Dual Exposure Research Articles

Association of Serotonin Transporter (SERT) Polymorphisms with Opioid Dependence and Dimensional Aspects of Cocaine Use in a Caucasian Cohort of Opioid Users.

IntroductionA functional tandem repeat polymorphism in the promoter of the serotonin transporter (SERT) gene (SLC6A4) has been studied for association to neuropsychiatric conditions, including substance use disorders. Short (S) forms of this repeat result in reduced transcription, and presumably greater synaptic levels of serotonin, which are involved in opioid and cocaine-induced reward. Dual exposure to heroin and cocaine is a common pattern of poly-drug use and is associated with considerable morbidity. We hypothesize that SLC6A4 variants are associated with cocaine exposure in subjects with an opioid dependence diagnosis (OD), and also in non-dependent opioid users (NOD). Other single nucleotide polymorphisms (SNPs) of SLC6A4 may also be likewise associated.Materials and MethodsThis study determined whether variants of the SLC6A4 promoter repeats and two intronic SNPs, rs16965628 and rs2066713, are associated with categorical diagnoses of opioid dependence (DSM-IV criteria) and with dimensional aspects of cocaine use, in a Caucasian cohort (n=591). Three groups of subjects were examined: (1) 276 subjects with opioid dependence diagnosis (OD); (2) 163 subjects who had used opioids for non-medical reasons but never had an opioid dependence diagnosis (NOD); (3) 152 healthy controls (HC).ResultsAside from high exposure to heroin in the OD group, relatively high exposure to cocaine was detected in both OD and NOD groups. The SERT repeat genotype (classified as “long-long” [LL] versus ”short-long” plus “short-short” [SL+SS]) was not associated with categorical opioid dependence diagnoses. A nominally significant association was identified with the [SL+SS] genotype of SLC6A4 and cocaine KMSK scores ≥“cutpoint” for a cocaine dependence diagnosis (p=0.026). The [SL+SS] genotype was associated with more rapid cocaine escalation than the LL genotype. No significant associations of rs16965628 and rs2066713 SNPs were found overall.ConclusionThe functional SERT promoter tandem repeat genotype may be associated to heavy cocaine exposure and more rapid escalation of cocaine use, in persons with and without opioid dependence diagnosis.

Family resilience and protective factors promote flourishing and school engagement among US children amid developmental disorder and adverse psychosocial exposure

Early life psychosocial adversities and developmental disorders are common among children in the United States. However, there is relatively little research on how family processes and neighborhood-level factors may promote well-being among children dually burdened with developmental disorders (DD) and adverse childhood experience (ACE). Using secondary analysis of the National Survey of Children’s Health 2016–2018 (N = 56,831), we examined the associations of family resilience and other protective factors with flourishing and school engagement among subgroups of children with dual exposure to DD and ACE. Results indicate that family resilience, family meals, and mother’s mental health promote flourishing and school engagement amid varying levels of exposure to ACE and DD. Social interventions designed to improve family and neighborhood resources can protect child well-being amid multiple adversities.

The Co-Occurrence of Child Maltreatment and Intimate Partner Violence in Families: Effects on Children's Externalizing Behavior Problems.

Children exposed to maltreatment are at risk of experiencing intimate partner violence (IPV) and behavioral problems. This study examined different forms of family violence that co-occur and their relationship to children's externalizing behaviors across developmental stages (early childhood, middle childhood, adolescence). Longitudinal data (N = 1,987) at baseline and 18 months and 36 months post-baseline from the NSCAW II were used. Mixture modeling was employed in which latent class models estimated subgroups of children who experienced co-occurring forms of family violence; regression models estimated which subgroups of children were at risk of externalizing behaviors. Three latent classes were identified across developmental stages: high family violence, low family violence, and child physical abuse and psychological aggression. For children in early childhood, a fourth class was identified: partner and child physical abuse and child psychological aggression. Results from regression models revealed differences in externalizing scores by class membership across developmental age groups and over time. That distinct classes of child maltreatment and IPV co-occur and differentially impact children's behavior suggests a need for strong prevention and intervention responses to address children's dual maltreatment and IPV exposure.

