The impact of prenatal maternal mental health on offspring socioemotional development is substantial and enduring. Existing literature primarily focuses on the effects of psychological distress ...during pregnancy, emphasizing adverse child outcomes. Recent studies, however, highlight the unique impact of positive maternal mental health on child outcomes. To elucidate the differential associations of maternal psychological distress and positive mental health during pregnancy with child outcomes, we conducted a systematic literature search and random-effects meta-analyses on studies investigating the associations of prenatal maternal mental health with child socioemotional development. Our analyses, comprising 74 studies with 321,966 mother-child dyads across 21 countries, revealed significant associations of prenatal psychological distress with both adverse and positive child socioemotional outcomes. Notably, the effect sizes for the association of psychological distress with positive child outcomes were smaller compared to adverse outcomes. Positive prenatal mental health, on the other hand, was significantly associated with positive socioemotional outcomes but not adverse outcomes. This meta-analysis highlights the independence of negative and positive prenatal mental health constructs and their distinct relationships with child socioemotional development. The findings underscore the importance of considering the positive spectrum of maternal mental health and developmental outcomes to enhance our understanding of prenatal influences on child development.
Systematic Review Registration:
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=335227
, identifier CRD42022335227.
It is commonly stated that mortality from acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) is decreasing.
To systematically review the literature assessing ARDS mortality over ...time and to determine patient- and study-level factors independently associated with mortality.
We searched multiple databases (MEDLINE, EMBASE, CINAHL, Cochrane CENTRAL) for prospective observational studies or randomized controlled trials (RCTs) published during the period 1984 to 2006 that enrolled 50 or more patients with ALI/ARDS and reported mortality. We pooled mortality estimates using random-effects meta-analysis and examined mortality trends before and after 1994 (when a consensus definition of ALI/ARDS was published) and factors associated with mortality using meta-regression models.
Of 4,966 studies, 89 met inclusion criteria (53 observational, 36 RCTs). There was a total of 18,900 patients (mean age 51.6 years; 39% female). Overall pooled weighted mortality was 44.3% (95% confidence interval CI, 41.8-46.9). Mortality decreased with time in observational studies conducted before 1994; no temporal associations with mortality were demonstrated in RCTs (any time) or observational studies (after 1994). Pooled mortality from 1994 to 2006 was 44.0% (95% CI, 40.1-47.5) for observational studies, and 36.2% (95% CI, 32.1-40.5) for RCTs. Meta-regression identified study type (observational versus RCT, odds ratio, 1.36; 95% CI, 1.08-1.73) and patient age (odds ratio per additional 10 yr, 1.27; 95% CI, 1.07-1.50) as the only factors associated with mortality.
A decrease in ARDS mortality was only seen in observational studies from 1984 to 1993. Mortality did not decrease between 1994 (when a consensus definition was published) and 2006, and is lower in RCTs than observational studies.
Summary
Perinatal depression and anxiety are common and associated with sleep problems in the offspring. Depression and anxiety are commonly comorbid, yet often studied independently. Our study used ...an integrative measure of anxiety and depressive symptoms to examine the associations of maternal mental health (mid‐pregnancy and postnatal) with infant sleep during the first year of life. A total of 797 mother–child dyads from the ‘Growing Up in Singapore Towards healthy Outcome’ cohort study provided infant sleep data at 3, 6, 9 and 12 months of age, using the caregiver reported Brief Infant Sleep Questionnaire. Maternal mental health was assessed at 26–28 weeks gestation and 3 months postpartum using the Edinburgh Postnatal Depression Scale, Beck Depression Inventory and State–Trait Anxiety Inventory. Bifactor modelling with the individual questionnaire items produced a general affect factor score that provided an integrated measure of anxiety and depressive symptoms. Linear mixed models were used to model the sleep outcomes, with adjustment for maternal age, education, parity, ethnicity, sex of the child and maternal sleep quality concurrent with maternal mental health assessment. We found that poorer mid‐pregnancy, but not postpartum, maternal mental health was associated with longer wake after sleep onset duration across the first year of life (β = 49, 95% confidence interval 13–85 min). Poor maternal mental health during mid‐pregnancy is linked to longer period of night awakening in the offspring during infancy. Interventions that aim to improve maternal antenatal mental health should examine infant sleep outcomes.
