A scoping review of multigenerational impacts of grandparental exposures on mental health in grandchildren.

PURPOSE OF REVIEW: The multigenerational effects of grandparental exposures on their grandchildren's mental health and neurodevelopment are gaining research attention. We conducted a scoping review to summarize the current epidemiological studies investigating pregnancy-related and environmental factors that affected grandparental pregnancies and mental health outcomes in their grandchildren. We also identified methodological challenges that affect these multigenerational health studies and discuss opportunities for future research. RECENT FINDINGS: We performed a literature search using PubMed and Embase and included 18 articles for this review. The most investigated grandparental pregnancy-related factors were the grandparental age of pregnancy (N = 6), smoking during pregnancy (N = 4), and medication intake (N = 3). The most frequently examined grandchild outcomes were autism spectrum disorder (N = 6) and attention-deficit/hyperactivity disorder (N = 4). Among these studies, grandparental smoking and the use of diethylstilbestrol were more consistently reported to be associated with neurodevelopmental disorders, while the findings for grandparental age vary across the maternal or paternal line. Grandmaternal weight, adverse delivery outcomes, and other spatial-temporal markers of physical and social environmental stressors require further scrutiny. The current body of literature has suggested that mental and neurodevelopmental disorders may be outcomes of unfavorable exposures originating from the grandparental generation during their pregnancies. To advance the field, we recommend research efforts into setting up multigenerational studies with prospectively collected data that span through at least three generations, incorporating spatial, environmental, and biological markers for exposure assessment, expanding the outcome phenotypes evaluated, and developing a causal analytical framework including mediation analyses specific for multigenerational research.

Inhibition of PD-1 Alters the SHP1/2-PI3K/Akt Axis to Decrease M1 Polarization of Alveolar Macrophages in Lung Ischemia-Reperfusion Injury.

Polarization of alveolar macrophages (AMs) into the M1 phenotype contributes to inflammatory responses and tissue damage that occur during lung ischemia-reperfusion injury (LIRI). Programmed cell death factor-1 (PD-1) regulates polarization of macrophages, but its role in LIRI is unknown. We examined the role of PD-1 in AM polarization in models of LIRI in vivo and in vitro. Adult Sprague-Dawley rats were subjected to ischemia-reperfusion with or without pretreatment with a PD-1 inhibitor, SHP1/2 inhibitor, or Akt activator. Lung tissue damage and infiltration by M1-type AMs were assessed. As an in vitro complement to the animal studies, rat alveolar macrophages in culture were subjected to oxygen/glucose deprivation and reoxygenation. Levels of SHP1/2 and Akt proteins were evaluated using Western blots, while levels of pro-inflammatory cytokines were measured using enzyme-linked immunosorbent assays. Injury upregulated PD-1 both in vivo and in vitro. Inhibiting PD-1 reduced the number of M1-type AMs, expression of SHP1 and SHP2, and levels of inflammatory cytokines. At the same time, it partially restored Akt activation. Similar results were observed after inhibition of SHP1/2 or activation of the PI3K/Akt pathway. PD-1 promotes polarization of AMs to the M1 phenotype and inflammatory responses through the SHP1/2-PI3K/Akt axis. Inhibiting PD-1 may be an effective therapeutic strategy to limit LIRI.

Parental Age and Childhood Risk for Cerebral Palsy in California.

OBJECTIVE: To investigate the associations between maternal or paternal age at the time of delivery and offspring's risk for cerebral palsy (CP) in California. STUDY DESIGN: We conducted a population-based, case-control study that included 8736 singleton CP cases and 90 250 singleton controls, matched by sex and birth year, selected from California birth certificate records from 1994 to 2010. We estimated OR and 95% CIs for CP diagnosis according to maternal and paternal age recorded on the birth certificates. Causal mediation analysis was performed to estimate direct and indirect effects of parental ages on CP with preterm delivery as a potential mediator. RESULTS: Children born to younger mothers (≤19 years) or older mothers (35-39 years; ≥40 years) had a greater risk of CP compared with children of mothers aged 25-29 years (ORs ranging from 1.13 to 1.59). Compared with paternal age 25-29 years, older paternal age (40-44 years; ≥45 years) also was associated with an increased risk for CP independent of maternal age. When analyzing jointly using both parents of ages 20-34 years as the reference, the greatest risk was estimated for older parents (≥35 years). Preterm birth was estimated to mediate 19%-34% of the total effects between maternal or paternal age and offspring CP risk. CONCLUSIONS: Young maternal age and an older age in either or both parents were associated with a greater risk of CP in their children. Although preterm birth was a mediator, additional factors related to parental age need further exploration to explain risk of CP.