Allostatic gene regulation of inhibitory synaptic factors in the rat ventral hippocampus in a juvenile/adult stress model of psychopathology.

Early life stress is an important vulnerability factor for the development of anxiety disorders, depression and late-onset cognitive decline. Recently, we demonstrated that juvenile stress (JS) lastingly enhanced long-term potentiation via reduction of steady-state glutamine synthetase mRNA expression and the associated dysregulation of the astrocytic glutamate-glutamine cycle in the rat ventral CA1. We now investigated the regulation of steady-state mRNA expression of neuronal gene products that determine GABAergic and glutamatergic neurotransmission in layers of the ventral and dorsal CA1 after JS. We further studied their interaction with stress in young adult age (AS) to address their putative role in psychopathology development. Strikingly, mRNA levels of the glutamic acid decarboxylase (GAD) isoforms GAD65 and of the GABA-A receptor α2 (Gabra2) were increased after single JS or AS, but not after combined JS/AS stress experience. In fact, JS/AS resulted in layer-specific reduction of Gabra2 and also of Gabra1 mRNA levels in the ventral CA1. Furthermore, GAD65 and Gabra2 mRNAs were correlated with glutamatergic AMPA and NMDA receptor subunit mRNAs after single JS and AS, but not after combined JS/AS. Together, these data indicate a loss of allostatic regulation of steady-state mRNA levels of key GABAergic components that may result in a dysregulation of excitation/ inhibition balance in the ventral CA1 upon dual stress exposure. Finally, individual differences in local glucocorticoid receptor mRNA expression may contribute to this regulation.

Performance of concrete under accelerated physical salt attack and carbonation

Conventional testing of physical salt attack (PSA) on concrete does not consider concomitant factors that may exist in service and alter the mechanisms and kinetics of PSA. This study adopted a combined testing approach where concrete was concurrently investigated under accelerated PSA and carbonation, simulating elements serving in heavy traffic and industrial zones, while implementing ambient conditions similar to that in geographic locations with previous cases of PSA. Based on the tested mixture design parameters [water-to-binder ratio, cement type, and supplementary cementitious materials], potential performance improvement and risks were identified. Thermal, mineralogical, and microscopy analyses elucidated the co-occurrence of complex degradation processes in concrete subjected to accelerated PSA and carbonation, which were distinctive from that induced by the single-factor PSA exposure. The synoptic results from this study may informatively improve guidance on mixture design of concrete when dual exposure to PSA and carbonation is expected in the field.

Sex- and age-dependent differences in nicotine susceptibility evoked by developmental exposure to tobacco smoke and/or ethanol in mice.

Either tobacco smoking or alcohol consumption during pregnancy sex-selectively increases susceptibility to drugs of abuse later in life. Considering that pregnant smoking women are frequently intermittent consumers of alcoholic beverages, here, we investigated whether a short-term ethanol exposure restricted to the brain growth spurt period when combined with chronic developmental exposure to tobacco smoke aggravates susceptibility to nicotine in adolescent and adult mice. Swiss male and female mice were exposed to tobacco smoke (SMK; research cigarettes 3R4F, whole-body exposure, 8 h/daily) or ambient air during the gestational period and until the tenth postnatal day (PN). Ethanol (ETOH, 2 g/Kg, 25%, i.p.) or saline was injected in the pups every other day from PN2 to PN10. There were no significant differences in cotinine (nicotine metabolite) and ethanol serum levels among SMK, ETOH and SMK + ETOH groups. During adolescence (PN30) and adulthood (PN90), nicotine (NIC, 0.5 mg/Kg) susceptibility was evaluated in the conditioned place preference and open field tests. NIC impact was more evident in females: SMK, ETOH and SMK + ETOH adolescent females were equally more susceptible to nicotine-induced place preference than control animals. At adulthood, SMK and SMK + ETOH adult females exhibited a nicotine-evoked hyperlocomotor profile in the open field, with a stronger effect in the SMK + ETOH group. Our results indicate that ethanol exposure during the brain growth spurt, when combined to developmental exposure to tobacco smoke, increases nicotine susceptibility with stronger effects in adult females. This result represents a worsened outcome from the early developmental dual exposure and may predispose nicotine use/abuse later in life.

