Displaying publications 21 - 40 of 305 in total

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  1. Leow CY, Willis C, Leow CH, Hofmann A, Jones M
    Mol Biochem Parasitol, 2019 12;234:111231.
    PMID: 31628972 DOI: 10.1016/j.molbiopara.2019.111231
    Schistosomes are parasitic blood flukes that infect approximately 250 million people worldwide. The disease known as schistosomiasis, is the second most significant tropical parasitic disease after malaria. Praziquantel is the only effective drug currently licensed for schistosomiasis and there are concerns about resistance to the drug. There has been much effort to develop vaccines against schistosomiasis to produce long-term protection in endemic regions. Surface-associated proteins, and in particular, those expressed in the body wall, or tegument, have been proposed as potential vaccine targets. Of these, annexins are thought to be of integral importance for the stability of this apical membrane system. Here, we present the structural and immunobiochemical characterization of four homologous annexins namely annexin B30, annexin B5a, annexin B7a and annexin B5b from S. mansoni. Bioinformatics analysis showed that there was no signal peptide predicted for any annexin in this study. Further analysis showed that each of all four annexin protein possesses a primary structure consisting of a short but variable N-terminal region and a long C-terminal core containing four homologous annexin repeats (I-IV), which contain five alpha-helices. The life cycle expression profile of each annexin was assessed using quantitative PCR. The results showed that the overall transcript levels of the each of four homologous annexins were relatively low in the egg stage, but increased gradually after the transition of cercariae (the invasive schistosome larvae) to schistosomula (the post-invasive larvae). Circular dichroism (CD) demonstrated that rAnnexin B30, rAnnexin B5a and rAnnexin 7a were folded, showing a secondary structure content rich in alpha-helices. The membrane binding affinity was enhanced when rAnnexin B30, rAnnexin B5a and rAnnexin 7a was incubated in the presence of Ca2+. All annexin members evaluated in this study were immunolocalized to the tegument, with immunoreactivity also occurring in cells and in muscle of adult parasites. All four recombinant annexins were immunoreactive and they were recognized by the sera of mice infected with S. mansoni. In conclusion, the overall results present the molecular characterization of annexin B30, annexin B5a, annexin B7a and annexin B5b from S. mansoni in host-parasite interactions and strongly suggest that the molecules could be useful candidates for vaccine or diagnostic development.
  2. Radhakrishnan H, Hartwig A, Charman WN, Llorente L
    Clin Exp Optom, 2015 Nov;98(6):527-34.
    PMID: 26450168 DOI: 10.1111/cxo.12296
    BACKGROUND: Differences in accommodation when reading Chinese, as compared to Latin, characters have been suggested to have a role in the higher prevalence of myopia in some Asian countries. Yeo and colleagues (Optom Vis Sci 2013; 90: 156-163) found that, in Chinese-literate children, accommodation was marginally more accurate (by less than 0.05 D), when reading Chinese text. This was attributed to the additional cognitive demand associated with interpreting the more complex Chinese symbols. The present study compared responses to single Chinese and Latin characters, while controlling for cognitive demand.
    METHODS: The monocular accommodative response was measured in Chinese-illiterate adults (10 emmetropes, mean spherical equivalent: -0.07 ± 0.42 D, age: 29.9 ± 4.2 years; 11 myopes, mean spherical equivalent: -4.28 ± 2.84 D, age: 31.7 ± 4.6 years) with an open-field autorefractor. Four Chinese and three Latin characters (approximately 1.15 degrees subtense) were individually presented on a display screen one metre away from the subject, while their vergence was varied over the range zero to 5.00 D using spectacle trial lenses. The slope and the accommodative error index (AEI) were calculated from the accommodative stimulus/response curves (ASRC).
    RESULTS: No statistically significant differences were found between refractive groups or among characters within the same refractive group in ARSC slopes (Latin: 0.87 ± 0.14 for myopes versus 0.81 ± 0.12 for emmetropes; Chinese: 0.84 ± 0.12 for myopes versus 0.85 ± 0.12 for emmetropes). No significant differences were found between characters in accommodative error index either (Latin, 0.78 ± 0.42 D for myopes versus 1.15 ± 0.72 D for emmetropes; Chinese, 0.74 ± 0.37 D for myopes versus 1.17 ± 0.83 D for emmetropes). However, accommodative error indices and accommodative errors were significantly higher for emmetropes.
