Effects Of Exposure Research Articles

Hold the chair: the link between short-term exposure and the managerial change in an emerging market during the pandemic

PurposeThis paper aims to study the effect of short-term firm-level exposure on managerial change during the COVID-19 pandemic in the Chinese economy. Such a link is not explored in the existing COVID-19 and resource-based theory (RBT) literature.Design/methodology/approachThe logit regression model is utilized to examine the effect of short-term exposure on the probability of managerial change in the Chinese economy. Logit models based on coarsened exact matching (CEM) are also used in the robustness checks part of the study. The results are robust to different specifications.FindingsThe obtained findings show that short-term exposure has a significantly positive effect on the probability of managerial change during the pandemic.Research limitations/implicationsUnder the RBT approach, this study sheds new light on the relationship between short-term financial exposure and managerial change under uncertainty during the pandemic.Practical implicationsC-Suite executives need to be prepared for short-term sudden shocks. According to the findings of the study, the relationship between short-term sudden shocks and short-term financial exposure is a factor that C-suite executives should pay attention to.Social implicationsShort-term sudden shocks can support managerial change, pushing society into uncertainty and negatively affecting the private sector. In this context, it has a structure that can amplify uncertainty.Originality/valueIn the existing COVID-19 literature, the effect of short-term exposure on the probability of managerial change is under researched, especially in the emerging markets-based RBT and COVID-19 literature. The present study offers an insight into the link between short-term exposure and the probability of managerial change during the pandemic.

Absolute versus Relative Poverty and Wealth: Cooperation in the Presence of Between-Group Inequality

Abstract While inequality in resource endowments has been shown to affect cooperation levels in groups, much of this evidence comes from studies of within-group inequality. In an online public goods experiment, we instead examine the effects of payoff-irrelevant inequality in resources between groups on cooperation within equal groups, i.e. the effect of mere exposure to inequality. When all groups are poor or rich, their contribution behaviour is very similar. Relative inequality, when poor and rich groups coexist, leads to lower contributions in rich groups. We find suggestive evidence that this may be related to stereotypes about the rich contributing less than the poor.

Chronic corticosterone exposure causes anxiety- and depression-related behaviors with altered gut microbial and brain metabolomic profiles in adult male C57BL/6J mice

AbstractChronic exposure to glucocorticoids in response to long-term stress is thought to be a risk factor for major depression. Depression is associated with disturbances in the gut microbiota composition and peripheral and central energy metabolism. However, the relationship between chronic glucocorticoid exposure, the gut microbiota, and brain metabolism remains largely unknown. In this study, we first investigated the effects of chronic corticosterone exposure on various domains of behavior in adult male C57BL/6J mice treated with the glucocorticoid corticosterone to evaluate them as an animal model of depression. We then examined the gut microbial composition and brain and plasma metabolome in corticosterone-treated mice. Chronic corticosterone treatment resulted in reduced locomotor activity, increased anxiety-like and depression-related behaviors, decreased rotarod latency, reduced acoustic startle response, decreased social behavior, working memory deficits, impaired contextual fear memory, and enhanced cued fear memory. Chronic corticosterone treatment also altered the composition of gut microbiota, which has been reported to be associated with depression, such as increased abundance of Bifidobacterium, Turicibacter, and Corynebacterium and decreased abundance of Barnesiella. Metabolomic data revealed that long-term exposure to corticosterone led to a decrease in brain neurotransmitter metabolites, such as serotonin, 5-hydroxyindoleacetic acid, acetylcholine, and gamma-aminobutyric acid, as well as changes in betaine and methionine metabolism, as indicated by decreased levels of adenosine, dimethylglycine, choline, and methionine in the brain. These results indicate that mice treated with corticosterone have good face and construct validity as an animal model for studying anxiety and depression with altered gut microbial composition and brain metabolism, offering new insights into the neurobiological basis of depression arising from gut-brain axis dysfunction caused by prolonged exposure to excessive glucocorticoids.