Accessible and Interactive Learning of Spectroscopic Parameterization through Computer-Aided Training

The importance of utilizing spectroscopic techniques for unraveling structural and compositional changes in nonreacting and reacting systems is unquestionable. Nowadays, efforts are directed towards the introduction of relevant spectroscopic techniques to undergraduate students in order to prepare them for future careers in industry and academia, where these techniques are becoming ever-more popular for material quality control, reaction monitoring, process control, etc. Educators have increasingly shifted to programming-based lessons due to intrinsic benefits such as improved and broad accessibility over interactive lessons, dual exposure to chemistry and computer science topics, remote teaching, etc. In this work, a MATLAB-based program is built to expose students at higher education levels (undergraduates and graduates) as well as new users to spectral parameter estimation towards the collection of Raman spectra in a timely manner with high signal to noise ratio (S/N). The development of this intermediate-level intuitive understanding in spectroscopic techniques has the potential to serve as the interface between course curricula and hands-on experience in advanced techniques.

Targeting MYD88-Mutant DLBCL with IRAKIMiDs: A Comparison to IRAK4 Kinase Inhibition and Evaluation of Synergy with Rational Combinations

Introduction: MYD88 mutations are found in 25% of DLBCL and are associated with an inferior survival. MYD88 is an adapter molecule, forming the core of the Myddosome complex. MYD88 mutations constitutively activate pathways such as NFқB, leading to lymphomagenesis. Essential to the Myddosome-dependent signaling pathway is the recruitment of IRAK4 which complexes with MYD88 to activate downstream effects. Targeting IRAK4 is therefore a rational therapeutic approach in MYD88-mutant lymphomas. First-in-class IRAKIMiDs, novel heterobifunctional degraders that target IRAK4 as well as the IMiD substrates Ikaros and Aiolos to enable the inhibition of both the NFkB and IRF4 pathways activated by MYD88 mutations, demonstrate potent efficacy in MYD88-mutant lymphomas (KTX-475, KTX-582, Walker D et al. AACR 2020). Herein, we compare the activity of IRAKIMiDs to IRAK4 kinase inhibitors and IMiDs alone in MYD88-mutant DLBCL, and evaluate rational combinations of IRAKIMiDs and other active agents in DLBCL for synergy. Methods: MYD88-mutant (n=4) and wild type (n=4) DLBCL cell lines were exposed to a panel of single agents (KTX-475, KTX-582, BAY1830839, CA-4948, CC-220, lenalidomide, pomalidomide, ibrutinib, umbralisib, venetoclax) in order to establish the drug concentration:cytotoxicity effect relationship. Cell viability was assessed using Celltiter-Glo assay at 24-hour intervals. IC50 values were computed. MYD88-mutant DLBCL cells were co-exposed to combinations of KTX-475 with venetoclax, ibrutinib, or umbralisib at concentrations representing their respective IC10-40 in order to determine synergy using the excess over bliss (EOB) method. Venetoclax, ibrutinib, and umbralisib were selected for combinational studies in order to target adverse pathways known to be associated in DLBCL biology. To confirm IRAK4 degradation, western blot and flow cytometry was performed. Apoptosis was evaluated with flow cytometry. Pre-treatment RNA-seq libraries were developed for the purpose of identifying GSEA and mutational analysis to predict response to IRAKIMiDs. Results: Exposure to IRAKIMiDs led to potent activity in MYD88-mutated DLBCL with IC50s in the low nanomolar range. IRAK4 degradation occured in a dose- and time-dependent manner and was observed as early as four hours after exposure. IRAKIMiDs induced superior cytotoxicity compared to two IRAK4 kinase inhibitors, including CA-4948 (Curis), which is currently under clinical investigation for relapsed/refractory NHL, as determined by lower IC50s in all cell lines. IRAKIMiD IC50s were also lower compared to pomalidomide, lenalidomide, and CC-220. KTX-475 was