Quantifying acyl-chain diversity in isobaric compound lipids containing monomethyl branched-chain fatty acids.

Compound lipids comprise a diverse group of metabolites present in living systems, and metabolic- and environmentally-driven structural distinctions across this family is increasingly linked to biological function. However, methods for deconvoluting these often isobaric lipid species are lacking or require specialized instrumentation. Notably, acyl-chain diversity within cells may be influenced by nutritional states, metabolic dysregulation, or genetic alterations. Therefore, a reliable, validated method of quantifying structurally similar even-, odd-, and branched-chain acyl groups within intact compound lipids will be invaluable for gaining molecular insights into their biological functions. Here we demonstrate the chromatographic resolution of isobaric lipids containing distinct combinations of straight-chain and branched-chain acyl groups via ultra-high-pressure liquid chromatography (UHPLC)-mass spectrometry (MS) using a C30 liquid chromatography column. Using metabolically-engineered adipocytes lacking branched-keto acid dehydrogenase A (Bckdha), we validate this approach through a combination of fatty acid supplementation and metabolic tracing using monomethyl branched-chain fatty acids and valine. We observe resolution of numerous isobaric triacylglycerols and other compound lipids, demonstrating the resolving utility of this method. This approach strengthens our ability to quantify and characterize the inherent diversity of acyl chains across the lipidome.

The cold chain delivery of organs for transplantation: from research laboratories and individual enthusiasts to pan- global networks in 50 years.

It is some 50 years since the first published reports appeared of ex vivo preservation of organs for transplantation. Over the intervening decades, organ preservation strategies have become one essential component of world-wide clinical transplant services. In the formative years, translational research in organ hypothermic preservation was grappling with the questions about whether static or dynamic storage was preferable, and the practical implications of those choices. Those studies were also informing the newly expanding clinical transplant services. During the middle years, both preservation modalities were practiced by individual group choices. By the 2000s, the shift in donor demographics demanded a re-evaluation of organ preservation strategies, and now a new era of research and development is promoting adoption of new technologies. In this review we outline many important academic studies which have contributed to this successful history, and give profile to the increasing innovative approaches which are being evaluated for the future. Doi.org/10.54680/fr24310110112.

Going beyond video game consumption when considering Internet Gaming Disorder.

BACKGROUND: Recognizing the crucial importance of understanding the impact of video games on health in today's gaming-dominated world, our study aimed to investigate the relationship between gaming time and Internet Gaming Disorder (IGD). Despite the widespread assumption that a connection exists between both, previous studies have revealed highly variable associations, highlighting significant weaknesses in establishing a robust link. METHODS: To unravel this complex relationship, we recruited two independent samples of League of Legends players. We combined the collection of self-reported and actual gameplay data, together with assessments of mental health, personality traits, and cognitive abilities. RESULTS: Surprisingly, none of the gaming variables demonstrated a robust and stable association with IGD, regardless of whether players spent less than or more than 30 hours per week gaming-a threshold suggested by the American Psychiatric Association as a potential indicator of disordered gaming. Notably, mental health factors, such as anxiety, depression and ADHD, emerged as the most influential predictors of IGD. CONCLUSION: These findings, replicated across two independent samples, challenge the prevailing belief that limiting screen time alone effectively combats IGD. Instead, mental health factors play a crucial role in mitigating risks associated with gaming. Policies focusing solely on restricting screen time are insufficient in reducing the prevalence or symptoms of IGD. Rather, a comprehensive approach that considers mental health and key personality traits must be adopted to safeguard the well-being of individuals engaged in gaming.

The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.

The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.

The structure and development of explore-exploit decision making.

