Neurocognitive Dysfunction and Diabetic Foot

Diabetic foot ulcers are one of the most serious complications associated with diabetes. People with diabetes experience an accelerated rate of age-related cognitive decline, and comorbid complications increase the likelihood of neurocognitive attenuation. The current body of research into neurocognitive functioning in individuals with diabetic foot ulcers is small, but suggests significantly increased rates of neurocognitive dysfunction, and that up to one quarter of this cohort have cognitive functioning consistent with dementia samples. This has implications for utilising disease self-management as the primary treatment model. Neurocognitive deficits mean that understanding, retaining, and adhering to management recommendations are likely to be difficult in this group. Further research is needed in this area to determine the specific neurocognitive profile associated with diabetic foot, including which cognitive domains are the most impacted. The provision of a framework for tailoring management strategies to assist this group with more efficacious disease management is also required

DNA binding and intercalation by novel porphyrins: role of charge and substituents probed by DNase I footprinting and topoisomerase I unwinding

AbstractPorphyrins carrying four charged sidechains, e.g., meso-tetrakis[4-N-methylpyridiniumyl]- and meso-tetrakis[4-N-(2-hydroxyethyl)pyridiniumyl]-porphyrin, bound and intercalated similarly into DNA as measured by helix stabilization and DNA unwinding studies in the presence of DNA topoisomerase I. Despite their different bulky sidechains, these complexes gave essentially identical DNase I footprinting patterns. In contrast, tetrasubstituted porphyrins carrying three phenyl rings and a single positively charged pyridiniumyl sidechain did not intercalate and exhibited little affinity for DNA. Thus, the presence of charged sidechains on the porphyrin rather than their identity appears to be critical for efficient DNA intercalation. The results are discussed in regard to current models for the porphyrin-DNA intercalation complex

Physical Activity Advertisements That Feature Daily Well-Being Improve Autonomy and Body Image in Overweight Women but Not Men

The reasons for exercising that are featured in health communications brand exercise and socialize individuals about why they should be physically active. Discovering which reasons for exercising are associated with high-quality motivation and behavioral regulation is essential to promoting physical activity and weight control that can be sustained over time. This study investigates whether framing physical activity in advertisements featuring distinct types of goals differentially influences body image and behavioral regulations based on self-determination theory among overweight and obese individuals. Using a three-arm randomized trial, overweight and obese women and men (aged 40–60 yr, n = 1690) read one of three ads framing physical activity as a way to achieve (1) better health, (2) weight loss, or (3) daily well-being. Framing effects were estimated in an ANOVA model with pairwise comparisons using the Bonferroni correction. This study showed that there are immediate framing effects on physical activity behavioral regulations and body image from reading a one-page advertisement about physical activity and that gender and BMI moderate these effects. Framing physical activity as a way to enhance daily well-being positively influenced participants' perceptions about the experience of being physically active and enhanced body image among overweight women, but not men. The experiment had less impact among the obese study participants compared to those who were overweight. These findings support a growing body of research suggesting that, compared to weight loss, framing physical activity for daily well-being is a better gain-frame message for overweight women in midlife

Association between the timing of childhood adversity and epigenetic patterns across childhood and adolescence:Findings from the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective cohort