selected for synergy assessments based on IC50 values. Synergy was observed after exposure to KTX-475 in conjunction with venetoclax, ibrutinib, or umbralisib as determined by EOB >0 in the MYD88-mutant OCI-LY10 model, with maximum values peaking at 72-96 hours. After dual drug exposure, IRAK4 degradation was validated by flow cytometry demonstrating that the addition of venetoclax, ibrutinib or umbralisib to KTX-475 did not impair IRAK4 degradation capabilities. RNA-seq interpretation is currently underway. Conclusions: Collectively, our results demonstrate that dual-function degraders targeting both IRAK4 and the IMiD substrates Ikaros and Aiolos can serve as a potential therapeutic option for poor prognosis MYD88-mutant DLBCL. Our data thus far demonstrate improved efficacy of IRAKIMiDs compared to IRAK4 kinase inhibitors or IMiDs alone in vitro, as well as synergy with other active agents in combination regimens. A promising lead IRAKIMiD candidate has been identified, with initiation of a first-in-human clinical trial in B-cell lymphomas planned for 2021. Disclosures Lue: Daiichi Sankyo: Honoraria; AstraZeneca: Speakers Bureau; Astex Pharmaceuticals: Honoraria; Kymera Therapeutics: Honoraria, Research Funding; Kura Oncology: Honoraria. Klaus:Kymera Therapeutics: Current Employment, Current equity holder in publicly-traded company. Kanik:Kymera Therapeutics: Current Employment, Current equity holder in publicly-traded company. McDonald:Kymera Therapeutics: Current Employment, Current equity holder in publicly-traded company. Gollob:Kymera Therapeutics: Current Employment, Current equity holder in publicly-traded company. Walker:Kymera Therapeutics: Current Employment, Current equity holder in publicly-traded company. O'Connor:Kymera Therapeutics: Current equity holder in private company, Honoraria, Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Current Employment, Current equity holder in publicly-traded company; Servier: Consultancy; Mundipharma: Other: Consulting; Astex Pharmaceuticals: Honoraria, Research Funding; Merck: Research Funding; Nomocan: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Other: Data Safety Monitoring Committee, Research Funding. Mainolfi:Kymera Therapeutics: Current Employment, Current equity holder in publicly-traded company.

Evaluation of heart rate variability, blood pressure and lipid profile alterations from dual transceiver mobile phone radiation exposure

Electromagnetic fields have been reported to alter electrical activities in the brain and heart. However, there is paucity of information on the potential functional alterations that magnetic fields from mobile phone could cause to the heart. This study investigated heart rate variability (HRV), blood pressure (BP) and lipid profile in Wistar rats exposed to electromagnetic field radiation from a dual transceiver mobile phone (DTrMP). Twenty-one male albino Wistar rats (140-180g) were randomly assigned to two major groups positioned 5m apart as follows: control: no phone (n=7) and treatment group (n=14) continuously exposed to electromagnetic field from Tecno T312 DTrMP 900/1800MHz set in silence mode. Experimental treatment consisted in 10min calls/day, directed to this device for a period of six weeks. Seven animals from the treatment group were allowed to recover for a period of two weeks after exposure. HRV, systolic, diastolic and mean arterial BP were noninvasively investigated, while serum lipid profile and heart tissue nitric oxide (NO) activities were determined using standard procedures. There was significant (p<0.05) increase in systolic, diastolic, mean arterial BP and a decrease in HRV. Serum high density lipoproteins decreased, while total cholesterol, atherogenic indices, and heart NO levels increased significantly in the radiation exposed animals. The alterations observed in exposed animals remained unchanged even after the recovery period. These results suggest that exposure to electromagnetic radiation from dual transceiver mobile phones could be a risk factor to increase in blood pressure.

