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Interferon-gamma 1b-induced gene expression alters neutrophil function in patients with chronic granulomatous disease
Interferon-gamma (IFN-γ) decreases infections in chronic granulomatous disease (CGD) with variably incomplete restoration of the fundamental CGD defect, converting oxygen to microbicidal oxidants during phagocytosis. We sought to understand other IFN-γ effects that could contribute to protection of CGD patients. We measured neutrophil function, gene expression, and biochemical parameters in nine CGD patients off IFN-γ and 10–12 hours after the first (1st) and fourth (4th) IFN-γ injection. Non-directed motility and bactericidal activity increased after IFN-γ administration; ingestion remained unchanged. Stimulated release of superoxide anion (O2-) was minimally changed. Treatment decreased expression of 483 genes and increased 386. Expression of eleven genes associated with neutrophil activity was upregulated. Genes not routinely associated with neutrophil function also demonstrated increased expression, including MHCI & II proteins, guanylate-binding proteins, and an enzyme synthesizing a nitric-oxide (NO) synthetase cofactor. CD11b expression, F-actin assembly, and CD 274 antigen were increased after treatment as was NO in neutrophil lysates. Formation of neutrophil extracellular traps after ingestion of staphylococci was increased off IFN-γ compared with controls but moved toward normal after IFN-γ administration. IFN-γ protects against infection in CGD by several mechanisms that could potentially support others with compromised host defense. Trial registration ClinicalTrials.gov NCT03548818
Circulating metabolites in patients with chronic heart failure are not related to gut leakage or gut dysbiosis
Background The gut microbiota produces numerous metabolites that can enter the circulation and exert effects outside the gut. Several studies have reported altered gut microbiota composition and circulating metabolites in patients with chronic heart failure (HF) compared to healthy controls. Limited data is available on the interplay between dysbiotic features of the gut microbiota and altered circulating metabolites in HF patients. We aimed to examine differences in circulating metabolites between people with and without chronic HF, and their association with gut microbiota dysbiosis and cardiac function. Methods We collected plasma, serum, and stool samples from 123 adult patients with stable chronic HF and left ventricular ejection fraction (LVEF) ≤40%, and healthy controls (plasma: n = 51, stool samples: n = 69). Metabolomic and lipidomic profiling of plasma was performed using liquid chromatography with tandem mass spectrometry. Principal component analysis was used to explore differences in circulating profiles. Over-representation analysis was performed to identify pathways in which relevant metabolites were involved. Stool samples were sequenced using shotgun metagenomics. We calculated a dysbiosis index based on differential abundances of microbial taxa in patients vs. controls. Results After adjusting for age, sex, and sampling location, we identified 67 enriched metabolites and 24 enriched lipids, and 115 depleted metabolites and 6 depleted lipids in HF patients compared to healthy controls. LVEF, N-terminal pro B-type natriuretic peptide, gut leakage markers, dysbiosis index, and fiber intake were not significantly related to any of the differentially abundant metabolites or lipids. Pathways related to energy metabolism differed most between HF patients and controls, however medication adjustment abolished all differences in circulating profiles. Conclusions Patients with chronic HF had distinct metabolomic and lipidomic profiles and energy metabolism differed significantly compared to healthy controls before adjusting for medication use. However, the alterations were not related to gut dysbiosis, gut leakage markers, cardiac function, or fiber intake.
Diversity on the bench: An analysis of gendered biases in the language of Australian Family Law Court judgments
In this paper we analyse gender-based biases in the language within complex legal judgments. Our aims are: (i) to determine the extent to which purported biases discussed in the literature by feminist legal scholars are identifiable from the language of legal judgments themselves, and (ii) to uncover new forms of bias represented in the data that may promote further analysis and interpretation of the functioning of the legal system. We consider a large set of 2530 judgments in family law in Australia over a 20 year period, examining the way that male and female parties to a case are spoken to and about, by male and female judges, in relation to their capacity to provide care for children subject to the decision. Structural topic modelling is used to develop coherent topics for sentences that fall under the notion of “capacity”, which are further differentiated by the gender of both the target of the sentence and the gender of the judge. The analysis reveals significant gendered differences in the language used in these documents, determined by both the gender of the target and the gender of the judge.