BackgroundChildhood adversity is a potent determinant of health across development and is associated with altered DNA methylation signatures, which might be more common in children exposed during sensitive periods in development. However, it remains unclear whether adversity has persistent epigenetic associations across childhood and adolescence. We aimed to examine the relationship between time-varying adversity (defined through sensitive period, accumulation of risk, and recency life course hypotheses) and genome-wide DNA methylation, measured three times from birth to adolescence, using data from a prospective, longitudinal cohort study.MethodsWe first investigated the relationship between the timing of exposure to childhood adversity between birth and 11 years and blood DNA methylation at age 15 years in the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective cohort study. Our analytic sample included ALSPAC participants with DNA methylation data and complete childhood adversity data between birth and 11 years. We analysed seven types of adversity (caregiver physical or emotional abuse, sexual or physical abuse [by anyone], maternal psychopathology, one-adult households, family instability, financial hardship, and neighbourhood disadvantage) reported by mothers five to eight times between birth and 11 years. We used the structured life course modelling approach (SLCMA) to identify time-varying associations between childhood adversity and adolescent DNA methylation. Top loci were identified using an R2 threshold of 0·035 (ie, ≥3·5% of DNA methylation variance explained by adversity). We attempted to replicate these associations using data from the Raine Study and Future of Families and Child Wellbeing Study (FFCWS). We also assessed the persistence of adversity-DNA methylation associations we previously identified from age 7 blood DNA methylation into adolescence and the influence of adversity on DNA methylation trajectories from ages 0-15 years.FindingsOf 13 988 children in the ALSPAC cohort, 609-665 children (311-337 [50-51%] boys and 298-332 [49-50%] girls) had complete data available for at least one of the seven childhood adversities and DNA methylation at 15 years. Exposure to adversity was associated with differences in DNA methylation at 15 years for 41 loci (R2 ≥0·035). Sensitive periods were the most often selected life course hypothesis by the SLCMA. 20 (49%) of 41 loci were associated with adversities occurring between age 3 and 5 years. Exposure to one-adult households was associated with differences in DNA methylation at 20 [49%] of 41 loci, exposure to financial hardship was associated with changes at nine (22%) loci, and physical or sexual abuse was associated with changes at four (10%) loci. We replicated the direction of associations for 18 (90%) of 20 loci associated with exposure to one-adult household using adolescent blood DNA methylation from the Raine Study and 18 (64%) of 28 loci using saliva DNA methylation from the FFCWS. The directions of effects for 11 one-adult household loci were replicated in both cohorts. Differences in DNA methylation at 15 years were not present at 7 years and differences identified at 7 years were no longer apparent by 15 years. We also identified six distinct DNA methylation trajectories from these patterns of stability and persistence.InterpretationThese findings highlight the time-varying effect of childhood adversity on DNA methylation profiles across development, which might link exposure to adversity to potential adverse health outcomes in children and adolescents. If replicated, these epigenetic signatures could ultimately serve as biological indicators or early warning signs of initiated disease processes, helping identify people at greater risk for the adverse health consequences of childhood adversity

De l’agressivité à la maternité. Étude longitudinale sur 30 ans auprès de filles agressives devenues mères : trajectoires de leur agressivité durant l’enfance, indicateurs de leurs caractéristiques parentales et développement de leurs enfants

L’agressivité chez les filles tend à ne pas se manifester de la même façon que chez les garçons ; de plus, elle suit une trajectoire longitudinale particulière. Les filles agressives envers leurs pairs ne se caractérisent pas tant par leurs manifestations de délinquance et de criminalité ; elles s’orientent plutôt vers une trajectoire de troubles sociaux et de santé mentale qui, à terme, compromet leur avenir scolaire, social et professionnel, de même que leur état de santé physique. Les compétences parentales des filles agressives, de même que le fonctionnement de leur famille, peuvent aussi être affectées ; dans ce cas, c’est la socialisation, la santé et le développement de toute une nouvelle génération d’enfants qui sont menacés. La Concordia Longitudinal Risk Project (Enquête longitudinale sur les risques, Université Concordia) suit un échantillon intergénérationnel de 1 770 sujets vivant à Montréal, dont un sous-échantillon de plus de 200 filles dites très agressives, et le compare avec un échantillon de garçons agressifs et un groupe témoin composé d’enfants des deux sexes. Les participants sont suivis de l’enfance à l’âge adulte sur une période de 30 ans. Le présent article décrit les trajectoires à long terme des filles agressives et les conséquences de cette agressivité sur une large variété d’éléments psychosociaux et de santé comme la maternité et la transmission des risques à la prochaine génération. Plus particulièrement, nous souhaitons : (1) établir les trajectoires des filles qui mènent de l’agressivité dans l’enfance au développement négatif à l’âge adulte, (2) établir les indicateurs de santé et les facteurs physiologiques connexes qui comportent des risques pour les filles agressives et leurs enfants et (3) évaluer comment l’agressivité à l’enfance se répercute sur le rôle maternel et le développement de la prochaine génération. Enfin, les retombées de nos conclusions seront discutées.Childhood aggression in girls may take different forms and follow different longitudinal trajectories from those typical of aggressive boys. Even when overt delinquency and criminality are avoided, girls who are aggressive towards their peers may follow a life course involving continuing social and mental health problems. From a longterm perspective, academic, social, health, and occupational achievement are likely to be negatively affected. Family functioning and parenting abilities may also be compromised, placing the offspring of these girls, a subsequent generation, at risk for social, health, and developmental problems. The Concordia Longitudinal Risk Project, which follows an intergenerational sample of 1770 inner-city Montrealers, includes a sub-sample of over 200 highly aggressive girls, with comparison groups of aggressive boys and normative children of both genders. Participants have been followed over a 30-year period, from childhood into adulthood. The present paper describes the long-term trajectories and sequelae of girlhood aggression in the context of a broad range of negative psychosocial and health outcomes, including parenting and the inter generational transfer of risk to offspring. More specifically, (1) trajectories by which childhood aggression places girls at risk for negative developmental outcomes are outlined, (2) health behaviours and physiological correlates that signify risk to aggressive girls and their offspring are delineated, and (3) pathways through which girlhood aggression influences parenting and offspring development are elucidated. Implications of these findings are discussed

