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Social interactions between parents and children are important for developing theory of mind, but these may be disrupted by aspects of the proximal home environment. The current study observed maternal sensitivity and its associations with child theory of mind and the housing environment (index by clutter and crowding) in a sample of mothers and their 3.5‐year‐old twins (N = 250 children). Maternal sensitivity and housing environment were measured from experimenter report and child theory of mind was measured through behavioural tasks. Results show that the association between maternal sensitivity and child theory of mind was moderated by the housing environment, where the positive associations between maternal sensitivity and child theory of mind were only observed at lower levels of clutter and crowding in the housing environment. Additional contextual variables and processes are discussed. [ABSTRACT FROM AUTHOR]

Early theory of mind development is influenced by a variety of experiences and contexts. Social interactions with parents and others are important for developing a theory of mind, but these social processes may be disrupted by aspects of the proximal home environment. The current study observed father‐child dyadic mutuality (a construct representing responsiveness, reciprocity, and cooperation during a structured interaction) and its associations with child theory of mind and household chaos in a sample of fathers and their 3‐ to 5‐year‐old children (N = 88 dyads). Dyadic mutuality was coded from videotaped structured tasks, household chaos was self‐reported by fathers through a questionnaire, and child theory of mind was measured through behavioral tasks. Measures of child expressive language ability, child executive function, and family socioeconomic status are included as covariates. Results show no main effect of either dyadic mutuality or household chaos on child theory of mind, but that the association between dyadic mutuality and child theory of mind was moderated by household chaos, whereby the association between higher observed dyadic mutuality and better child theory of mind abilities was evident only at low and mean levels of chaos. Findings suggest that higher levels of household chaos may disturb the beneficial social interactions between parents and children that influence theory of mind development. Additional contextual variables and processes are discussed. [ABSTRACT FROM AUTHOR]

Background: Postnatal maternal anxiety is common (estimates as high as 40% prevalence) and is associated with altered mother–infant interactions (e.g., reduced maternal emotional expression and engagement). Neural circuitry supporting infants' face and emotion processing develops in their first year. Thus, early exposure to maternal anxiety may impact infants' developing understanding of emotional displays. We examine whether maternal anxiety is associated with individual differences in typically developing infants' neural responses to emotional faces. Methods: One hundred and forty two mother–infant dyads were assessed when infants were 5, 7, or 12 months old. Infants' electroencephalographic (EEG) data were recorded while passively viewing female happy, fearful, and angry faces. Three event‐related potential (ERP) components, each linked to face and emotion processing, were evaluated: NC, N290, and P400. Infant ERP amplitude was related to concurrent maternal‐report anxiety assessed with the Spielberger State‐Trait Anxiety Inventory (Trait form). Results: Greater maternal anxiety predicted more negative NC amplitude for happy and fearful faces in left and mid‐central scalp regions, beyond covarying influences of maternal depression symptoms, infant negative emotionality, and infant age. Conclusions: Postnatal maternal anxiety is related to infants' neural processing of emotional expressions. Infants of mothers endorsing high trait anxiety may need additional attentional resources to process happy and fearful faces (expressions less likely experienced in mother–infant interactions). Future research should investigate mechanisms underlying this association, given possibilities include experiential, genetic, and prenatal factors. [ABSTRACT FROM AUTHOR]

Parents' responses to children's negative emotional states play a key role in the socialization of emotion regulation skills in childhood. Much of the prior research on child ER has focused on early development using cross‐sectional designs. The current study addresses these gaps by using a longitudinal design to examine individual differences of ER at two times points in middle childhood. We examined the development of children's ER by testing hypotheses about the interplay of parent response to emotions and household chaos in the prediction of individual differences in children's ER. Participants were the mothers of children at 6 and 9 years of age among 224 families in a socioeconomically diverse sample that was part of an ongoing longitudinal study. Mothers completed questionnaires regarding themselves, their children, and their home environment. Mothers' reports of better child ER at both time points were positively associated with mothers' more supportive responses and negatively associated with mothers' less non‐supportive responses, as well as lower household chaos. Chaos statistically moderated the link between non‐supportive parental responses to emotion and child ER, but only at 6 years of age. The strength of the link between child ER and non‐supportive parental responses to emotions was strong only at lower levels of household chaos. At the beginning of middle childhood, family processes linking parent responses to child emotions and children's developing ER may not function at higher levels of household chaos. [ABSTRACT FROM AUTHOR]