Developmental Milestones of Infancy and Associations with Later Childhood Neurodevelopmental Outcomes in the Adolescent Brain Cognitive Development (ABCD) Study.

The age at attaining infancy developmental milestones has been associated with later neurodevelopmental outcomes, but evidence from large and diverse samples is lacking. We investigated this by analyzing data of 5360 singleton children aged 9-10 from 17 states in the US enrolled in the Adolescent Brain Cognitive Development (ABCD) study during 2016-2020. Delays in four milestones (first roll over, unaided sitting, unaided walking, and speaking first words) were defined using the 90th percentile of age at attainment reported by children's biological mothers. Childhood neurocognitive function was measured by research assistants using the NIH toolbox, and children reported their behavioral problems using the Brief Problem Monitor. Linear mixed-effects models were employed to investigate the association between delays in single or multiple milestones and childhood neurobehavioral outcomes. Delays in first roll over, unaided sitting, or walking were associated with poorer childhood neurocognitive function, while delay in speaking first words was associated with both poorer neurocognitive function and behavioral problems. Children who had delays in both motor and language milestones had the worst neurocognitive function and behavioral outcomes. Our results suggest that delays in motor and language milestone attainment during infancy are predictive of childhood neurobehavioral outcomes.

Preparation and modification of PS-PMMA microspheres and their application in high performance liquid chromatography.

Polymer microspheres have been widely used as a stationary phase for liquid chromatography. In this work, we prepared and synthesized polystyrene-methyl methacrylate (PS-PMMA) microspheres, modified them, characterized the microspheres to have good chromatographic properties, and then used them as a high-performance liquid chromatography (HPLC) stationary phase to explore their applications. First, the PS-PMMA microspheres were hydrolyzed, and the separation of benzene homologues/alkaloids was explored. Then, on the basis of hydrolysis, diazo resin (DR) was used as a coupling agent to further modify the surface of the microspheres with amphoteric glycopeptide vancomycin. The modified microspheres were used as a HPLC stationary phase to explore the application of the stationary phase in the separation of chiral drugs. This work is important to broaden the application of functional chiral columns for antibiotics and to expand the application of PS-PMMA microspheres in HPLC.

Characterizing the Neural Correlates of Response Inhibition and Error Processing in Children With Symptoms of Irritability and/or Attention-Deficit/Hyperactivity Disorder in the ABCD Study®.

Attention-deficit/hyperactivity disorder (ADHD), characterized by symptoms of inattention and/or hyperactivity and impulsivity, is a neurodevelopmental disorder associated with executive dysfunctions, including response inhibition and error processing. Research has documented a common co-occurrence between ADHD and pediatric irritability. The latter is more characterized by affective symptoms, specifically frequent temper outbursts and low frustration tolerance relative to typically developing peers. Shared and non-shared neural correlates of youths with varied profiles of ADHD and irritability symptoms during childhood remain largely unknown. This study first classified a large sample of youths in the Adolescent Brain Cognitive Development (ABCD) study at baseline into distinct phenotypic groups based on ADHD and irritability symptoms (N = 11,748), and then examined shared and non-shared neural correlates of response inhibition and error processing during the Stop Signal Task in a subset of sample with quality neuroimaging data (N = 5,948). Latent class analysis (LCA) revealed four phenotypic groups, i.e., high ADHD with co-occurring irritability symptoms (n = 787, 6.7%), moderate ADHD with low irritability symptoms (n = 901, 7.7%), high irritability with no ADHD symptoms (n = 279, 2.4%), and typically developing peers with low ADHD and low irritability symptoms (n = 9,781, 83.3%). Latent variable modeling revealed group differences in the neural coactivation network supporting response inhibition in the fronto-parietal regions, but limited differences in error processing across frontal and posterior regions. These neural differences were marked by decreased coactivation in the irritability only group relative to youths with ADHD and co-occurring irritability symptoms and typically developing peers during response inhibition. Together, this study provided initial evidence for differential neural mechanisms of response inhibition associated with ADHD, irritability, and their co-occurrence. Precision medicine attending to individual differences in ADHD and irritability symptoms and the underlying mechanisms are warranted when treating affected children and families.