A critical component of human learning reflects the balance people must achieve between focusing on the utility of what they know versus openness to what they have yet to experience. How individuals decide whether to explore new options versus exploit known options has garnered growing interest in recent years. Yet, the component processes underlying decisions to explore and whether these processes change across development remain poorly understood. By contrasting a variety of tasks that measure exploration in slightly different ways, we found that decisions about whether to explore reflect (a) random exploration that is not explicitly goal-directed and (b) directed exploration to purposefully reduce uncertainty. While these components similarly characterized the decision-making of both youth and adults, younger participants made decisions that were less strategic, but more exploratory and flexible, than those of adults. These findings are discussed in terms of how people adapt to and learn from changing environments over time.Data has been made available in the Open Science Foundation platform (osf.io).

Occupational effects in patients with post-COVID-19 syndrome.

BACKGROUND: It is well recognized that some individuals experience persistent symptoms following an initial SARS-CoV-2 infection. Symptoms affect physical, cognitive and mental well-being and can adversely impact activities of daily living, including the ability to work. AIMS: To examine the impact of post-COVID-19 syndrome with respect to effects on quality of life and impact on work in a cohort of people referred to a 'Long COVID' service. METHODS: All triaged patients (over 18 years with symptoms more than 12 weeks since the initial infection) completed a symptom assessment questionnaire. Occupation and working status (at work, at work struggling with symptoms and off work) were also recorded. Impact on function and quality of life was assessed using the EQ5D5L questionnaire. RESULTS: A total of 214 patients (median age 51.0 years, 135 females) were seen from January to September 2021. Analysis of occupational status showed: 18% were working, 40% were working but struggling and 35% had stopped working due to symptoms. Those unable to work reported significantly more fatigue, a greater perception of the need for support and lower quality-of-life scores. CONCLUSIONS: This study shows the extensive impact of post-COVID-19 syndrome on the ability to return to work. Specific return-to-work guidance is needed to support a large proportion of those struggling with the condition. The involvement of the Occupational Health team should form part of the multidisciplinary, collaborative approach to support rehabilitation and improve long-term outcomes for this condition.

Childhood unpredictability and the development of exploration.

Early in development, the process of exploration helps children gather new information that fosters learning about the world. Yet, it is unclear how childhood experiences may influence the way humans approach new learning. What influences decisions to exploit known, familiar options versus trying a novel alternative? We found that childhood unpredictability, characterized by unpredictable caregiving and unstable living environments, was associated with reduced exploratory behavior. This effect holds while controlling for individual differences, including anxiety and stress. Individuals who perceived their childhoods as unpredictable explored less and were instead more likely to repeat previous choices (habitual responding). They were also more sensitive to uncertainty than to potential rewards, even when the familiar options yielded lower rewards. We examined these effects across multiple task contexts and via both in-person (N = 78) and online replication (N = 84) studies among 10- to 13-y-olds. Results are discussed in terms of the potential cascading effects of unpredictable environments on the development of decision-making and the effects of early experience on subsequent learning.

Combined positron emission tomography and contrast enhanced CT (PET/CeCT) is a feasible single investigation in the staging of oesophagogastric cancers: single-centre pilot study experience during the COVID-19 pandemic.

INTRODUCTION: Staging of oesophagogastric (OG) cancers usually involves endoscopy (OGD), and separate visits for contrast enhanced computed tomography (CeCT) and positron emission tomography (PET/CT). At the height of the COVID-19 pandemic, some of our patients underwent single-visit combined staging with PET/CeCT. We compare this novel pathway with standard separate imaging in time to completion of staging, to start of treatment, and cost. METHODS: We identified all patients discussed at our OG multidisciplinary team (MDT) meeting in 2020. Clinical records revealed dates of investigations and treatments. Data were tabulated in Excel, with statistical analysis in SPSS. All patients followed the same MDT process and image reviewing criteria. Costs were compared using prices supplied by finance departments. RESULTS: A total of 211 new patients were discussed at our MDT in 2020. Of these, 48 patients had combined PET/CeCT staging, and 68 had separate scans. Median time (interquartile range) in days from OGD to final imaging was 9 (6-23) for the combined group versus 21 (16-28) for the separate group (p≤0.001). Median time (days) from OGD to treatment start was 37 (29-52) for combined versus 55 (40-71) for separate (p≤0.001). No combined scans were of insufficient diagnostic quality for the MDT. PET/CeCT had a potential cost saving of £113 per patient. CONCLUSIONS: PET/CeCT allows accurate radiological staging of OG cancers with a single scan. Patients completed staging and started treatment faster, with a potential saving of £10,509 in one year. PET/CeCT has become standard staging at our trust, and we aim to incorporate radiotherapy planning images too.

