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Growth failure in infants born with CHD is a persistent problem, even in those provided with adequate nutrition.
To summarise the published data describing the change in urinary metabolites during metabolic maturation in infants with CHD and identify pathways amenable to therapeutic intervention
Studies using qualitative or quantitative methods to describe urinary metabolites pre- and post-cardiac surgery and the relationship with growth in infants with CHD.
Sources of evidence:
NICE Healthcare Databases website was used as a tool for multiple searches.
347 records were identified, of which 37 were duplicates. Following the removal of duplicate records, 310 record abstracts and titles were screened for inclusion. The full texts of eight articles were reviewed for eligibility, of which only two related to infants with CHD. The studies included in the scoping review described urinary metabolites in 42 infants. A content analysis identified two overarching themes of metabolic variation predictive of neurodevelopmental abnormalities associated with anaerobic metabolism and metabolic signature associated with the impact on gut microbiota, inflammation, energy, and lipid digestion.
The results of this scoping review suggest that there are considerable gaps in our knowledge relating to metabolic maturation of infants with CHD, especially with respect to growth. Surgery is a key early life feature for CHD infants and has an impact on the developing biochemical phenotype with implications for metabolic pathways involved in immunomodulation, energy, gut microbial, and lipid metabolism. These early life fingerprints may predict those individuals at risk for neurodevelopmental abnormalities.
Reaction time variability (RTV) has been estimated using Gaussian, ex-Gaussian, and diffusion model (DM) indices. Rarely have studies examined interrelationships among these performance indices in childhood, and the use of reaction time (RT) computational models has been slow to take hold in the developmental psychopathology literature. Here, we extend prior work in adults by examining the interrelationships among different model parameters in the ABCD sample and demonstrate how computational models of RT can clarify mechanisms of time-on-task effects and sex differences in RTs.
This study utilized trial-level data from the stop signal task from 8916 children (9–10 years old) to examine Gaussian, ex-Gaussian, and DM indicators of RTV. In addition to describing RTV patterns, we examined interrelations among these indicators, temporal patterns, and sex differences.
There was no one-to-one correspondence between DM and ex-Gaussian parameters. Nonetheless, drift rate was most strongly associated with standard deviation of RT and tau, while nondecisional processes were most strongly associated with RT, mu, and sigma. Performance worsened across time with changes driven primarily by decreasing drift rate. Boys were faster and less variable than girls, likely attributable to girls’ wide boundary separation.
Intercorrelations among model parameters are similar in children as has been observed in adults. Computational approaches play a crucial role in understanding performance changes over time and can also clarify mechanisms of group differences. For example, standard RT models may incorrectly suggest slowed processing speed in girls that is actually attributable to other factors.
Symptoms related to chronic stress are prevalent and entail high societal costs, yet there is a lack of international consensus regarding diagnostics and treatment. A new stress-related diagnosis, exhaustion disorder, was introduced into the Swedish version of ICD-10 in 2005. Since then, use of the diagnosis has increased rapidly.
To create the first comprehensive synthesis of research on exhaustion disorder to report on the current state of knowledge. Preregistration: Open Science Framework (osf.io), doi 10.17605/OSF.IO/VFDKW.
A PRISMA-guided scoping review of all empirical studies of exhaustion disorder was conducted. Searches were run in the MEDLINE, PsycInfo and Web of Science databases. Data were systematically charted and thematically categorised based on primary area of investigation.
Eighty-nine included studies were sorted into six themes relating to lived experience of exhaustion disorder (n = 9), symptom presentation and course (n = 13), cognitive functioning (n = 10), biological measures (n = 24), symptom measurement scales (n = 4) and treatment (n = 29). Several studies indicated that individuals with exhaustion disorder experience a range of psychiatric and somatic symptoms beyond fatigue, but robust findings within most thematic categories were scarce. The limited number of studies, lack of replication of findings and methodological limitations (e.g. small samples and scarcity of specified primary outcomes) preclude firm conclusions about the diagnostic construct.
More research is needed to build a solid knowledge base for exhaustion disorder. International collaboration regarding the conceptualisation of chronic stress and fatigue is warranted to accelerate the growth of evidence.