When children transition to school between the ages of 4 and 6 years, they must learn to control their attention and behaviour to be successful. Concurrently, executive function (EF) is an important skill undergoing significant development in childhood. To understand changes occurring during this period, we examined the role of parenting in the development of children's EF from 4 to 6 years old. Participants were mother and child dyads (N = 151). Children completed cognitive tasks to assess overall EF at age 4 and age 6. At both time points, mothers and children completed interaction tasks which were videotaped and coded to assess various parenting dimensions. Results indicated that children with high EF at age 4 were more likely to have high EF at age 6. In addition, results suggested that higher levels of positive parenting across the transition to school promote stability of individual differences in EF. Highlights: This study investigated the association between parenting and the development of children's executive function (EF) skills across the transition to school.Children's EF and mothers' parenting were assessed at age 4 and age 6.The stability of individual differences in EF was linked to positive parenting.Parenting practises may be related to the stability of individual difference in EF across the transition to school. [ABSTRACT FROM AUTHOR]

Processing of positive and negative facial expressions in infancy follows a distinct course with a bias towards fearful facial expressions starting at 7 months of age; however, little is known about the developmental trajectory of fear processing and other facial expressions, and if this bias is driven by specific regions of the face. This study used eye tracking to examine the processing of positive and negative emotional faces in independent groups of 5‐ (n = 43), 7‐ (n = 60), and 12‐month‐old infants (n = 70). Methods: Infants were shown static images of female faces exhibiting happy, anger, and fear expressions, for one‐second each. Total looking time and looking time for areas of interest (AOIs) including forehead and eyes (top), mouth and chin (bottom), and contour of each image were computed. Infants across all ages looked longer to fear faces than angry or happy faces. Negative emotions generally elicited greater looking times for the top of the face than did happy faces. In addition, we also found that at 12 months of age infants looked longer for the bottom of the faces than did 5‐month‐olds. Our study suggests that the visual bias to attend longer to fearful faces may be in place by 5 months of age, and between 5 and 12 months of age, there seems to be a developmental shift towards looking more to the bottom of the faces. Statement of contribution: What is already known in this subject?Bias for fear face processing is present at 7 months of age.Using older data collection systems, we have some idea about which facial features recruit infant attention.What the present study adds?Well‐controlled paradigm that examines both positive and negative facial expressions, to different areas of interest in the face.Use of the same paradigm to test a cross‐sectional sample of infants in distinct developmental stages – 5, 7, and 12 months. [ABSTRACT FROM AUTHOR]

Understanding the role that mental health issues play in justice-involved youth poses challenges for research, policy, and practice. While mental health problems are generally not risk factors for criminal behavior according to the risk-needs-responsivity (RNR) framework of correctional psychology practice, prevalence rates are very high and RNR principles suggest that mental health as a responsivity variable may moderate the success of interventions targeted to criminogenic needs. In this study we investigated the relationships among mental health status, criminogenic needs treatment, and recidivism in a sample of 232 youth referred for court-ordered assessments and followed through their community supervision sentence (probation). Youth with mental health needs were no more likely than youth without these needs to reoffend, regardless of whether those needs were treated. Youth who received mental health treatment also more frequently had their criminogenic needs matched across several domains, suggesting an association between mental health treatment and intermediate treatment targets. However, mental health did not moderate the effect of criminogenic needs treatment: youth who had a greater proportion of criminogenic needs targeted through appropriate services were less likely to reoffend, regardless of mental health status. Findings are consistent with the RNR stance that, within a correctional context in which the primary goal of intervention is preventing recidivism, treatment for mental health needs should be in addition to criminogenic needs treatment, not in replacement of it. They also point to the need for continued research to understand precisely how mental health treatment interacts with intervention targeting criminogenic needs. [ABSTRACT FROM AUTHOR]