Robust within-session modulations of IAT scores may reveal novel dynamics of rapid change.

The Implicit Association Test (IAT) is employed in the domain of social psychology as a measure of implicit evaluation. Participants in this task complete blocks of trials where they are asked to respond to categories and attributes (e.g., types of faces and types of words). Reaction times in different blocks sharing certain response combinations are averaged and then subtracted from blocks with other response combinations and then normalized, the result of which is taken as a measure indicating implicit evaluation toward or away from the given categories. One assumption of this approach is stationarity of response time distributions, or at a minimum, that temporal dynamics in response times are not theoretically relevant. Here we test these assumptions, examine the extent to which response times change within the IAT blocks and, if so, how trajectories of change are meaningful in relation to external measures. Using multiple data sets we demonstrate within-session changes in IAT scores. Further, we demonstrate that dissociable components in the trajectories of IAT performance may be linked to theoretically distinct processes of cognitive biases as well as behaviors. The present work presents evidence that IAT performance changes within the task, while future work is needed to fully assess the implications of these temporal dynamics.

Autonomic modulation, spontaneous baroreflex sensitivity and fatigue in young men after COVID-19.

Impaired autonomic modulation and baroreflex sensitivity (BRS) have been reported during and after COVID-19. Both impairments are associated with negative cardiovascular outcomes. If these impairments were to exist undetected in young men after COVID-19, they could lead to negative cardiovascular outcomes. Fatigue is associated with autonomic dysfunction during and after COVID-19. It is unclear if fatigue can be used as an indicator of impaired autonomic modulation and BRS after COVID-19. This study aims to compare parasympathetic modulation, sympathetic modulation, and BRS between young men who had COVID-19 versus controls and to determine if fatigue is associated with impaired autonomic modulation and BRS. Parasympathetic modulation as the high-frequency power of R-R intervals (lnHFR-R), sympathetic modulation as the low-frequency power of systolic blood pressure variability (LFSBP), and BRS as the -index were measured by power spectral density analysis. These variables were compared between 20 young men who had COVID-19 and 24 controls. Independent t-tests and Mann-Whitney U tests indicated no significant difference between the COVID-19 and the control group in: lnHFR-R, P=0.20; LFSBP, P=0.11, and -index, P=0.20. Fatigue was not associated with impaired autonomic modulation or BRS. There is no difference in autonomic modulations or BRS between young men who had COVID-19 compared to controls. Fatigue did not seem to be associated with impaired autonomic modulation or impaired BRS in young men after COVID-19. Findings suggest that young men might not be at increased cardiovascular risk from COVID-19-related dysautonomia and impaired BRS.

Multiple sclerosis health-related quality of life utility values from the UK MS register.

Background: New interventions for multiple sclerosis (MS) commonly require a demonstration of cost-effectiveness using health-related quality of life (HRQoL) utility values. The EQ-5D is the utility measure approved for use in the UK NHS funding decision-making. There are also MS-specific utility measures - e.g., MS Impact Scale Eight Dimensions (MSIS-8D) and MSIS-8D-Patient (MSIS-8D-P). Objectives: Provide EQ-5D, MSIS-8D and MSIS-8D-P utility values from a large UK MS cohort and investigate their association with demographic/clinical characteristics. Methods: UK MS Register data from 14,385 respondents (2011 to 2019) were analysed descriptively and using multivariable linear regression, with self-report Expanded Disability Status Scale (EDSS) scores. Results: The EQ-5D and MSIS-8D were both sensitive to differences in demographic/clinical characteristics. An inconsistency found in previous studies whereby mean EQ-5D values were higher for an EDSS score of 4 rather than 3 was not observed. Similar utility values were observed between MS types at each EDSS score. Regression showed EDSS score and age were associated with utility values from all three measures. Conclusions: This study provides generic and MS-specific utility values for a large UK MS sample, with the potential for use in cost-effectiveness analyses of treatments for MS.

