Relationships Between Self-Reported Smoking, Household Environmental Tobacco Smoke Exposure and Depressive Symptoms in a Pregnant Minority Population

This study sought to examine relationships between depressive symptoms and prenatal smoking and/or household environmental tobacco smoke exposure (HHETSE) among urban minority women. We analyzed private, audio computer-assisted self interview data from a clinic-based sample of 929 minority pregnant women in Washington, DC. Depressive symptoms were assessed via the Beck Depression Inventory Fast Screen. HH-ETSE, current smoking, and former smoking were assessed via self-report. Depression levels and demographic characteristics were compared: (1) among nonsmokers, for those reporting HH-ETSE versus no HH-ETSE; and (2) among smokers, for those reporting current smoking (in last 7 days) versus former smokers. Measures associated with HH-ETSE/current smoking in bivariate analysis at P\0.20 were included in adjusted logistic regression models. HH-ETSE, as a possible indicator of a social smoking network, was assessed as a mediator for the relationship between depression and current smoking. Results: Non-smokers reporting moderate-to-severe depressive symptoms showed significantly higher adjusted odds of prenatal HH-ETSE (AOR 2.5, 95% CI [1.2, 5.2]). Smokers reporting moderate-to-severe or mild depressive symptoms showed significantly higher adjusted odds of current smoking (AOR 1.9, 95% CI [1.1, 3.5] and AOR 1.8, 95% CI [1.1, 3.1], respectively). Among smokers, HH-ETSE was a significant mediator for the association between moderate-to-severe symptoms and current smoking. In conclusion, health care providers should be aware that depressed urban minority women are at risk of continued smoking/HH-ETSE during pregnancy. Interventions designed to encourage behavior change should include screening for depression, and build skills so that women are better able to address the social environment

Assessing spatial non-uniformities in lithium-ion battery state of charge using ultrasound immersion testing

Enhancing the performance, safety and reliability of battery management systems is crucial for advancing the state of the art in battery electric vehicles. Current research explores the potential of ultrasound to monitor state of charge (SoC) changes in individual cells. Understanding spatial variations in SoC is essential, as non-uniformities could lead to sub-optimal performance, premature ageing, and possible safety risks. This study uses ultrasound immersion C-scans to map wave speed and attenuation at different SoC levels during battery cycling. Results indicate non-uniform wave speed and attenuation suggestive of SoC spatial variations within single cells, emphasising the importance of addressing this issue. Acoustic measurements under various C-rates and relaxation periods are discussed, providing insights into lithium-ion rearrangement in graphite particles. Potential causes of structure and manufacturing variations of the cell are discussed, highlighting the need to address these issues to prevent overcharging or overdischarging in specific battery areas

Vitamin K1 intake is associated with lower risk for all-cause and cardiovascular disease mortality in community-dwelling older Australian women

Background and aims: Assessing the relationship between vitamin K1 intakes, using region-specific food databases, with both all-cause, and cardiovascular disease (CVD) mortality warrants further investigation to inform future preventative strategies. Consequently, we examined the aforementioned associations in the Perth Longitudinal Study of Ageing Women (PLSAW). Methods and results: 1436 community-dwelling older Australian women (mean ± SD age 75.2 ± 2.7 years) completed a validated food frequency questionnaire at baseline (1998). Vitamin K1 intake was calculated based on an Australian vitamin K food database, supplemented with published data. All-cause and CVD mortality data was obtained from linked health records. Associations were examined using restricted cubic splines within Cox-proportional hazard models, adjusted for a range of cardiovascular and lifestyle related risk factors. Over 15 years of follow-up, 601 (41.9%) women died, with 236 deaths (16.4%) due to CVD. Compared to women with the lowest vitamin K1 intakes (Quartile 1, median 49.1 μg/day), those with the highest intakes (Quartile 4, median 119.3 g/day) had lower relative hazards for all-cause mortality (HR 0.66 95%CI 0.51–0.86) and CVD mortality (HR 0.61 95%CI 0.41–0.92). A plateau in the inverse association was observed from vitamin K1 intakes of approximately ≥ 80 g/day. Conclusion: Higher vitamin K1 intakes were associated with lower risk for both all-cause and CVD mortality in community-dwelling older women, independent of CVD related risk factors. A higher intake of vitamin K1 rich foods, such as leafy green vegetables, may support cardiovascular health

Identification of a novel gene regulating amygdala-mediated fear extinction.

