Ferrocenyl Chalcone Derivatives as Possible Antimicrobial Agents

The swift spread of infections caused by drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), has quickly become a worldwide concern as infections spread from healthcare settings to the wider community. While ferrocenyl chalcones, which are chalcone derivatives with antimicrobial activity, have gained attention from researchers, further study is needed to assess their cytotoxicity. Ten newly developed chalcones, in which ring A was replaced with a ferrocenyl moiety and ring B contained increasing alkyl chain lengths from 1 to 10 carbons, were assessed. Using twofold broth microdilution, the minimum inhibitory concentration (MIC) of five of the ten compounds were lower against Gram-positive organisms (MICs from 0.008 mg ml−1 to 0.063 mg ml−1) than Gram-negative organisms (MICs = 0.125 mg ml−1). These novel ferrocenyl chalcone compounds were effective against three types of clinically isolated drug-resistant S. aureus, including an MRSA, and against other non-resistant clinically isolated and laboratory-adapted Gram-positive bacteria. The same compounds inhibited growth in non-resistant bacteria by potentially obstructing cellular respiration in Gram-positive bacteria. Images obtained through scanning electron microscopy revealed fully lysed bacterial cells once exposed to a selected compound that showed activity. The results indicate that these newly developed compounds could be important antimicrobial agents in the treatment of infections from clinically resistant bacteria

Infection control in the UK: an antimicrobial resistance perspective

The spread of healthcare-associated infections has become a matter of global concern. These infections, which were once solely limited to hospital settings, have emerged in the community. Reduced infection control practices strengthen this rapid spread of infections, which has led to the increase in the occurrence of multidrug resistant organisms. The state of infection control in the United Kingdom is of extreme importance because of several reported cases of infections caused by these organisms. In addition to antimicrobial usage in human medicine, antimicrobial agents used in agriculture must be considered as major factors in the prevalence of resistant organisms and the implications to the UK. However, this increased occurrence of antimicrobial resistant bacteria and their resulting infections could be reduced with the application of effective policies for antibiotic use in agricultural environments, stringent decontamination and sterilisation techniques and better regulations that encourage the search for, and development of, new and novel drugs. Keywords: Infection control, healthcare associated infections, antimicrobial drug resistance, prophylaxis, health policy

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Reward Versus Nonreward Sensitivity of the Medial Versus Lateral Orbitofrontal Cortex Relates to the Severity of Depressive Symptoms

BackgroundThe orbitofrontal cortex (OFC) is implicated in depression. The hypothesis investigated was whether the OFC sensitivity to reward and nonreward is related to the severity of depressive symptoms.MethodsActivations in the monetary incentive delay task were measured in the IMAGEN cohort at ages 14 years (n = 1877) and 19 years (n = 1140) with a longitudinal design. Clinically relevant subgroups were compared at ages 19 (high-severity group: n = 116; low-severity group: n = 206) and 14.ResultsThe medial OFC exhibited graded activation increases to reward, and the lateral OFC had graded activation increases to nonreward. In this general population, the medial and lateral OFC activations were associated with concurrent depressive symptoms at both ages 14 and 19 years. In a stratified high-severity depressive symptom group versus control group comparison, the lateral OFC showed greater sensitivity for the magnitudes of activations related to nonreward in the high-severity group at age 19 (p = .027), and the medial OFC showed decreased sensitivity to the reward magnitudes in the high-severity group at both ages 14 (p = .002) and 19 (p = .002). In a longitudinal design, there was greater sensitivity to nonreward of the lateral OFC at age 14 for those who exhibited high depressive symptom severity later at age 19 (p = .003).ConclusionsActivations in the lateral OFC relate to sensitivity to not winning, were associated with high depressive symptom scores, and at age 14 predicted the depressive symptoms at ages 16 and 19. Activations in the medial OFC were related to sensitivity to winning, and reduced reward sensitivity was associated with concurrent high depressive symptom scores

Differential predictors for alcohol use in adolescents as a function of familial risk