Multiple timescales of learning indicated by changes in evidence-accumulation processes during perceptual decision-making.

Evidence accumulation models have enabled strong advances in our understanding of decision-making, yet their application to examining learning has not been common. Using data from participants completing a dynamic random dot-motion direction discrimination task across four days, we characterized alterations in two components of perceptual decision-making (Drift Diffusion Model drift rate and response boundary). Continuous-time learning models were applied to characterize trajectories of performance change, with different models allowing for varying dynamics. The best-fitting model included drift rate changing as a continuous, exponential function of cumulative trial number. In contrast, response boundary changed within each daily session, but in an independent manner across daily sessions. Our results highlight two different processes underlying the pattern of behavior observed across the entire learning trajectory, one involving a continuous tuning of perceptual sensitivity, and another more variable process describing participants' threshold of when enough evidence is present to act.

Realistic and complex visual chasing behaviors trigger the perception of intentionality.

We not only perceive the physical state of the environment, but also the causal structures underlying the physical state. Determining whether an object has intentionality is a key component of this process. Among all possible intentions, the intention that has arguably been studied the most is chasing-often via a reasonably simple and stereotyped computer algorithm ("heat-seeking"). The current study investigated the perception of multiple types of chasing approaches and thus whether it is the intention of chasing that triggers the perception of chasing, whether the chasing agent and the agent being chased play equally important roles, and whether the perception of chasing requires the presence of both agents. We implemented a well-studied wolf chasing a sheep paradigm where participants viewed recordings of a disc (the wolf) chasing another disc (the sheep) among other distracting discs. We manipulated the types of chasing algorithms, the density of the distractors, the target agent in the task, and the presence of the agent being chased. We found that the participants could successfully identify the chasing agent in all conditions where both agents were present, albeit with different levels of performance (e.g., participants were best at detecting the chasing agent when the chasing agent engaged in a direct chasing strategy and were worst at detecting a human-controlled chasing agent). This work therefore extends our understanding of the types of cues that are and are not utilized by the visual system to detect the chasing intention.

Working memory is supported by learning to represent items as actions.

Working memory is typically described as a set of processes that allow for the maintenance and manipulation of information for proximal actions, yet the "action" portion of this construct is commonly overlooked. In contrast, neuroscience-informed theories of working memory have emphasized the hierarchical nature of memory representations, including both goals and sensory representations. These two representational domains are combined for the service of actions. Here, we tested whether, as it is commonly measured (i.e., with computer-based stimuli and button-based responses), working memory involved the planning of motor actions (i.e., specific button presses). Next, we examined the role of motor plan learning in successful working memory performance. Results showed that visual working memory performance was disrupted by unpredictable motor mappings, indicating a role for motor planning in working memory. Further, predictable motor mappings were in fact learned over the course of the experiment, thereby causing the measure of working memory to be partially a measure of participants' ability to learn arbitrary associations between visual stimuli and motor responses. Such learning was not highly specific to certain mappings; in sequences of short tasks, participants improved in their abilities to learn to represent items as actions in working memory. We discuss implications for working memory theories in light of hierarchical structure learning and ecological validity.

Transcriptomic response and immunological responses to chimpanzee adenovirus- and MVA viral-vectored vaccines for RSV in healthy adults.

