Consequences of early adverse rearing experience(EARE) on development： insights from non-human primate studies

Early rearing experiences are important in one＇s whole life, whereas early adverse rearing experience（EARE） is usually related to various physical and mental disorders in later life. Although there were many studies on human and animals, regarding the effect of EARE on brain development, neuroendocrine systems, as well as the consequential mental disorders and behavioral abnormalities, the underlying mechanisms remain unclear. Due to the close genetic relationship and similarity in social organizations with humans, non-human primate（NHP） studies were performed for over 60 years. Various EARE models were developed to disrupt the early normal interactions between infants and mothers or peers. Those studies provided important insights of EARE induced effects on the physiological and behavioral systems of NHPs across life span, such as social behaviors（including disturbance behavior, social deficiency, sexual behavior, etc）, learning and memory ability, brain structural and functional developments（including influences on neurons and glia cells, neuroendocrine systems, e.g., hypothalamic-pituitary-adrenal（HPA） axis, etc）. In this review, the effects of EARE and the underlying epigenetic mechanisms were comprehensively summarized and the possibility of rehabilitation was discussed.

Early life adversity as a risk factor for cognitive impairment and Alzheimer’s disease

Neurological conditions,including cognitive impairment and Alzheimer’s disease(AD),impose a huge burden on society,affecting millions of people globally.In addition to genetic factors,recent studies indicate that environmental and experiential factors may contribute to the pathogenesis of these diseases.Early life adversity(ELA)has a profound impact on brain function and health later in life.In rodent models,exposure to ELA results in specific cognitive deficits and aggravated AD pathology.Extensive concerns have been raised regarding the higher risk of developing cognitive impairments in people with a history of ELA.In this review,we scrutinize findings from human and animal studies focusing on the connection of ELA with cognitive impairment and AD.These discoveries suggest that ELA,especially at early postnatal stages,increases susceptibility to cognitive impairment and AD later in life.In terms of mechanisms,ELA could lead to dysregulation of the hypothalamus-pituitary-adrenal axis,altered gut microbiome,persistent inflammation,oligodendrocyte dysfunction,hypomyelination,and aberrant adult hippocampal neurogenesis.Crosstalks among these events may synergistically contribute to cognitive impairment later in life.Additionally,we discuss several interventions that may alleviate adverse consequences of ELA.Further investigation into this crucial area will help improve ELA management and reduce the burden of related neurological conditions.

DNA Methylation,Behavior and Early Life Adversity

The impact of early physical and social environments on life-long phenotypes is well known. Moreover, we have documented evidence for gene-environment interactions where identical gene variants are associated with different phenotypes that are dependent on early life adversity. What are the mechanisms that embed these early life experiences in the genome？ DNA methylation is an enzymatically- catalyzed modification of DNA that serves as a mechanism by which similar sequences acquire cell type identity during cellular differentiation and embryogenesis in the same individual. The hypothesis that will be discussed here proposes that the same mechanism confers environmental-exposure specific identity upon DNA providing a mechanism for embedding environmental experiences in the genome, thus affecting long-term phenotypes. Particularly important is the environment early in life including both the prenatal and postnatal social environments.

Bleeding risk stratification in an era of aggressive management of acute coronary syndromes

Major bleeding is currently one of the most common non-cardiac complications observed in the treatment of patients with acute coronary syndrome(ACS). Hemorrhagic complications occur with a frequency of 1% to 10% during treatment for ACS. In fact, bleeding events are the most common extrinsic complication associated with ACS therapy. The identification of clinical characteristics and particularities of the antithrombin therapy associated with an increased risk of hemorrhagic complications would make it possible to adopt prevention strategies, especially among those exposed to greater risk. The international societies of cardiology renewed emphasis on bleeding risk stratification in order to decide strategy and therapy for patients with ACS. With this review, we performed an update about the ACS bleeding risk scores most frequently used in daily clinical practice.