Activity of the Lactate Dehydrogenase Inhibitor Oxamic Acid against the Fermentative Bacterium \u3ci\u3eStreptococcus mitis/oralis\u3c/i\u3e: Bactericidal Effects and Prevention of Daptomycin Resistance In Vitro and in an Ex Vivo Model

Streptococcus mitis/oralis is a fermentative bacterium that relies on lactate dehydrogenase to balance its redox poise and keep glycolysis active. Metabolomic analysis of an in vitro– derived daptomycin-resistant (DAP-R) S. mitis/oralis strain (351-D10) revealed differences in glucose catabolism relative to its DAP-susceptible (DAP-S) parental strain, 351. Metabolic changes associated with the transition to this DAP-R phenotype suggested that inhibiting glycolysis could alter DAP susceptibility. In addition, the strong reliance of S. mitis/oralis on glycolysis for energy and biosynthetic intermediates suggested that inhibiting glycolysis would adversely affect growth and biomass accumulation. To test these hypotheses, we used the lactate dehydrogenase inhibitor oxamic acid (OXA) to assess its efficacy against DAP-S S. mitis/oralis strain 351 during DAP exposures in vitro and ex vivo. As expected, OXA was growth inhibitory to S. mitis/oralis in a dose-dependent manner in vitro; however, it did not alter in vitro DAP susceptibility profiles. In contrast, OXA did prevent the emergence of DAP-R in an ex vivo model of simulated endocardial vegetations. These data suggest that metabolic inhibitors directed against this fermentative bacterium with limited metabolic capabilities could enhance killing and potentially forestall the emergence of DAP resistance

Anisotropic Inflation from Charged Scalar Fields

We consider models of inflation with U(1) gauge fields and charged scalar fields including symmetry breaking potential, chaotic inflation and hybrid inflation. We show that there exist attractor solutions where the anisotropies produced during inflation becomes comparable to the slow-roll parameters. In the models where the inflaton field is a charged scalar field the gauge field becomes highly oscillatory at the end of inflation ending inflation quickly. Furthermore, in charged hybrid inflation the onset of waterfall phase transition at the end of inflation is affected significantly by the evolution of the background gauge field. Rapid oscillations of the gauge field and its coupling to inflaton can have interesting effects on preheating and non-Gaussianities.Comment: minor changes, references added, figures are modified, conforms JCAP published versio

The Relationship Between Gambling Problems and the Five-Factor Model of Personality: A Systematic Review and Meta-Analysis

Objectives: The aim of the present meta-analysis was to synthesize results from the association between problem gambling (PG) and dimensions of the five factor model of personality and to identify potential moderators (gambling diagnosis: yes/no, comorbidity: yes/no and trait assessment: four or fewer items vs. five items or more) of these associations in meta-regressions. Methods: Searches were conducted in six databases; Medline, Web of Science, PsychInfo, Google Scholar, OpenGrey, and Cochrane Library (conducted on February, 22, 2021). Included studies: (1) reported a relationship between PG and at least one of the personality traits in the five-factor model, (2) contained information of zero-order correlations or sufficient data for such calculations, and (3) were original articles published in any European language. Case-studies, qualitative studies, and reviews were excluded. All articles were independently screened by two authors. Final agreement was reached through discussion or by consulting a third author. Risk of bias of the included studies was assessed by the Newcastle-Ottawa Scale. Data were synthesized using a random effects model. Results: In total 28 studies, comprising 20,587 participants, were included. The correlations between PG and the traits were as follows: Neuroticism: 0.273 (95% CI = 0.182, 0.358), conscientiousness −0.296 (95% CI = −0.400, −0.185), agreeableness −0.163 (95% CI = −0.223, −0.101), openness −0.219 (95% CI = −0.308, −0.127), and extroversion −0.083 (95% CI = −0.120, −0.046). For all meta-analyses the between study heterogeneity was significant. Presence of gambling diagnosis was the only moderator that significantly explained between-study variance showing a more negative correlation to extroversion when participants had a gambling diagnosis compared to when this was not the case. Discussion: The results indicated some publication bias. Correcting for this by a trim-and-fill procedure showed however that the findings were consistent. Clinicians and researchers should be aware of the associations between personality traits and PG. Previous studies have for example showed neuroticism to be related to treatment relapse, low scores on conscientiousness to predict treatment drop-out and agreeableness to reduce risk of treatment drop-out.publishedVersio

COVID-19 vaccination uptake amongst ethnic minority communities in England: a linked study exploring the drivers of differential vaccination rates

