Oxidative stress induces release of mitochondrial DNA into the extracellular space in human placental villous trophoblast BeWo cells.

Circulating cell-free mitochondrial DNA (ccf-mtDNA) is an indicator of cell death, inflammation, and oxidative stress. ccf-mtDNA in pregnancies with placental dysfunction differs from that in healthy pregnancies, and the direction of this difference depends on gestational age and method of mtDNA quantification. Reactive oxygen species (ROS) trigger release of mtDNA, yet it is unknown whether trophoblast cells release mtDNA in response to oxidative stress, a common feature of pregnancies with placental pathology. We hypothesized that oxidative stress would induce cell death and release of mtDNA from trophoblast cells. BeWo cells were treated with antimycin A (10-320 µM) or rotenone (0.2-50 µM) to induce oxidative stress. A multiplex real-time quantitative PCR (qPCR) assay was used to quantify mtDNA and nuclear DNA in membrane-bound, non-membrane-bound, and vesicle-bound forms in cell culture supernatants and cell lysates. Treatment with antimycin A increased ROS (P < 0.0001), induced cell necrosis (P = 0.0004) but not apoptosis (P = 0.6471), and was positively associated with release of membrane-bound and non-membrane-bound mtDNA (P < 0.0001). Antimycin A increased mtDNA content in exosome-like extracellular vesicles (vesicle-bound form; P = 0.0019) and reduced autophagy marker expression (LC3A/B, P = 0.0002; p62, P < 0.001). Rotenone treatment did not influence mtDNA release or cell death (P > 0.05). Oxidative stress induces release of mtDNA into the extracellular space and causes nonapoptotic cell death and a reduction in autophagy markers in BeWo cells, an established in vitro model of human trophoblast cells. Intersection between autophagy and necrosis may mediate the release of mtDNA from the placenta in pregnancies exposed to oxidative stress.NEW & NOTEWORTHY This is the first study to test whether trophoblast cells release mitochondrial (mt)DNA in response to oxidative stress and to identify mechanisms of release and biological forms of mtDNA from this cellular type. This research identifies potential cellular mechanisms that can be used in future investigations to establish the source and biomarker potential of circulating mtDNA in preclinical experimental models and humans.

Machine Learning: a new era for cardiovascular pregnancy physiology and cardio-obstetrics research.

The maternal cardiovascular system undergoes functional and structural adaptations during pregnancy and postpartum to support increased metabolic demands of offspring and placental growth, labor, and delivery, as well as recovery from childbirth. Pregnancy thus poses physiological stress upon the maternal cardiovascular system, and in the absence of an appropriate response it imparts potential risks for cardiovascular complications and adverse outcomes. The proportion of pregnancy-related maternal deaths from cardiovascular events has been steadily increasing, contributing to high rates of maternal mortality. Despite advances in cardiovascular physiology research, there is still no comprehensive understanding of maternal cardiovascular adaptations in healthy pregnancies, and with far less known about pregnancy with complications. Further, current tools for prognosis of cardiovascular complications during pregnancy are limited. Machine learning (ML) offers new and effective tools for investigating mechanisms involved in pregnancy-related cardiovascular complications as well as the development of potential therapies. The main goal of this review is to summarize existing research that uses ML to understand mechanisms of cardiovascular physiology during pregnancy and develop prediction models for clinical application in pregnant patients. We also provide an overview of ML fundamentals and a discussion about platforms that can be used to enhance understanding of cardiovascular adaptations to pregnancy. Finally, we address the interpretability and explainability of ML outcomes, consequences of model bias, and ethics of ML use.

Living through a pandemic: depression and anxiety experienced by youth living with HIV in South Africa.