Effects of Over-Time Exposure to Partisan Media and Coverage of Polarization on Perceived Polarization

ABSTRACT America is said to be more polarized than ever before, and extensive research examines the causes and effects of political polarization. A less studied but more pronounced trend is that citizens perceive society and politics as sharply divided. We focus on news exposure as a key reason for these perceptions. We disentangle the unique effects of exposure to partisan outlets and to news coverage of polarization in general, whether in partisan or centrist news media. We rely on 9 months of online behavioral data (127,400,000 visits) from large samples in the U.S. and Poland (total N = 2,462 & 2,120), paired with a three-wave panel survey on participants' attitudes and perceptions. We measure individual exposure, over-time and unobtrusively, to partisan outlets as well as to news coverage of polarization through a fine-tuned BERT-based machine learning classifier. We find that both exposures increase perceived polarization, independently, in both countries. Yet, in both contexts, it is news coverage of polarization, regardless of whether it is ideologically left, right, or centrist news outlets, that is the strongest driver of perceived polarization. These changes are confined to personal-level polarization (perceived distance between oneself and members of the opposing party), while no measure significantly influences perceptions of society, more generally, as being polarized. These findings have important implications for our understanding of how the media’s increasing tendency to focus on conflict as a central reporting frame can be the driver of often exaggerated perceptions of partisan divisions.

Effect of carbon black and silicon dioxide nanoparticle exposure on corona receptor ACE2 and TMPRSS2 expression in the ocular surface.

The Coronavirus disease 2019 (COVID-19) pandemic has led to a global health crisis, including ocular symptoms, primarily targeting the Angiotensin-Converting Enzyme 2 (ACE2) receptor. PM2.5 air pollution may increase infection risk by altering ACE2 expression. Silicon Dioxide (SiO2) and carbon black (CB), major components of PM2.5 from sands and vehicle emissions, were studied for their effects on ACE2 and Transmembrane Protease Serine 2 (TMPRSS2) expression in corneal and conjunctival cells, and ocular tissues. Human corneal epithelial cells (HCECs) and conjunctival epithelial cells (HCjECs) were exposed to nanoparticles (NPs) for 24 hours, assessing viability via WST-8 assay. TNF-α, IL-6, and IL-1β levels in the medium were measured. An in vivo rat study administered NPs via eye drops, with Rose Bengal staining to evaluate damage. ACE2, TMPRSS2, and Angiotensin II (AngII) protein expressions were quantified by Western blot. ACE2 expression in HCjECs increased with NP exposure, while it decreased in HCECs. CB exposure increased TNF-α, IL-6, and IL-1β levels in HCECs. In vivo, corneal exposure to CB decreased ACE2 expression, whereas conjunctival exposure to SiO2 increased ACE2 expression. These changes suggest that SiO2 exposure may increase the risk of COVID-19 through the ocular surface, while CB exposure may decrease it.

Examining Between- and Within-subjects Effects of Posting and Exposure to Alcohol-Related Social Media Content on Drinking Over Time.

Social media content featuring alcoholic beverages is posted and viewed by college students. Limited longitudinal research suggests that increased alcohol-related content (ARC) posting and exposure is associated with increased alcohol consumption among college students over time. Emerging evidence suggests this association may be bidirectional, with drinking predicting later ARC posting. The current study examined longitudinal bidirectional associations between alcohol consumption and: posting ARC (aim 1) and friend ARC exposure (aim 2). College students engaging in heavy or problematic drinking (N = 384; Mage = 20.04; 74.2% female; 79.6% White) completed four surveys (baseline, 1-month, 3-month, 6-month). Each survey assessed social media use (including ARC posting) and alcohol use, along with ARC posting behaviors of their social network (i.e., important friends). Random-intercept cross-lagged panel models revealed significant large associations only at the within-subjects level for posting ARC, but significant medium-large between- and within-subjects associations for ARC exposure. Within-subjects, greater alcohol consumption predicted posting 1 month later, and posting at the 3-month follow-up predicted increased drinking at 6-months (aim 1). Between-subjects, individuals who reported greater social network ARC exposure were more likely to report greater alcohol consumption. Within-subjects, greater-than-average ARC exposure at 1-month predicted decreased alcohol consumption at 3-months (aim 2). Results suggest the relationship between alcohol consumption and alcohol posting (self and ARC exposure) is complex and not necessarily bidirectional, with associations between posting and drinking fluctuating within subjects, while between- and within-subjects associations were observed for exposure and drinking. Associations between posting and drinking vary within individuals over time, while associations between exposure and drinking exist for groups, indicating the more people are exposed, the more alcohol they consume.