Cohorts of healthy younger adults (18-50yrs) and healthy older adults (60-75yrs) were immunized intramuscularly or intranasally with an adenovirus-vectored RSV vaccine (PanAd3-RSV) as a prime dose and boosted with PanAd3-RSV or a poxvirus-vectored vaccine (MVA-RSV) encoding the same insert. Whole blood gene expression was measured at baseline, 3- and 7-days post vaccination. Intramuscular prime vaccination with PanAd3-RSV induced differential expression of 643 genes (DEGs, FDR < 0.05). Intranasal prime vaccination with PanAd3-RSV did not induce any differentially expressed genes (DEGs) in blood samples at 3 days post vaccination. Intranasally primed participants showed greater numbers of DEGS on boosting than intramuscularly primed participants. The most highly enriched biological processes related to DEGs after both prime and boost vaccination were type-1 interferon related pathways, lymphocytic and humoral immune responses.

Development of a Novel Method of Assessing Potential Loss of Control in Internet Gaming Disorder.

As video game play has increased in popularity, so too have reports that a subset of individuals play games in a way that causes negative consequences to their lives, which has resulted in the proposed inclusion of Internet Gaming Disorder (IGD) as a formal mental health diagnosis. Given the mass popularity of video games, it is critical that screening materials for this proposed disorder are sufficiently sensitive to ensure that individuals who suffer harm are identified, while those who do not are not mislabeled as such. Here we examined the extent to which participants' responses to a typical IGD questionnaire predicted academic behaviors that could be associated with harm. We recruited 42 college students and tracked their gaming and studying habits weekly over the course of one semester, taking particular note of weeks in which participants did or did not have exams. We predicted that college students overall would spend less time engaging with video games and more time with academics when they had exams, but such modulations would be smaller among individuals with more initial IGD symptoms (i.e., the "more IGD symptoms" group, as compared to the "fewer IGD symptoms" group, would show loss of control). We did not find that college students overall spent less time engaging with video games and more time with academics when they had exams, but post-hoc effect size analyses indicated that our study was underpowered. Implications of potential results using this methodology are discussed and estimates of powerful sample sizes are provided.

A gutsy performance: the potential for supplementation of short-chain fatty acids to benefit athletic health, exercise performance, and recovery.

The gut microbiome is known to play an important role in the day-to-day physiology and health of the human host. It is, therefore, not surprising that there is interest surrounding the gut microbiome and its potential to benefit athletic health and performance. This has, in part, been driven by the consideration that gut bacterial by-products (i.e. metabolic waste) could be harnessed by the host and utilised for a beneficial outcome. The concept of harnessing bacterial metabolites as beneficial health modulators has developed the theory of leveraging short-chain fatty acids (SCFAs) as novel supplements for enhancing athletic performance. This review discusses the current literature investigating SCFA administration in cellular, animal, and human models, with the aim of linking the demonstrated physiological/biochemical mechanisms to potential exercise/athletic benefit. In addition, practical implications and factors relating to SCFA-supplementation in athletic populations are considered. The literature demonstrates a tangible rationale that SCFAs can have a positive impact on human physiology to afford benefits to the athletic population. These advantages include the capacity to improve respiratory immunity to combat elevated levels/severity of upper respiratory tract infections often reported in athletes; the blunting of pro-inflammatory and pro-fibrotic pathways to aid in exercise recovery; and the role of SCFAs as usable energy sources and metabolism modulators to fuel exercise and improve performance and/or endurance capacity. However, there is currently minimal research completed in human participants and thus further investigations into the direct benefit of SCFAs in exercise performance and/or recovery-based studies are required.

Expectation effects in working memory training.