Prenatal Exposure to Per- and Polyfluoroalkyl Substances and Facial Features at 5 Years of Age: A Study from the Danish National Birth Cohort.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are widespread persistent pollutants. Evidence regarding neurodevelopmental effects of PFAS have been mixed. The relation between PFAS exposure and anatomical markers that have been suggested to correlate with fetal brain development have not been studied. OBJECTIVES: We investigated the association between prenatal PFAS exposures and three craniofacial features in children measured at 5 years of age. METHODS: Measures of palpebral fissure length (PFL), philtrum groove, and upper-lip thickness were generated from standardized digital facial photographs from 656 children in the Danish National Birth Cohort. PFL was classified into two groups (shorter; normal), and the philtrum (grooved; smooth; normal) and upper-lip (thick; thin; normal) measures into three groups each. Six PFAS were measured in maternal plasma (median=8 gestational wk). Multinomial logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for each facial feature using the normal group as the reference according to log2-PFAS concentration (in nanograms per milliliter) or PFAS tertiles, adjusting for potential confounders, including maternal alcohol intake and smoking. Stratified analyses by maternal alcohol intake or child's sex were performed. RESULTS: Prenatal exposure to each PFAS was associated with elevated odds for a shorter PFL, with the strongest association observed for perfluorodecanoic acid (PFDA; per doubling OR=2.02; 95% CI: 1.11, 3.70). Some nonlinear associations were found for philtrum measures: the second tertile of PFDA and perfluorononanoic acid were associated with grooved philtrum, whereas the second tertile of perfluoroheptane sulfonate with smooth philtrum. The associations between PFAS exposure and a shorter PFL were stronger among mothers who consumed alcohol in the first trimester, some sex-specific associations were noted for philtrum and upper-lip measures. DISCUSSION: Prenatal PFAS exposures might influence fetal craniofacial development. A larger study is needed to replicate the potential modifying effects observed for alcohol exposure and to clarify whether associations of craniofacial markers observed reflect specific neurologic deficits. https://doi.org/10.1289/EHP9478.

Perinatal and birth correlates of childhood irritability in Taiwan's national epidemiological study.

BACKGROUND: Childhood irritability, characterized by low frustration tolerance and developmentally-inappropriate temper outbursts, is a transdiagnostic symptom in child psychiatry. Little is known regarding the influences of early experience and environmental exposure on irritability from a perinatal perspective. This study examined the associations between irritability and multiple perinatal and birth factors. METHODS: Drawn Taiwan's National Epidemiological Study of Child Mental Disorders, 5124 children (2591 females) aged 7.7 to 14.6 years (mean 11.2 years) and their parents completed the Affective Reactivity Index, a well-established irritability measure. Parents completed a survey on parental, perinatal, and birth characteristics. Multiple linear regression models were performed to examine the associations between perinatal and birth characteristics and child irritability reported across informants. RESULTS: Maternal smoking, vaginal bleeding, and pre-eclampsia during pregnancy and phototherapy for jaundice >3 days were associated with high irritability after adjusting for child's age, sex, and parental characteristics. Findings were consistent across parent- and child-rated irritability. LIMITATIONS: Retrospective assessment of early exposures may be subject to recall bias despite previously-established validity and reliability. Longitudinal research with prospective assessments of early life exposures is recommended to confirm our findings. This exploratory approach of multiple survey items also precludes more in-depth assessments of perinatal risks for developing irritability. CONCLUSIONS: This study provides novel evidence suggesting a perinatal link with irritability in a national sample of youths. Given that irritability predicts adverse mental health and life outcomes, identifying its perinatal and birth predictors may inform early etiology, guiding timely assessment and intervention.

Rates of Neuropsychiatric Disorders and Gestational Age at Birth in a Danish Population.