Youth living with HIV (YLHIV) face significant psychosocial challenges and are at increasedrisk of developing depression and anxiety. This study aims to invesBgate symptoms ofdepression, anxiety and associaBons with psychosocial factors in YLHIV during the first andthird waves of the COVID-19 pandemic. This longitudinal study enrolled 135 YLHIV (ages 12-21) in Cape Town, South Africa. Measures administered telephonically included theCoRonavIruS Health Impact Survey (CRISIS quesBonnaire), Center for Epidemiologic StudiesDepression Scale (CES-D), Beck Anxiety Inventory and Beck Youth Inventory. During the firstwave of COVID-19, 7.5% and 8.0% of YLHIV were depressed (<18 and ≥18 years,respecBvely), and 10% and 4% of parBcipants were anxious (<18 and ≥18 years). During thethird wave, 8.9% and 40.6% of YLHIV were depressed (<18 and ≥18 years), and 13.3% and12.5% (<18 and ≥18 years) were anxious. Depression and anxiety were measured using cutoffscores provided by clinical measures. Symptoms of depression and anxiety in YLHIVescalated over the course of the COVID-19 pandemic. Socio-economic factors, substanceuse, disrupted support and stability concerns were associated with depression and anxiety.These data highlight the increasing need of mental health support and social intervenBonsfor YLHIV in post-pandemic South Africa.

Maternal and fetal mitochondrial gene dysregulation in hypertensive disorders of pregnancy.

Mitochondrial dysfunction has been implicated in pregnancy-induced hypertension (PIH). The role of mitochondrial gene dysregulation in PIH, and consequences for maternal-fetal interactions, remain elusive. Here, we investigated mitochondrial gene expression and dysregulation in maternal and placental tissues from pregnancies with and without PIH; further, we measured circulating mitochondrial DNA (mtDNA) mutational load, an index of mtDNA integrity. Differential gene expression analysis followed by Time Course Gene Set Analysis (TcGSA) was conducted on publicly available high throughput sequencing transcriptomic data sets. Mutational load analysis was carried out on peripheral mononuclear blood cells from healthy pregnant individuals and individuals with preeclampsia. Thirty mitochondrial differentially expressed genes (mtDEGs) were detected in the maternal cell-free circulating transcriptome, whereas nine were detected in placental transcriptome from pregnancies with PIH. In PIH pregnancies, maternal mitochondrial dysregulation was associated with pathways involved in inflammation, cell death/survival, and placental development, whereas fetal mitochondrial dysregulation was associated with increased production of extracellular vesicles (EVs) at term. Mothers with preeclampsia did not exhibit a significantly different degree of mtDNA mutational load. Our findings support the involvement of maternal mitochondrial dysregulation in the pathophysiology of PIH and suggest that mitochondria may mediate maternal-fetal interactions during healthy pregnancy.NEW & NOTEWORTHY This study identifies aberrant maternal and fetal expression of mitochondrial genes in pregnancies with gestational hypertension and preeclampsia. Mitochondrial gene dysregulation may be a common etiological factor contributing to the development of de novo hypertension in pregnancy-associated hypertensive disorders.

Circulating Cell-Free Mitochondrial DNA in Pregnancy.

Circulating cell-free mitochondrial DNA (ccf-mtDNA) released upon cell injury or death stimulates diverse pattern recognition receptors to activate innate immune responses and initiate systemic inflammation. In this review, we discuss the temporal changes of ccf-mtDNA during pregnancy and its potential contribution to adverse pregnancy outcomes in pregnancy complications.

Persistent accelerated epigenetic ageing in a longitudinal cohort of vertically infected HIV-positive adolescents.

We have previously shown accelerated ageing in adolescents perinatally infected with HIV (PHIV +), based on discrepancies between epigenetic and chronological age. The current study examines follow-up longitudinal patterns of epigenetic ageing and the association of epigenetic ageing with cognition as well as whole brain structure changes in PHIV + and healthy controls enrolled in the Cape Town Adolescent Antiretroviral Cohort Study (CTAAC). The Illumina EPIC array was used to generate blood DNA methylation data from 60 PHIV + adolescents and 36 age-matched controls aged 9-12 years old at baseline and again at a 36-month follow-up. Epigenetic clock software estimated two measures of epigenetic age acceleration: extrinsic epigenetic accelerated ageing (EEAA) and age acceleration difference (AAD) at both time points. At follow-up, each participant completed neuropsychological testing, structural magnetic resonance imaging, and diffusion tensor imaging. At follow-up, PHIV infection remains associated with increased EEAA and AAD. Accelerated epigenetic ageing remained positively associated with viral load and negatively associated with CD4 ratio. EEAA was positively associated with whole brain grey matter volume and alterations in whole brain white matter integrity. AAD and EEAA were not associated with cognitive function within the PHIV + group. Measures of epigenetic ageing, as detected in DNA methylation patterns, remain increased in PHIV + adolescents across a 36-month period. Associations between epigenetic ageing measures, viral biomarkers, and alterations in brain micro- and macrostructure also persist at 36-month follow-up. Further study should determine if epigenetic age acceleration is associated with cognitive functional changes due to brain alterations in later life.