    CONCLUSION: Under controlled cognitive demand, Chinese and Latin characters elicited similar responses in both individual refractive groups. This study fails to support the hypothesis that development of myopia in some Asian populations is associated with larger lags of accommodation when reading or viewing Chinese characters.
    Study site: Manchester, United Kingdom
  3. Hermawan AA, Teh KL, Talei A, Chua LHC
    J Environ Manage, 2021 Nov 01;297:113298.
    PMID: 34280854 DOI: 10.1016/j.jenvman.2021.113298
    The discharge of high levels of heavy metals into the environment is of concern due to its toxicity to aquatic life and potential human health impacts. Biofiltration systems have been used in urban environments to address nutrient contamination, but there is also evidence that such systems can be effective in reducing heavy metals concentration in stormwater. However, the accumulation pattern of heavy metals and lifespan of such systems, which are important in engineering design, have not been thoroughly explored. This study investigated the accumulation patterns of lead (Pb), copper (Cu), zinc (Zn), manganese (Mn), and iron (Fe), which are common in urban runoff, in non-vegetated filtration columns using three different types of filter media, namely sand (S), and mixtures of sand with fly ash (sand-fly ash mix, SF), and with zeolite (sand-zeolite mix, SZ). The columns were assessed in terms of infiltration rate, the mass of heavy metals accumulation at different depths, and formation of crust layer (schmutzdecke) at the surface. The results show that most of the heavy metals accumulated at the top 5-10 cm of the filter media. However, Zn was found adsorbed to a depth of 15 cm in S and SZ columns, while Mn and Fe were present in column S throughout the entire 30 cm depth of the filter media. The presence especially of Zn, Mn, and Fe in the deeper portions of the filter media before the top 5 cm layer reached its maximum adsorption capacity, hints that transport to the deeper layers is not necessarily dependent on saturation of the upper layers for these heavy metals. SF accumulated heavy metals most at the top 5 cm of the filter media layer, and retained twice the mass of heavy metals in the crust layer, compared to S and SZ columns. SF also yielded the lowest value of infiltration rate of 31 mm/h. Considering both metals accumulation and clogging potential of the filter media, the periodic maintenance of these systems is suggested to be approximately between 1.5 and 3 years.
  4. Kalckert A, Perera AT, Ganesan Y, Tan E
    Exp Brain Res, 2019 Jul;237(7):1821-1832.
    PMID: 31079236 DOI: 10.1007/s00221-019-05539-6
    The rubber hand illusion (RHI) is a perceptual phenomenon in which participants experience ownership over a fake model hand through synchronous visuotactile stimulation. Several studies have shown that the illusion occurs only when both hands are in close proximity to each other. In the present study, we systematically examined the role of relative position (lateral, distal) and distance (13-75 cm) of the model hand (with respect to participants' real hand) on illusion experience across both lateral and distal positions. Furthermore, we also compared different facets of the subjective illusion experience; the experience of the model hand being part of one's body (i.e., ownership) and the perceptual fusion of vision and touch (i.e., referral of touch). In two experiments we observed indications for a stronger illusion experiences in distal compared to lateral positions of identical distances, indicating that the illusory effects may vary as a function of the relative position of the hand. Our results also showed that manipulations of distance differently modulated both facets of the illusion. While ownership was restricted to near distances, referral of touch sensations remained stable at farther distances. These results are interpreted in relation to variations in sensory weighting across different planes.
  5. Bukhsh A, Lee SWH, Pusparajah P, Schmitt A, Khan TM
    Health Qual Life Outcomes, 2017 Oct 12;15(1):200.
    PMID: 29025432 DOI: 10.1186/s12955-017-0776-8
    BACKGROUND: Numerous study tools on diabetes self-care have been introduced; however, most existing tools do not show expectable and meaningful correlations with patients' glycaemic control. The Diabetes Self-Management Questionnaire (DSMQ) was designed to appraise self-care activities which can predict glycaemic control outcomes. However, this tool has not been validated in Pakistan. Therefore, the aim of this study was to translate and examine the psychometric properties of the Urdu version of DSMQ among type 2 diabetes patients.

