Pregnancy stressors and postpartum symptoms of depression and anxiety:the moderating role of a cognitivebehavioural therapy(CBT)intervention

Background Little is known about the association between stressors(especially positive stressors)during pregnancy and postpartum depression and anxiety.Aims We investigated the association between positive and negative stress events during different stages of pregnancy and postpartum mental health outcomes among low-income pregnant women with symptoms of anxiety in Pakistan and evaluated whether an intervention based on cognitive behavioural therapy(CBT)had a regulatory effect.Methods Participants were 621 pregnant Pakistani women with mild anxiety.Using the Pregnancy Experience Scale-Brief Version,six scores were created to assess positive and negative stressors.We performed a multivariate linear regression to examine whether these six scores,measured both at baseline and in the third trimester,were associated with postpartum anxiety and depressive symptoms.The effect of the intervention on this relationship was examined by adding an interaction term to the regression model.Results Hassles frequency measured in the third trimester was positively associated with depression(B=0.22,95%confidence interval(Cl):0.09 to 0.36)and anxiety(B=0.19,95%Cl:0.08to 0.30).At the same timepoint,uplifts intensity was negatively associated with symptoms of depression(B=-0.82,95%Cl:1.46 to-0.18)and anxiety(B=-0.70,95%Cl:-1.25 to-0.15),whereas hassles intensity was positively related to symptoms of depression(B=1.02,95%Cl:0.36 to 1.67)and anxiety(B=0.90,95%Cl:0.34 to 1.47).The intensity ratio of hassles to uplifts reported in the third trimester was positively related to both depression(B=1.40,95%Cl:0.59 to 2.20)and anxiety(B=1.26,95%Cl:0.57 to 1.96).The intervention strengthened the overall positive effects of uplfts and the negative effects of hassles.Pregnancy experiences at baseline during early pregnancy to mid-pregnancy were not associated with mental health outcomes.Conclusions Stressors in the third trimester but not earlier in pregnancy were associated with postpartum symptoms of anxiety and depression.The CBT intervention modified the association between pregnancy stressors and postpartum mental health outcomes.Programmes that promote positive experiences and reduce negative experiences,especially in late pregnancy,may mitigate postpartum mental health consequences.

Graphene quantum dots rescue protein dysregulation of pancreatic β-cells exposed to human islet amyloid polypeptide

The amyloid aggregation of peptides and proteins is a hallmark of neurological disorders and type 2 diabetes.Human islet amyloid polypeptide(IAPP),co-secreted with insulin by pancreaticβ-cells,plays dual roles in both glycemic control and the pathology of type 2 diabetes.While IAPP can activate the NLRP3 inflammasome and modulate cellular autophagy,apoptosis and extracellular matrix metabolism,no data is available concerning intracellular protein expression upon exposure to the polypeptide.More surprisingly,how intracellular protein expression is modulated by nanoparticle inhibitors of protein aggregation remains entirely unknown.In this study,we first examined the changing proteomes ofβTC6,a pancreaticβ-cell line,upon exposure to monomeric,oligomeric and fibrillar IAPP,and detailed cellular protein expression rescued by graphene quantum dots(GQDs),an IAPP inhibitor.We found that 29 proteins were significantly dysregulated by the IAPP species,while majority of these proteins were nucleotide-binding proteins.Collectively,our liquid chromatography tandem-mass spectrometry,fluorescence quenching,helium ion microscopy,cytotoxicity and discreet molecular dynamics simulations data revealed a remarkable capacity of GQDs in regulating aberrant protein expression through H-bonding and hydrophobic interactions,pointing to nanomedicine as a new frontier against human amyloid diseases.

Physical and toxicological profiles of human IAPP amyloids and plaques

Although much has been learned about the fibrillization kinetics, structure and toxicity of amyloid proteins, the properties of amyloid fibrils beyond the saturation phase are often perceived as chemically and biologically inert, despite evidence suggesting otherwise. To fill this knowledge gap, we examined the physical and biological characteristics of human islet amyloid polypeptide(IAPP) fibrils that were aged up to two months. Not only did aging decrease the toxicity of IAPP fibrils, but the fibrils also sequestered fresh IAPP and suppressed their toxicity in an embryonic zebrafish model. The mechanical properties of IAPP fibrils in different aging stages were probed by atomic force microscopy and sonication, which displayed comparable stiffness but age-dependent fragmentation, followed by self-assembly of such fragments into the largest lamellar amyloid structures reported to date. The dynamic structural and toxicity profiles of amyloid fibrils and plaques suggest that they play active, long-term roles in cell degeneration and may be a therapeutic target for amyloid diseases.