Liquid Biopsy In Stage Iv Non-Small Cell Lung And Prostate Cancers And Prevalence Of Ethnicity And Risk Factors: A Va Medcial Center Experience

Abstract Introduction/Objective The advent of Liquid biopsy (LB) is a milestone in precision oncology. This minimally invasive revolutionary technique analyses circulating tumor DNA and detects signature genomic alterations. Advanced-stage prostate cancers are more common in African Americans both in general and veteran patient population, while general cohort Caucasians are more prone to advanced/metastatic NSCLC. Risk factor for these cancers is smoking; agent orange exposure and its relationship with aggressiveness/ethnicity for veterans is sparse in the literature. We performed a QA study for advanced lung/prostate cancers of veteran patients on LB. Methods QA documentation from Foundation One (Cambridge MA, NGS) on LB performed for the regional Veteran Affairs Medical Center (VAMC) from May 2019 to April 2020 were reviewed. The testing was performed on advanced NSCLC/prostate cancer cases with evidence of advanced tumor progression. Data for ethnicity, risk factors, post therapy PSA, Gleason score and genetic mutations noted. Results A total of 30 LBs were performed over this time period. Of 30 LBs, 23 were prostate and 7 were lung cancers. 2/30 had unknown ethnic background. 19/28 (67.8%) were of African American origin, 18 of which had advanced prostate cancers. 11/28 were white, of which 3/30 were advanced NSCLC. One patient declined to reveal risk factor exposure, hence 17/29 (58.6%) had smoking, 15/29 (51.7%) had a risk of herbicide, agent orange exposure; and, 10/29 (34.4%) had both risk factor exposures. 6/29 (20.6%) African American veterans had combined risk factors. 9/10 (90%) veterans which had dual exposure presented with either Gleason score of 9 or as metastasis. Post therapy PSA ranged from 0.5 to 1870 ng/ml and did not corelate with the aggressiveness of the cancer or therapy response. Conclusion Veteran patient population has slightly higher incidence of ethnic African Americans presenting with advanced NSCLC/prostate cancers compared to general patient cohort. Although incidence of smoking is similar, combined exposure with agent orange, increases the aggressiveness of the disease three-fold. Real-time monitoring of the therapy response and multimodal benefits by LB is of immense help in morbidly ill veterans, compared to post- therapy PSA monitoring or invasive tissue biopsy. Role of LB should also be explored for early screening/triaging the veterans.

Tuning of face expertise with a racially heterogeneous face-diet

ABSTRACT The contact hypothesis posits that a racially-homogenous face-diet, in part, accounts for the other-race effect (ORE)—a difficulty in recognizing other-race faces. This account does not specify whether racial homogeneity of face exposure is necessary to achieving native-level expertise for own-race faces. Here we propose three new models that complement and extend the contact hypothesis: the experience-limited, the capacity-limited, and the enhancement hypotheses, each with differing predictions in the context of abundant exposure to multiple race categories. The experience-limited account proposes that greater experience always leads to better performance. The alternative capacity-limited account allows for detrimental effects of racially-heterogeneous exposure. The enhancement account predicts heterogeneity of exposure confers added benefits. In two experiments we examined face recognition in a group with sustained lifetime exposure to Caucasian and East Asian faces (dual exposure) in comparison to two mono exposure groups. Dual-exposure individuals showed native-like performance on the face recognition tasks for both Caucasian and East Asian faces. We found no evidence of a detrimental or an enhancing effect of racially-heterogeneous face exposure. Overall, our results support the experience-limited account of face expertise. We conclude that a racially homogeneous face-diet is not necessary to achieve native-level face expertise.