Effects of Repeated Exposure to Ambient Cold on the Development of Inflammatory Pain in a Rat Model of Knee Arthritis

This study investigated the effects of ambient cold exposure on inflammatory pain development, synovial cytokine levels, and spinal cord glial cell activation. Male Sprague–Dawley rats (6 weeks old) were divided into Cold and RT groups. The Cold group was exposed to cold (4 ± 1 °C) for 6 h/day for 5 consecutive days, while the RT group remained at room temperature (22 ± 1 °C). On day 6, knee arthritis was induced via intra-articular carrageenan injection. Pain was assessed by weight-bearing forces (WBFs) of the affected limb. Synovial pro-inflammatory (IL-1 β, IL-6, and TNF-α) and anti-inflammatory (IL-10) cytokines were measured by ELISA, while spinal cord microglia and astrocytes activation were evaluated via immunohistochemistry. WBFs were maximally reduced 4 h post-carrageenan injection, gradually recovering afterward. Cold-exposed rats showed significantly decreased WBF on days 1 and 2 post-injection compared to the RT group. In the Cold group, synovial cytokines (IL-1β, IL-6, IL-10) were significantly elevated 4 h post-injection, with no change in TNF-α levels. Additionally, OX42-positive cells (microglia) significantly increased 1 h post-injection in the Cold group, while GFAP-positive cells (astrocyte) remained unchanged. Repeated ambient cold exposure enhances inflammatory pain development through the regulation of synovial cytokines and microglia activation in the spinal cord in carrageenan-induced knee arthritis.

The joint effect of vitamin-D status and tobacco exposure on overweight and obesity in children.

This study aimed to explore the combined effects of serum vitamin-D level and tobacco exposure on the risk of overweight and obesity in children. This cross-sectional study analysed the data of 11636 children aged 2-17 years from the National Health and Nutrition Examination Surveys database between 2007 and 2018. Univariable and multivariate weighted logistic regression models were used to analyse the associations of serum vitamin-D or cotinine levels with overweight and obesity in children as well as the combined effects of serum vitamin-D and cotinine on the risk of overweight and obesity in children. Subgroup analysis was performed in terms of gender, age, race and household smokers. OR with corresponding 95 % CI was presented. The elevated risk of overweight and obesity in children was found in those with serum vitamin-D < 20 ng/ml (OR = 1·44, 95 % CI: 1·29, 1·61). Also, the odds of overweight and obesity in children was 1·14 (OR = 1·14, 95 % CI: 1·01, 1·29) in children with cotinine ≥ 0·05 ng/ml. Relative to participants with serum vitamin-D ≥ 20 ng/ml and cotinine < 0·05 ng/ml, increased risk of overweight and obesity was identified in those with serum vitamin-D < 20 ng/ml and cotinine < 0·05 ng/ml (OR = 1·45, 95 % CI: 1·26, 1·68) and serum vitamin-D < 20 ng/ml and cotinine ≥ 0·05 ng/ml (OR = 1·62, 95 % CI: 1·38, 1·91). Serum vitamin-D and cotinine exposure had combined effects on the risk of overweight and obesity in children.