Limited impact of a bioeroding sponge, Cliona sp., on Ostrea chilensis from Foveaux Strait, New Zealand.

Bioeroding sponges can cause extensive damage to aquaculture and wild shellfish fisheries. It has been suggested that heavy sponge infestations that reach the inner cavity of oysters may trigger shell repair and lead to adductor detachment. Consequently, energy provision into shell repair could reduce the energy available for other physiological processes and reduce the meat quality of commercially fished oysters. Nevertheless, the impacts of boring sponges on oysters and other shellfish hosts are inconclusive. We studied the interaction between boring sponges and their hosts and examined potential detrimental effects on an economically important oyster species Ostrea chilensis from Foveaux Strait (FS), New Zealand. We investigated the effect of different infestation levels with the bioeroding sponge Cliona sp. on commercial meat quality, condition, reproduction, and disease susceptibility. Meat quality was assessed with an index based on visual assessments used in the FS O. chilensis fishery. Meat condition was assessed with a common oyster condition index, while histological methods were used to assess sex, gonad stage, reproductive capacity, and pathogen presence. Commercial meat quality and condition of O. chilensis were unaffected by sponge infestation. There was no relationship between sex ratio, gonad developmental stage, or gonad index and sponge infestation. Lastly, we found no evidence that sponge infestation affects disease susceptibility in O. chilensis. Our results suggest that O. chilensis in FS is largely unaffected by infestation with Cliona sp. and therefore reinforces the growing body of evidence that the effects of sponge infestation can be highly variable among different host species, environments, and habitats.

Preexposure Prophylaxis Implementation in a Reproductive Health Setting: Perspectives From Planned Parenthood Providers and Leaders.

Integrating pregnancy and HIV prevention services would make reproductive health care settings an optimal venue for the promotion and delivery of preexposure prophylaxis (PrEP) to cisgender women. However, these settings have been slow to adopt PrEP. Planned parenthood clinicians and leaders possess critical insight that can help accelerate PrEP implementation in reproductive health care settings and elements of the Consolidated Framework for Implementation Research (i.e., relative priority of the intervention to staff, implementation climate, available resources to implement the intervention, and staff access to knowledge and information about the intervention) can shed light on elements of Planned Parenthood's inner setting that can facilitate PrEP implementation. In this study, individual 60-min interviews were conducted with clinical care team members (n = 10), leadership team members (n = 6), and center managers (n = 2) to explore their perspectives on PrEP implementation and associated training needs. Transcripts were transcribed verbatim and thematically analyzed. Despite having variable PrEP knowledge, participants (100% women, 61% non-Hispanic White) expressed positive attitudes toward implementing PrEP. Barriers and facilitators toward providing PrEP were reported at the structural, provider, and patient levels. Participants desired PrEP training that incorporated culturally competent patient-provider communication. Although participants identified ways that Planned Parenthood uniquely enabled PrEP implementation, barriers must be overcome to optimize promotion and delivery of PrEP to cisgender women.

Patient genetics is linked to chronic wound microbiome composition and healing.

The clinical importance of microbiomes to the chronicity of wounds is widely appreciated, yet little is understood about patient-specific processes shaping wound microbiome composition. Here, a two-cohort microbiome-genome wide association study is presented through which patient genomic loci associated with chronic wound microbiome diversity were identified. Further investigation revealed that alternative TLN2 and ZNF521 genotypes explained significant inter-patient variation in relative abundance of two key pathogens, Pseudomonas aeruginosa and Staphylococcus epidermidis. Wound diversity was lowest in Pseudomonas aeruginosa infected wounds, and decreasing wound diversity had a significant negative linear relationship with healing rate. In addition to microbiome characteristics, age, diabetic status, and genetic ancestry all significantly influenced healing. Using structural equation modeling to identify common variance among SNPs, six loci were sufficient to explain 53% of variation in wound microbiome diversity, which was a 10% increase over traditional multiple regression. Focusing on TLN2, genotype at rs8031916 explained expression differences of alternative transcripts that differ in inclusion of important focal adhesion binding domains. Such differences are hypothesized to relate to wound microbiomes and healing through effects on bacterial exploitation of focal adhesions and/or cellular migration. Related, other associated loci were functionally enriched, often with roles in cytoskeletal dynamics. This study, being the first to identify patient genetic determinants for wound microbiomes and healing, implicates genetic variation determining cellular adhesion phenotypes as important drivers of infection type. The identification of predictive biomarkers for chronic wound microbiomes may serve as risk factors and guide treatment by informing patient-specific tendencies of infection.