Allergic asthma is a chronic lung disease initiated and driven by Th2 cytokines IL-4/-13. In macrophages, IL-4/-13 bind IL-4 receptors, which signal through insulin receptor substrate (IRS)-2, inducing M2 macrophage differentiation. M2 macrophages correlate with disease severity and poor lung function, although the mechanisms that regulate M2 polarization are not understood. Following IL-4 exposure, suppressor of cytokine signaling (SOCS)1 is highly induced in human monocytes. We found that siRNA knockdown of SOCS1 prolonged IRS-2 tyrosine phosphorylation and enhanced M2 differentiation, although siRNA knockdown of SOCS3 did not affect either. By co-immunoprecipitation, we found that SOCS1 complexes with IRS-2 at baseline, and this association increased after IL-4 stimulation. Because SOCS1 is an E3 ubiquitin ligase, we examined the effect of proteasome inhibitors on IL-4-induced IRS-2 phosphorylation. Proteasomal inhibition prolonged IRS-2 tyrosine phosphorylation, increased ubiquitination of IRS-2, and enhanced M2 gene expression. siRNA knockdown of SOCS1 inhibited ubiquitin accumulation on IRS-2, although siRNA knockdown of SOCS3 had no effect on ubiquitination of IRS-2. Monocytes from healthy and allergic individuals revealed that SOCS1 is induced by IL-4 in healthy monocytes but not allergic cells, whereas SOCS3 is highly induced in allergic monocytes. Healthy monocytes displayed greater ubiquitination of IRS-2 and lower M2 polarization than allergic monocytes in response to IL-4 stimulation. Here, we identify SOCS1 as a key negative regulator of IL-4-induced IRS-2 signaling and M2 differentiation. Our findings provide novel insight into how dysregulated expression of SOCS increases IL-4 responses in allergic monocytes, and this may represent a new therapeutic avenue for managing allergic disease. [ABSTRACT FROM AUTHOR]

Background: There is a renewed call to address preventable foetal deaths in high-income countries, especially where progress has been slow. The Centers for Disease Control and Prevention released publicly, for the first time, the initiating cause and estimated timing of foetal deaths in 2014. The objective of this study is to describe risk and characteristics of antepartum versus intrapartum stillbirths in the U.S., and frequency of pathological examination to determine cause.Methods: We conducted a cross-sectional study of singleton births (24-43 weeks) using 2014 U.S. Fetal Death and Natality data available from the National Center for Health Statistics. The primary outcome was timing of death (antepartum (n = 6200), intrapartum (n = 453), and unknown (n = 5403)). Risk factors of interest included maternal sociodemographic, behavioural, medical and obstetric factors, along with foetal sex. We estimated gestational week-specific stillbirth hazard, risk factors for intrapartum versus antepartum stillbirth using multivariable log-binomial regression models, conditional probabilities of intrapartum and antepartum stillbirth at each gestational week, and frequency of pathological examination by timing of death.Results: The gestational age-specific stillbirth hazard was approximately 2 per 10,000 foetus-weeks among preterm gestations and > 3 per 10,000 foetus-weeks among term gestations. Both antepartum and intrapartum stillbirth risk increased in late-term and post-term gestations. The risk of intrapartum versus antepartum stillbirth was higher among those without a prior live birth, relative to those with at least one prior live birth (RR 1.32; 95% CI 1.08-1.61) and those with gestational hypertension, relative to those with no report of gestational hypertension (RR 1.47; 95% CI 1.09-1.96), and lower among Black, relative to white, individuals (RR 0.70; 95% CI 0.55-0.89). Pathological examination was not performed/planned in 25% of known antepartum stillbirths and 29% of known intrapartum stillbirths.Conclusion: These findings suggest greater stillbirth risk in the late-term and post-term periods. Primiparous mothers had greater risk of intrapartum than antepartum still birth, suggesting the need for intrapartum interventions for primiparous mothers in this phase of pregnancy to prevent some intrapartum foetal deaths. Efforts are needed to improve understanding, prevention and investigation of foetal deaths as well as improve stillbirth data quality and completeness in the United States. [ABSTRACT FROM AUTHOR]

