was no difference in the NAA/Cho and NAA/Cr ratios (mean [SD]) in the fetal brain in women with diabetes compared with controls (1.74 [0.79] versus 1.79 [0.64], P = .81; and 0.78 [0.28] versus 0.94 [0.36], P = .12, respectively), but the Cho/Cr ratio was marginally lower (0.46 [0.11] versus 0.53 [0.10], P = .04). There was no difference in mean [SD] anterior white, posterior white, and deep gray matter ADC between patients and controls (1.16 [0.12] versus 1.16 [0.08], P = .96; 1.54 [0.16] versus 1.59 [0.20], P = .56; and 1.49 [0.23] versus 1.52 [0.23], P = .89, respectively) or volume of the cerebrum (243.0 mL [22.7 mL] versus 253.8 mL [31.6 mL], P = .38). CONCLUSIONS: Acquiring multimodal MR imaging of the fetal brain at 3T from pregnant women with diabetes is feasible. Further study of fetal brain metabolism in maternal diabetes is warranted.

Does physical education influence eye-hand coordination? The Lifestyles of our Kids intervention study.

In Australian government-funded primary schools, the responsibility for physical education (PE) falls mainly on general classroom teachers, many of whom possess limited PE training. This study sought to examine the impact of specialist-taught PE on eye-hand coordination (EHC) development. In this 4-year cluster-randomized intervention, participants were 187 boys and 172 girls initially in grade 2 in 29 primary schools, where no school employed university-trained specialist PE teachers. In 13 (intervention) schools, specialist PE teachers conducted 268 PE classes (two 45-minute sessions/wk) from grade 2 to grade 6. The intervention was based on traditional PE educational objectives, including fundamental motor skills, but did not specifically focus on EHC. The remaining 16 (control) schools continued with common-practice PE taught by general classroom teachers (30-60 min/wk). EHC was measured by a ball throw and wall-rebound catch test and recorded at ages 8, 10, and 12 (SD 0.3) at ends of grades 2, 4, and 6, respectively. There was steady yearly improvement of EHC in both groups, but no evidence of any intervention effect in boys (P=.88) or girls (P=.20). The introduction of specialist-taught PE during 4 years of primary school did not influence EHC development. Considering evidence that classroom teachers make little contribution to PE in this jurisdiction, together with the steady progression of EHC over the 4 years, other influences such as organized sport, after-school activities, natural development, and parental instruction are conceivably more influential factors in EHC development during primary school years.

Assessment of myocardial fibrosis with T1 mapping MRI.

Myocardial fibrosis can arise from a range of pathological processes and its presence correlates with adverse clinical outcomes. Cardiac magnetic resonance (CMR) can provide a non-invasive assessment of cardiac structure, function, and tissue characteristics, which includes late gadolinium enhancement (LGE) techniques to identify focal irreversible replacement fibrosis with a high degree of accuracy and reproducibility. Importantly the presence of LGE is consistently associated with adverse outcomes in a range of common cardiac conditions; however, LGE techniques are qualitative and unable to detect diffuse myocardial fibrosis, which is an earlier form of fibrosis preceding replacement fibrosis that may be reversible. Novel T1 mapping techniques allow quantitative CMR assessment of diffuse myocardial fibrosis with the two most common measures being native T1 and extracellular volume (ECV) fraction. Native T1 differentiates normal from infarcted myocardium, is abnormal in hypertrophic cardiomyopathy, and may be particularly useful in the diagnosis of Anderson-Fabry disease and amyloidosis. ECV is a surrogate measure of the extracellular space and is equivalent to the myocardial volume of distribution of the gadolinium-based contrast medium. It is reproducible and correlates well with fibrosis on histology. ECV is abnormal in patients with cardiac failure and aortic stenosis, and is associated with functional impairment in these groups. T1 mapping techniques promise to allow earlier detection of disease, monitor disease progression, and inform prognosis; however, limitations remain. In particular, reference ranges are lacking for T1 mapping values as these are influenced by specific CMR techniques and magnetic field strength. In addition, there is significant overlap between T1 mapping values in healthy controls and most disease states, particularly using native T1, limiting the clinical application of these techniques at present.

Differential visceral blood flow in the hyperdynamic circulation of patients with liver cirrhosis.

BACKGROUND: With advancing liver disease and the development of portal hypertension, there are major alterations in somatic and visceral blood flow. Using phase-contrast magnetic resonance angiography, we characterised alterations in blood flow within the hepatic, splanchnic and extra-splanchnic circulations of patients with established liver cirrhosis. AIM: To compare blood flow in splanchnic and extra-splanchnic circulations in patients with varying degrees of cirrhosis and healthy controls. METHODS: In a single-centre prospective study, 21 healthy volunteers and 19 patients with established liver disease (Child's stage B and C) underwent electrocardiogram-gated phase-contrast-enhanced 3T magnetic resonance angiography of the aorta, hepatic artery, portal vein, superior mesenteric artery, and the renal and common carotid arteries. RESULTS: In comparison to healthy volunteers, resting blood flow in the descending thoracic aorta was increased by 43% in patients with liver disease (4.31 ± 1.47 vs. 3.31 ± 0.80 L/min, P = 0.011). While portal vein flow was similar (0.83 ± 0.38 vs. 0.77 ± 0.35 L/min, P = 0.649), hepatic artery flow doubled (0.50 ± 0.46 vs. 0.25 ± 0.15 L/min, P = 0.021) and consequently total liver blood flow increased by 30% (1.33 ± 0.84 vs. 1.027 ± 0.5 L/min, P = 0.043). In patients with liver disease, superior mesenteric artery flow was threefold higher (0.65 ± 0.35 vs. 0.22 ± 0.13 L/min, P < 0.001), while total renal blood flow was reduced by 40% (0.37 ± 0.14 vs. 0.62 ± 0.22 L/min, P < 0.001) and total carotid blood flow unchanged (0.62 ± 0.20 vs. 0.65 ± 0.13 L/min, P = 0.315). CONCLUSIONS: Rather than a generalised systemic hyperdynamic circulation, liver disease is associated with dysregulated splanchnic vasodilatation and portosystemic shunting that, while inducing a high cardiac output, causes compensatory extra-splanchnic vasoconstriction - the 'splanchnic steal' phenomenon. These circulatory disturbances may underlie many of the manifestations of advanced liver disease.