Accelerated epigenetic aging in adolescents living with HIV is associated with altered development of brain structures.

We recently demonstrated that adolescents perinatally infected with HIV-1 (PHIV+) have accelerated aging as measured by a highly accurate epigenetic biomarker of aging known as the epigenetic clock. However, whether epigenetic age acceleration in PHIV+ impacts brain development at the macro- and microstructural levels of brain anatomy has not been studied. We report on a cross-sectional study of PHIV+ enrolled in the Cape Town Adolescent Antiretroviral Cohort (CTAAC). The Illumina Infinium Methylation EPIC array was used to generate DNA methylation data from the blood samples of 180 PHIV+ aged 9 to 12 years. The epigenetic clock software and method was used to estimate two measures, epigenetic age acceleration (AgeAccelerationResidual) and extrinsic epigenetic age acceleration (EEAA). Each participant underwent T1 structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). In order to investigate the associations of chronological age, sex, epigenetic age acceleration and treatment variables (CNS penetration effectiveness score (CPE)) of antiretroviral regimen on brain structure in PHIV+, we developed stepwise multiple regression models in R (version 3.4.3, 2017) including grey and white matter volumes, cortical thickness, cortical surface area and DTI measures of white matter microstructural integrity. The mean DNAm age (16.01 years) of the participants was higher than their mean chronological age (10.77 years). Epigenetic age acceleration contributed more to regional alterations of brain volumes, cortical thickness, cortical surface areas and neuronal microstructure than chronological age, in a range of regions. CPE positively contributed to volume of the brain stem. Understanding the drivers of epigenetic age acceleration could lead to valuable insights into structural brain alterations, and the persistence of neurocognitive disorders in seen in PHIV+ .

HIV-Related Stigma and Psychological Adjustment Among Perinatally HIV-Infected Youth in Cape Town, South Africa.

The effect of chronic HIV-infection on psychological adjustment, including the impact of HIV-related stigma in perinatally HIV-infected (PHIV+) youth across Africa is largely unknown. This study examined psychological adjustment and HIV-related stigma using the Strengths and Difficulties Questionnaire (SDQ) and a 10-item stigma questionnaire in a cohort of PHIV+ youth in Cape Town, South Africa. The relationships between SDQ scores, elevated viral load, and suboptimal antiretroviral therapy (ART) adherence were also explored. Among 473 PHIV+ youth (aged 9-14 years, on ART > 6 months at enrollment), higher perceived HIV-related stigma was associated with higher scores across all adolescent and caregiver-reported SDQ difficulty subscales. Higher socioeconomic status (SES) was associated with lower scores on adolescent self- and caregiver-reported hyperactivity subscales. Higher adolescent-reported prosocial scores were associated with lower odds of self-reported suboptimal ART adherence, and higher caregiver-reported conduct scores were associated with higher odds of elevated viral load. No associations were observed between perceived HIV-related stigma and treatment outcomes. These findings highlight the potentially detrimental impact of perceived stigma on psychological adjustment in PHIV+ youth. The use of psychosocial metrics and interventions aimed at reducing illness related stigma in PHIV+ youth is also considered.

The association between mental health and metabolic outcomes in youth living with perinatally acquired HIV in the Cape Town Adolescent Antiretroviral Cohort.