Activation of AMP-activated protein kinase (AMPK) is thought to convey many of the beneficial effects of exercise via its inhibitory effect on acetyl-CoA carboxylase 2 (ACC2) and promotion of fatty ...acid oxidation. Hence, AMPK and ACC have become major drug targets for weight loss and improved insulin action. However, it remains unclear whether or how activation of the fatty acid oxidation pathway without a concomitant increase in energy expenditure could be beneficial. Here, we have used either pharmacological (administration of the AMPK agonist 5
′ aminoimidazole-4-carboxamide-riboside) or genetic means (mutation of the
ACC2 gene in mice) to manipulate fatty acid oxidation to determine whether this is sufficient to promote leanness. Both of these strategies increased whole-body fatty acid oxidation without altering energy expenditure or adiposity. We conclude that negative energy balance is a prerequisite for weight reduction, and increased fatty acid oxidation per se has little, if any, effect to reduce adiposity.
► Coercing the body to preferentially burn fat does not decrease body fat ► Chronic lipid oxidation decreases glucose oxidation, but not glycolysis ► Increased energy expenditure is requisite for leanness ► Utilizing fat as the primary energy source does not cause leanness
The molecular mechanisms underlying constitutive nuclear factor-κB (NF-κB) activation in solid tumors has not been elucidated. We show that Annexin-1 (ANXA1) is involved in this process, and ...suppression of ANXA1 in highly metastatic breast cancer cells impedes migration and metastasis capabilities in vitro and in vivo. ANXA1 expression correlates with NF-κB activity, suggesting that ANXA1 may be required for the constitutive activity of IκB kinase (IKK) and NF-κB in highly metatstatic breast cancer. Gel-filtration analysis demonstrated that ANXA1 co-elutes with the members of the IKK complex and NF-κB signaling pathway, and immunoprecipitation confirmed that ANXA1 can bind to and interact with IKKγ or NEMO, but not IKKα or IKKβ. Importantly, silencing of ANXA1 prevents the interaction of NEMO and RIP1, which indicates that ANXA1 is required for the recruitment of RIP1 to the IKK complex, which may be important for the activation of NF-κB. Downstream targets of NF-κB include uPA and CXCR4, which can be modulated by ANXA1 silencing. CXCR4-mediated migration of breast cancer cell lines in response to CXCL12 was significantly modulated by ANXA1, indicating its importance in the tissue-specific migration of breast cancer cells. Chromatin immunoprecipitation experiments confirmed that in ANXA1 overexpressed cells, NF-κB was recruited to CXCR4 promoter without external stimulation, indicating that ANXA1 is critical for the constitutive activation of NF-κB in breast cancer to promote metastasis. Finally, we show that ANXA1 overexpression enhances metastasis and reduces survival in an intracardiac metastasis model, while ANXA1-deficient mice crossed with MMTV-PyMT mice display significantly less metastasis than their heterozygous littermates, indicating that ANXA1 is an important gene in breast cancer metastasis. Our data reveal that ANXA1 can constitutively activate NF-κB in breast cancer cells through the interaction with the IKK complex, and suggests that modulating ANXA1 levels has therapeutic potential to suppress breast cancer metastasis. PUBLICATION ABSTRACT
Facial eczema (FE) is a hepato‐mycotoxicosis found mainly in New Zealand sheep and cattle. When genetics was found to be a factor in FE susceptibility, resistant and susceptible selection lines of ...Romney sheep were established to enable further investigations of this disease trait. Using the Illumina OvineSNP50 BeadChip, we conducted a selection‐sweep experiment on these FE genetic lines. Two analytical methods were used to detect selection signals, namely the Peddrift test (Dodds & McEwan, 1997) and fixation index FST (Weir & Hill, 2002). Of 50 975 single nucleotide polymorphism (SNP) markers tested, there were three that showed highly significant allele frequency differences between the resistant and susceptible animals (Peddrift nominal P < 0.000001). These SNP loci are located on chromosomes OAR1, OAR11 and OAR12 that coincide precisely with the three highest genomic FST peaks. In addition, there are nine less significant Peddrift SNPs (nominal P ≤ 0.000009) on OAR6 (n = 2), OAR9 (n = 2), OAR12, OAR19 (n = 2), OAR24 and OAR26. In smoothed FST (five‐SNP moving average) plots, the five most prominent peaks are on OAR1, OAR6, OAR7, OAR13 and OAR19. Although these smoothed FST peaks do not coincide with the three most significant Peddrift SNP loci, two (on OAR6 and OAR19) overlap with the set of less significant Peddrift SNPs above. Of these 12 Peddrift SNPs and five smoothed FST regions, none is close to the FE candidate genes catalase and ABCG2; however, two on OAR1 and one on OAR13 fall within suggestive quantitative trait locus regions identified in a previous genome screen experiment. The present studies indicated that there are at least eight genomic regions that underwent a selection sweep in the FE lines.