    METHOD: Standard forward-backward translation was used to translate the DSMQ into Urdu language. A convenience sample of 130 patients with type 2 diabetes was collected to assess the Urdu version's psychometric properties. Reliability was assessed by Cronbach's coefficient α and validity was assessed using confirmatory factor analysis and criterion-related correlations.

    RESULTS: High internal consistency was found for all DSMQ scales (Sum scale: α = 0.96, Glucose Management: 0.91; Dietary Control: 0.88; Physical Activity: 0.89; Health-Care Use: 0.73). The DSMQ subscales showed significant correlations with HbA1c (Glucose Management: -0.75; Dietary Control: -0.76; Physical Activity: -0.71; Health-Care Use: -0.64; Sum Scale: -0.78; all p  0.05). Adequate fit to the data was achieved for single factor model after successively modelling all significant correlations between the items' error terms, with Chi2 = 106.6, df = 84, p = 0.049; TLI = 0.98, CFI = 0.99 and RMSEA = 0.05 (90% CI 0.01-0.07). Whereas a comparatively lower fit indices to data were observed in case of four factor model.

    CONCLUSION: The findings support the Urdu version of the DSMQ as a reliable and valid instrument for assessing self-care activities associated with glycaemic control in type 2 diabetes patients.
  6. Fiala B, Maschwitz U, Pong TY, Helbig AJ
    Oecologia, 1989 Jun;79(4):463-470.
    PMID: 28313479 DOI: 10.1007/BF00378662
    In the humid tropics of SE Asia there are some 14 myrmecophytic species of the pioneer tree genus Macaranga (Euphorbiaceae). In Peninsular Malaysia a close association exists between the trees and the small, non-stinging myrmicine Crematogaster borneensis. These ants feed mainly on food bodies provided by the plants and have their colonies inside the hollow internodes. In a ten months field study we were able to demonstrate for four Macaranga species (M. triloba, M. hypoleuca, M. hosei, M. hulletti) that host plants also benefit considerably from ant-occupation. Ants do not contribute to the nutrient demands of their host plant, they do, however, protect it against herbivores and plant competition. Cleaning behaviour of the ants results in the removal of potential hervivores already in their earliest developmental stages. Strong aggressiveness and a mass recruiting system enable the ants to defend the host plant against many herbivorous insects. This results in a significant decrease in leaf damage due to herbivores on ant-occupied compared to ant-free myrmecophytes as well as compared to non-myrmecophytic Macaranga species. Most important is the ants' defense of the host plant against plant competitors, especially vines, which are abundant in the well-lit pioneer habitats where Macaranga grows. Ants bite off any foreign plant part coming into contact with their host plant. Both ant-free myrmecophytes and non-myrmecophytic Macaranga species had a significantly higher incidence of vine growth than specimens with active ant colonies. This may be a factor of considerable importance allowing Macaranga plants to grow at sites of strongest competition.
  7. Gucciardi DF, Zhang CQ, Ponnusamy V, Si G, Stenling A
    J Sport Exerc Psychol, 2016 Apr;38(2):187-202.
    PMID: 27390084 DOI: 10.1123/jsep.2015-0320
    The aims of this study were to assess the cross-cultural invariance of athletes' self-reports of mental toughness and to introduce and illustrate the application of approximate measurement invariance using Bayesian estimation for sport and exercise psychology scholars. Athletes from Australia (n = 353, Mage = 19.13, SD = 3.27, men = 161), China (n = 254, Mage = 17.82, SD = 2.28, men = 138), and Malaysia (n = 341, Mage = 19.13, SD = 3.27, men = 200) provided a cross-sectional snapshot of their mental toughness. The cross-cultural invariance of the mental toughness inventory in terms of (a) the factor structure (configural invariance), (b) factor loadings (metric invariance), and (c) item intercepts (scalar invariance) was tested using an approximate measurement framework with Bayesian estimation. Results indicated that approximate metric and scalar invariance was established. From a methodological standpoint, this study demonstrated the usefulness and flexibility of Bayesian estimation for single-sample and multigroup analyses of measurement instruments. Substantively, the current findings suggest that the measurement of mental toughness requires cultural adjustments to better capture the contextually salient (emic) aspects of this concept.