Youth living with perinatally acquired HIV (YLPHIV) have been found to have a range of mental disorders. Some adult HIV studies have linked mental health to adverse metabolic outcomes due to dysregulation of the sympathetic nervous system and hypothalamic-pituitary-adrenal axis, but this association has not previously been explored in YLPHIV.We investigated the association of mental health measures with metabolic outcomes in YLPHIV and HIV-uninfected youth (HIV-U) and linear regression was used to assess the adjusted associations.Overall, 203 YLPHIV (median age = 10.7years; 52% female; mean duration on ART 8 years, 12% CD4 count <500 cells/µL, 18% viral load >50 copies/mL) and 44 HIV-U (median age = 10.3 years; 55% female) were enrolled. YLPHIV had higher median total cholesterol (4.2 vs 3.9 mmol/L, p = 0.049) and triglyceride (0.9 vs 0.7 mmol/L, p < 0.001) compared to HIV-U. We found higher percentage of poor functional competence (40% vs 25%, p = 0.02) and self-concept (23% vs 9%, p = 0.03) and higher depression (6% vs 2%, p < 0.01), anger (6% vs 2%, p = 0.04) and disruptive behaviour (4% vs 0%, p < 0.01) in YLPHIV as compared to HIV-U. Among YLPHIV, higher scores of anger were associated with higher total cholesterol and higher low-density lipoprotein (ß = 0.010, p = 0.041 and ß = 0.012, p = 0.048 respectively) and disruptive behaviour with higher low-density lipoprotein (ß = 0.010, p = 0.043) after adjusting for age, sex and BMIZ.This is the one of first study to investigate the association of mental health with metabolic outcomes among YLPHIV. The association of increased anger and disruptive behaviour with increased lipid concentration is a novel finding. Further longitudinal studies are needed to evaluate the causal relationships between mental health and metabolic outcomes.

Youth perinatal HIV-associated neurocognitive disorders: association with functional impairment.

HIV-associated functional impairment may cause cognitive impairment secondary to the viral infection, hence, associations between cognitive impairment and functional impairment in youth living with HIV are important to assess. We sought to determine whether cognitive impairment is associated with functional impairment and if it carries higher risk for also having functional impairment. We collected parent-rated information regarding youth functional impairment on four different measures and administered a cognitive battery to youth to determine cognitive impairment, 203 HIV-infected youth and 44 HIV-uninfected controls. Degree of cognitive impairment correlated strongly with decreased function: CBCL, r = -.17, p = .01; VABS2, r = -.28, p < .001; repeated-grades, r = .26, p < .001. Presence of cognitive impairment was associated with increased risk of functional impairment: 3.47 (CIS); 1.71 (CBCL); 2.17 (VABS2); 2.97 (repeated-grades). Repeated-grades strongly associated with cognitive impairment and functional impairment. We found strong associations between HIV-infected youth functional impairment on CBCL, VABS2 and repeated-grades with degree of cognitive impairment; and that when cognitive impairment was present youth had higher risk of experiencing functional impairment as well. Asking whether youth have repeated a grade at school could be a helpful screening question for assessing potential functional impairment and provide clinicians with an indication as to whether a further in-depth assessment is required.

Pharmacotherapy for post traumatic stress disorder (PTSD).