Importance: Nonoptimal gestational durations could be associated with neurodevelopmental disabilities, yet evidence regarding finer classification of gestational age and rates of multiple major neuropsychiatric disorders beyond childhood is limited. Objective: To comprehensively evaluate associations between 6 gestational age groups and rates of 9 major types and 8 subtypes of childhood and adult-onset neuropsychiatric disorders. Design, Setting, and Participants: This cohort study evaluated data from a nationwide register of singleton births in Denmark from January 1, 1978, to December 31, 2016. Data analyses were conducted from October 1, 2019, through November 15, 2020. Exposures: Gestational age subgroups were classified according to data from the Danish Medical Birth Register: very preterm (20-31 completed weeks), moderately preterm (32-33 completed weeks), late preterm (34-36 completed weeks), early term (37-38 completed weeks), term (39-40 completed weeks, reference), and late or postterm (41-45 completed weeks). Main Outcomes and Measures: Neuropsychiatric diagnostic records (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes F00-F99) were ascertained from the Danish Psychiatric Central Register up to August 10, 2017. Poisson regression was used to estimate the incidence rate ratio (IRR) and 95% CI for neuropsychiatric disorders, adjusting for selected sociodemographic factors. Results: Of all 2 327 639 singleton births studied (1 194 925 male newborns [51.3%]), 22 647 (1.0%) were born very preterm, 19 801 (0.9%) were born moderately preterm, 99 488 (4.3%) were born late preterm, 388 416 (16.7%) were born early term, 1 198 605 (51.5%) were born at term, and 598 682 (25.7%) were born late or postterm. A gradient of decreasing IRRs was found from very preterm to late preterm for having any or each of the 9 neuropsychiatric disorders (eg, very preterm: IRR, 1.49 [95% CI, 1.43-1.55]; moderately preterm: IRR, 1.23 [95% CI, 1.18-1.28]; late preterm: IRR, 1.17 [95% CI, 1.14-1.19] for any disorders) compared with term births. Individuals born early term had 7% higher rates (IRR, 1.07 [95% CI, 1.06-1.08]) for any neuropsychiatric diagnosis and a 31% higher rate for intellectual disability (IRR, 1.31 [95% CI, 1.25-1.37]) compared with those born at term. The late or postterm group had lower IRRs for most disorders, except pervasive developmental disorders, for which the rate was higher for postterm births compared with term births (IRR, 1.06 [95% CI, 1.03-1.09]). Conclusions and Relevance: Higher incidences of all major neuropsychiatric disorders were observed across the spectrum of preterm births. Early term and late or postterm births might not share a homogeneous low risk with individuals born at term. These findings suggest that interventions that address perinatal factors associated with nonoptimal gestation might reduce long-term neuropsychiatric risks in the population.

Recent research progress in the construction of active free radical nanoreactors and their applications in photodynamic therapy.

Photodynamic therapy is the most important treatment strategy in free radical therapy. However, tumor microenvironment hypoxia is a key obstacle in PDT. In order to overcome this obstacle, the strategy of in situ production of O2/radicals by catalytic reaction in solid tumors was proposed. In recent years, it has been found that there are many oxygen-independent carbon-based free radicals that can generate toxic active free radicals under laser irradiation and lead to tumor cell death. Based on the rational design of multifunctional nano-medicine, the active free radical nano-generator has opened up a new way for the highly developed nanotechnology and tumor cooperative therapy to improve the therapeutic effect. In this paper, the research status of active free radical nano-generators, especially reactive oxygen species, including the construction mechanism of active free radical nanomaterials, is reviewed and the application of free radical nano-generators in tumor therapy is emphasized.

Associations of parental birth characteristics with autism spectrum disorder (ASD) risk in their offspring: a population-based multigenerational cohort study in Denmark.

BACKGROUND: Fetal exposure risk factors are associated with increased autism spectrum disorder (ASD) risk. New hypotheses regarding multigenerational risk for ASD have been proposed, but epidemiological evidence is largely lacking. We evaluated whether parental birth characteristics, including preterm birth and low birthweight, were associated with ASD risk in offspring. METHODS: We conducted a nationwide register-based cohort study that included 230 174 mother-child and 157 926 father-child pairs in Denmark. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for offspring ASD according to parental preterm (<37 weeks) and low birthweight (<2500 g) status, with or without adjustment for certain grandmaternal sociodemographic factors. Mediation analyses were performed for selected parental and offspring health-related factors. RESULTS: Offspring of mothers or fathers with adverse birth characteristics had about 31-43% higher risk for ASD (maternal preterm birth, OR = 1.31, 95% CI= 1.12, 1.55; maternal low birthweight, OR = 1.35, 95% CI: 1.17,1.57; paternal preterm birth, OR = 1.43, 95% CI = 1.18, 1.73; paternal low birthweight, OR = 1.38, 95% CI= 1.13, 1.70). Parents born very preterm (<32 weeks) marked a nearly 2-fold increase in ASD risk in their children. These associations were slightly attenuated upon adjustment for grandmaternal sociodemographic factors. Mediation analyses suggested that parental social-mental and offspring perinatal factors might explain a small magnitude of the total effect observed, especially for maternal birth characteristic associations. CONCLUSIONS: Offspring of parents born with adverse characteristics had an elevated risk for ASD. Transmission of ASD risk through maternal and paternal factors should be considered in future research on ASD aetiology.