Copula-based exposure risk dynamic simulation of dual heavy metal mixed pollution accidents at the watershed scale

Most heavy metal exposure and pollution results from multiple industrial activities, including metal processing in refineries, and microelectronics. These issues pose a great threat to human health, ecological balance, and even societal stability. During 2012–2017, China, in particular, faced the challenge of 23 heavy metals accidents, six of which were extraordinarily serious accidents. Accidental environmental pollution is rarely caused by a single heavy metal, but rather by heavy metal mixtures. To address the need for a joint exposure risk assessment for heavy metal mixed pollution accidents at the watershed scale, a Copula-based exposure risk dynamic simulation model was proposed. A coupled hydrodynamic and accidental heavy metal exposure model is constructed for an hourly simulation of the exposure fate of heavy metals from each risk source once accidental leakage has occurred. The Copula analysis was introduced to calculate the dual heavy metal joint exposure probability in real time. This method was applied to an acute Cr6+-Hg2+ joint exposure risk assessment for 43 electroplating plants in nine sub-watersheds within the Dongjiang River downstream basin. The results indicated seven risk sources (i.e., S1, S4, H18, H23, H27–H28, and H34) that presented relatively high exposure risk to their surrounding sub-watersheds. Spatially, the acute exposure risk level was highest in the tributary basin (sub-watershed XW) than in the mainstream (sub-watershed DW2) and the river network (sub-watershed RW) of the lower reaches of the Dongjiang River. This research highlights an effective probabilistic approach for performing a joint exposure risk analysis of heavy metal mixed pollution accidents at the watershed scale.

The Effects of Dual Atmosphere Exposure Duration and Temperature on the Growth of Iron Oxide on Ferritic Stainless Steels

Literature within the past two decades has highlighted the ongoing issue of dual atmosphere corrosion in solid oxide fuel cell (SOFC) systems. This corrosion phenomenon occurs as a result of simultaneous exposure of ferritic stainless steel interconnects to the anodic fuel gas on one side and cathodic air stream on the opposing side. In this, the air-exposed side of the metal interconnect undergoes fast, anomalous corrosion and metal loss in the form of iron oxide overgrowth with whisker and platelet-type morphology. Studies have indicated that the corrosion is favored at lower temperatures in comparison to temperatures above 800 °C. This poses an issue for the current trend of lowering SOFC operating temperatures and utilizing cost-effective ferritic stainless steels as interconnect materials. In this study, the oxidation behavior of two ferritic stainless steels is examined under dual atmosphere exposure conditions. A series of experiments with varying time, temperature, and steel compositions were carried out to better understand the effects of these variables on severity and morphology of corrosion products. A mechanism which describes the localized overgrowth of iron oxide in platelet and whisker form and the porous oxide sub-layer is proposed. The transition from a thin, protective, and dense chromia scale under nominal ambient conditions to porous, non-protective scaling under dual atmosphere conditions will be discussed.

Palmitate exacerbates bisphenol A toxicity via induction of ER stress and mitochondrial dysfunction

Combined exposure to dietary nutrients and environmental chemicals may elicit significantly different physiological effects than single exposures. Exposure to dietary saturated fats and environmental toxins is a physiologically-significant dual exposure that is particularly associated with lower socioeconomic status, potentially placing these individuals at heightened risk of xenobiotic toxicities. However, no prior studies have examined interactions between specific lipids and environmental xenobiotics in modulating cellular health. Using primary mouse embryonic fibroblasts, we have discovered that prior exposure to the saturated fatty acid, palmitate, exacerbates cellular toxicity associated with the industrial plasticizer, bisphenol A (BPA). Cell death upon BPA exposure following palmitate pre-treatment was greater than that occurring with either exposure alone. Mechanistically, cell death was preceded by increased endoplasmic reticulum stress and loss of mitochondrial membrane potential in palmitate plus BPA exposed cells, leading to increased caspase-3 cleavage and subsequent apoptosis. Interestingly, inclusion of the unsaturated fatty acid, oleate, along with palmitate during the pre-treatment period completely abrogated the ER stress, mitochondrial toxicity, and cell death induced by subsequent exposure to BPA. Thus, our data identify for the first time an important interaction between a fatty acid and an environmental toxin and have implications for developing nutritional interventions to mitigate the deleterious effects of such xenobiotic exposures.