BACKGROUND: Despite generally high coronavirus disease 2019 (COVID-19) vaccination rates in the UK, vaccination hesitancy and lower take-up rates have been reported in certain ethnic minority communities. METHODS: We used vaccination data from the National Immunisation Management System (NIMS) linked to the 2011 Census and individual health records for subjects aged ≥40 years (n = 24 094 186). We estimated age-standardized vaccination rates, stratified by ethnic group and key sociodemographic characteristics, such as religious affiliation, deprivation, educational attainment, geography, living conditions, country of birth, language skills and health status. To understand the association of ethnicity with lower vaccination rates, we conducted a logistic regression model adjusting for differences in geographic, sociodemographic and health characteristics. ResultsAll ethnic groups had lower age-standardized rates of vaccination compared with the white British population, whose vaccination rate of at least one dose was 94% (95% CI: 94%-94%). Black communities had the lowest rates, with 75% (74-75%) of black African and 66% (66-67%) of black Caribbean individuals having received at least one dose. The drivers of these lower rates were partly explained by accounting for sociodemographic differences. However, modelled estimates showed significant differences remained for all minority ethnic groups, compared with white British individuals. CONCLUSIONS: Lower COVID-19 vaccination rates are consistently observed amongst all ethnic minorities

Issues on Generating Primordial Anisotropies at the End of Inflation

We revisit the idea of generating primordial anisotropies at the end of inflation in models of inflation with gauge fields. To be specific we consider the charged hybrid inflation model where the waterfall field is charged under a U(1) gauge field so the surface of end of inflation is controlled both by inflaton and the gauge fields. Using delta N formalism properly we find that the anisotropies generated at the end of inflation from the gauge field fluctuations are exponentially suppressed on cosmological scales. This is because the gauge field evolves exponentially during inflation while in order to generate appreciable anisotropies at the end of inflation the spectator gauge field has to be frozen and scale invariant. We argue that this is a generic feature, that is, one can not generate observable anisotropies at the end of inflation within an FRW background.Comment: V3: new references added, JCAP published versio

Obesity, Ethnicity, and Risk of Critical Care, Mechanical Ventilation, and Mortality in Patients Admitted to Hospital with COVID-19: Analysis of the ISARIC CCP-UK Cohort

OBJECTIVE: The aim of this study was to investigate the association of obesity with in-hospital coronavirus disease 2019 (COVID-19) outcomes in different ethnic groups. METHODS: Patients admitted to hospital with COVID-19 in the United Kingdom through the Clinical Characterisation Protocol UK (CCP-UK) developed by the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) were included from February 6 to October 12, 2020. Ethnicity was classified as White, South Asian, Black, and other minority ethnic groups. Outcomes were admission to critical care, mechanical ventilation, and in-hospital mortality, adjusted for age, sex, and chronic diseases. RESULTS: Of the participants included, 54,254 (age = 76 years; 45.0% women) were White, 3,728 (57 years; 41.1% women) were South Asian, 2,523 (58 years; 44.9% women) were Black, and 5,427 (61 years; 40.8% women) were other ethnicities. Obesity was associated with all outcomes in all ethnic groups, with associations strongest for black ethnicities. When stratified by ethnicity and obesity status, the odds ratios for admission to critical care, mechanical ventilation, and mortality in black ethnicities with obesity were 3.91 (3.13-4.88), 5.03 (3.94-6.63), and 1.93 (1.49-2.51), respectively, compared with White ethnicities without obesity. CONCLUSIONS: Obesity was associated with an elevated risk of in-hospital COVID-19 outcomes in all ethnic groups, with associations strongest in Black ethnicities

Impact of cardiometabolic multimorbidity and ethnicity on cardiovascular/renal complications in patients with COVID-19

OBJECTIVE: Using a large national database of people hospitalised with COVID-19, we investigated the contribution of cardio-metabolic conditions, multi-morbidity and ethnicity on the risk of in-hospital cardiovascular complications and death. METHODS: A multicentre, prospective cohort study in 302 UK healthcare facilities of adults hospitalised with COVID-19 between 6 February 2020 and 16 March 2021. Logistic models were used to explore associations between baseline patient ethnicity, cardiometabolic conditions and multimorbidity (0, 1, 2, >2 conditions), and in-hospital cardiovascular complications (heart failure, arrhythmia, cardiac ischaemia, cardiac arrest, coagulation complications, stroke), renal injury and death. RESULTS: Of 65 624 patients hospitalised with COVID-19, 44 598 (68.0%) reported at least one cardiometabolic condition on admission. Cardiovascular/renal complications or death occurred in 24 609 (38.0%) patients. Baseline cardiometabolic conditions were independently associated with increased odds of in-hospital complications and this risk increased in the presence of cardiometabolic multimorbidity. For example, compared with having no cardiometabolic conditions, 1, 2 or ≥3 conditions was associated with 1.46 (95% CI 1.39 to 1.54), 2.04 (95% CI 1.93 to 2.15) and 3.10 (95% CI 2.92 to 3.29) times higher odds of any cardiovascular/renal complication, respectively. A similar pattern was observed for all-cause death. Compared with the white group, the South Asian (OR 1.19, 95% CI 1.10 to 1.29) and black (OR 1.53 to 95% CI 1.37 to 1.72) ethnic groups had higher risk of any cardiovascular/renal complication. CONCLUSIONS: In hospitalised patients with COVID-19, cardiovascular complications or death impacts just under half of all patients, with the highest risk in those of South Asian or Black ethnicity and in patients with cardiometabolic multimorbidit