The effect of exogenous melatonin and melatonin receptor agonists on intensive care unit and hospital length of stay: A systematic review and meta-analysis
Introduction Melatonin supplements and melatonin receptor agonists are linked to reduced delirium in the Intensive Care Unit (ICU) which we hypothesised may affect the length of stay (LOS) in ICU or in hospital. In this review, we identified and critically appraised the literature on the effect of exogenous melatonin and melatonin receptor agonists on the ICU and/or hospital LOS among adults admitted to the ICU. Methods Six electronic databases and three trial registries were searched for randomised controlled trials (RCTs). Screening, risk of bias assessment, quality appraisal, and level of evidence assessment were conducted and cross-checked by two reviewers independently. Meta-analyses with disease-specific subgroups were conducted to assess the mean difference in LOS for exogenous melatonin and melatonin receptor agonists compared with a placebo. Results Twenty RCTs were reviewed with 14 having a low risk of bias. For ICU LOS (18 studies) there was significant statistical heterogeneity (I2 = 73%); compared with placebo the 95% prediction interval for the mean difference was −3.18 and 1.39 days. For hospital stay (12 studies, I2 = 79%) the 95% prediction interval ranged from −6.68 to 3.52. Removing two statistical outliers, and correcting for publication bias, there was no overall statistically significant difference in mean ICU LOS (p-value = 0.298) or mean hospital LOS (p-value = 0.456). The subgroup analysis found statistically significant improvements for those who underwent coronary artery bypass graft surgery (ICU LOS −0.47 days, 95% CI: −0.78 to −0.16, p-value = 0.003); and patients with COVID-19 (hospital LOS −3.90 days, 95% CI: −6.28 to −1.51, p-value = 0.001). Conclusion There was a very low certainty of evidence that melatonin and melatonin receptor agonists were associated with reductions in ICU and hospital LOS in ICU patients overall. However, further research is needed for surgical patients and those with pneumonia.
Vitamin D3 reduces the viability of cancer cells in vitro and retard the EAC tumors growth in mice
Prior studies from our laboratory have shown that cancer cells exposed to vitamin D3 exhibited reduced proliferation in breast cancer cells due to the upregulation of p53 and downregulation of cyclin-D1. Furthermore, in mice, our group has demonstrated that administration of 125 µg/kg of vitamin D3 retarded the growth of EAC tumors. But, it is unknown whether vitamin D3 exerts similar anti-cancer effects against cell lines representing carcinomas of the liver, colon and rectum, cervix, and brain. It is also unknown whether administration of vitamin D3 by i.p alone is sufficient for better tumor inhibition or combined administration consisting of i.p. and intratumoral (i.t.) routes is required. Furthermore, the ability of vitamin D3 in reducing the tumor growth in normal and diabetic mice has not been studied to date. Addressing these lacunae, we have prepared the dose and time response curves for vitamin D3 against different cancer cells and assessed the impact on pathways regulating cell survival and cell proliferation. A dose-dependent decrease in the (a) number of proliferating cells; (b) viability and (c) an increase in apoptosis (as evidenced by increased cleaved caspase-3) were observed with vitamin D treatment. Mechanistically, low dose vitamin D3 (15.62µM and 31.25µM) increased the expression of p53 and p21 at 24h and 48h of treatment. Interestingly, we could only observe minor changes in the expression of Bax, Bcl2 and Survivin proteins with vitamin D3 treatment. In mice, i.p. and i.t. combination reduced the tumor growth much more effectively compared to i.p. alone. Our data also showed that vitamin D3 could retard tumors developing in normal and hyperglycaemic mice. In summary, vitamin D3 is a potent anti-cancer agent, hence, is recommend for further development to treat cancers.
When automation hits jobs: Entrepreneurship as an alternative career path
This study investigates the relationship between occupational automation risks and workers’ transitions to entrepreneurship using data from the Current Population Survey. We find that employees facing automation-related job displacement are inclined to shift toward unincorporated entrepreneurship, emphasizing entrepreneurship as a viable alternative career path. Noteworthy variations emerge when examining specific automation technologies, revealing a positive association between industrial robots and entrepreneurial transitions, whereas artificial intelligence displays a negative relationship. Gender disparities are observed, with female workers exhibiting a lower likelihood than males of transitioning into entrepreneurship. This study also shows a heightened prominence of entrepreneurial transitions during the early stages of the COVID-19 pandemic. By illuminating entrepreneurship as a response to job displacement, our results offer crucial policy insights into the labor market implications of automation.