An Abeis procera-derived tetracyclic triterpene containing a steroid-like nucleus core and a lactone side chain attenuates in vitro survival of both Fasciola hepatica and Schistosoma mansoni

Two economically and biomedically important platyhelminth species, Fasciola hepatica (liver fluke) and Schistosoma mansoni (blood fluke), are responsible for the neglected tropical diseases (NTDs) fasciolosis and schistosomiasis. Due to the absence of prophylactic vaccines, these NTDs are principally managed by the single class chemotherapies triclabendazole (F. hepatica) and praziquantel (S. mansoni). Unfortunately, liver fluke resistance to triclabendazole has been widely reported and blood fluke insensitivity/resistance to praziquantel has been observed in both laboratory settings as well as in endemic communities. Therefore, the identification of new anthelmintics is necessary for the sustainable control of these NTDs in both animal and human populations. Here, continuing our work with phytochemicals, we isolated ten triterpenoids from the mature bark of Abies species and assessed their anthelmintic activities against F. hepatica and S. mansoni larval and adult lifecycle stages. Full 1H and 13C NMR-mediated structural elucidation of the two most active triterpenoids revealed that a tetracyclic steroid-like nucleus core and a lactone side chain are associated with the observed anthelmintic effects. When compared to representative mammalian cell lines (MDBK and HepG2), the most potent triterpenoid (700015; anthelmintic EC50s range from 0.7 μM–15.6 μM) displayed anthelmintic selectivity (selectivity indices for F. hepatica: 13 for newly excysted juveniles, 46 for immature flukes, 2 for mature flukes; selectivity indices for S. mansoni: 14 for schistosomula, 9 for immature flukes, 4 for adult males and 3 for adult females) and induced severe disruption of surface membranes in both liver and blood flukes. S. mansoni egg production, a process responsible for pathology in schistosomiasis, was also severely inhibited by 700015. Together, our results describe the structural elucidation of a novel broad acting anthelmintic triterpenoid and support further investigations developing this compound into more potent analogues for the control of both fasciolosis and schistosomiasis. Keywords: Abies procera, Abies grandis, Triterpenoid, Anthelmintic drug discovery, Neglected tropical diseases, Fasciola hepatica, Schistosoma manson

Vegetation demographics in Earth System Models: A review of progress and priorities

Numerous current efforts seek to improve the representation of ecosystem ecology and vegetation demographic processes within Earth System Models (ESMs). These developments are widely viewed as an important step in developing greater realism in predictions of future ecosystem states and fluxes. Increased realism, however, leads to increased model complexity, with new features raising a suite of ecological questions that require empirical constraints. Here, we review the developments that permit the representation of plant demographics in ESMs, and identify issues raised by these developments that highlight important gaps in ecological understanding. These issues inevitably translate into uncertainty in model projections but also allow models to be applied to new processes and questions concerning the dynamics of real-world ecosystems. We argue that stronger and more innovative connections to data, across the range of scales considered, are required to address these gaps in understanding. The development of first-generation land surface models as a unifying framework for ecophysiological understanding stimulated much research into plant physiological traits and gas exchange. Constraining predictions at ecologically relevant spatial and temporal scales will require a similar investment of effort and intensified inter-disciplinary communication