Interleukin (IL)-4 and IL-13 were discovered approximately 30 years ago and were immediately linked to allergy and atopic diseases. Since then, new roles for IL-4 and IL-13 and their receptors in normal gestation, fetal development and neurological function and in the pathogenesis of cancer and fibrosis have been appreciated. Studying IL-4/-13 and their receptors has revealed important clues about cytokine biology and led to the development of numerous experimental therapeutics. Here we aim to highlight new discoveries and consolidate concepts in the field of IL-4 and IL-13 structure, receptor regulation, signaling and experimental therapeutics. [ABSTRACT FROM AUTHOR]

Immunopathology is a major cause of influenza-associated morbidity and mortality worldwide. However, the role and regulatory mechanisms of CD4 T cells in severe lung immunopathology following acute influenza infection are poorly understood. In this paper, we report that the emergence of immunopathogenic CD4 T cells is under the control of a transmembrane immunoadaptor DAP12 pathway during influenza infection. We find that the mice lacking DAP12 have unaltered viral clearance but easily succumb to influenza infection as a result of uncontrolled immunopathology. Such immunopathology is associated with markedly increased CD4 T cells displaying markedly increased cytotoxicity and Fas ligand expression. Furthermore, the immunopathogenic property of these CD4 T cells is transferrable. Thus, depletion of CD4 T cells or abrogation of Fas/Fas ligand signaling pathway improves survival and immunopathology. We further find that DAP12 expressed by dendritic cells plays an important role in controlling the immunopathogenic CD4 T cells during influenza infection. Our findings identify a novel pathway that controls the level of immune-pathogenic CD4 T cells during acute influenza infection. [ABSTRACT FROM AUTHOR]

Genetically modified dendritic cell (DC)-based vaccines have not been explored for immunization against tuberculosis. A gene-modified DC vaccine expressing Mycobacterium tuberculosis (M.tb) antigen 85A (Ag85A) was developed by using a recombinant replication-deficient adenoviral gene transfer vector (AdAg85A). AdAg85A-transduced DC vaccine (AdAg85/DC) expressed higher levels of IL-12 and was much more immunogenic than Ag85 protein-loaded (pro/DC) or CD4/CD8 T cell peptide-loaded (pep/DC) DC vaccines. Compared to pro/DC or pep/DC, AdAg85/DC elicited a remarkably higher level of ex vivo IFN-γ production by CD4 and CD8 T cells at weeks 2, 6, and 12 postimmunization, which was coupled with higher frequencies of antigen-specific T cells. By an in vivo CD8 or CD4 T cell cytotoxicity (CTL) assay, AdAg85/DC was shown to provoke much higher and more sustained levels of CD8 and CD4 CTL activity up to 12 weeks postimmunization. Intramuscular (im) AdAg85/DC immunization was more potent than the iv route of AdAg85/DC immunization. Such stronger immunogenicity of im AdAg85/DC vaccination was corroborated with better protection from M.tb challenge. Our results thus suggest that genetically modified DC-based TB vaccine is superior to subunit DC vaccines and has the potential for therapeutic applications.Molecular Therapy (2006) 13, 766–775; doi: 10.1016/j.ymthe.2005.10.018 [ABSTRACT FROM AUTHOR]

In the present study we examined the neural correlates of facial emotion processing in the first year of life using ERP measures and cortical source analysis. EEG data were collected cross‐sectionally from 5‐ (N = 49), 7‐ (N = 50), and 12‐month‐old (N = 51) infants while they were viewing images of angry, fearful, and happy faces. The N290 component was found to be larger in amplitude in response to fearful and happy than angry faces in all posterior clusters and showed largest response to fear than the other two emotions only over the right occipital area. The P400 and Nc components were found to be larger in amplitude in response to angry than happy and fearful faces over central and frontal scalp. Cortical source analysis of the N290 component revealed greater cortical activation in the right fusiform face area in response to fearful faces. This effect started to emerge at 5 months and became well established at 7 months, but it disappeared at 12 months. The P400 and Nc components were primarily localized to the PCC/Precuneus where heightened responses to angry faces were observed. The current results suggest the detection of a fearful face in infants' brain can happen shortly (~200–290 ms) after the stimulus onset, and this process may rely on the face network and develop substantially between 5 to 7 months of age. The current findings also suggest the differential processing of angry faces occurred later in the P400/Nc time window, which recruits the PCC/Precuneus and is associated with the allocation of infants' attention. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented related to association of physical and psychological illness with intensive care unit (ITU) recovery, published in a 2014 issue of the periodical.