What is known from the existing literature about adolescent knowledge and attitudes towards dementia and interventions to enhance this? A scoping review
Objectives Individuals with dementia often experience stigmatisation and social exclusion. To develop dementia-friendly communities, it is important to take a life-course approach to enhance the perception of dementia in the general population. Currently, we lack an overall understanding of adolescent perceptions of dementia. This scoping review is the first to identify the existing literature on the knowledge and attitudes held by adolescents (aged 10–19 years) towards dementia. Methods A JBI Scoping Review. Four bibliographic databases (MEDLINE, PsycINFO, EMBASE, and CINAHL) were searched to identify eligible studies. Eligibility criteria included qualitative and quantitative studies examining the knowledge and attitudes of adolescents (10–19-year-olds) towards dementia. Studies were screened for eligibility, with data extracted using JBI tools and synthesised in relation to i) knowledge and attitudes and ii) interventions. Results In total 21 publications were identified from the UK, Slovenia, the United States, Taiwan, Canada, Israel, South Africa, and South Korea. Ten of these studies included interventions. Overall, studies reported adolescents to have a relatively low level of objective knowledge about dementia. Conversely, attitudes towards dementia were largely reported to be neutral-positive. However, adolescents living with a relative with dementia often held predominantly negative attitudes towards the condition. Gender and having a family member living with dementia were important predictors of both knowledge and attitudes. Interventions to date are educational or intergenerational in focus and appear similarly effective in increasing attitudes and awareness towards dementia. Conclusions The current scoping review identified a small but emergent body of literature on adolescent knowledge and attitudes towards dementia. The synthesised findings indicate low objective knowledge to be a particularly useful target for intervention and alongside other findings, will be useful to inform future research, particularly the development of high-quality intervention studies.
Trends in gestational age at birth in the city of São Paulo, Brazil between 2012 and 2019
Studies have shown that excessive obstetric interventions such as induced labor and caesarean sections have contributed to the shortening of the length of gestation, leading to a left shift in gestational age (GA) at birth. The aim of this study was to analyze trends in GA and the contribution of associated factors to changes in São Paulo city, Brazil during the period 2012–2019. We conducted an observational time-series study of births in São Paulo using data from Brazil’s national live births information system (SINASC). We calculated the annual percent change (APC) of births by GA between 2012 and 2019 and between the first and second four-year periods of the time series by applying log transformation to the percentages, followed by Prais-Winsten regression. A total of 1,525,759 live births were analyzed. From 2015, there was an increase in the proportion of live births between 39 and 40 weeks from 2015 and a fall in the proportion of early term (37–38 weeks) and preterm (< 37 weeks) births throughout the study period. The APC of births at 39 and 40 weeks was 7.9% and 5.7%, respectively, while the proportion of births at other gestational ages showed a statistically significant reduction over the study period. These reductions were more pronounced in the first four-year period (2012–2015). The same trend was observed when the data were analyzed by type of delivery, type of service (public or private), maternal age, and maternal education level. The findings show that there was a right shift in the GA curve during the study period and a reduction in the proportion of preterm and early term births. These changes were more pronounced in births that occurred in private hospitals. These changes reflect public policies implemented to reduce obstetric interventions such as induced labor and caesarean section before labor, especially before 39 weeks of gestation.
Cost-effectiveness of oil and milk fortification by scale for reducing Vitamin A and Vitamin D deficiency in India
Background Although broad-scale data might suggest low prevalence, millions of children in India still suffer from Vitamin A and Vitamin D deficiencies despite India’s existing guidelines for Vitamin A deficiency. To address the issue, the Government of India has recommended fortification of oil and milk to improve Vitamin A and Vitamin D consumption. However, there is limited information on the health benefits and cost-effectiveness of fortifying oil and milk at scale. Objective To estimate the health benefits and cost-effectiveness of supplementation programme and fortification of milk and oil among children under 5 years, pregnant women, women in the reproductive age group, and the elderly. Data and methods To measure the health benefits associated with supplementation and fortification of oil and milk, the number of DALYs that are currently lost due to Vitamin A and Vitamin D deficiencies were estimated. For Vitamin A related mortality, a reduction of 4%, 12% and 23% were assumed while the assumptions for estimating morbidity benefits were derived from Global Burden of Disease. For the costing exercise, we considered the following two scenarios: (1) high-dose vitamin A supplementation for children and pregnant women; (2) industrial fortification of oil for children, pregnant women, women in the reproductive age group, and the elderly. Results Overall, intervention related to Vitamin A could avert 1,119,044 Years of Life Lost (YLLs) at a 23% reduction, 194,616 YLLs at 4%, and 583,849 YLLs at 12% and 28,534 YLDs. Intervention related to Vitamin D could avert 99,219 YLDs. The total cost for supplying supplements to approximately 109,965 thousand children and 26,920 thousand pregnant women is around 26 million USD. The cost to fortify is 7.6 million USD for oil and 9.8 million USD for milk fortification for children and women. The overall cost effectiveness ratio of the fortification programme is 150. Conclusion Fortification could emerge as a potentially superior long-term solution, considering the widespread consumption of oil and milk, offering a broader reach to the population.