Purpose
MYCN
onco-gene amplification in neuroblastoma confers patients to the high-risk disease category for which prognosis is poor and more aggressive multimodal treatment is indicated. This ...retrospective study leverages machine learning techniques to develop a computed tomography (CT)–based model incorporating semantic and non-semantic features for non-invasive prediction of
MYCN
amplification status in pediatric neuroblastoma.
Methods
From 2009 to 2020, 54 pediatric patients treated for neuroblastoma at a specialized children’s hospital with pre-treatment contrast-enhanced CT and
MYCN
status were identified (training cohort,
n
= 44; testing cohort,
n
= 10). Six morphologic features and 107 quantitative gray-level texture radiomics features extracted from manually drawn volume-of-interest were analyzed. Following feature selection and class balancing, the final predictive model was developed with eXtreme Gradient Boosting (XGBoost) algorithm. Accumulated local effects (ALE) plots were used to explore main effects of the predictive features. Tumor texture maps were also generated for visualization of radiomics features.
Results
One morphologic and 2 radiomics features were selected for model building. The XGBoost model from the training cohort yielded an area under the receiver operating characteristics curve (AUC-ROC) of 0.930 (95%
CI
, 0.85–1.00), optimized F1-score of 0.878, and Matthews correlation coefficient (MCC) of 0.773. Evaluation on the testing cohort returned AUC-ROC of 0.880 (95%
CI
, 0.64–1.00), optimized F1-score of 0.933, and MCC of 0.764. ALE plots and texture maps showed higher “GreyLevelNonUniformity” values, lower “Strength” values, and higher number of image-defined risk factors contribute to higher predicted probability of
MYCN
amplification.
Conclusion
The machine learning model reliably classified
MYCN
amplification in pediatric neuroblastoma and shows potential as a surrogate imaging biomarker.
Pithomycotoxicosis, more commonly known as facial eczema (FE), is a liver disease that occurs predominantly in New Zealand because of its toxigenic Pithomyces chartarum strains. The first reported ...case was in sheep in 1887. Since the 1930s, a number of studies have been conducted in an attempt to mitigate the problems FE has on the sheep and dairy industries. The research in these studies included work on fungicide and biological control of the saprophytic fungus, use of different pasture plants to inhibit fungal growth, stock management with respect to pasture fungal spore counts and the use of zinc prophylaxis on animals. The finding that there was a genetic basis in FE sensitivity in sheep prompted research for a genetic approach to mitigation in the form of a diagnostic DNA test for susceptibility to the disease. Recently, we have used the Illumina OvineSNP50 BeadChip to develop a genome‐enabled prediction approach to screen for FE‐tolerant sheep. Our current best genomic prediction for FE is for the Romney breed and has an accuracy of 0.38. This prediction accuracy is not as high as the individual accuracy gained by an artificial challenge test (0.64). However, it has the advantage of being a non‐invasive test and can be provided as part of genomic testing for other traits at minimal cost.
Studies have identified lifestyle risk factors for perinatal depression, but none have examined the cumulative effect of these risk factors in pregnant women.
We considered the following six factors ...during pregnancy: poor diet quality (Healthy eating index for Singapore pregnant women<median), poor sleep quality (global Pittsburgh sleep quality index score > 5), physical inactivity (<600 MET-minutes/week), vitamin D insufficiency (<50 nmol/l), smoking before or during pregnancy, and the perceived need for social support. Probable depression was assessed using the Edinburgh postnatal depression scale during pregnancy (>15) and at three months postpartum (≥13). Prevalence risk ratios were calculated with Poisson regressions while adjusting for potential confounders.
Of 535 pregnant women, 207 (39%) had zero or one risk factor, 146 (27%) had two, 119 (22%) had three, 48 (9%) had four, and 15 (3%) had ≥5 risk factors at 26–28 weeks' gestation. These six lifestyle habits contributed to 32% of the variance in depressive symptoms during pregnancy. The prevalence of being probably depressed was 6.4 (95% CI 2.1, 19.8; ptrend < 0.001) for expecting women who had ≥4 risk factors compared to women who had ≤1 risk factor. No association was observed between the number of risk factors and depressive symptoms at 3 months postpartum (ptrend = 0.746).
Pregnant women with ≥4 lifestyle risk factors showed a higher prevalence of depression during pregnancy, while no associations were observed for postpartum depression.
This cohort is registered under the Clinical Trials identifier NCT01174875;
http://www.clinicaltrials.gov/ct2/show/NCT01174875?term=GUSTO&rank=2
•The cumulative effect of lifestyle factors on perinatal depression is unexplored.•Six lifestyle factors contributed 32% of the variance in prenatal depressive symptoms.•Pregnant women with ≥4 risk factors showed a higher risk of prenatal depression.•No association observed between prenatal risk factors and postnatal depression.
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