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Standardising lipid testing and reporting in the United Kingdom; a joint statement by HEART UK and The Association for Laboratory Medicine
Get PDFAtherosclerotic cardiovascular disease remains a major cause of premature death in the UK. Lipid testing is a key tool used to assess cardiovascular risk and guide clinical management decisions. There are currently no national guidelines to provide evidence-based recommendations on lipid testing and reporting for UK laboratories and clinicians. Here we present consensus guidance, following a review of published evidence by a multidisciplinary group of UK experts across a range of laboratory and clinical services. Recommendations include: the composition of a standard lipid profile; indications for, and composition of, an enhanced lipid profile including apolipoprotein B and lipoprotein (a); use of the Sampson-NIH calculation for LDL-c estimation; and guidance on when to flag abnormal results. This consensus guidance on lipid testing and reporting in the UK has been endorsed by HEART UK and The Association for Laboratory Medicine
Ameliorated delivery of amphotericin B to macrophages using chondroitin sulfate surface-modified liposome nanoparticles
Get PDFBackground: The neglected tropical disease leishmaniasis has significant adverse effects from current treatments and limited therapeutic options are currently available. Objective: The aim of this study was to develop a surface-modified nano-liposomal drug delivery system, anchored with chondroitin sulfate (CS), to effectively transport Amphotericin B (AmB) to macrophages. Methods: Conventional liposome formulations (CL-F) and CS-coated surface-modified liposome formulations (CS-SML-F) were formulated by the thin film hydration method and characterized for particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency with long-term stability. In-vitro drug release using simulation medium, deformability index (DI) by using a polycarbonate membrane, and cell uptake studies among murine macrophages via flow cytometry were analyzed. Scanning and transmission electron microscopy were used to study the surface morphology and shape of the particles. Results: Optimized conventional liposome CL-F6, CL-F9 and surface-modified liposomes CS-SML-F6 and CS-SML-F9 exhibited particle size diameters around 280 nm with a PDI of approximately 0.3 over six months of storage at 5 °C, maintaining stable surface charge (circa −30 mV). Sustained drug release peaked between 4 and 12 h and surface morphology showed a uniform distribution of spherical liposome particles. Cell uptake measured by flow cytometry showed the highest rate of macrophage targeting by the CS-SML-Fs. Conclusion: These findings have demonstrated that CS surface-modification has enhanced nanoparticle targeting to macrophage binding sites, particularly the cysteine-rich domain, potentially advancing macrophage-targeted drug delivery systems
Amentoflavone, New Hope against SARS-CoV-2: An Outlook through its Scientific Records and an in silico Study
Get PDFBackground: The plant-derived bioflavonoid amentoflavone has many important biological activities, among them remarkable antiviral effects, even against severe acute respiratory syndrome Coronavirus (SARS-CoV). It inhibits severe acute respiratory syndrome coronavirus (SARS-CoV) with an IC50 value of 8.3 μM. TMPRSS-2 activity is now thought to be the only factor necessary for cell entry and viral pathogenesis). In comparison, 3CLPRO is needed for COVID-19 replication and maturation during its life cycle. Aim: This study aims to perform an in silico study on amentoflavone activity against structural and non-structural severe acute respiratory syndrome coronavirus (SARS-CoV)-2 3-chymotrypsin-like protease (3CLPRO) and human transmembrane protease serine 2 (TMPRSS-2) proteins. Materials and Methods: Molecular docking studies were carried out using compounds against 3CLPRO and TMPRSS-2 proteins through the Swiss model, Uniport, PROCHECK, Swiss PDB viewer, PyMol, PyRx, and Desmond (Schrödinger package) computerized software. Results: Amentoflavone showed strong interactions -9.5 and -7.4 kcal/mol with 3CLPRO and TMPRSS2 proteins, respectively. In any case, it had higher binding affinities than currently approved antiviral drugs, which are underutilized in coronavirus disease (COVID-19). Conclusion: Amentoflavone may be one of the potential leads (drug candidate) to fight human coronavirus, including SARS-CoV-2. Further in vivo studies are needed to support the findings of this study
The effects of isolated game elements on adherence rates in food response inhibition training
Get PDFFood response inhibition training (food-RIT) is found to aid weight loss and reduce snacking of foods high in sugar, salt and fat. However, these interventions suffer from a lack of adherence, with gamification proposed as a solution to increase engagement. The effect of gamification is unclear, however, with a lack of research investigating the effects of single game elements in improving adherence to interventions. This study investigates whether isolated game elements (social or feedback) improve adherence, engagement and effectiveness of food-RIT compared to a standard non-gamified intervention. Two hundred and fifty-two participants (169 female) were randomly assigned to either non-gamified F-RIT, a training gamified with feedback elements or a training gamified with social elements. Participants completed measures of snacking frequency and food evaluation before and after a 14-day training period, with adherence and motivation recorded during this time. There were no significant effects of adding either feedback or social gamification elements on training adherence, motivation or effectiveness. There was no meaningful support for adding isolated game elements to food-RIT to improve intervention adherence, raising questions about the magnitude of simple gamification effects. Future research may benefit from systematically assessing the combined effects of multiple gamification elements