A study of the binary marginal effect of technical barriers to trade on the export of shellfish and aquatic products in China
This study aims to examine the impact of technical barriers to trade (TBT) on China’s shellfish exports, focusing on both the intensive margin (trade volume) and the extensive margin (trade type). The research includes shellfish and aquatic products such as scallops, mussels, clams, oysters, and abalone, using HS-6 codes from 2003 to 2020. Panel data is employed for analysis. The findings reveal that TBT notifications positively influence the extensive margin by increasing export types but have a less significant effect on the intensive margin. Economic scale, variable trade cost, and productivity level affect both margins. To mitigate the effects of TBT, China should diversify its shellfish exports. Additionally, reducing trade costs can further enhance China’s shellfish export competitiveness.
Incidence of depression and anxiety in children and adolescents following COVID-19 infection
While the COVID-19 pandemic has significantly impacted mental health, limited information exists on the relationship between COVID-19 infection and mental health disorders in children and adolescents. This study explored the association between COVID-19 infection, infection severity, and the risk of depression and anxiety among school-aged youth. Data from the 2019–2021 Utah All Payers Claims Database (APCD) was used to identify children and adolescents (aged 6–15 years in 2019) covered by private insurance or Medicaid. Depression and anxiety diagnoses in 2021 were identified using diagnosis codes. Entropy balancing was applied to balance baseline differences between youth with and without a COVID-19 infection in 2020. Weighted logistic regression was conducted to identify factors associated with incidence of depression and anxiety. A total of 154,579 subjects were included, with an average age of 10.8 years (SD: 2.8); 48% were female. Youth with a COVID-19 infection had a 49% higher likelihood of having new depression or anxiety diagnoses in 2021 (OR = 1.49, p < 0.01). Compared to youth without COVID-19 infection, those with moderate symptoms had a 40% higher likelihood (OR = 1.40, p < 0.01), and those with severe symptoms had a 60% higher likelihood (OR = 1.60, p < 0.01) of developing depression or anxiety. This population-level study found that COVID-19 infection, especially severe cases, is associated with an increased risk of depression and anxiety in children and adolescents. These findings underscore the importance of targeted mental health interventions for youth impacted by the infection.
Modelling taxi drop-off decisions in FIFO lanes via survival and discrete choice analysis
Traffic congestion frequently occurs in the drop-off zones of large integrated passenger hubs, posing significant challenges to the efficient utilization of lane space. This study develops a First-In-First-Out (FIFO) taxi drop-off decision-making model, incorporating both static and dynamic Logit frameworks grounded in panel data analysis. The model accounts for heterogeneity across vehicles, temporal variations, and spatial factors influencing drop-off decisions. Key explanatory variables include the probability of current forced parking time reaching the ‘waiting patience’ threshold, the relative parking position of the vehicle, the likelihood of the current parking spot being the expected one, and the ratio of travel time. A mixed distribution model of passenger patience was constructed through survival analysis and calibrated to reflect empirical data accurately. The model estimation results indicate that passenger patience significantly influences drop-off decisions. All models—static, dynamic, and Cox proportional hazards—achieved prediction accuracies exceeding 70%, with the dynamic model outperforming others when ample sample data is available. This study is novel in integrating both panel data-based discrete choice models and survival analysis to describe dynamic taxi drop-off decisions in congested FIFO lanes. The behavioral insight into the sunk cost effect – where drivers tend to wait longer after repeated forced stops – is quantitatively confirmed. Furthermore, the model introduces interpretable explanatory variables that reflect real-world operational constraints and driver psychology. To further elucidate the temporal dynamics of drop-off behavior, the study integrates survival analysis, particularly the Cox proportional hazards model. Findings reveal that extended forced parking durations, longer travel times, and increased instances of forced stops are associated with decreased hazard rates, suggesting a higher tolerance for prolonged waiting. This behavior is attributed to the sunk cost effect, where drivers, having invested time in waiting, are more inclined to continue waiting rather than proceed to drop off passengers. These insights underscore the necessity of incorporating driver psychological behaviors into traffic management strategies. Recommendations include implementing ‘no-waiting zones’ in drop-off areas, establishing mandatory drop-off time thresholds based on median survival times, introducing parking pricing policies for prolonged stops to internalize spatial costs, and utilizing real-time guidance systems (e.g., variable message signs) to prompt timely passenger drop-offs. Such measures aim to mitigate the adverse effects of prolonged forced stops and enhance the operational efficiency of drop-off zones.