Air quality and mental health: evidence, challenges and future directions

Background: Poor air quality is associated with poor health. Little attention is given to the complex array of environmental exposures and air pollutants that affect mental health during the life course. // Aims: We gather interdisciplinary expertise and knowledge across the air pollution and mental health fields. We seek to propose future research priorities and how to address them. // Method: Through a rapid narrative review, we summarise the key scientific findings, knowledge gaps and methodological challenges. // Results: There is emerging evidence of associations between poor air quality, both indoors and outdoors, and poor mental health more generally, as well as specific mental disorders. Furthermore, pre-existing long-term conditions appear to deteriorate, requiring more healthcare. Evidence of critical periods for exposure among children and adolescents highlights the need for more longitudinal data as the basis of early preventive actions and policies. Particulate matter, including bioaerosols, are implicated, but form part of a complex exposome influenced by geography, deprivation, socioeconomic conditions and biological and individual vulnerabilities. Critical knowledge gaps need to be addressed to design interventions for mitigation and prevention, reflecting ever-changing sources of air pollution. The evidence base can inform and motivate multi-sector and interdisciplinary efforts of researchers, practitioners, policy makers, industry, community groups and campaigners to take informed action. // Conclusions: There are knowledge gaps and a need for more research, for example, around bioaerosols exposure, indoor and outdoor pollution, urban design and impact on mental health over the life course

Association between the timing of childhood adversity and epigenetic patterns across childhood and adolescence:findings from the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective cohort

BACKGROUND: Childhood adversity is a potent determinant of health across development and is associated with altered DNA methylation signatures, which might be more common in children exposed during sensitive periods in development. However, it remains unclear whether adversity has persistent epigenetic associations across childhood and adolescence. We aimed to examine the relationship between time-varying adversity (defined through sensitive period, accumulation of risk, and recency life course hypotheses) and genome-wide DNA methylation, measured three times from birth to adolescence, using data from a prospective, longitudinal cohort study.METHODS: We first investigated the relationship between the timing of exposure to childhood adversity between birth and 11 years and blood DNA methylation at age 15 years in the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective cohort study. Our analytic sample included ALSPAC participants with DNA methylation data and complete childhood adversity data between birth and 11 years. We analysed seven types of adversity (caregiver physical or emotional abuse, sexual or physical abuse [by anyone], maternal psychopathology, one-adult households, family instability, financial hardship, and neighbourhood disadvantage) reported by mothers five to eight times between birth and 11 years. We used the structured life course modelling approach (SLCMA) to identify time-varying associations between childhood adversity and adolescent DNA methylation. Top loci were identified using an R 2 threshold of 0·035 (ie, ≥3·5% of DNA methylation variance explained by adversity). We attempted to replicate these associations using data from the Raine Study and Future of Families and Child Wellbeing Study (FFCWS). We also assessed the persistence of adversity-DNA methylation associations we previously identified from age 7 blood DNA methylation into adolescence and the influence of adversity on DNA methylation trajectories from ages 0-15 years. FINDINGS: Of 13 988 children in the ALSPAC cohort, 609-665 children (311-337 [50-51%] boys and 298-332 [49-50%] girls) had complete data available for at least one of the seven childhood adversities and DNA methylation at 15 years. Exposure to adversity was associated with differences in DNA methylation at 15 years for 41 loci (R 2 ≥0·035). Sensitive periods were the most often selected life course hypothesis by the SLCMA. 20 (49%) of 41 loci were associated with adversities occurring between age 3 and 5 years. Exposure to one-adult households was associated with differences in DNA methylation at 20 [49%] of 41 loci, exposure to financial hardship was associated with changes at nine (22%) loci, and physical or sexual abuse was associated with changes at four (10%) loci. We replicated the direction of associations for 18 (90%) of 20 loci associated with exposure to one-adult household using adolescent blood DNA methylation from the Raine Study and 18 (64%) of 28 loci using saliva DNA methylation from the FFCWS. The directions of effects for 11 one-adult household loci were replicated in both cohorts. Differences in DNA methylation at 15 years were not present at 7 years and differences identified at 7 years were no longer apparent by 15 years. We also identified six distinct DNA methylation trajectories from these patterns of stability and persistence. INTERPRETATION: These findings highlight the time-varying effect of childhood adversity on DNA methylation profiles across development, which might link exposure to adversity to potential adverse health outcomes in children and adolescents. If replicated, these epigenetic signatures could ultimately serve as biological indicators or early warning signs of initiated disease processes, helping identify people at greater risk for the adverse health consequences of childhood adversity.FUNDING: Canadian Institutes of Health Research, Cohort and Longitudinal Studies Enhancement Resources, EU's Horizon 2020, US National Institute of Mental Health.</p