Exposure to the antiretroviral drug dolutegravir impairs structure and neurogenesis in a forebrain organoid model of human embryonic cortical development

IntroductionFor many therapeutic drugs, including antiretroviral drugs used to treat people living with HIV-1 (PLWH), we have little data on the potential effects on the developing human brain due to limited access to tissue and historical constraints on the inclusion of pregnant populations in clinical trials. Human induced pluripotent stem cells (iPSCs) offer a new avenue to gain insight on how drugs may impact human cell types representative of the developing central nervous system. To prevent vertical transmission of HIV and promote the health of pregnant PLWH, antiretroviral therapy must be initiated and/or maintained throughout pregnancy. However, many antiretroviral drugs are approved for widespread use following clinical testing only in non-pregnant populations and there may be limited information on potential teratogenicity until pregnancy outcomes are evaluated. The integrase strand transfer inhibitor dolutegravir (DTG) is a frontline antiretroviral drug that is effective in viral suppression of HIV but was previously reported to be associated with a slight increase in the risk for neural tube defects in one study, although this has not been replicated in other cohorts.MethodsTo directly investigate the potential impact of DTG on human cortical neurogenesis, we measured the effects of daily drug exposure on the early stages of corticogenesis in a human iPSC-based forebrain organoid model. We quantified organoid size and structure and analyzed gene and protein expression to evaluate the impact of several doses of DTG on organoid development.ResultsWe observed deficits in organoid structure and impaired neurogenesis in DTG-treated organoids compared to vehicle-treated control organoids after 20 or 40 days in culture. Our highest dose of DTG (10 μM) resulted in significantly smaller organoids with a reduced density of neural rosette structures compared to vehicle-treated controls. Mechanistically, RNA-sequencing and immunohistological analysis suggests dysregulated amino acid transport and activation of the integrated stress response in the DTG-treated organoids, and functionally, a small molecule integrated stress response inhibitor (ISRIB) could partially rescue increased expression of proteins related to cell cycle regulation.DiscussionTogether, these results illustrate the potential for human iPSC-based strategies to reveal biological processes during neurogenesis that may be affected by therapeutic drugs and provide complementary data in relevant human cell types to augment preclinical investigations of drug safety during pregnancy.

Identifying the genetic association between severe autoimmune type 2 diabetes and the risk of focal epilepsy

BackgroundObservational studies suggested a bidirectional relationship between severe autoimmune type 2 diabetes and focal epilepsy. However, it remains debated whether and in which direction a causal association exists. This genetics-based study aimed to explore the relationships of severe autoimmune type 2 diabetes (T2DM) and focal epilepsy outcomes with two sample Mendelian randomization (TSMR) method.MethodsGenetic instruments were obtained from large-scale genome-wide meta-analysis of severe autoimmune T2DM (Ncase = 452, Ncontrol = 2,744), and focal epilepsy (Ncase = 929, Ncontrol = 212,532) of European ancestry. A series of analyses were performed to select eligible genetic instruments robustly associated with each of the traits using summary-level statistics. Inverse variance weighted was used for primary analysis, with alternative 11 MR methods. A scatter plot was utilized to illustrate the association between single nucleotide polymorphism (SNP) effects on the exposure and SNP effects on the outcome. The Wald ratio for individual SNPs and their cumulative effects was depicted using a forest plot. And diagnostics and sensitivity analyses were used to evaluate if the causal estimates are robust to violations of MR underlying assumptions, including pleiotropy, heterogeneity assessment, and leave-one-out analysis. Then the results were validated using CURATED database of DisGeNET platform.ResultsFor forward analysis, genetic predisposition to severe autoimmune T2DM was associated with an increased risk of focal epilepsy (Inverse variance weighted (IVW) method: OR = 1.11, 95% CI = 1.03-1.18, p = 0.012). For reverse analysis, there was no enough instrument variables of focal epilepsy on severe autoimmune T2DM. Further, the interrelation between severe autoimmune T2DM and focal epilepsy was demonstrated via variant-disease association network analysis using the instrument SNPs.DiscussionThis MR study supports a causal link between severe autoimmune T2DM and focal epilepsy. More effort should be made to screen seizure in severe autoimmune T2DM, unravel its clinical implications, and explore its role as a putative modifiable risk factor.