Inhibition of p38 MAPK Mitigates Lung Ischemia Reperfusion Injury by Reducing Blood-Air Barrier Hyperpermeability.

Background: Lung ischemia reperfusion injury (LIRI) is a complex pathophysiological process activated by lung transplantation and acute lung injury. The p38 mitogen-activated protein kinase (MAPK) is involved in breakdown of the endothelial barrier during LIRI, but the mechanism is still unclear. Therefore, we investigated the function of p38 MAPK in LIRI in vivo and in vitro. Methods: Sprague-Dawley rats were subjected to ischemia reperfusion with or without pretreatment with a p38 MAPK inhibitor. Lung injury was assessed using hematoxylin and eosin staining, and pulmonary blood-air barrier permeability was evaluated using Evans blue staining. A rat pulmonary microvascular endothelial cell line was infected with lentiviral expressing short hairpin (sh)RNA targeting p38 MAPK and then cells were subjected to oxygen/glucose deprivation and reoxygenation (OGD/R). Markers of endothelial destruction were measured by western blot and immunofluorescence. Results: In vivo LIRI models showed structural changes indicative of lung injury and hyperpermeability of the blood-air barrier. Inhibiting p38 MAPK mitigated these effects. Oxygen/glucose deprivation and reoxygenation promoted hyperpermeability of the endothelial barrier in vitro, but knockdown of p38 MAPK attenuated cell injury; maintained endothelial barrier integrity; and partially reversed injury-induced downregulation of permeability protein AQP1, endothelial protective protein eNOS, and junction proteins ZO-1 and VE-cadherin while downregulating ICAM-1, a protein involved in destroying the endothelial barrier, and ET-1, a protein involved in endothelial dysfunction. Conclusion: Inhibition of p38 MAPK alleviates LIRI by decreasing blood-air hyperpermeability. Blocking p38 MAPK may be an effective treatment against acute lung injury.

Prenatal exposure to perfluoroalkyl substances and behavioral difficulties in childhood at 7 and 11 years.

BACKGROUND: Perfluoroalkyl substances (PFAS) are suggested to interfere with thyroid hormone during pregnancy and influence fetal neurodevelopment. Epidemiological evidence regarding behavioral difficulties in childhood associated with prenatal PFAS exposure has been inconclusive. OBJECTIVE: We evaluated the association between prenatal PFAS exposure and behavioral difficulties at 7 and 11 years, and investigated the potential mediating role of maternal thyroid hormones. METHODS: Using pooled samples in the Danish National Birth Cohort established between 1996 and 2002, we estimated the associations between concentrations of six types of PFAS in maternal plasma (median, 8 gestational weeks) and child behavioral assessments from the Strength and Difficulties Questionnaire (SDQ), reported by parents at 7 years (n = 2421), and by parents (n = 2070) and children at 11 years (n = 2071). Behavioral difficulties were defined as having a composite SDQ score above the 90th percentile for total difficulties and externalizing or internalizing behaviors. We used logistic regression to estimate the adjusted Odds Ratio (OR) by doubling increase of prenatal PFAS (ng/ml). The possible mediating effect of maternal thyroid function classified based on thyroid stimulating hormone (TSH) and free thyroxine (fT4) levels were evaluated. RESULTS: Prenatal perfluorononanoic acid (PFNA) was consistently associated with total and externalizing behavioral difficulties in all three SDQ measures reported by parents (OR = 1.40, 95% CI: 1.14-1.73 for age 7; OR = 1.27, 95% CI: 1.05-1.53 for age 11) or children (OR = 1.32, 95% CI: 1.11-1.58) while no consistent associations were observed for other types of PFAS. A small magnitude of natural indirect effects via maternal thyroid dysfunction (ORs ranged from 1.01 to 1.03) of several PFAS were observed for parent-reported total and externalizing behaviors at 7 years only. DISCUSSION: Prenatal PFNA exposure was associated with externalizing behavioral difficulties in childhood in repeated SDQ measures at 7 and 11 years. The slight mediating effects of maternal thyroid hormones in early gestation warrant further evaluation.