Kidney transplant (KT) recipients are at high risk for developing severe COVID-19. Lowering immunosuppression levels in KT recipients with COVID-19 encourages native immune responses but can raise the risk of rejection. Donor-derived cell-free DNA (dd-cfDNA), reported as a fraction of total cfDNA, is a proven biomarker for KT rejection. Total cfDNA levels are elevated in patients with COVID-19, which may depress dd-cfDNA fractions, potentially leading to missed rejections. A retrospective analysis of 29 KT recipients hospitalized with COVID-19 between April and November 2020 examined total and dd-cfDNA levels. Blood samples were collected after onset of COVID-19, with follow-up samples collected from a subset of patients, when infection had likely subsided. After COVID-19 diagnosis, the median total cfDNA level was elevated (7.9 multiples of median [MoM]). A significant decrease in total cfDNA levels was observed between the first and second time points (6.2 MoM, 1.0 MoM; P <001). A significant positive association was identified between total cfDNA levels and COVID-19 severity (P =.02; R2 =.19). Two patients with biopsy-proven acute cellular rejection had dd-cfDNA fractions below the 1% cutoff for rejection (0.20% and 0.78%), with elevated total cfDNA levels of 7.9 MoM and 41.8 MoM, respectively. In this preliminary study, total cfDNA levels were elevated in KT patients with COVID-19, subsiding after resolution of infection. High total cfDNA levels may confound dd-cfDNA results, leading to failure to identify rejection. Considering total cfDNA levels is important in interpretation of dd-cfDNA tests for assessment of rejection in KT patients with COVID-19 or other infection. [ABSTRACT FROM AUTHOR]

Changes in heart rate are a useful physiological measure in infant studies. We present an algorithm for calculating the heart rate (HR) from oxyhemoglobin pulsation in functional near-infrared spectroscopy (fNIRS) signals. The algorithm is applied to data collected from 10 infants, and the HR derived from the fNIRS signals is compared against the HR as calculated by electrocardiography. We show high agreement between the two HR signals for all infants (r > 0.90), and also compare stimulus-related HR responses as measured by the two methods and find good agreement despite high levels of movement in the infants. This algorithm can be used to measure changes in HR in infants participating in fNIRS studies without the need for additional HR sensors. [ABSTRACT FROM AUTHOR]

• Donor-derived cell-free DNA (dd-cfDNA) is a validated biomarker for active rejection (AR). • We investigated how dd-cfDNA may impact biopsy decisions in renal transplant recipients. • About one-fourth of biopsies ordered after assessment by traditional markers show AR. • We found a 64% rate of AR in biopsies ordered within 2 weeks of dd-cfDNA testing. Donor-derived cell-free DNA (dd-cfDNA) in plasma is an established noninvasive biomarker for allograft injury and rejection. A single-nucleotide polymorphism (SNP)–based massively multiplexed polymerase chain reaction methodology can be used to quantify dd-cfDNA in kidney transplant recipients. In this study we describe our clinical experience in using a SNP-based dd-cfDNA assay for the management of active rejection in renal transplant recipients. To assess the clinical utility of a clinically available SNP-based massively multiplexed polymerase chain reaction dd-cfDNA assay, we analyzed biopsy data contemporaneous to dd-cfDNA results at 33 participating clinics and calculated the rate of rejection in dd-cfDNA-matched biopsy results. A total of 1347 dd-cfDNA test samples from 879 patients were accessioned from October 3, 2019, to November 2, 2020. The dd-cfDNA testing classified 25.2% (340/1347) of samples as high-risk (dd-cfDNA fraction ≥ 1%). Clinical follow-up was available for 32.1% (109/340) of the high-risk results, which included samples from 28 patients with definitive biopsy results within 2 weeks of dd-cfDNA testing. Pathology reports indicated a 64% (18/28) rate of active rejection in biopsy result–matched samples. Total cfDNA measurements indicated a skewed distribution and a correlation with dd-cfDNA-derived patient risk classification. This is the first report showing the impact of dd-cfDNA on patient management in a multicenter real-world clinical cohort. The data indicate that incorporating dd-cfDNA testing into practice may improve physician decision making regarding renal allograft recipients. [ABSTRACT FROM AUTHOR]