There is a growing body of research focused on developing and evaluating behavioral training paradigms meant to induce enhancements in cognitive function. It has recently been proposed that one mechanism through which such performance gains could be induced involves participants' expectations of improvement. However, no work to date has evaluated whether it is possible to cause changes in cognitive function in a long-term behavioral training study by manipulating expectations. In this study, positive or negative expectations about cognitive training were both explicitly and associatively induced before either a working memory training intervention or a control intervention. Consistent with previous work, a main effect of the training condition was found, with individuals trained on the working memory task showing larger gains in cognitive function than those trained on the control task. Interestingly, a main effect of expectation was also found, with individuals given positive expectations showing larger cognitive gains than those who were given negative expectations (regardless of training condition). No interaction effect between training and expectations was found. Exploratory analyses suggest that certain individual characteristics (e.g., personality, motivation) moderate the size of the expectation effect. These results highlight aspects of methodology that can inform future behavioral interventions and suggest that participant expectations could be capitalized on to maximize training outcomes.

Frequency and prediction of persistent urinary tract dilation in third trimester and postnatal urinary tract dilation in infants following diagnosis in second trimester.

OBJECTIVE: To determine the frequency, associated characteristics and prognostic value of the current risk stratification system for prenatal urinary tract dilation (UTD) for predicting persistent UTD in the third trimester and subsequent postnatal UTD in the infant, following diagnosis in the second trimester. METHODS: This was a single-institution retrospective cohort study of singleton pregnancies diagnosed with unilateral or bilateral UTD in the second trimester (before 28 weeks' gestation) with follow-up in the third trimester (at or after 28 weeks) between January 2017 and May 2019. In all cases, the prenatal diagnosis and stratification to low-risk (Grade A1) or increased-risk (Grade A2-3) UTD was made using the 2014 UTD consensus classification system. The primary outcomes included persistent prenatal UTD in the third trimester and postnatal UTD up to 6 months of age. We performed multivariable analysis to assess whether patient and second- and third-trimester sonographic characteristics (such as UTD laterality, other renal abnormality (calyceal dilation, abnormal parenchymal appearance, abnormal ureter or bladder) and anteroposterior renal pelvic diameter (AP-RPD)) were associated with the study outcomes. We assessed the predictive value of the current risk stratification system (Grade A1 vs Grade A2-3) in the second and third trimesters for persistent prenatal UTD and postnatal UTD using the area under the receiver-operating-characteristics curve (AUC). RESULTS: Of 26 620 second-trimester ultrasound assessments in the study period, 347 patients were diagnosed with UTD in the second trimester and had third-trimester follow-up, of whom 150/347 (43% (95% CI, 38-49%)) had persistent UTD in the third trimester. Among the 282/347 (81%) patients with postnatal follow-up available, the frequency of postnatal UTD was 49/282 (17% (95% CI, 13-22%)), and among the subset with persistent UTD in the third trimester, the frequency of postnatal UTD was 46/102 (45% (95% CI, 35-55%)). The most frequent postnatal diagnosis was transient UTD (76%), followed by duplicated collecting system (10%). Of infants originally diagnosed with UTD in the second trimester, 2% (7/347) required surgery; stated differently, of the 49 infants with postnatal UTD, 14% (7/49) required surgery. At second-trimester diagnosis, sonographic predictors of both persistent prenatal UTD and postnatal UTD included the presence of other renal abnormality and UTD Grade A2-3. At third-trimester follow-up, predictors of postnatal UTD were larger mean AP-RPD and UTD Grade A2-3, while all cases had other renal abnormality. Second-trimester diagnosis of UTD Grade A2-3 had satisfactory discrimination for predicting persistent prenatal UTD (AUC, 0.64 (95% CI, 0.58-0.70)) and postnatal UTD (AUC, 0.72 (95% CI, 0.63-0.81)), as did third-trimester UTD Grade A2-3 for predicting postnatal UTD (AUC, 0.66 (95% CI, 0.56-0.76)). CONCLUSIONS: The majority of cases of prenatal UTD did not result in postnatal UTD, and of those that did, very few required surgery. Follow-up third-trimester assessment after a second-trimester diagnosis of UTD is warranted. The current risk stratification system by UTD grade, based on the 2014 UTD consensus classification, can be used to predict postnatal UTD with fair accuracy. Further research is needed to determine whether the predictive performance of this system can be improved by incorporating additional risk factors. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.