A terrestrial (lacustrine and fluvial) palaeoclimate record from Hoxne (Suffolk, UK) shows two temperate phases separated by a cold episode, correlated with MIS 11 subdivisions corresponding to isotopic events 11.3 (Hoxnian interglacial period), 11.24 (Stratum C cold interval), and 11.23 (warm interval with evidence of human presence). A robust, reproducible multiproxy consensus approach validates and combines quantitative palaeotemperature reconstructions from three invertebrate groups (beetles, chironomids, and ostracods) and plant indicator taxa with qualitative implications of molluscs and small vertebrates. Compared with the present, interglacial mean monthly air temperatures were similar or up to 4.0°C higher in summer, but similar or as much as 3.0°C lower in winter; the Stratum C cold interval, following prolonged nondeposition or erosion of the lake bed, experienced summers 2.5°C cooler and winters between 5°C and 10°C cooler than at present. Possible reworking of fossils into Stratum C from underlying interglacial assemblages is taken into account. Oxygen and carbon isotopes from ostracod shells indicate evaporatively enriched lake water during Stratum C deposition. Comparative evaluation shows that proxy-based palaeoclimate reconstruction methods are best tested against each other and, if validated, can be used to generate more refined and robust results through multiproxy consensus.
The spectrum of adverse mental health trajectories caused by sexual abuse, broadly defined as exposure to rape and unwanted physical sexual contact, is well-known. Few studies have systematically appraised the epidemiology and impact of sexual abuse among boys and men. New meta-analytic insights (k = 44; n = 45 172) reported by Zarchev and colleagues challenge assumptions that men experiencing mental ill health rarely report sexual abuse exposure. Adult-onset sexual abuse rates of 1–7% are observed in the general population, but for men experiencing mental ill health, adult lifetime prevalence was 14.1% (95% CI 7.3–22.4%), with past-year exposure 5.3% (95% CI 1.6–12.8%). We note that these rates are certainly underestimates, as childhood sexual abuse exposures were excluded. Boys and men with a sexual abuse history experience substantial disclosure and treatment barriers. We draw attention to population health gains that could be achieved via implementation of gender-sensitive assessment and intervention approaches for this at-risk population.
Clinical cases covering the spectrum of upper limb pathology are presented here. In the hand, these include congenital hand deficiencies, Dupuytren’s disease, rheumatoid disease, nerve lesions and tendon transfers. In the elbow, this includes osteoarthritis and in the shoulder, massive cuff tear, scapula winging and painful shoulder arthroplasty. Clinical examination findings for each of the cases are highlighted.
OBJECTIVES/GOALS: The major objective of this project is two points. First, is to repeat and confirm previous observations that there is elevated cytosolic Line1 DNA in the cytoplasm of cells derived from old mice compared to young. Second is to identify which Line1s in the genome are contributing to this free DNA and test if targeting them rescues the age-related phenotype. METHODS/STUDY POPULATION: This project will focus on data collected from both tissues and primary cells derived from multiple tissues. Using cellular/tissue fractionation kits, we isolate specifically from the cytoplasm. This specificity is confirmed by western blotting. Measurement of the Line1 levels is measured by quantitative PCR. Subsequently, these cytoplasmic samples are sent off for sequencing in order to quantify the length of the free DNA in the cytoplasm and to identify which Line1 genomic families the cytosolic DNA originates. Additionally, FISH is utilized to visualize Line1 DNA in the cytoplasm of aged versus young cells RESULTS/ANTICIPATED RESULTS: We anticipate this research to confirm the hypothesis that extranuclear Line1 DNA accumulates with age in both tissues and primary fibroblasts. Additionally, we expect to be able to determine which specific families of genomic Line1 is driving this extranuclear DNA, which would suggest the active retrotransopable elements that are directly involved in this aging related phenotype. Assuming successful identification of such families, we can then target and silence these specific elements to determine not only if cytoplasmic Line1 in aged mice decreases, but additionally if the healthspan and/or lifespan of these mice improves DISCUSSION/SIGNIFICANCE: Dereoressed Line1s have been shown to be involved in detrimental phenotypes, including autoimmune disease, cancer, and inflammaging. Targeting retrotransposons, either directly through degradation of transcriptional product of LINE1s or indirectly by improving function of regulators, will be crucial in ablating aging phenotypes
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Anxiety is a common human emotion and is experienced by all people at some point in life. It is characterized by a state of apprehension about a perceived threat or potentially dangerous situation. In addition, fear is a negative emotion caused by the belief that someone or something is dangerous, likely to cause pain, or a threat. At mild to moderate levels, anxiety can be adaptive, motivating, and can help improve performance and attention. For example, prior to a significant life event such as an important test or presentation, some individuals may experience anxiety, which could serve as a motivator to work harder and perform better. Similarly, fear can be an adaptive response when one is confronted with a life-threatening situation, and a fight or flight response to danger is present and adaptive across many animal species. However, for some, anxiety or fear may be overwhelming, distressing, and interfere with functioning. This may require a person to seek treatment depending on the level of interference and could also result in the development of a psychiatric condition.