Abstract: Traditional models of future alcohol use in adolescents have used variable-centered approaches, predicting alcohol use from a set of variables across entire samples or populations. Following the proposition that predictive factors may vary in adolescents as a function of family history, we used a two-pronged approach by first defining clusters of familial risk, followed by prediction analyses within each cluster. Thus, for the first time in adolescents, we tested whether adolescents with a family history of drug abuse exhibit a set of predictors different from adolescents without a family history. We apply this approach to a genetic risk score and individual differences in personality, cognition, behavior (risk-taking and discounting) substance use behavior at age 14, life events, and functional brain imaging, to predict scores on the alcohol use disorders identification test (AUDIT) at age 14 and 16 in a sample of adolescents (N = 1659 at baseline, N = 1327 at follow-up) from the IMAGEN cohort, a longitudinal community-based cohort of adolescents. In the absence of familial risk (n = 616), individual differences in baseline drinking, personality measures (extraversion, negative thinking), discounting behaviors, life events, and ventral striatal activation during reward anticipation were significantly associated with future AUDIT scores, while the overall model explained 22% of the variance in future AUDIT. In the presence of familial risk (n = 711), drinking behavior at age 14, personality measures (extraversion, impulsivity), behavioral risk-taking, and life events were significantly associated with future AUDIT scores, explaining 20.1% of the overall variance. Results suggest that individual differences in personality, cognition, life events, brain function, and drinking behavior contribute differentially to the prediction of future alcohol misuse. This approach may inform more individualized preventive interventions

Differential predictors for alcohol use in adolescents as a function of familial risk

Abstract: Traditional models of future alcohol use in adolescents have used variable-centered approaches, predicting alcohol use from a set of variables across entire samples or populations. Following the proposition that predictive factors may vary in adolescents as a function of family history, we used a two-pronged approach by first defining clusters of familial risk, followed by prediction analyses within each cluster. Thus, for the first time in adolescents, we tested whether adolescents with a family history of drug abuse exhibit a set of predictors different from adolescents without a family history. We apply this approach to a genetic risk score and individual differences in personality, cognition, behavior (risk-taking and discounting) substance use behavior at age 14, life events, and functional brain imaging, to predict scores on the alcohol use disorders identification test (AUDIT) at age 14 and 16 in a sample of adolescents (N = 1659 at baseline, N = 1327 at follow-up) from the IMAGEN cohort, a longitudinal community-based cohort of adolescents. In the absence of familial risk (n = 616), individual differences in baseline drinking, personality measures (extraversion, negative thinking), discounting behaviors, life events, and ventral striatal activation during reward anticipation were significantly associated with future AUDIT scores, while the overall model explained 22% of the variance in future AUDIT. In the presence of familial risk (n = 711), drinking behavior at age 14, personality measures (extraversion, impulsivity), behavioral risk-taking, and life events were significantly associated with future AUDIT scores, explaining 20.1% of the overall variance. Results suggest that individual differences in personality, cognition, life events, brain function, and drinking behavior contribute differentially to the prediction of future alcohol misuse. This approach may inform more individualized preventive interventions

Novel Ferrocenyl Chalcone Compounds as Possible Antimicrobial Agents

The increased prevalence of drug-resistant bacteria has quickly become a global concern as infections spread from healthcare settings to the wider community. The rapid spread of infections caused by bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) is partly facilitated by misuse and abuse of conventional drug therapies and a decreased development of new drugs. Chalcones, which are a class of plant-based flavonoids, have become the focus of much research in medicinal chemistry since they inhibit bacterial growth. Ferrocenyl chalcones, which are chalcone derivatives, have gained further attention from researchers. In these compounds, ring A is replaced with a ferrocenyl moiety. Key characteristics of ferrocenyl chalcones include their small size, lipophilicity, an important feature allowing diffusion across cell membranes, ease of chemical modification and accessible one-electron-oxidation potential. Early classes of ferrocenyl chalcones were reportedly toxic to mammalian cells. This cytotoxicity to mammalian cells encouraged the need to develop next-generation ferrocenyl chalcone compounds that are less toxic. Using 2-fold broth microdilution, results demonstrated that 5 of the 10 newly developed ferrocenyl chalcones possessed greater antimicrobial activity against Gram-positive organisms than Gram-negative organisms. These novel ferrocenyl chalcone compounds were active against three (3) types of drug-resistant S. aureus, including a MRSA, and other non-resistant Gram-positive bacteria. These compounds contain increasing alkyl chain lengths from 5-10 on ring B. The same compounds inhibited growth in non-resistant bacteria by obstructing cellular respiration in Gram-positive bacteria. The results indicate that these newly developed compounds could be important antimicrobial agents in the treatment of infections from clinically resistant bacteria