Predictive equation derived from 6,497 doubly labelled water measurements enables the detection of erroneous self-reported energy intake
Get PDFNutritional epidemiology aims to link dietary exposures to chronic disease, but the instruments for evaluating dietary intake are inaccurate. One way to identify unreliable data and the sources of errors is to compare estimated intakes with the total energy expenditure (TEE). In this study, we used the International Atomic Energy Agency Doubly Labeled Water Database to derive a predictive equation for TEE using 6,497 measures of TEE in individuals aged 4 to 96 years. The resultant regression equation predicts expected TEE from easily acquired variables, such as body weight, age and sex, with 95% predictive limits that can be used to screen for misreporting by participants in dietary studies. We applied the equation to two large datasets (National Diet and Nutrition Survey and National Health and Nutrition Examination Survey) and found that the level of misreporting was >50%. The macronutrient composition from dietary reports in these studies was systematically biased as the level of misreporting increased, leading to potentially spurious associations between diet components and body mass index
The ARK2N (C18ORF25) Genetic Variant Is Associated with Muscle Fiber Size and Strength Athlete Status
Get PDFBackground: Data on the genetic factors contributing to inter-individual variability in muscle fiber size are limited. Recent research has demonstrated that mice lacking the Arkadia (RNF111) N-terminal-like PKA signaling regulator 2N (Ark2n; also known as C18orf25) gene exhibit reduced muscle fiber size, contraction force, and exercise capacity, along with defects in calcium handling within fast-twitch muscle fibers. However, the role of the ARK2N gene in human muscle physiology, and particularly in athletic populations, remains poorly understood. The aim of this study was threefold: (a) to compare ARK2N gene expression between power and endurance athletes; (b) to analyze the relationship between ARK2N gene expression and muscle fiber composition; and (c) to investigate the association between the functional variant of the ARK2N gene, muscle fiber size, and sport-related phenotypes. Results: We found that ARK2N gene expression was significantly higher in power athletes compared to endurance athletes (p = 0.042) and was positively associated with the proportion of oxidative fast-twitch (type IIA) muscle fibers in untrained subjects (p = 0.017, adjusted for age and sex). Additionally, we observed that the ARK2N rs6507691 T allele, which predicts high ARK2N gene expression (p = 3.8 × 10−12), was associated with a greater cross-sectional area of fast-twitch muscle fibers in strength athletes (p = 0.015) and was over-represented in world-class strength athletes (38.6%; OR = 2.2, p = 0.023) and wrestlers (33.8%; OR = 1.8, p = 0.044) compared to controls (22.0%). Conclusions: In conclusion, ARK2N appears to be a gene specific to oxidative fast-twitch myofibers, with its functional variant being associated with muscle fiber size and strength-athlete status
Interaction between the supernova remnant W44 and the infrared dark cloud G034.77-00.55: Shock induced star formation
Get PDFContext. We have studied the dense gas morphology and kinematics towards the infrared dark cloud (IRDC) G034.77-00.55, shock-interacting with the SNR W44, to identify evidence of early-stage star formation induced by the shock. Aims. We used high angular resolution N2H+(1−0) images across G034.77-00.55, obtained with the Atacama Large Millimeter/sub-Millimeter Array. N2H+ is a well-known tracer of dense and cold material, optimal for identifying gas that has the highest potential to harbour star formation. Methods. The N2H+ emission is distributed in two elongated structures, one towards the dense ridge at the edge of the source and one towards the inner cloud. Both elongations are spatially associated with well-defined mass-surface density features. The velocities of the gas in the two structures (i.e. 38–41 km s−1 and 41–43 km s−1) are consistent with the lowest velocities of the J- and C-type parts, respectively, of the SNR-driven shock. A third velocity component is present at 43–45.5 km s–1. The dense gas shows a fragmented morphology with core-like fragments at scales consistent with the Jeans lengths, masses of ~1–20 M⊙, densities of (n(H2)≥105 cm–3) sufficient to host star formation in free-fall timescales (a few 104 yr), and with virial parameters that suggest a possible collapse. Results. The W44 driven shock may have swept up the encountered material, which is now seen as a dense ridge, almost detached from the main cloud, and an elongation within the inner cloud, well constrained in both N2H+ emission and mass surface density. This shock compressed material may have then fragmented into cores that are either in a starless or pre-stellar stage. Additional observations are needed to confirm this scenario and the nature of the cores
The JWST-PRIMAL archival survey A JWST/NIRSpec reference sample for the physical properties and Lyman-α absorption and emission of ∼600 galaxies at z = 5.0 − 13.4