Pinoresinol enhances oral barrier integrity and function in human buccal cell monolayers
The oral epithelial barrier plays a crucial role in maintaining oral health by protecting against microbial invasion and mechanical stress while regulating selective permeability. Disruption of this barrier contributes to inflammation and the development of oral diseases such as gingivitis and periodontitis. Pinoresinol, a lignan with antioxidant, antimicrobial, and anti-inflammatory properties, has demonstrated health benefits in systemic diseases; however, its effects on oral epithelial barrier integrity remain unclear. This study investigated the potential of pinoresinol to enhance oral epithelial barrier function using TR146 cell monolayers. Pinoresinol treatment significantly reduced apparent permeability and increased transepithelial electrical resistance, indicating improved barrier integrity. Additionally, pinoresinol upregulated the expression of tight junction-associated molecules, including occludin, MarvelD3, claudin-1, and claudin-3, at both the mRNA and protein levels, enhanced their localization as shown by immunofluorescence. These findings suggest that pinoresinol reinforces the oral epithelial barrier and may help prevent barrier dysfunction associated with oral diseases.
Identification of silibinin and isotretinoin as potent up-regulators of sFRP4 (Wnt antagonist): In silico prediction and in vitro validation in breast cancer
Secreted frizzled-related protein 4 (sFRP4) plays a fundamental role in the regulation of Wnt signalling, which is crucial for cellular proliferation and differentiation. The sFRP4 has garnered significant interest as a therapeutic target for metabolic diseases and cancer due to its mechanism of action. Although existing sFRP4 modulators show limited specificity and notable off-target effects, our study explores the potential of known bioactive compounds as more selective and less toxic alternatives. This study is based on the analysis of expression profiles, which demonstrated that the sFRP4 gene exhibits aberrant expression in multiple cancers, including breast cancer. The protein’s primary involvement in cancer signaling pathways was determined through pathway enrichment analysis. The study employed molecular docking analyses and MD simulations to identify breast cancer-fighting small molecules with docking energies of less than −6 kcal/mol, targeting the sFRP4 binding hotspot using 100 natural or synthetic small molecules. Out of 100 screened compounds, Silibinin and Isotretinoin were selected based on docking results and further validated in vitro. In vitro investigations were carried out using the colorimetric MTT assay to assess cell viability and cytotoxicity based on metabolic activity. The potential of Silibinin and isotretinoin to upregulate the tumour suppressor sFRP4 was further examined using ELISA and real-time quantitative PCR. Our study identified potential compounds for high-potential drug candidates against sFRP4, demonstrating their effectiveness in cancer cell death and upregulating sFRP4 expression through improved drug design methods and experimental studies. In conclusion, our in-silico findings could facilitate the discovery of potential therapeutic agents against breast cancer. Silibinin and Isotretinoin impede cancer cell development in vitro; nonetheless, this study demonstrated that they directly upregulate sFRP4 and induce apoptosis in breast cancer cells.