Recent years have seen advances in our understanding of the neural circuits associated with trauma-related disorders, and the development of relevant assays for these behaviors in rodents. Although inherited factors are known to influence individual differences in risk for these disorders, it has been difficult to identify specific genes that moderate circuit functions to affect trauma-related behaviors. Here, we exploited robust inbred mouse strain differences in Pavlovian fear extinction to uncover quantitative trait loci (QTL) associated with this trait. We found these strain differences to be resistant to developmental cross-fostering and associated with anatomical variation in basolateral amygdala (BLA) perineuronal nets, which are developmentally implicated in extinction. Next, by profiling extinction-driven BLA expression of QTL-linked genes, we nominated Ppid (peptidylprolyl isomerase D, a member of the tetratricopeptide repeat (TPR) protein family) as an extinction-related candidate gene. We then showed that Ppid was enriched in excitatory and inhibitory BLA neuronal populations, but at lower levels in the extinction-impaired mouse strain. Using a virus-based approach to directly regulate Ppid function, we demonstrated that downregulating BLA-Ppid impaired extinction, while upregulating BLA-Ppid facilitated extinction and altered in vivo neuronal extinction encoding. Next, we showed that Ppid colocalized with the glucocorticoid receptor (GR) in BLA neurons and found that the extinction-facilitating effects of Ppid upregulation were blocked by a GR antagonist. Collectively, our results identify Ppid as a novel gene involved in regulating extinction via functional actions in the BLA, with possible implications for understanding genetic and pathophysiological mechanisms underlying risk for trauma-related disorders

Pulmonary Metagenomic Sequencing Suggests Missed Infections in Immunocompromised Children

This article is made available for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing.BACKGROUND: Despite improved diagnostics, pulmonary pathogens in immunocompromised children frequently evade detection, leading to significant mortality. Therefore, we aimed to develop a highly sensitive metagenomic next-generation sequencing (mNGS) assay capable of evaluating the pulmonary microbiome and identifying diverse pathogens in the lungs of immunocompromised children. METHODS: We collected 41 lower respiratory specimens from 34 immunocompromised children undergoing evaluation for pulmonary disease at 3 children's hospitals from 2014-2016. Samples underwent mechanical homogenization, parallel RNA/DNA extraction, and metagenomic sequencing. Sequencing reads were aligned to the National Center for Biotechnology Information nucleotide reference database to determine taxonomic identities. Statistical outliers were determined based on abundance within each sample and relative to other samples in the cohort. RESULTS: We identified a rich cross-domain pulmonary microbiome that contained bacteria, fungi, RNA viruses, and DNA viruses in each patient. Potentially pathogenic bacteria were ubiquitous among samples but could be distinguished as possible causes of disease by parsing for outlier organisms. Samples with bacterial outliers had significantly depressed alpha-diversity (median, 0.61; interquartile range [IQR], 0.33-0.72 vs median, 0.96; IQR, 0.94-0.96; P < .001). Potential pathogens were detected in half of samples previously negative by clinical diagnostics, demonstrating increased sensitivity for missed pulmonary pathogens (P < .001). CONCLUSIONS: An optimized mNGS assay for pulmonary microbes demonstrates significant inoculation of the lower airways of immunocompromised children with diverse bacteria, fungi, and viruses. Potential pathogens can be identified based on absolute and relative abundance. Ongoing investigation is needed to determine the pathogenic significance of outlier microbes in the lungs of immunocompromised children with pulmonary disease

AXL/MERTK inhibitor ONO-7475 potently synergizes with venetoclax and overcomes venetoclax resistance to kill <i>FLT3</i>-ITD acute myeloid leukemia

FMS-like Tyrosine Kinase 3 (FLT3) mutation is associated with poor survival in acute myeloid leukemia (AML). The specific Anexelekto/MER Tyrosine Kinase (AXL) inhibitor, ONO-7475, kills FLT3-mutant AML cells with targets including Extracellular- signal Regulated Kinase (ERK) and Myeloid Cell Leukemia 1 (MCL1). ERK and MCL1 are known resistance factors for Venetoclax (ABT-199), a popular drug for AML therapy, prompting the investigation of the efficacy of ONO-7475 in combination with ABT-199 in vitro and in vivo. ONO-7475 synergizes with ABT-199 to potently kill FLT3-mutant acute myeloid leukemia cell lines and primary cells. ONO-7475 is effective against ABT-199-resistant cells including cells that overexpress MCL1. Proteomic analyses revealed that ABT-199-resistant cells expressed elevated levels of pro-growth and anti-apoptotic proteins compared to parental cells, and that ONO-7475 reduced the expression of these proteins in both the parental and ABT-199-resistant cells. ONO-7475 treatment significantly extended survival as a single in vivo agent using acute myeloid leukemia cell lines and PDX models. Compared to ONO-7474 monotherapy, the combination of ONO-7475/ABT-199 was even more potent in reducing leukemic burden and prolonging the survival of mice in both model systems. These results suggest that the ONO-7475/ABT-199 combination may be effective for AML therapy