Synthetic bodies: protocols for intra-acting

Our bodies are porous entities that interconnect with and depend on the broader collectivity of human and nonhuman life that exists within a shared environment. Using the figuration of synthetic bodies, this exposition aims to examine the relationships in which we are enmeshed as our bodies absorb and excrete chemicals. With a focus on involuntary exposure to industrially manufactured chemicals (as opposed to exposure to naturally occurring chemicals or voluntary experimentation with chemicals of all types), this exposition invites readers to learn about the chemicals to which we are exposed and by which we are affected. With the ubiquity of chemicals in the environment, who are we becoming? How do chemicals affect us and how do we interact with them? How can we live well with chemicals in spite of their potential to harm? Adopting a decolonial feminist, posthumanist, and new materialist approach and embracing queer ecological sensibilities, this exposition develops protocols for embodied and materially embedded research practices that trace the effects of exposure to chemicals in everyday life. In so doing, it aims to demonstrate how we might build resilience through encounters with toxicity, contamination, and impurity. &lt;style&gt; /* rules to make button only show up in META */ .download-accessible { display:none; } .meta-right-col .download-accessible { display: inline-block; padding: 9px; margin-bottom:25px; border: 1px solid black; background-color:white; } &lt;/style&gt; &lt;a class="download-accessible" href="download-media?work=3155507&amp;amp;file=3155516" title="This accessible PDF is a derivative of the original which it is meant to support and not replace."&gt;Download Accessible PDF&lt;/a&gt;

Comparative Proteomics Highlights that GenX Exposure Leads to Metabolic Defects and Inflammation in Astrocytes.

Exposure to PFAS such as GenX (HFPO dimer acid) has become increasingly common due to the replacement of older generation PFAS in manufacturing processes. While neurodegenerative and developmental effects of legacy PFAS exposure have been studied in depth, there is a limited understanding specific to the effects of GenX exposure. To investigate the effects of GenX exposure, we exposed Drosophila melanogaster to GenX and assessed the motor behavior and performed quantitative proteomics of fly brains to identify molecular changes in the brain. Additionally, metabolic network-based analysis using the iDrosophila1 model unveiled a potential link between GenX exposure and neurodegeneration. Since legacy PFAS exposure has been linked to Parkinson's disease (PD), we compared the proteome data sets between GenX-exposed flies and a fly model of PD expressing human α-synuclein. Considering the proteomic data- and network-based analyses that revealed GenX may be regulating GABA-associated pathways and the immune system, we next explored the effects of GenX on astrocytes, as astrocytes in the brain can regulate GABA. An array of assays demonstrated GenX exposure may lead to mitochondrial dysfunction and neuroinflammatory response in astrocytes, possibly linking non-cell autonomous neurodegeneration to the motor deficits associated with GenX exposure.

Association between secondhand smoke and liver injury among US non-smoking adults: Mediation analysis of body mass index in the NHANES.

Liver injury is a primary factor in the pathogenesis of most liver diseases, which can lead to liver failure. Secondhand smoke (SHS) is a serious public problem. This research explored the correlation between SHS and the indicators of liver injury. This cross-sectional study was based on the National Health and Nutrition Examination Survey (NHANES) 2011-2016. The relationship between SHS and indicators of liver injury was explored by the weighted linear regression model and smooth curve fitting. The weighted threshold saturation effect model tested the relationship and inflection point between them. Mediation analyses were used to explore whether body mass index (BMI) mediates the correlation between SHS and liver injury indicators. Our cross-sectional study included 3811 non-smoking participants (aged 20-80 years). The full covariate adjustment model (β= -0.05; 95% CI: -0.08 - -0.02) showed a significant and negative correlation between log cotinine and albumin (ALB). Compared to the unexposed group, the ALB, and total protein (TP) were decreased by 0.16 g/dL, 0.26 g/dL in the heavy exposure group [ALB: -0.16 (-0.26 - -0.05), TP: -0.26 (-0.38 - -0.13)], respectively. Smoothed curve fitting revealed a nonlinear relationship between log cotinine and fibrosis-4 index (FIB-4 score), with the inflection point of log cotinine at -1.72. When log cotinine was < -1.72, the log cotinine significantly and positively correlated with the FIB-4 score (β=0.27; 95% CI: 0.06-0.49). BMI partially mediated the effect of SHS exposure on ALB or TP. SHS has harmful effects on the liver in never-smoking adults. BMI partially mediated the effect of SHS exposure on ALB or TP. More prospective and basic research in the future is necessary to focus on validating our results.