BACKGROUND: Posttraumatic stress disorder (PTSD) is a prevalent and disabling disorder. Evidence that PTSD is characterised by specific psychobiological dysfunctions has contributed to a growing interest in the use of medication in its treatment. OBJECTIVES: To assess the effects of medication for reducing PTSD symptoms in adults with PTSD. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 11, November 2020); MEDLINE (1946-), Embase (1974-), PsycINFO (1967-) and PTSDPubs (all available years) either directly or via the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR). We also searched international trial registers. The date of the latest search was 13 November 2020. SELECTION CRITERIA: All randomised controlled trials (RCTs) of pharmacotherapy for adults with PTSD. DATA COLLECTION AND ANALYSIS: Three review authors (TW, JI, and NP) independently assessed RCTs for inclusion in the review, collated trial data, and assessed trial quality. We contacted investigators to obtain missing data. We stratified summary statistics by medication class, and by medication agent for all medications. We calculated dichotomous and continuous measures using a random-effects model, and assessed heterogeneity. MAIN RESULTS: We include 66 RCTs in the review (range: 13 days to 28 weeks; 7442 participants; age range 18 to 85 years) and 54 in the meta-analysis.  For the primary outcome of treatment response, we found evidence of beneficial effect for selective serotonin reuptake inhibitors (SSRIs) compared with placebo (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.59 to 0.74; 8 studies, 1078 participants), which improved PTSD symptoms in 58% of SSRI participants compared with 35% of placebo participants, based on moderate-certainty evidence.  For this outcome we also found evidence of beneficial effect for the noradrenergic and specific serotonergic antidepressant (NaSSA) mirtazapine: (RR 0.45, 95% CI 0.22 to 0.94; 1 study, 26 participants) in 65% of people on mirtazapine compared with 22% of placebo participants, and for the tricyclic antidepressant (TCA) amitriptyline (RR 0.60, 95% CI 0.38 to 0.96; 1 study, 40 participants) in 50% of amitriptyline participants compared with 17% of placebo participants, which improved PTSD symptoms. These outcomes are based on low-certainty evidence. There was however no evidence of beneficial effect for the number of participants who improved with the antipsychotics (RR 0.51, 95% CI 0.16 to 1.67; 2 studies, 43 participants) compared to placebo, based on very low-certainty evidence. For the outcome of treatment withdrawal, we found evidence of a harm for the individual SSRI agents compared with placebo (RR 1.41, 95% CI 1.07 to 1.87; 14 studies, 2399 participants). Withdrawals were also higher for the separate SSRI paroxetine group compared to the placebo group (RR 1.55, 95% CI 1.05 to 2.29; 5 studies, 1101 participants). Nonetheless, the absolute proportion of individuals dropping out from treatment due to adverse events in the SSRI groups was low (9%), based on moderate-certainty evidence. For the rest of the medications compared to placebo, we did not find evidence of harm for individuals dropping out from treatment due to adverse events. AUTHORS' CONCLUSIONS: The findings of this review support the conclusion that SSRIs improve PTSD symptoms; they are first-line agents for the pharmacotherapy of PTSD, based on moderate-certainty evidence. The NaSSA mirtazapine and the TCA amitriptyline may also improve PTSD symptoms, but this is based on low-certainty evidence. In addition, we found no evidence of benefit for the number of participants who improved following treatment with the antipsychotic group compared to placebo, based on very low-certainty evidence. There remain important gaps in the evidence base, and a continued need for more effective agents in the management of PTSD.

Global Systematic Review of Common Mental Health Disorders in Adults Living with HIV.

PURPOSE OF THE REVIEW: By reviewing the most recent common mental health disorders (CMHD) studies in people living with HIV (PLWH) (2018-2020), this review discusses the prevalence of CMHD, factors associated with CMHD in PLWH, mental health in PLWH from vulnerable groups, the impact of CMHD on HIV disease progression and adherence to antiretroviral therapy and the efficacy of different treatment approaches. RECENT FINDINGS: After screening for eligibility 142 studies were included in the final systematic review. Only 27% of studies were conducted in Sub-Saharan Africa, which carries the highest burn of HIV disease globally. Despite the well-established increased risk of CMHD in PLWH, the current prevalence remains high, with studies reporting 28%-62% of PLWH having mental health symptoms. CONCLUSION: Despite the significant challenges that CMHDs present to successful HIV treatment, there are many mental health treatments and interventions which can improve outcomes in PLWH and opportunities to task-shift and integrate mental health care with HIV care.

Genetic evidence supports a range extension for the Brazilian cownose ray Rhinoptera brasiliensis in the western North Atlantic.

We report 24 new records of the Brazilian cownose ray Rhinoptera brasiliensis outside its accepted geographic range. Sequencing of a 442-base pair portion of the mitochondrial NADH dehydrogenase subunit 2 gene for 282 Rhinoptera samples revealed eight records off the east coast of the USA and 16 from the eastern Gulf of Mexico. Both sexes of all life stages were documented in all seasons over multiple years in the Indian River and Lake Worth lagoons, Florida, indicating that their range extends further in the western North Atlantic than previously described.

Depression, anxiety and stress among Australian nursing and midwifery undergraduate students during the COVID-19 pandemic: a cross-sectional study.