Get PDFContext. One of the surprising early findings with JWST has been the discovery of a strong “roll-over” or a softening of the absorption edge of Lyα in a large number of galaxies at z ≳ 6, in addition to systematic offsets from photometric redshift estimates and fundamental galaxy scaling relations. This has been interpreted as strong cumulative damped Lyα absorption (DLA) wings from high column densities of neutral atomic hydrogen (H I), signifying major gas accretion events in the formation of these galaxies. Aims. To explore this new phenomenon systematically, we assembled the JWST/NIRSpec PRImordial gas Mass AssembLy (PRIMAL) legacy survey of 584 galaxies at z = 5.0 − 13.4, designed to study the physical properties and gas in and around galaxies during the reionization epoch. Methods. We characterized this benchmark sample in full and spectroscopically derived the galaxy redshifts, metallicities, star formation rates, and ultraviolet (UV) slopes. We defined a new diagnostic, the Lyα damping parameter DLyα, to measure and quantify the net effect of Lyα emission strength, the H I fraction in the intergalactic medium, or the local H I column density for each source. The JWST-PRIMAL survey is based on the spectroscopic DAWN JWST Archive (DJA-Spec). We describe DJA-Spec in this paper, detailing the reduction methods, the post-processing steps, and basic analysis tools. All the software, reduced spectra, and spectroscopically derived quantities and catalogs are made publicly available in dedicated repositories. Results. We find that the fraction of galaxies showing strong integrated DLAs with NHI > 1021 cm−2 only increases slightly from ≈60% at z ≈ 6 up to ≈65 − 90% at z > 8. Similarly, the prevalence and prominence of Lyα emission is found to increase with decreasing redshift, in qualitative agreement with previous observational results. Strong Lyα emitters (LAEs) are predominantly found to be associated with low-metallicity and UV faint galaxies. By contrast, strong DLAs are observed in galaxies with a variety of intrinsic physical properties, but predominantly at high redshifts and low metallicities. Conclusions. Our results indicate that strong DLAs likely reflect a particular early assembly phase of reionization-era galaxies, at which point they are largely dominated by pristine H I gas accretion. At z = 8 − 10, this gas gradually cools and forms into stars that ionize their local surroundings, forming large ionized bubbles and producing strong observed Lyα emission at z < 8
The effects of autistic traits in adolescents on the efficacy of paediatric Intensive Interdisciplinary Pain Treatment (IIPT)
Get PDFAutistic adolescents are at greater risk of chronic pain, but it is unclear how autistic features may relate to individual aspects of chronic pain. As autism traits exist in the general population as well, it is important to know if autistic traits could impact how effective chronic pain management is for adolescents. Here we examined autistic traits in 112 patients (12-18yrs) recruited from a UK national specialist adolescent pain rehabilitation programme. Participants completed screening questionnaires for autistic traits upon entry to the programme, as well as clinically recognised pain measures before and after the 3-week treatment program. Autistic traits predicted greater psychological challenges at treatment onset. Critically, autistic traits were not related to the magnitude of improvement in pain measures during the pain management program. Our study suggests that adolescents with greater autistic traits may benefit from existing pain rehabilitation programs at similar rates to their peers. Additionally, these data suggest no reason for therapeutic pessimism for autistic pain patients. We do however acknowledge that these data may differ in populations with an autistic diagnosis, and that barriers may still exist for autistic people in treatment for pain. PERSPECTIVE: Autistic traits were explored in patients undergoing an Intensive Interdisciplinary Pain Treatment (IIPT). Higher autistic traits correlated with more pain related psychological difficulties at intake. Autistic traits were not related to the magnitude of improvement following IIPT. Our data therefore suggests that autism should not be a barrier to IIPT. DATA AVAILABILITY: Data is held in the PAIRED Pain Rehabilitation Database: Bath and Bristol, individual data used in the current analyses are therefore not available
Remembering what did not happen: the role of hypnosis in memory recall and false memories formation
Get PDFMemory recall is subject to errors that can lead to the formation of false memories. Several factors affect memory processes, such as attention deficits or emotional distress. Additionally, cardiovascular diseases may lead to cognitive decline and memory loss, also increasing the occurrence of false events recall. Hypnosis has proved to affect the autonomic nervous system, positively impacting the cardiovascular response. Hypnosis has also been suggested as a tool to enhance memory and autobiographical events recall in both healthy and unhealthy individuals; however, this approach has led to several controversies. Particularly, the employment of hypnosis in autobiographical recall (hypnotic regression) has been accused of favouring the creation of false memories, leading to therapeutic fallacy. In this paper, we review the current literature on the mechanisms behind the creation of false memories and the role played by hypnosis in memory enhancement and false memory recall. The evidence here collected suggests that cardiovascular diseases affect brain health contributing to cognitive decline and memory impairments, also increasing the occurrence of false memories. Hypnosis induces an increase in parasympathetic activity and a decrease in sympathetic activity, suggesting a potential role in preventing some cardiovascular diseases, such as hypertension, which in turn may improve brain health. Additionally, hypnosis has been shown to have some effectiveness in enhancing memory functions, although contradictory findings reported by several studies make it difficult to draw proper conclusions. Hypnotic regression and guided imagery should be used with caution as they may unintentionally lead to false memory recall. Nevertheless, further studies are required to better understand the effects of hypnosis on the brain and the heart and how it can be used to enhance memory, especially in people with cognitive decline
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