SAMCell: Generalized label-free biological cell segmentation with segment anything
Background: When analyzing cells in culture, assessing cell morphology (shape), confluency (density), and growth patterns are necessary for understanding cell health. These parameters are generally obtained by a skilled biologist inspecting light microscope images, but this can become very laborious for high-throughput applications. One way to speed up this process is by automating cell segmentation. Cell segmentation is the task of drawing a separate boundary around each cell in a microscope image. This task is made difficult by vague cell boundaries and the transparent nature of cells. Many techniques for automatic cell segmentation exist, but these methods often require annotated datasets, model retraining, and associated technical expertise. Results: We present SAMCell, a modified version of Meta’s Segment Anything Model (SAM) trained on an existing large-scale dataset of microscopy images containing varying cell types and confluency. Our approach works on a wide range of microscopy images, including cell types not seen in training and on images taken by a different microscope. We also present a user-friendly UI that reduces the technical expertise needed for this automated microscopy technique. Conclusions: Using SAMCell, biologists can quickly and automatically obtain cell segmentation results of higher quality than previous methods. Further, these results can be obtained through our custom Graphical User Interface, thus decreasing the human labor required in cell culturing.
Experimental study on polymer friction composite with natural friction modifiers for brake pads
The increasing concern over environmental pollution from brake dust and the adverse impacts of conventional brake pad materials, such as metallic, semi-metallic, and ceramic composites, has prompted the exploration of more sustainable alternatives. Traditional brake pads release harmful non-exhaust emissions that contribute to air pollution and wear down quickly, posing both environmental and operational challenges. This study investigates the development and performance evaluation of polymer friction composites enhanced with natural friction modifiers sourced from agricultural waste materials like walnut shell, coconut shell, and groundnut shell powders. These materials were selected for their biodegradability, lightweight properties, and cost-effectiveness. Three types of polymer reinforced composites—WPRC (Walnut Powder Reinforced Composite), CNPRC (Coconut Shell Powder Reinforced Composite), and GNPRC (Groundnut Shell Powder Reinforced Composite)—were manufactured according to ASTM G99 standards. A pin-on-disc tribometer or an L27 Taguchi experimental setup were used to measure friction and wear. The tests showed that WPRC had the best general performance of all the composites that were tried. It had stable coefficients of friction and a low specific wear rate. The results indicate that natural friction modifiers could improve the environmental and operational performance of polymer composites, by replacing existing brake pad materials with a more environmentally friendly alternative.
Earmarking donations to boost study participation? Evidence from a field experiment
Charitable donations are often the most suitable available way to incentivize study participation, yet their optimal design remains unclear. In a preregistered field experiment, we invited 6,711 psychology faculty at top-200 universities to complete a survey in exchange for a US $5 donation to test whether allowing prospective participants to earmark the donation for a specific purpose increases study participation. Contrary to preregistered hypotheses derived from previous literature, the results showed no significant increase in study participation rates when participants could earmark their donation compared to a random allocation of funds. These findings suggest that while earmarking has been shown to enhance overall donation rates, its effectiveness may not extend to incentivizing study participation.
Normative serum cortisol levels in second and third trimesters and their associated factors: A prospective cohort study from Sri Lanka
Objective To describe the normative serum cortisol levels during 25–29 weeks of POG and the association of maternal, psychological, and social factors on serum cortisol in the second and third trimesters in a cohort of pregnant women. Methods All eligible pregnant women registered in the maternal care program in Anuradhapura district, Sri Lanka, from July to September 2019 were invited to the Rajarata Pregnancy Cohort (RaPCo). An interviewer-administered questionnaire-based symptom analysis and clinical assessment were conducted at baseline in the first trimester and at follow-up from 25 to 29 weeks POG. We assessed fasting early morning serum cortisol levels at the follow-up visit. Results The study sample included 1010 pregnant women with a mean age in years and POG in weeks at baseline of 28 (±6) and 10 (±3), respectively. The mean (SD, 97% percentile) serum cortisol level in all pregnant women was 10.93 (±3.83, 20.95) μg/dL, with no significant difference between singleton and twin pregnancies ( p = 0.138). None of the study participants had a cortisol level exceeding the upper limit of 42 μg/dL, and 464 (45.9%) had levels less than 10 μg/dL. Serum cortisol levels were higher in women with an advanced POG, with a mean of 10.33 µg/dL (95%CI: 9.68–10.98) at 24 weeks POG and 12.23 µg/dL (95%CI: 11.15–13.32) at 29 weeks POG ( p = 0.049). Primi-gravidity ( p = 0.004), history of miscarriage ( p = 0.010), BMI categories ( p = 0.044), and POG ( p = 0.002) were independently associated with serum cortisol levels in robust regression. An EPDS score of more than 9 was not associated with serum cortisol ( p = 0.633). Conclusion The pregnant women in rural Sri Lanka reported a low mean serum cortisol level, which gradually increased with the POG. Significantly higher mean serum cortisol was associated with primi-gravidity, history of miscarriage, pre-pregnancy BMI, and POG at cortisol test, but not psychological factors.