Association of Grandparental and Parental Age at Childbirth With Autism Spectrum Disorder in Children.

Importance: Advanced parental age has been associated with autism spectrum disorders (ASDs) in children. However, little is known about the association between grandparental age at the time of birth of the parent and the risk of ASD in the grandchildren. Objective: To estimate the associations between parental and grandparental age and ASD risk in children. Design, Setting, and Participants: This population-based, multigenerational cohort study used data from Danish national health registries. A parental age cohort was constructed to evaluate the association between parental age and ASD in 1 476 783 singleton children born from 1990 to 2013, and a multigenerational cohort was also constructed including 362 438 fathers and 458 234 mothers born from 1973 to 1990 for whom information on grandparental age was available. Data analyses were conducted from November 1, 2018, through February 7, 2020. Exposures: Parental age at childbirth and grandparental age at the time of the birth of the parent. Main Outcomes and Measures: Diagnoses of ASD in children were obtained from the Danish Psychiatric Central Register (1994-2017). Logistic regression analysis was used to estimate the associations between parental or grandparental age and ASD in children. Results: Of the 1 476 783 children born from 1990 to 2013, 758 066 (51.3%) were male, and 27 616 (1.9%) had ASD (20 467 [74.1%] were male). Advanced paternal or maternal age over 30 years was monotonically associated with increased ASD risk, with odds ratios (ORs) of 1.56 (95% CI, 1.45-1.68) for maternal age 40 years and older and 1.57 (95% CI, 1.39-1.78) for paternal age 50 years and older, compared with parents aged 25 to 29 years. In the multigenerational cohort, 9364 grandchildren (1.7%) had ASD. This study found U-shaped associations, in that ASD risk was higher among grandchildren of younger (≤19 years) maternal grandmothers (OR, 1.68; 95% CI, 1.52-1.85), younger maternal grandfathers (OR, 1.50; 95% CI, 1.26-1.78), and younger paternal grandmothers (OR, 1.18; 95% CI, 1.04-1.34), and older (≥40 years) paternal grandmothers (OR, 1.40; 95% CI, 1.03-1.90) compared with the grandchildren of grandparents who were aged 25 to 29 years at the time of giving birth to the parents. Conclusions and Relevance: These findings corroborate previous studies suggesting that advanced parental age is independently associated with increased ASD risk in children. This study also found that children with young maternal grandparents and children with young and old paternal grandparents had elevated ASD risk. Possible transmission of ASD risk across generations should be considered in etiological research on ASD.

[Dexamethasone on alleviating lung ischemia/reperfusion injury in rats by regulating PI3K/AKT pathway].