OBJECTIVES: To assess depression, anxiety and stress among undergraduate nursing and midwifery students during the COVID-19 pandemic, and identify socio-demographic and educational characteristics associated with higher depression, anxiety and stress scores. METHODS: Cross-sectional study during August-September 2020, using an anonymous, online, self-administered survey. E-mail invitations with a survey link were sent to 2,907 students enrolled in the Bachelor of Nursing suite of courses, offered across four campuses of a single university in Victoria, Australia. Depression, anxiety and stress were assessed using the DASS-21. Data on socio-demographic and educational characteristics, self-rated physical health and exposure to COVID-19 were also collected. DASS-21 subscale scores were compared with existing data for various pre-pandemic and COVID-19 samples. Multiple regression was used to investigate factors associated with higher scores on depression, anxiety and stress subscales. RESULTS: The response rate was 22% (n=638). Mean scores on all DASS-21 subscales were significantly higher (p<0.001) than means from all comparative sample data. The proportions of students reporting moderate to severe symptoms of depression, anxiety and stress were 48.5%, 37.2% and 40.2% respectively. Being a woman, being younger, having completed more years of study and having poorer self-rated general health were all significantly associated (p<0.05) with higher scores on at least one DASS-21 subscale. CONCLUSIONS: Almost half of participants reported at least moderate symptoms of depression; more than a third reported at least moderate symptoms of anxiety or stress. Poor psychological wellbeing can impact students' successful completion of their studies and therefore, has implications for nursing and midwifery workforce recruitment and retention. During and after pandemics, universities should consider screening undergraduate students not only for anxiety and stress, but also for depression. Clear, low-cost referral pathways should be available, should screening indicate that further diagnosis or treatment is required.

Tendency to ruminate and anxiety are associated with altered alpha and beta oscillatory power dynamics during memory for contextual details.

Rumination occurs when an individual becomes mentally stuck and cannot redirect attention away from an unwanted thought demonstrating cognitive inflexibility. Cognitive flexibility is important for various cognitive functions, including episodic memory. Trait rumination is a partial mediator in the relationship between depression and overgeneral episodic memory, suggesting that rumination may negatively influence memory for contextual details. Oscillations in the alpha (8-12 Hz) and beta (13-30 Hz) frequency bands are crucial for various cognitive functions (e.g., attention control and episodic memory) and may help to explain the relationship between trait rumination and memory for contextual details. Our study uses EEG recorded during a source memory task to assess how alpha and beta oscillations during memory for contextual details may change as a function of trait rumination, anxiety, and depression level (n = 43). The source memory task instructs participants to remember objects and their associated contextual details. Memory for contextual details is lessened for participants higher in trait rumination paired with higher trait anxiety. Oscillations were analyzed in posterior parietal/occipital regions. During encoding, an interaction of nonclinical depression level and rumination predicts higher alpha power for items that were later not successfully remembered. During test, depression and rumination interact and predict higher alpha power for both successful and unsuccessful memory. These results suggest that trait anxiety, depression, and rumination impact accuracy and alpha oscillatory dynamics during contextual memory via changes in attention control.

Cell-free mitochondrial DNA increases in maternal circulation during healthy pregnancy: a prospective, longitudinal study.

Mitochondrial DNA (mtDNA) exposed to the extracellular space due to cell death has immunostimulatory properties. Case-control studies reported a positive association between odds of developing preeclampsia and circulating mtDNA. These findings are based on relative quantification protocols that do not allow determination of absolute concentrations of mtDNA and are highly sensitive to nuclear DNA contamination. Furthermore, circulating mtDNA concentrations in response to normal pregnancy, which is an inflammatory state characterized by continuous placental cell apoptosis, have not been established. The main objective of this study was to determine longitudinal changes in circulating mtDNA from preconception to first trimester, third trimester, and postpartum in healthy pregnant women. Absolute real-time PCR quantification of mtDNA and nuclear DNA (nDNA) was performed on whole genomic extracts from serum using TaqMan probes and chemistry. Serum cell-free mtDNA and nDNA concentrations were greater in late pregnancy as compared with early pregnancy and postpartum. Pregnant women carrying neonates at the upper quartile of birth length distribution had higher concentrations of mtDNA in late pregnancy compared with pregnancies carrying neonates at the lower quartile. The correlation between circulating mtDNA and nDNA concentrations varied by sex (i.e., pregnancies carrying female vs. male fetuses). This study is the first to establish temporal patterns of circulating cell-free mtDNA concentrations in normal human pregnancy using absolute DNA quantification techniques. Concentrations of circulating mtDNA in normal pregnancy may be used as reference values for the development of clinical prognostic or diagnostic tests in pregnant women with, or at risk of developing, gestational complications.