  8. Syahrom A, Abdul Kadir MR, Harun MN, Öchsner A
    Med Eng Phys, 2015 Jan;37(1):77-86.
    PMID: 25523865 DOI: 10.1016/j.medengphy.2014.11.001
    Artificial bone is a suitable alternative to autografts and allografts, however their use is still limited. Though there were numerous reports on their structural properties, permeability studies of artificial bones were comparably scarce. This study focused on the development of idealised, structured models of artificial cancellous bone and compared their permeability values with bone surface area and porosity. Cancellous bones from fresh bovine femur were extracted and cleaned following an established protocol. The samples were scanned using micro-computed tomography (μCT) and three-dimensional models of the cancellous bones were reconstructed for morphology study. Seven idealised and structured cancellous bone models were then developed and fabricated via rapid prototyping technique. A test-rig was developed and permeability tests were performed on the artificial and real cancellous bones. The results showed a linear correlation between the permeability and the porosity as well as the bone surface area. The plate-like idealised structure showed a similar value of permeability to the real cancellous bones.
  9. Syahrom A, Abdul Kadir MR, Abdullah J, Öchsner A
    Med Eng Phys, 2013 Jun;35(6):792-9.
    PMID: 22959618 DOI: 10.1016/j.medengphy.2012.08.011
    In the development of artificial cancellous bones, two major factors need to be considered: the integrity of the overall structure and its permeability. Whilst there have been many studies analysing the mechanical properties of artificial and natural cancellous bones, permeability studies, especially those using numerical simulation, are scarce. In this study, idealised cancellous bones were simulated from the morphological indices of natural cancellous bone. Three different orientations were also simulated to compare the anisotropic nature of the structure. Computational fluid dynamics methods were used to analyse fluid flow through the cancellous structures. A constant mass flow rate was used to determine the intrinsic permeability of the virtual specimens. The results showed similar permeability of the prismatic plate-and-rod model to the natural cancellous bone. The tetrakaidecahedral rod model had the highest permeability under simulated blood flow conditions, but the plate counterpart had the lowest. Analyses on the anisotropy of the virtual specimens showed the highest permeability for the horizontal orientation. Linear relationships were found between permeability and the two physical properties, porosity and bone surface area.
  10. Ladwig KH, Johar H, Miller I, Atasoy S, Goette A
    Sci Rep, 2023 Mar 31;13(1):5284.
    PMID: 37002346 DOI: 10.1038/s41598-023-32412-y
    The Covid-19 pandemic during its early phases posed significant psychological threats particularly for medical frontline personal. It is unclear whether the medical workforce with the passage of time has adapted to these threats or have generalized to wider medical settings. An online survey was conducted reaching 1476 physicians in Germany with valid data from 1327 participants. Depression and anxiety were screened with the PHQ-2 and the GAD-2. Among a subtotal of 1139 (86.6%) physicians reporting personal treatment experiences with Covid-19 patients, 553 (84.8%) worked in a private practice (PP) and 586 (88.3%) in a hospital (HP). Covid-19 provoked profound conflicts between professional and ethical values: more physicians in PPs than HPs reported external constraints on their medical care being in conflict with the code of medical ethics (39.1 vs. 34.4%, p 
  11. Kunzmann A, Todinanahary G, Msuya FE, Alfiansah Y
    Trop Life Sci Res, 2023 Sep;34(3):279-302.
    PMID: 37860099 DOI: 10.21315/tlsr2023.34.3.15
    Aquaculture is still in early development in Madagascar and Tanzania, while in Indonesia, aquaculture has a long history. In Madagascar, villagers are farming seaweed and sea cucumbers, as part of small-scale community-based aquaculture (CBA). They followed a contractual model between a private farming company and farmers. Local non-governmental organisations (NGOs) and public institutions in Madagascar jointly strive to reverse the trend of ongoing anthropogenic coastal degradation. In Tanzania, the cultivation of red seaweeds has been established for over 30 years, with declining production attributed to climate change. While shrimp farming still involves, to some extent, clearing of mangroves in Tanzania, seaweed culture has only mild impact on coastal ecosystems. Farming areas provide shelter and habitat for juvenile fish, crabs and other organisms. Therefore, NGOs ask for support to improve culture methods. Various problems and shortcomings in Indonesia have been clearly identified, including issues related to new aquaculture areas, pollutants, emerging diseases, insufficient broodstock and fry supply, as well as a lack of technology and manpower. To address these challenges and ensure the growth of aquaculture production, the government has implemented national policies and established training and broodstock centers throughout the country. In Madagascar, the CBA programme stands out as a success story and can serve as a template for other coastal regions and countries. In Tanzania, the adoption of CBA model for co-culture could be the future. In Indonesia, due to a very long coastlines and complicated legislation, IMTA seems to be particularly suitable, as successfully tested in model regions.