K2-66b and K2-106b: Two Extremely Hot Sub-Neptune-size Planets with High Densities

We report precise mass and density measurements of two extremely hot sub-Neptune-size planets from the K2 mission using radial velocities, K2 photometry, and adaptive optics imaging. K2-66 harbors a close-in sub-Neptune-sized (2.49_(-0.24)^(+0.34)R_⊕) planet (K2-66b) with a mass of 21.3 ± 3.6 M_⊕. Because the star is evolving up the subgiant branch, K2-66b receives a high level of irradiation, roughly twice the main-sequence value. K2-66b may reside within the so-called "photoevaporation desert," a domain of planet size and incident flux that is almost completely devoid of planets. Its mass and radius imply that K2-66b has, at most, a meager envelope fraction (<5%) and perhaps no envelope at all, making it one of the largest planets without a significant envelope. K2-106 hosts an ultra-short-period planet (P = 13.7 hr) that is one of the hottest sub-Neptune-size planets discovered to date. Its radius (1.82_(-0.14)^(+0.20) R_⊕) and mass (9.0 ± 1.6 M_⊕) are consistent with a rocky composition, as are all other small ultra-short-period planets with well-measured masses. K2-106 also hosts a larger, longer-period planet (R_p = 2.77_(-0.23^(+0.37)R_⊕, P = 13.3 days) with a mass less than 24.4 M_⊕ at 99.7% confidence. K2-66b and K2-106b probe planetary physics in extreme radiation environments. Their high densities reflect the challenge of retaining a substantial gas envelope in such extreme environments

Tentative Evidence for Water Vapor in the Atmosphere of the Neptune-Size Exoplanet HD 106315 c

We present a transmission spectrum for the Neptune-size exoplanet HD 106315 c from optical to infrared wavelengths based on transit observations from the Hubble Space Telescope/Wide Field Camera 3, K2, and Spitzer. The spectrum shows tentative evidence for a water absorption feature in the 1.1−1.7μm wavelength range with a small amplitude of 30 ppm (corresponding to just 0.8±0.04 atmospheric scale heights). Based on an atmospheric retrieval analysis, the presence of water vapor is tentatively favored with a Bayes factor of 1.7 - 2.6 (depending on prior assumptions). The spectrum is most consistent with either enhanced metallicity, high altitude condensates, or both. Cloud-free solar composition atmospheres are ruled out at >5σ confidence. We compare the spectrum to grids of cloudy and hazy forward models and find that the spectrum is fit well by models with moderate cloud lofting or haze formation efficiency, over a wide range of metallicities (1−100× solar). We combine the constraints on the envelope composition with an interior structure model and estimate that the core mass fraction is ≳0.3. With a bulk composition reminiscent of that of Neptune and an orbital distance of 0.15 AU, HD 106315 c hints that planets may form out of broadly similar material and arrive at vastly different orbits later in their evolution

Tentative Evidence for Water Vapor in the Atmosphere of the Neptune-Size Exoplanet HD 106315 c

We present a transmission spectrum for the Neptune-size exoplanet HD 106315 c from optical to infrared wavelengths based on transit observations from the Hubble Space Telescope/Wide Field Camera 3, K2, and Spitzer. The spectrum shows tentative evidence for a water absorption feature in the $1.1 - 1.7\mu$m wavelength range with a small amplitude of 30 ppm (corresponding to just $0.8 \pm 0.04$ atmospheric scale heights). Based on an atmospheric retrieval analysis, the presence of water vapor is tentatively favored with a Bayes factor of 1.7 - 2.6 (depending on prior assumptions). The spectrum is most consistent with either enhanced metallicity, high altitude condensates, or both. Cloud-free solar composition atmospheres are ruled out at $>5\sigma$ confidence. We compare the spectrum to grids of cloudy and hazy forward models and find that the spectrum is fit well by models with moderate cloud lofting or haze formation efficiency, over a wide range of metallicities ($1 - 100\times$ solar). We combine the constraints on the envelope composition with an interior structure model and estimate that the core mass fraction is $\gtrsim0.3$. With a bulk composition reminiscent of that of Neptune and an orbital distance of 0.15 AU, HD 106315 c hints that planets may form out of broadly similar material and arrive at vastly different orbits later in their evolution.Comment: Submitted to AAS journals; 19 pages, 12 figure