Pharmacokinetic/pharmacodynamic analysis of geographic atrophy lesion area in patients receiving pegcetacoplan treatment or sham.

Pegcetacoplan is a complement C3/C3b inhibitor indicated for the treatment of geographic atrophy (GA). A population pharmacokinetic (PK)/pharmacodynamic (PD) analysis of pegcetacoplan used GA lesion area measurements from three clinical studies to determine the effect of pegcetacoplan exposure on GA progression. A base disease progression model was developed using data from sham-treated eyes and untreated fellow eyes, followed by treatment effect assessment in dose-response and PK/PD models. In total, 1501 patients from FILLY (NCT02503332), OAKS (NCT03525613), and DERBY (NCT03525600) received intravitreal pegcetacoplan 15 mg monthly or every other month (EOM) or sham treatment monthly or EOM and were included in the population analysis of lesion area. Disease progression over time was adequately described as linear-with-time over the 24-month maximal study duration. Disease-specific covariates associated with slower lesion growth were unilateral, unifocal, and subfoveal GA lesions and >20 intermediate or large drusen groups (≥63 μm) at baseline. The dose-response model estimated 0.80-fold (95% CI: 0.75, 0.84) and 0.83-fold (95% CI: 0.78, 0.87) reductions in GA lesion growth rate with pegcetacoplan monthly and EOM, respectively, versus sham. A relationship between vitreous humor concentration and GA lesion growth rate was quantified as 2.6% per unit of log-transformed vitreous pegcetacoplan concentration in the PK/PD model. PK/PD predictions of treatment effect based on exposure (pegcetacoplan monthly: 0.80 [90% CI: 0.77, 0.84]; pegcetacoplan EOM: 0.83 [90% CI: 0.80, 0.86]) were consistent with predictions based on dose response. These results support the benefit of pegcetacoplan administered monthly or EOM in slowing GA lesion growth.

The head of invasive cardiologists as a target of professional exposure to ionizing radiation

Exposure to ionizing radiation has recognized detrimental cancer and non-cancer health effects. These effects are now well-proven not only for high doses &gt; 1,000 millisieverts (mSv) associated with head radiotherapy but also for moderate (100–1,000 mSv) and even low (&lt; 100 mSv) doses, of interest for professionally exposed cardiologists. The head of interventional cardiologists is highly exposed to ionizing radiation, with possible damage to the eye and brain. Unprotected interventional cardiologists experience head radiation doses up to ten times greater than chest doses below lead aprons, with marked exposure to the left hemisphere of the brain reaching up to 2 Sv—equivalent to 10,000 chest X-rays over a professional lifetime. This narrative review aims to provide an overview of the background of radioprotection, the biological mechanisms involved, and the epidemiological evidence regarding the health effects of head exposure to ionizing radiation in invasive cardiologists. These health effects include cataracts, brain cancer, cerebrovascular diseases, neurodegeneration, and mood disorders. The evidence gathered from other exposed populations, which experienced similar eye and brain doses, has also been reviewed. This is important because the doses, risks, and effects are consistent in cases of repeated exposures, which occur more frequently for patients, and in situations involving chronic low doses, as seen with interventional cardiologists. Despite these risks, effective protective measures—such as suspended lead ceilings, curtains, and specialized eyewear—can reduce radiation exposure to near-zero levels. In some fields, like interventional cardiac electrophysiology, a groundbreaking near-zero radiation approach using non-fluoroscopic methods has been created, eliminating radiation exposure and alleviating orthopedic stress and operational discomfort. The race to zero radiation in interventional cardiology is ongoing.