A multi-disciplinary expert group met to discuss vitamin D deficiency in the UK and strategies for improving population intakes and status. Changes to UK Government advice since the 1st Rank Forum on Vitamin D (2009) were discussed, including rationale for setting a reference nutrient intake (10 µg/d; 400 IU/d) for adults and children (4+ years). Current UK data show inadequate intakes among all age groups and high prevalence of low vitamin D status among specific groups (e.g. pregnant women and adolescent males/females). Evidence of widespread deficiency within some minority ethnic groups, resulting in nutritional rickets (particularly among Black and South Asian infants), raised particular concern. Latest data indicate that UK population vitamin D intakes and status reamain relatively unchanged since Government recommendations changed in 2016. Vitamin D food fortification was discussed as a potential strategy to increase population intakes. Data from dose–response and dietary modelling studies indicate dairy products, bread, hens’ eggs and some meats as potential fortification vehicles. Vitamin D3 appears more effective than vitamin D2 for raising serum 25-hydroxyvitamin D concentration, which has implications for choice of fortificant. Other considerations for successful fortification strategies include: (i) need for ‘real-world’ cost information for use in modelling work; (ii) supportive food legislation; (iii) improved consumer and health professional understanding of vitamin D’s importance; (iv) clinical consequences of inadequate vitamin D status and (v) consistent communication of Government advice across health/social care professions, and via the food industry. These areas urgently require further research to enable universal improvement in vitamin D intakes and status in the UK population.
To examine the relationship between depression, anxiety and wellbeing in doctors.
The relationship between doctor wellbeing and mental health diagnoses is not well evidenced in the literature. There is a lack of comparable measurement of wellbeing in doctors within the National Health Service, meaning the effectiveness of wellbeing interventions is unknown.
A cross-sectional survey containing the PHQ9, GAD7 and WEMWBS questionnaires to measure depression, anxiety and wellbeing respectively, was advertised online nationally. The relationships between the total scores were explored using Spearman's rho correlation coefficients and Chi square tests. Thematic analysis of semi-structured interviews offered further insights.
Sixty-seven doctors returned completed questionnaires. 29.9% had PHQ9 scores >5 and 41.8% had GAD7 scores >5. Therefore, over a quarter of the participants had a score that would suggest a management plan was needed for depression, and a third for anxiety. Moderate negative correlation between the total WEMWBS scores and the total PHQ , rs= –0.775, p = 0.00, N = 67 and GAD7 scores rs= –0.724, , p = 0.00, N = 67 was seen. Statistically significant differences between those with low wellbeing scores (WEMWBS < 40) and normal wellbeing scores (WEMWBS ≥ 40) in relation to the need for a management plan for depression (PHQ9 > 10) X2 (1, N = 67) = 12.395, p = 0.00 and anxiety (GAD7>10) X2 (1, N = 67) = 5.611, p = 0.018 were seen. The main themes identified from the interviews (n = 10) were the importance of social support outside of work, cynicism about an NHS plan check-in and a tendancy to neglect wellbeing until it has dipped.
There is a moderate negative correlation between anxiety, depression and wellbeing, but they are not opposites and separate measures for wellbeing should be used. It is clinically useful to note that only those with a WEMWBS score of <45 had a PHQ9 score suggesting the need for treatment of depression.
Doctors’ mental health is a national concern – the General Medical Council, British Medical Association and Health Education England pledge to improve their well-being. Well-being has no common definition, instead pathogenic measures such as burnout are published as a demonstration of doctors’ wellbeing. Yet, the relationship between burnout and wel-being has not been explored.
to investigate the relationship between burnout and well-being.
they are negatively associated, but not opposites.