Ten priority questions for increasing the consistency and success in hatchery production of the European flat oyster for habitat restoration

The European flat oyster, Ostrea edulis, once formed extensive reef habitats throughout European seas and estuaries. These reefs are now largely functionally extinct, yet interest and support for their restoration is rapidly growing. A major bottleneck to scaling up oyster reef restoration is the lack of available oysters to supply the growing demand. This study aimed to identify the ten questions which, if answered, would increase the consistency and success in hatchery production of O. edulis for habitat restoration. Candidate questions were submitted by representatives from twelve commercial and research hatcheries across Europe. The list of 98 candidate questions were collaboratively discussed by experts from nine research hatcheries across eight countries in Europe, to identify the top ten questions via an iterative and open process. Questions were grouped into the following themes: conditioning and feeding, larval rearing, disease and water quality, hatchery protocol, genetics, and hatchery management. There were several overarching topics spanning these themes, including diet optimisation, maximising the effective population size, and developing the technical skillbase in order to increase hatchery production to meet the projected increase in demand for oyster seed for habitat restoration efforts. We anticipate this list will provide a starting point for collaborative research efforts across Europe, as well as assisting policy makers and funders in identifying key knowledge gaps

Longitudinal associations between adolescent catch-up sleep, white-matter maturation and internalizing problems

International audienceSleep is an important contributor for neural maturation and emotion regulation during adolescence, with long-term effects on a range of white matter tracts implicated in affective processing in at-risk populations. We investigated the effects of adolescent sleep patterns on longitudinal changes in white matter development and whether this is related to the emergence of emotional (internalizing) problems. Sleep patterns and internalizing problems were assessed using self-report questionnaires in adolescents recruited in the general population followed up from age 14-19 years (N = 111 White matter structure was measured using diffusion tensor imaging (DTI) and estimated using fractional anisotropy (FA). We found that longitudinal increases in time in bed (TIB) on weekends and increases in TIB-variability between weekdays to weekend, were associated with an increase in FA in various interhemispheric and cortico-striatal tracts. Extracted FA values from left superior longitudinal fasciculus mediated the relationship between increases in TIB on weekends and a decrease in internalizing problems. These results imply that while insufficient sleep might have potentially harmful effects on long-term white matter development and internalizing problems, longer sleep duration on weekends (catch-up sleep) might be a natural counteractive and protective strategy

Irregular sleep habits, regional grey matter volumes, and psychological functioning in adolescents

International audienceChanging sleep rhythms in adolescents often lead to sleep deficits and a delay in sleep timing between weekdays and weekends. The adolescent brain, and in particular the rapidly developing structures involved in emotional control, are vulnerable to external and internal factors. In our previous study in adolescents at age 14, we observed a strong relationship between weekend sleep schedules and regional medial prefrontal cortex grey matter volumes. Here, we aimed to assess whether this relationship remained in this group of adolescents of the general population at the age of 16 (n = 101; mean age 16.8 years; 55% girls). We further examined grey matter volumes in the hippocampi and the amygdalae, calculated with voxel-based morphometry. In addition, we investigated the relationships between sleep habits, assessed with self-reports, and regional grey matter volumes, and psychological functioning, assessed with the Strengths and Difficulties Questionnaire and tests on working memory and impulsivity. Later weekend wake-up times were associated with smaller grey matter volumes in the medial prefrontal cortex and the amygdalae, and greater weekend delays in wake-up time were associated with smaller grey matter volumes in the right hippocampus and amygdala. The medial prefrontal cortex region mediated the correlation between weekend wake up time and externalising symptoms. Paying attention to regular sleep habits during adolescence could act as a protective factor against the emergence of psychopathology via enabling favourable brain development