The Effects of Dual Atmosphere Exposure Duration and Temperature on the Growth of Iron Oxide on Ferritic Stainless Steels

In this study, the oxidation behavior of two ferritic steels with different amounts of chromium is examined under dual atmosphere exposure conditions. Experiments with varying time and temperature were carried out to understand the effects of these variables and difference in chromium concentration on severity and morphology of oxidation products. Higher amounts of alloyed chromium in the steel leads to better passivation against iron oxidation. With increased exposure time, however, the passivating scale breaks down leading to iron oxide overgrowth. This phenomenon appears more pronounced at lower temperatures and complete passivation of both steels was observed at the higher temperature (700°C) after 100 h of exposure. A hypothesis with regards to the presence of hydrogen during exposure is presented along with discussion on observed oxidation behavior.

Exposure to nicotine-free and flavor-free e-cigarette vapors modifies the pulmonary response to tobacco cigarette smoke in female mice.

Most of electronic cigarette (e-cigarette) users are also smoking tobacco cigarettes. Because of the relative novelty of this habit, very little is known on the impact of vaping on pulmonary health, even less on the potential interactions of dual e-cigarette and tobacco cigarette use. Therefore, we used well-established mouse models to investigate the impact of dual exposure to e-cigarette vapors and tobacco cigarette smoke on lung homeostasis. Groups of female BALB/c mice were exposed to room air, tobacco smoke only, nicotine-free flavor-free e-cigarette vapors only or both tobacco smoke and e-cigarette vapors. Moreover, since tobacco smoke and electronic cigarette vapors both affect circadian processes in the lungs, groups of mice were euthanized at two different time points during the day. We found that dual-exposed mice had altered lung circadian gene expression compared with mice exposed to tobacco smoke alone. Dual-exposed mice also had different frequencies of dendritic cells, macrophages, and neutrophils in the lung tissue compared with mice exposed to tobacco smoke alone, an observation also valid for B-lymphocytes and CD4+ and CD8+ T lymphocytes. Exposure to e-cigarette vapors also impacted the levels of immunoglobulins in the bronchoalveolar lavage and serum. Finally, e-cigarette and dual exposures increased airway resistance compared with mice exposed to room air or tobacco smoke alone, respectively. Taken together, these data suggest that e-cigarette vapors, even without nicotine or flavors, could affect how the lungs react to tobacco cigarette smoke exposure in dual users, potentially altering the pathological course triggered by smoking.

Megapixel time-gated SPAD image sensor for 2D and 3D imaging applications

We present a 1 Mpixel single-photon avalanche diode camera featuring 3.8 ns time gating and 24 kfps frame rate, fabricated in 180 nm CMOS image sensor technology. We designed two pixels with a pitch of 9.4 µm in 7 T and 5.75 T configurations respectively, achieving a maximum fill factor of 13.4%. The maximum photon detection probability is 27%, median dark count rate is 2.0 cps, variation in gating length is 120 ps, position skew is 410 ps, and rise/fall time is &lt; 550 p s , all FWHM at 3.3 V excess bias. The sensor was used to capture 2D/3D scenes over 2 m with resolution (least significant bit) of 5.4 mm and precision better than 7.8 mm (rms). We demonstrate extended dynamic range in dual exposure operation mode and show spatially overlapped multi-object detection in single-photon time-gated time-of-flight experiments.