Pulmonary tuberculosis (TB), caused by Mycobacterium tuberculosis, is the leading cause of death due to a bacterial pathogen. Emerging epidemiologic evidence suggests that the leading risk factor associated with TB mortality is cigarette smoke exposure. Despite this, it remains poorly understood what is the effect of cigarette smoke exposure on anti-TB immunity and whether its potential detrimental effect can be reversed by cigarette smoking cessation. In our current study, we have investigated the impact of both continuous and discontinuous cigarette smoke exposure on the development of anti-mycobacterial type 1 immunity in murine models. We find that while continuous cigarette smoke exposure severely impairs type 1 immunity in the lung, a short-term smoking cessation allows rapid restoration of anti-mycobacterial immunity. The ability of continuous cigarette smoke exposure to dampen type 1 protective immunity is attributed locally to its affects on innate immune cells in the lung. Continuous cigarette smoke exposure locally, by not systemically, impairs APC accumulation and their production of TNF, IL-12, and RANTES, blunts the recruitment of CD4+IFN-γ+ T cells to the lung, and weakens the formation of granuloma. On the other hand, smoking cessation was found to help restore type 1 immunity by rapidly improving the functionality of lung APCs, enhancing the recruitment of CD4+IFN-γ+ T cells to the lung, and promoting the formation of granuloma. Our study for the first time demonstrates that continuous, but not discontinuous, cigarette smoke exposure severely impedes the lung expression of anti-TB Th1 immunity via inhibiting innate immune activation and lung T cell recruitment. Our findings thus suggest cigarette smoking cessation to be beneficial to the control of pulmonary TB. [ABSTRACT FROM AUTHOR]

Asthma development and pathogenesis are influenced by the interactions of airway epithelial cells and innate and adaptive immune cells in response to allergens. Oxidative stress is an important mediator of asthmatic phenotypes in these cell types. Nuclear erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that is the key regulator of the response to oxidative and environmental stress. We previously demonstrated that Nrf2-deficient mice have heightened susceptibility to asthma, including elevated oxidative stress, inflammation, mucus, and airway hyperresponsiveness (AHR) (Rangasamy T, Guo J, Mitzner WA, Roman J, Singh A, Fryer AD, Yamamoto M, Kensler TW, Tuder RM, Georas SN, Biswal S. J Exp Med 202: 47-59, 2005). Here we dissected the role of Nrf2 in lung epithelial cells and tested whether genetic or pharmacological activation of Nrf2 reduces allergic asthma in mice. Cell-specific activation of Nrf2 in club cells of the airway epithelium significantly reduced allergen-induced AHR, inflammation, mucus, Th2 cytokine secretion, oxidative stress, and airway leakiness and increased airway levels of tight junction proteins zonula occludens-1 and E-cadherin. In isolated airway epithelial cells, Nrf2 enhanced epithelial barrier function and increased localization of zonula occludens-1 to the cell surface. Pharmacological activation of Nrf2 by 2-trifluoromethyl-2=-methoxychalone during the allergen challenge was sufficient to reduce allergic inflammation and AHR. New therapeutic options are needed for asthma, and this study demonstrates that activation of Nrf2 in lung epithelial cells is a novel potential therapeutic target to reduce asthma susceptibility. [ABSTRACT FROM AUTHOR]

Abstract: Influenza epidemics and pandemics cause significant morbidity and mortality worldwide associated with severe immunopathology in the lung, and the mechanisms of such immunopathogenesis still remain poorly understood. While human studies help to understand influenza immunopathology, they provide only limited mechanistic information. On the other hand, recent studies using experimental animal models have significantly enhanced our understanding of the complex mechanisms involved in the immunopathogenesis during primary influenza or influenza-associated bacterial superinfection. This includes the involvement of acute inflammatory responses (macrophages, neutrophils, dendritic cells, toll-like receptors, cytokines, chemokines), CD4 and CD8 T cells, tissue remodeling processes, and contribution of bacterial superinfection. In particular, progress has been made in uncoupling the mechanisms that are involved in both anti-viral host defense and in immunopathogenesis from those that solely contribute to lung immunopathology. Uncoupling such events will facilitate the discovery of new intervention strategies to treat pulmonary immunopathology associated with influenza infection. [Copyright &y& Elsevier]