An online cross-sectional national survey was distributed to doctors of all grades and specialties via the Royal Colleges and doctor organisations. The Oldenburg Burnout Inventory (OLBI) measured burnout, and the Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS) measured well-being. Correlation coefficients between total scores of these measures estimated the relationship. Additionally, semi-structured interviews explored personal definitions of wellbeing and its relationship with burnout. Thematic analysis was carried out.
64 doctors completed the OLBI and WEMWBS. Comparing the total scores for the questionnaires with Spearman's rho indicates a moderate negative correlation (rs= –0.658, p = 0.00, n = 64). Total scores were made into binary variables, a Chi-square test showed that a low WEMWBS score (<40) and a very high risk OLBI score (≥2.85 exhaustion and ≥2.6 disengagement) were statistically significantly associated (X 2 (1, N = 64) = 4.232, p = 0.04). Three themes emerged from the 10 interviews conducted: the importance of networks/relationships outside work; scepticism towards the proposal of an NHS wellbeing check-in; and how participants do not strive to improve their wellbeing until its decline.
This research demonstrates that wellbeing and burnout have only a moderate negative correlation when using commonly employed measurement tools. Therefore, measures of burnout are not a surrogate for wellbeing. Further research could adopt a salutogenic approach by using the WEMWBS to monitor doctors’ wellbeing and could explore interventions to increase well-being, rather than waiting for its decline.
The coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of personal protective equipment (PPE), underscoring the urgent need for simple, efficient, and inexpensive methods to decontaminate masks and respirators exposed to severe acute respiratory coronavirus virus 2 (SARS-CoV-2). We hypothesized that methylene blue (MB) photochemical treatment, which has various clinical applications, could decontaminate PPE contaminated with coronavirus.
The 2 arms of the study included (1) PPE inoculation with coronaviruses followed by MB with light (MBL) decontamination treatment and (2) PPE treatment with MBL for 5 cycles of decontamination to determine maintenance of PPE performance.
MBL treatment was used to inactivate coronaviruses on 3 N95 filtering facepiece respirator (FFR) and 2 medical mask models. We inoculated FFR and medical mask materials with 3 coronaviruses, including SARS-CoV-2, and we treated them with 10 µM MB and exposed them to 50,000 lux of white light or 12,500 lux of red light for 30 minutes. In parallel, integrity was assessed after 5 cycles of decontamination using multiple US and international test methods, and the process was compared with the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method.
Overall, MBL robustly and consistently inactivated all 3 coronaviruses with 99.8% to >99.9% virus inactivation across all FFRs and medical masks tested. FFR and medical mask integrity was maintained after 5 cycles of MBL treatment, whereas 1 FFR model failed after 5 cycles of VHP+O3.
MBL treatment decontaminated respirators and masks by inactivating 3 tested coronaviruses without compromising integrity through 5 cycles of decontamination. MBL decontamination is effective, is low cost, and does not require specialized equipment, making it applicable in low- to high-resource settings.
Linoleic acid (LA), an essential n-6 fatty acid (FA), is critical for fetal development. We investigated the effects of maternal high LA (HLA) diet on offspring cardiac development and its relationship to circulating FA and cardiovascular function in adolescent offspring, and the ability of the postnatal diet to reverse any adverse effects. Female Wistar Kyoto rats were fed low LA (LLA; 1·44 % energy from LA) or high LA (HLA; 6·21 % energy from LA) diets for 10 weeks before pregnancy and during gestation/lactation. Offspring, weaned at postnatal day 25, were fed LLA or HLA diets and euthanised at postnatal day 40 (n 6–8). Maternal HLA diet decreased circulating total cholesterol and HDL-cholesterol in females and decreased total plasma n-3 FA in males, while maternal and postnatal HLA diets decreased total plasma n-3 FA in females. α-Linolenic acid (ALA) and EPA were decreased by postnatal but not maternal HLA diets in both sexes. Maternal and postnatal HLA diets increased total plasma n-6 and LA, and a maternal HLA diet increased circulating leptin, in both male and female offspring. Maternal HLA decreased slopes of systolic and diastolic pressure–volume relationship (PVR), and increased cardiac Col1a1, Col3a1, Atp2a1 and Notch1 in males. Maternal and postnatal HLA diets left-shifted the diastolic PVR in female offspring. Coronary reactivity was altered in females, with differential effects on flow repayment after occlusion. Thus, maternal HLA diets impact lipids, FA and cardiac function in offspring, with postnatal diet modifying FA and cardiac function in the female offspring.