Prospects for silvicultural enhancement of fire resistance in mesic westside forests of the Pacific Northwest
Increasing wildfire activity in mesic, temperate Pacific Northwest forests west of the Cascade Range crest has stimulated interest in understanding whether alternative forest management practices could reduce risk of stand-replacing fire. To explore how management can enhance fire resistance in these forests and assess tradeoffs among resistance enhancement, carbon sequestration and storage, and economic returns, we conducted 40-year simulations of stand development with BioSum, a framework for conducting landscape analysis with the Forest Vegetation Simulator (FVS), utilizing a statistically representative and spatially balanced sample of Forest Inventory and Analysis (FIA) plots. Simulation outcomes under business-as-usual silviculture were contrasted with fire-aware silviculture, and treatment optimization logic was developed and applied to represent landscape-scale outcomes under business-as-usual and fire-focused management scenarios. Simulation results indicate that fire-aware prescriptions and fire-focused management can meaningfully enhance stand- and landscape-scale fire resistance of westside forests under less than extreme fire weather, but at the cost of lower economic returns and reduced net carbon storage and sequestration over the 40-year analysis window. Shifting from business-as-usual regeneration harvests with short rotations to fire-aware, episodic selection harvest improved fire resistance the most, especially in young privately-owned forests, and with only modest tradeoffs in carbon and economic outcomes. While fire-aware treatments generally reduced net present value from forest operations over business-as-usual, most treatments still generated positive net present value and could be implemented without subsidy. Fire-aware prescriptions that removed and utilized non-merchantable harvest residues instead of burning them, via either pile or broadcast burning, partially mitigated carbon emissions associated with fire-aware treatments, with about the same improvement in fire resistance. Given the currently limited institutional and financial capacity to implement fire resistance enhancing treatments at scale, the insights from this analysis may aid managers seeking to elevate fire resistance to prioritize where and how to manage.
Compartment-specific adaptive responses and dysregulation under NQO1 deficiency in diabetic kidney disease: A transcriptomic GSEA-based investigation
Diabetic kidney disease (DKD) involves oxidative stress–driven damage to glomeruli (Gloms) and proximal convoluted tubules (PCT). NAD(P)H: quinone oxidoreductase 1 (NQO1) regulates redox balance, but its compartment-specific role remains unclear. Streptozotocin (STZ)-induced hyperglycemia increased albuminuria and foot process effacement, with NQO1 KO (NKO) mice exhibiting greater podocyte injury than WT, indicating exacerbated glomerular damage. To investigate the underlying mechanisms, we conducted compartment-specific transcriptomic Gene Set Enrichment Analysis (GSEA) in Gloms and PCT. In Gloms, ribosome biogenesis and immune pathways were upregulated in WT-STZ compared to WT but suppressed in NKO-STZ compared to STZ, indicating impaired protein synthesis and immune regulation in NQO1 deficiency. In PCT, ribosome activity, oxidative phosphorylation, glutathione metabolism, and cytoskeletal pathways were elevated in WT-STZ compared to WT but suppressed in NKO-STZ compared to WT-STZ. However, ribosome activity was relatively less affected than in Gloms. Additionally, adherens junction activation was more pronounced in WT-STZ Gloms than in NKO mice Gloms, suggesting a compensatory mechanism to maintain podocyte foot process integrity. This response involved key cytoskeletal genes, including Actg1, Ctnna1, Tjp1, Rhoa, and Iqgap1. These findings highlight compartment-specific adaptive responses to STZ-induced hyperglycemia and underscore NQO1’s role in regulating these adaptations. Our results suggest that enhancing NQO1 activity may restore redox balance and preserve nephron integrity, supporting its potential as a therapeutic target for DKD. Furthermore, the observed compartment-specific responses highlight the need for precision redox therapies tailored to glomerular and tubular vulnerabilities.