  12. Wilting A, Fischer F, Abu Bakar S, Linsenmair KE
    BMC Ecol, 2006;6:16.
    PMID: 17092347
    The continued depletion of tropical rainforests and fragmentation of natural habitats has led to significant ecological changes which place most top carnivores under heavy pressure. Various methods have been used to determine the status of top carnivore populations in rainforest habitats, most of which are costly in terms of equipment and time. In this study we utilized, for the first time, a rigorous track classification method to estimate population size and density of clouded leopards (Neofelis nebulosa) in Tabin Wildlife Reserve in north-eastern Borneo (Sabah). Additionally, we extrapolated our local-scale results to the regional landscape level to estimate clouded leopard population size and density in all of Sabah's reserves, taking into account the reserves' conservation status (totally protected or commercial forest reserves), their size and presence or absence of clouded leopards.
  13. Abdullah WZW, Mackey BM, Karatzas KAG
    J Food Prot, 2018 Jan;81(1):93-104.
    PMID: 29271685 DOI: 10.4315/0362-028X.JFP-17-190
    Salmonella is an important foodborne pathogen, whose ability to resist stress and survive can vary among strains. This variability is normally not taken into account when predictions are made about survival in foods with negative consequences. Therefore, we examined the contribution of variable phenotypic properties to survival under stress in 10 Salmonella serovars. One strain (Typhimurium 10) was intentionally RpoS-negative; however, another strain (Heidelberg) showed an rpoS mutation, rendering it inactive. We assessed an array of characteristics (motility, biofilm formation, bile resistance, acid resistance, and colony morphology) that show major variability among strains associated with a 10- to 19-fold difference between the highest and the lowest strain for most characteristics. The RpoS status of isolates did not affect variability in the characteristics, with the exception of resistance to NaCl, acetic acid, lactic acid, and the combination of acetic acid and salt, where the variability between the highest and the lowest strain was reduced to 3.1-fold, 1.7-fold, 2-fold, and 1.7-fold, respectively, showing that variability was significant among RpoS-positive strains. Furthermore, we also found a good correlation between acid resistance and lysine decarboxylase activity, showing its importance for acid resistance, and demonstrated a possible role of RpoS in the lysine decarboxylase activity in Salmonella.
  14. Leow CY, Willis C, Hofmann A, Jones MK
    Br J Pharmacol, 2015 Apr;172(7):1653-63.
    PMID: 25176442 DOI: 10.1111/bph.12898
    Neglected tropical diseases are a group of some 17 diseases that afflict poor and predominantly rural people in developing nations. One significant disease that contributes to substantial morbidity in endemic areas is schistosomiasis, caused by infection with one of five species of blood fluke belonging to the trematode genus Schistosoma. Although there is one drug available for treatment of affected individuals in clinics, or for mass administration in endemic regions, there is a need for new therapies. A prominent target organ of schistosomes, either for drug or vaccine development, is the peculiar epithelial syncytium that forms the body wall (tegument) of this parasite. This dynamic layer is maintained and organized by concerted activity of a range of proteins, among which are the abundant tegumentary annexins. In this review, we will outline advances in structure-function analyses of these annexins, as a means to understanding tegument cell biology in host-parasite interaction and their potential exploitation as targets for anti-schistosomiasis therapies.
  15. Tiede A, Abdul Karim F, Jiménez-Yuste V, Klamroth R, Lejniece S, Suzuki T, et al.
    Haematologica, 2021 07 01;106(7):1902-1909.