Association between problem gambling and personality traits: a longitudinal study among the general Norwegian population

ObjectiveThe present study investigates the longitudinal relationship between problematic gambling (PG) and the five factor model’s personality traits using autoregressive cross-lagged models.MethodsThe data used in the current study was collected by a national survey in 2013 (n = 10,081) and a follow-up study (n = 5,848) in 2015. PG was measured using Canadian Problem Gambling Index (CPGI) while personality was assessed using Mini-International Personality Item Pool (MINI-IPIP). Participants who completed the CPGI and all the personality items during both waves (n = 2,702) were analysed.ResultsThe results show that neuroticism had positive cross-lagged associations with CPGI. In contrast, conscientiousness and agreeableness in 2013 were found to have inverse cross-lagged effect on CPGI in 2015. Finally, openness and extraversion did not have any cross-lagged associations with CPGI.ConclusionPG poses serious negative implications for the involved individuals as well as their associated close social circle. Hence, it is important to understand predictors of PG for prevention purposes. Personality traits are one of the influential frameworks for examining uncontrolled psychopathological behaviors like PG. The study findings offer significant theoretical as well as practical implications

Portuguese validation of the Internet Addiction Test: An empirical study

Abstract Background and aims Research into Internet addiction (IA) has increased greatly over the last decade. Despite its various definitions and general lack of consensus regarding its conceptualisation amongst researchers, instruments for measuring this phenomenon have proliferated in a number of countries. There has been little research on IA in Portugal and this may be partly due to the absence of standardised measurement tools for assessing IA. Methods This study attempted to address this issue by adapting a Portuguese version of the Internet Addiction Test (IAT) via a translation-back translation process and Confirmatory Factor Analysis in a sample of 593 Portuguese students that completed a Portuguese version of the IAT along with questions related to socio-demographic variables. Results The findings suggested that the IAT appears to be a valid and reliable instrument for measuring IA among Portuguese young adults as demonstrated by its satisfactory psychometric properties. However, the present findings also suggest the need to reword and update some of the IAT's items. Prevalence of IA found in the sample was 1.2% and is discussed alongside findings relating to socio-demographic correlates. Limitations and implications of the present study are also discussed. Conclusions The present study calls for a reflection of the IAT while also contributing to a better understanding of the basic aspects of IA in the Portuguese community since many health practitioners are starting to realise that Internet use may pose a risk for some individuals

Enhancing clinical and public health interpretation of accelerometer-assessed physical activity with age-referenced values based on UK Biobank data

Purpose: Higher accelerometer-assessed volume and intensity of physical activity (PA) have been associated with a longer life expectancy but can be difficult to translate into recommended doses of PA. We aimed to: (a) improve interpretability by producing UK Biobank age-referenced centiles for PA volume and intensity; (b) inform public-health messaging by examining how adding recommended quantities of moderate and vigorous PA affect PA volume and intensity. Methods: 92,480 UK-Biobank participants aged 43-80 with wrist-worn accelerometer data were included. Average acceleration and intensity gradient were derived as proxies for PA volume and intensity. We generated sex-specific centile curves using Generalized Additive Models for Location Scale and Shape (GAMLSS) and modelled the effect of adding moderate (walking) or vigorous (running) activity on the combined change in the volume and intensity centiles (change in PA profile). Results: In men, volume was lower as age increased while intensity was lower after age 55; in women, both volume and intensity were lower as age increased. Adding 150-minutes moderate PA weekly - 5 x 30-minutes walking - increased the PA profile by 4 percentage points. Defining moderate PA as brisk walking ~doubled the increase (9 percentage points) while 75-minutes vigorous PA weekly (5 x 15-minutes running) trebled the increase (13 percentage points). Conclusion: These UK Biobank reference centiles provide a benchmark for interpretation of accelerometer data. Application of our translational methods demonstrate that meeting PA guidelines through shorter duration vigorous activity is more beneficial to the PA profile (volume and intensity) than longer duration moderate activity