"I'm in the Bluesky Tonight": Insights from a year worth of social data.

Pollution of online social spaces caused by rampaging d/misinformation is a growing societal concern. However, recent decisions to reduce access to social media APIs are causing a shortage of publicly available, recent, social media data, thus hindering the advancement of computational social science as a whole. We present a large, high-coverage dataset of social interactions and user-generated content from Bluesky Social to address this pressing issue. The dataset contains the complete post history of over 4M users (81% of all registered accounts), totalling 235M posts. We also make available social data covering follow, comment, repost, and quote interactions. Since Bluesky allows users to create and like feed generators (i.e., content recommendation algorithms), we also release the full output of several popular algorithms available on the platform, along with their timestamped "like" interactions. This dataset allows novel analysis of online behavior and human-machine engagement patterns. Notably, it provides ground-truth data for studying the effects of content exposure and self-selection and performing content virality and diffusion analysis.

Thriving Beyond Adversity: A Prospective Longitudinal Cohort Study Using a Strength-Based Approach Depicts Indigenous Adolescents with Less Adverse Childhood Experiences (ACEs) Had Fewer Neurodevelopmental Disorders (NDDs)

Improving social and emotional well-being (SEWB) among Indigenous adolescents is crucial. Since neurodevelopmental disorders (NDDs) are common in Indigenous people and adverse childhood experiences (ACEs) are important contributors to negative health outcomes throughout the lifespan, we investigated whether limited ACE exposure is associated with reduced risk of NDDs in Australian Indigenous teens using the data from multiple waves (Wave 1 to Wave 9, and Wave 11) of the Longitudinal Study of Indigenous Children (LSIC). We also examined the role of other protective factors, such as Indigenous cultural identity and school connectedness, against NDDs. A strengths-based approach using mixed-effects logistic regression models examined the protective effect of limited ACE exposure (from LSIC waves 1–9) on NDDs (outcome from LSIC wave 11), adjusting for sociodemographic factors. The NDDs included autism, ADHD, intellectual, neurological, and specific learning disabilities. Of the 370 individuals analysed, 73.2% valued Indigenous cultural identity, and 70.5% were strongly connected at school. More than one-fourth (27.8%) reported limited ACE exposure, while the majority was not diagnosed with NDDs (93%). Longitudinal analysis revealed limited ACE exposure was 6.01 times (95% CI: 1.26–28.61; p = 0.024) more likely to be protective against NDDs compared to those exposed to multiple ACEs. Moreover, valuing cultural identity (aOR = 2.81; 95% CI: 1.06–7.39; p = 0.038) and girls (aOR = 13.88; 95% CI: 3.06–62.84; p = 0.001) were protective against NDDs compared to their respective counterparts. Our findings highlight the need to prevent ACE exposure and promote Indigenous cultural identity in preventing negative health outcomes and the exacerbation of health inequities to strengthen the SEWB of Indigenous communities.

TRPM8 channels, cold and headache: data of experimental and clinical studies

Abstract – Different types of headaches, including migraine, may have a causal relationship with cold exposure, and this relationship can be either positive or negative, i.e. cold can both provoke and alleviate cephalalgia. Various representatives of the transient receptor potential ion channel superfamily, in particular TRPM8, act as molecular thermoreceptors that provide signal transduction in the response to low temperatures. These channels, which are known to mediate the normal cold sensation and play a role in both cold-induced pain and cryoanalgesia, are often considered as a promising target for the development of principally new anti-migraine drugs. This review summarizes recently obtained data on the TRPM8 structure and function, and their role in the pathogenesis of migraine, as well as discusses the intriguingly inconsistent results of studying TRPM8 agonists and antagonists in experimental headache models and clinical trials. Analyzing data from various studies allows to conclude that TRPM8 activation can be both pro- and antinociceptive; this correlates with the reported dual effect of cold exposure on the induction and resolution of headaches, leaving open the question on the vector of the TRPM8 pharmacological modulation required to produce anticephalgic effect.