    PMID: 32327501 DOI: 10.3324/haematol.2019.241554
    During factor VIII prophylaxis for severe hemophilia A, bleeding risk increases with time when factor VIII activity is below 1%. Maintaining trough activity above 1% does not protect all patients from bleeding. The relationship between factor VIII activity during prophylaxis and bleeding risk has not been thoroughly studied. We investigated factor VIII activity and annualized bleeding rate for spontaneous bleeds during prophylaxis. A population pharmacokinetic model derived from three clinical trials was combined with dosing data and bleed information from patient diaries. Each patients' time on prophylaxis was divided into five categories of predicted activity (0-1%, >1-5%, >5-15%, >15-50%, and >50%). Exposure time, mean factor VIII activity, and bleed number (from patient diaries) were calculated for each activity category, and annualized bleeding rates estimated using negative binomial regression and a parametric model. Relationships between these bleeding rates and factor VIII activity were evaluated by trial phase (pivotal vs. extension) and age (adults/adolescents [≥12 years] vs. children [0-<12 years]). In total (N=187; 815 patient-years' exposure), factor VIII activity was predicted to reach >1% for 85.64% of the time. Annualized bleeding rate decreased as factor VIII activity increased in each trial phase and age group. However, for a given activity level, bleeding rate differed substantially by trial phase, and age. This suggests that bleeding risk can change over time and is influenced by factors independent of factor VIII pharmacokinetics and trough levels. Target trough and prophylactic regimen should consider patient age, joint disease activity, and other bleeding risk determinants.
  16. Rahmat RF, Andreas TSM, Fahmi F, Pasha MF, Alzahrani MY, Budiarto R
    J Healthc Eng, 2019;2019:5810540.
    PMID: 31316743 DOI: 10.1155/2019/5810540
    Compression, in general, aims to reduce file size, with or without decreasing data quality of the original file. Digital Imaging and Communication in Medicine (DICOM) is a medical imaging file standard used to store multiple information such as patient data, imaging procedures, and the image itself. With the rising usage of medical imaging in clinical diagnosis, there is a need for a fast and secure method to share large number of medical images between healthcare practitioners, and compression has always been an option. This work analyses the Huffman coding compression method, one of the lossless compression techniques, as an alternative method to compress a DICOM file in open PACS settings. The idea of the Huffman coding compression method is to provide codeword with less number of bits for the symbol that has a higher value of byte frequency distribution. Experiments using different type of DICOM images are conducted, and the analysis on the performances in terms of compression ratio and compression/decompression time, as well as security, is provided. The experimental results showed that the Huffman coding technique has the capability to compress the DICOM file up to 1 : 3.7010 ratio and up to 72.98% space savings.
  17. Lim MC, Lukman KA, Giloi N, Jeffree MS, Saupin SS, Sidek ZN, et al.
    PLoS One, 2023;18(2):e0281217.
    PMID: 36812176 DOI: 10.1371/journal.pone.0281217
    Concerns about the health and safety of working populations as well as preventive actions to reduce heat-related illnesses and fatalities have intensified as global warming and heatwaves continue to rise as a result of climate change. This study aimed to translate and culturally-adapted the translated Malay version of the Heat Strain Score Index (HSSI) questionnaire so that it can be utilized as a screening tool for heat stress among the Malay-speaking outdoor workers. The original English version of HSSI underwent forward-backward translation and was cross-culturally adapted into the Malay language by bilingual translators based on established guidelines. The content validation was reviewed by a six-member expert committee including the representative of outdoor workers. Face validation was carried out among 10 outdoor workers involved with various work tasks. Psychometric analysis was conducted based on a cross-sectional study among 188 workers who were eligible. Exploratory Factor Analysis (EFA) was used for construct validity while internal consistency reliability was performed using Cronbach's alpha. The interclass correlation coefficient (ICC) was used to calculate the test-retest reliability. Both content and face validity were acceptable with the overall content validity index being 1.00, while the universal face validity index was 0.83. The factor analysis using varimax rotation extracted four factors which explained 56.32% of the cumulative percentage of variance and factor loading ranging from 0.415 to 0.804. The internal consistency reliability was acceptable with Cronbach's alpha ranging from 0.705 to 0.758 for all the factors. The overall ICC value was 0.792 (95% CI; 0.764-0.801) which signifies good reliability. The findings from this study indicate that the Malay version of HSSI is a reliable and culturally-adapted instrument. Further validation is needed so that it can be used extensively assess the heat stress among susceptible Malay-speaking outdoor workers in Malaysia who are exposed to hot humid environments.