OBJECTIVE: To investigate the protective effect and mechanism of dexamethasone in lung ischemia/reperfusion injury (LIRI) rats. METHODS: (1) Part one experiment: 24 Sprague-Dawley (SD) rats were divided into four groups according to the random number method (n = 6): standard ventilation group (N group), normal saline group (NS group), LIRI group, and dexamethasone+LIRI group (DEX group). The rat model of LIRI was established by clamping the left pulmonary hilum for 1 hour and reperfusing it for 2 hours. The DEX group was given dexamethasone 3 mg/kg 5 minutes before reperfusion, and NS group was injected with normal saline. Group N did not receive any treatment. The left lung tissue of the rats in each group were taken alive 2 hours after reperfusion. The lung tissue was harvested for lung wet/dry mass ratio (W/D) measurement. Hematoxylin-eosin (HE) staining and electron microscopy was used to observe the pathological changes of lung tissue and to assess the degree of injury. Ultrastructural changes of lung tissue were observed under electron microscope. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL-1ß, IL-6) in lung tissue were detected by enzyme linked immunosorbent assay (ELISA). The expressions of phosphorylated protein kinase B (p-AKT) was detected by Western Blot. (2) Part two experiment: intervention with phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway inhibitor LY294002 to further explore the mechanism of dexamethasone in reducing lung injury induced by LIRI. Twenty-four SD rats were divided into four groups according to the random number method (n = 6): N group, LIRI group, DEX group, and dexamethasone+LY294002+LIRI group (LY group). All the groups except the LY group were treated with membrane and intervention according to part one experiment. The LY group was injected with LY294002 0.3 mg/kg after injection of dexamethasone. The expressions of M1 macrophage polarization markers CD11c, CD16, and M2 macrophage polarization markers CD206, Arg1 were detected by immunohistochemistry. RESULTS: (1) Part one experiment: compared with N group, the morphological and ultrastructural changes of lung tissue in the LIRI group were significantly changed, lung injury score, lung W/D ratio and TNF-α, IL-1ß, IL-6 levels were significantly increased, and p-AKT expression was significantly decreased. Compared with the LIRI group, the morphological and ultrastructural changes of the lung tissue in the DEX group were significantly improved, and the lung injury score was reduced (5.00±0.89 vs. 8.83±0.75), lung W/D ratio and TNF-α, IL-1ß, IL-6 levels were significantly decreased [lung W/D ratio: 6.25±0.56 vs. 8.27±0.72, TNF-α (ng/L): 93.28±16.42 vs. 205.90±25.30, IL-1ß (ng/L): 130.10±10.81 vs. 209.10±19.20, IL-6 (ng/L): 195.80±21.17 vs. 310.50±20.77], p-AKT expression was significantly increased [p-AKT/AKT: (57.58±8.80)% vs. (36.62±9.25)%], and the differences were statistically significant (all P < 0.05). There was no significant difference in each index between NS group and N group. (2) Part two experiment: compared with the N group, the expression of macrophage polarization markers CD11c, CD16, CD206 and Arg1 in the LIRI group were significantly increased. Compared with the LIRI group, the expressions of CD11c and CD16 in the lung tissue of the DEX group were significantly decreased, and the expressions of CD206 and Arg1 were significantly increased. The intervention of PI3K/AKT signaling pathway inhibitor LY294002 significantly blocked the effect of dexamethasone on LIRI-mediated macrophage polarization (CD11c immunohistochemical score: 7.20±0.36 vs. 5.00±0.34, CD16 immunohistochemical score: 8.20±0.48 vs. 7.40±0.64, CD206 immunohistochemical score: 5.80±0.59 vs. 7.40±0.28, Arg1 immunohistochemical score: 7.20±0.72 vs. 8.80±0.48, all P < 0.05). CONCLUSIONS: Dexamethasone pretreatment can alleviate the intrapulmonary inflammatory response and lung injury caused by LIRI in rats. The mechanism of action is related to the polarization direction of pulmonary macrophagesvia activation of the PI3K/AKT pathway by dexamethasone.

Conversations Regarding Personhood: Use of the Patient Dignity Question in an Outpatient Psycho-Oncology Clinic.

Background: The Patient Dignity Question (PDQ) is a single question, which directly asks the patient, "What should I know about you as a person to help me take the best care of you that I can?" Research has demonstrated that the PDQ enhances quality health care within an inpatient palliative care setting; however, no research to date has examined the PDQ in an outpatient setting, particularly a psycho-oncology setting. Objective: The PDQ was administered as part of routine clinical care in an outpatient psycho-oncology clinic to enhance patient-centered care. Methods: Individuals diagnosed with cancer (n = 66) were referred for individual psychotherapy primarily for anxiety and/or depression. After gathering a thorough patient history during the initial psychology consult, patients were asked the PDQ as it was worded without further prompting. Patient responses were then qualitatively analyzed to measure the most common themes. Results: The themes expressed by patients in response to the PDQ included Who I Am (59.7%), which referenced individual characteristics and core personality traits, What My Cancer Journey Has Been (21.7%) described how patients' lives have been impacted since receiving a cancer diagnosis, and What I Want to Achieve (18.4%) in which patients described what goals they wanted to achieve in their lives (both general and specific to psychotherapy). Conclusions: Data from this small pilot study show promise that this brief assessment tool can be readily added to a psychological intake assessment and patients appreciated being asked about their personhood. Incorporating the PDQ into standard psychological care allows patients to be "seen" and helps us to acknowledge the person in the patient.