Ultrasound‐Responsive Lipid Nanoparticles for Targeted Therapy and Controlled Drug Release in Non‐Small Cell Lung Cancer

AbstractMultifunctional drug delivery systems offer tremendous potential for improving antitumor efficacy, precise drug targeting, and controlled drug release in treating non‐small cell lung cancer (NSCLC). In this study, the study develops a novel tumor‐targeting ultrasound‐responsive lipid nanoparticle (TUSL) platform capable of responding to external stimulation, enabling precise drug delivery with controlled release at the tumor site while minimizing systemic exposure and side effects. The TUSL platform is designed to carry doxorubicin (DOX) and tetrandrine (TET), specifically for drug‐resistant NSCLC. The developed TUSL exhibits a nano sized spherical structure with a hydrodynamic size of 141.8 nm, accommodating anti‐cancer drugs with loading capacities of 3.8% and 6.2% for TET and DOX, respectively. TUSL is engineered to target the epidermal growth factor receptor (EGFR) while demonstrating an ultrasound‐triggered drug release profile. Through the generation of CO2 bubbles upon ultrasound stimulation, the TUSL enhances DOX and TET internalization into tumor cells. In tumor‐bearing mice, TUSL administration demonstrates a superior tumor accumulation with minimal off‐target toxicity. The combined treatment with DOX and TET within TUSL exhibits synergistic effects, effectively inhibiting the growth of drug‐resistant NSCLC tumors. These findings highlight the efficacy of the EGFR‐targeted TUSL formulation in overcoming drug resistance and enhancing therapeutic outcomes in NSCLC.

Tolerance of free-living larval stage of a parasite from coastal mining areas in northern Humboldt Current to copper pollution at low and high temperatures.

Metal pollution is a worldwide problem and one of the greatest threats to ecosystem integrity due to its toxicity, persistence, and bioaccumulation in biological systems. Anthropogenic pollution impacts marine organisms and host-parasite dynamics, with the northern Chilean coast experiencing elevated copper levels in marine waters and sediments due to mining activities. In this study, we assessed the effects of exposure to copper concentrations at low and high-water temperatures on the survival and longevity of the marine parasite Himasthla sp. cercariae (Trematoda: Digenea) using the snail Echinolittorina peruviana as its first intermediate host. Snails were collected from intertidal rocky pools in northern Chile (23°S). To assess parasite survival and longevity, cercariae were collected from a pool of infected snails, and their mortality was recorded every 6 hours until all cercariae were dead. In a preliminary experiment conducted at 19°C, cercariae were exposed to different copper concentrations (0.2, 1.5, 3.0, and 6.0 mg/L) for 78 hours. Cercariae showed tolerance to copper. However, at the higher copper concentration (6 mg/L), survival was negatively impacted (50%) at 54 hours. In contrast, at the lower concentration (0.2 mg/L) and in the control group, cercariae sustained a 73-90% survival rate even after 54 hours. Based on these findings, we conducted subsequent experiments involving two copper treatments (0.2 and 3.0 mg/L) and two temperatures (14 and 22°C). Survival and longevity were significantly higher at lower temperature and copper concentration (14°C and 0.2 mg/L). Conversely, at higher temperature and copper concentration (22°C and 3 mg/L), survival and longevity decreased to only 66 hours. Our results show that Himasthla sp. cercariae tolerated most copper concentrations, with vulnerability observed primarily in high water temperatures, indicating an adverse effect on cercariae performance. This study contributes valuable insights into how parasites respond to environmental pollution, in marine ecosystems influenced by anthropogenic activities.