Background: Non-invasive micro-ultrasound was evaluated as a method to quantify intrauterine growth phenotypes in mice. Improved methods are required to accelerate research using genetically-altered mice to investigate the interactive roles of genes and environments on embryonic and placental growth. We determined (1) feasible age ranges for measuring specific variables, (2) normative growth curves, (3) accuracy of ultrasound measurements in comparison with light microscopy, and (4) weight prediction equations using regression analysis for CD-1 mice and evaluated their accuracy when applied to other mouse strains. Methods: We used 30-40 MHz ultrasound to quantify embryonic and placental morphometry in isofluraneanesthetized pregnant CD-1 mice from embryonic day 7.5 (E7.5) to E18.5 (full-term), and for C57Bl/6J, B6CBAF1, and hIGFBP1 pregnant transgenic mice at E17.5. Results: Gestational sac dimension provided the earliest measure of conceptus size. Sac dimension derived using regression analysis increased from 0.84 mm at E7.5 to 6.44 mm at E11.5 when it was discontinued. The earliest measurement of embryo size was crown-rump length (CRL) which increased from 1.88 mm at E8.5 to 16.22 mm at E16.5 after which it exceeded the field of view. From E10.5 to E18.5 (full term), progressive increases were observed in embryonic biparietal diameter (BPD) (0.79 mm to 7.55 mm at E18.5), abdominal circumference (AC) (4.91 mm to 26.56 mm), and eye lens diameter (0.20 mm to 0.93 mm). Ossified femur length was measureable from E15.5 (1.06 mm) and increased linearly to 2.23 mm at E18.5. In contrast, placental diameter (PD) and placental thickness (PT) increased from E10.5 to E14.5 then remained constant to term in accord with placental weight. Ultrasound and light microscopy measurements agreed with no significant bias and a discrepancy of less than 25%. Regression equations predicting gestational age from individual variables, and embryonic weight (BW) from CRL, BPD, and AC were obtained. The prediction equation BW = -0.757 + 0.0453 (CRL) + 0.0334 (AC) derived from CD-1 data predicted embryonic weights at E17.5 in three other strains of mice with a mean discrepancy of less than 16%. Conclusion: Micro-ultrasound provides a feasible tool for in vivo morphometric quantification of embryonic and placental growth parameters in mice and for estimation of embryonic gestational age and/or body weight in utero. [ABSTRACT FROM AUTHOR]

Background: The lung is divided into two major compartments: the alveolar space and the parenchyma. The alveolar macrophages are the first line of leukocytes in the lung taking up incoming microbes or microbial antigens whereas the parenchymal dendritic cells (DCs) are believed to be the sole potent antigen presenting cells (APCs) in the lung. Both resting alveolar macrophages and parenchymal DCs express CD11c. Several important questions remain to be elucidated: 1] to which extent the alveolar space and lung parenchymal CD11c+ APCs differ in their phenotype and ability to activate naïve T cells; 2] whether they differ in their ability to activate antigen-experienced or -primed T cells; and 3] whether these lung CD11c+ APC populations differ from the splenic CD11c+ APCs which have been commonly used for understanding APC biology. Results: CD11c+ APCs from the alveolar space, lung parenchyma, and the spleen display differential co-stimulatory molecule expression and cytokine responsiveness upon stimulation. Alveolar space APCs are weak activators of naïve T cells compared to lung parenchymal and splenic CD11c+ APC populations. However, alveolar space APCs are able to potently activate the in vivo microbial antigen-primed T cells to a similar extent as lung parenchymal and splenic APCs. Conclusion: Together our findings indicate that alveolar CD11c+ APCs have a specialized T cell-activating function, capable of activating antigen-primed, but not naïve, T cells whereas lung CD11c+ APCs are capable of activating both the naïve and antigen-primed T cell populations. [ABSTRACT FROM AUTHOR]