  18. Wank I, Mittmann C, Kreitz S, Chestnykh D, Mühle C, Kornhuber J, et al.
    Neuropharmacology, 2024 Apr 16;253:109948.
    PMID: 38636728 DOI: 10.1016/j.neuropharm.2024.109948
    Alcohol consumption is a widespread phenomenon throughout the world. However, how recreational alcohol use evolves into alcohol use disorder (AUD) remains poorly understood. The Smpd3 gene and its coded protein neutral sphingomyelinase (NSM) are associated with alcohol consumption in humans and alcohol-related behaviors in mice, suggesting a potential role in this transition. Using multiparametric magnetic resonance imaging, we characterized the role of NSM in acute and chronic effects of alcohol on brain anatomy and function in female mice. Chronic voluntary alcohol consumption (16 vol% for at least 6 days) affected brain anatomy in WT mice, reducing regional structure volume predominantly in cortical regions. Attenuated NSM activity prevented these anatomical changes. Functional MRI linked these anatomical adaptations to functional changes: Chronic alcohol consumption in mice significantly modulated resting state functional connectivity (RS FC) in response to an acute ethanol challenge (i.p. bolus of 2 g kg-1) in heterozygous NSM knockout (Fro), but not in WT mice. Acute ethanol administration in alcohol-naïve WT mice significantly decreased RS FC in cortical and brainstem regions, a key finding that was amplified in Fro mice. Regarding direct pharmacological effects, acute ethanol administration increased the regional cerebral blood volume (rCBV) in many brain areas. Here, chronic alcohol consumption otherwise attenuated the acute rCBV response in WT mice but enhanced it in Fro mice. Altogether, these findings suggest a differential role for NSM in acute and chronic functional brain responses to alcohol. Therefore, targeting NSM may be useful in the prevention or treatment of AUD.
  19. Zainal H, Rolf A, Zhou H, Vasquez M, Escher F, Keller T, et al.
    PMID: 39191369 DOI: 10.1016/j.jocmr.2024.101087
    AIMS: Myocardial inflammation is increasingly detected non-invasively by tissue mapping with cardiovascular magnetic resonance (CMR). Intraindividual agreement with endomyocardial biopsy (EMB) or marker of myocardial injury, high-sensitive troponin (hs-cTnT) in patients with clinically suspected viral myocarditis not understood.

    METHODS AND RESULTS: Prospective multicentre study of consecutive patients with clinically suspected myocarditis who underwent blood testing for hs-cTnT, CMR and EMB as a part of diagnostic work-up. EMB was considered positive based on immunohistological criteria in line with the ESC definitions. CMR diagnoses employed tissue mapping using sequence-specific cut-off for native T1 and T2 mapping; active inflammation was defined as T1≥2SD and T2≥2SD above the mean of normal range. Hs-cTnT of greater than 13.9ng/1 was considered significant. A total of 114 patients (age (mean±SD) 54±16, 65% males) were included, of which 79(69%) had positive EMB-criteria, 64(56%) CMR criteria, and a total of 58 (51%) positive troponin. Agreement between EMB and CMR diagnostic criteria was poor (CMR vs. ESC: AUCs: 0.51 (0.39-0.62)). The agreement between the significant hs-cTnT rise and CMR-based diagnosis of myocarditis was good (AUC: 0.84 (0.68-0.92); p<0.001), but poor for EMB (0.50 (0.40-0.61). Hs-cTnT was significantly associated with native T1 and T2, hs-CRP and NT-pro BNP (r=0.37, r=0.35, r=0.30, r=0.25 p<0.001), but not immunohistochemical criteria or viral presence.

    CONCLUSIONS: In clinically suspected viral myocarditis, all diagnostic approaches reflect the pathophysiological elements of myocardial inflammation, however the differing underlying drivers only partially overlap. The EMB and CMR diagnostic algorithms are neither interchangeable in terms of interpretation of myocardial inflammation nor in their relationship with myocardial injury.

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