Parents report fewer executive functioning problems and repetitive behaviors in young dual-language speakers with autism

ABSTRACT More dual language learners (DLLs) are being identified early with autism spectrum disorder (ASD). However, many families are still being advised against dual language exposure, despite a lack of evidence of negative impacts on language development in ASD. Research in typically developing children has noted advantages for bilinguals in domains such as executive functioning and social skills, but less is known about the effects in ASD. The present study evaluated differences in executive functioning and social communication in young children (n = 55) with ASD. Dual-language learners with ASD had significantly fewer parent reported executive functioning problems and repetitive behaviors; parent-reported social communication skills were generally comparable across groups. Our findings indicate that the bilingual advantage in executive functioning may extend to children with neurodevelopmental conditions.

Parental transgenerational epigenetic inheritance related to dietary crude oil exposure in Danio rerio.

Transgenerational inheritance from both parental lines can occur by genetic and epigenetic inheritance. Maternal effects substantially influence offspring survival and fitness. However, investigation of the paternal contribution to offspring success has been somewhat neglected. In the present study, adult zebrafish were separated into female and male groups exposed for 21days to either a control diet or to a diet containing water accommodated fractions of crude oil. Four F1 offspring groups were obtained: (1) control (non-exposed parents), (2) paternally exposed, (3) maternally exposed and (4) dual-parent-exposed. To determine the maternal and paternal influence on their offspring, we evaluated responses from molecular to whole organismal levels in both generations. Growth rate, hypoxia resistance and heart rate did not differ among parental groups. However, global DNA methylation in heart tissue was decreased in oil-exposed fish compared with control parents. This decrease was accompanied by an upregulation of glycine N-methyltransferase. Unexpectedly, maternal, paternal and dual exposure all enhanced survival of F1 offspring raised in oiled conditions. Regardless of parental exposure, however, F1 offspring exposed to oil exhibited bradycardia. Compared with offspring from control parents, global DNA methylation was decreased in the three offspring groups derived from oil-exposed parents. However, no difference between groups was observed in gene regulation involved in methylation transfer, suggesting that the changes observed in the F1 populations may have been inherited from both parental lines. Phenotypic responses during exposure to persistent environmental stressors in F1 offspring appear to be influenced by maternal and paternal exposure, potentially benefitting offspring populations to survive in challenging environments.

Cohort profile: ADEF Helsinki - a longitudinal register-based study on exposure to alcohol and drugs during foetal life.

Purpose:The need for longitudinal studies on prenatal substance exposure (PSE) extending into adulthood is widely recognised. In particular, studies on the dual effect of exposure to substances and adverse childhood experiences are needed. This register-based matched cohort study investigates the effect of this dual exposure on the health and development of youth with PSE. The follow-up is from birth to young adulthood.Participants:The exposed youth were born in 1992–2001 to mothers with a significant substance misuse problem during pregnancy. The mothers were identified in primary care maternity clinics in the Helsinki metropolitan area and referred for intensified pregnancy follow-up in a tertiary care setting (HAL-clinics). Data from hospital medical records were collected for the mothers during the pregnancy follow-up and linked with register data from multiple national health and social welfare registers obtained for each mother–child dyad from birth until the end of 2015–2018. Similar register data were gathered for three matched mother–child dyads without any evidence of the mother’s substance misuse in national health and social welfare registers. The study consists of 615 exposed and 1787 unexposed youth aged 15–24 years.Findings to date:A majority of the exposed youth (64%) had been in out-of-home care at least once compared with 8% among the unexposed. Outpatient and inpatient hospital care due to mental or behavioural disorders were two to three times more common among the exposed than among the unexposed. The exposed had less often completed secondary school education and had more often needed social assistance.Future plans:The data comprise a wide range of information on infant health, youth’s mental and somatic health and development, out-of-home care history, and mother’s life situation at the delivery and later health. Risk and protective factors for different long-term developmental outcomes in adolescence or in young adulthood will be studied.