Discovery Of Child Research Articles

Fasting identifies SLIT2 as a novel driver of doxorubicin cardiotoxicity

Intermittent fasting strategies, including alternate day fasting (ADF), may attenuate aging phenotypes and reduce cardiovascular risk in part by stimulating brown adipogenesis. However, in the setting of cardiotoxic doxorubicin (Dox) chemotherapy, we recently described a novel toxicity of sustained ADF, which stimulated cachexia and cardiac atrophy in mice. Presently, we tested the effect of fasting initiated after Dox chemotherapy and found that fasting caused a decline in lean body mass and left ventricular mass index, but increased body fat content, liver weight, and brown adipose tissue (BAT) weight index vs Dox-treated mice. Dox + ADF induced SLIT2, which regulates thermogenesis and metabolic function in BAT. Dox plus recombinant SLIT2 decreased left ventricular ejection fraction vs Dox alone. Plasma proteomics from patients showed that SLIT2 was the top protein associated with Dox cardiomyopathy vs other non-ischemic cardiomyopathy. This study suggests that SLIT2, an activator of brown adipogenesis, is a novel driver of Dox cardiotoxicity. This research was supported by NIH (R01HL155344, K08HL138262, P30DK056341, P30DK020579), Children's Discovery Institute of Washington University and St. Louis Children's Hospital (MC-FR-2020-919), and Longer Life Foundation. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A study on children's multi-sensorial experiences of nature: design approaches and preferences for primary school architecture case studies in Glasgow, Scotland, UK

PurposeProviding improved access to nature within educational settings can promote stronger child–nature connections and is conditional on making evidence-based decisions for the planning, design and refurbishment of school architecture. The study offers insight into ways of reconnecting children with nature by examining the distribution and classification of diverse natural elements for enhancing children's visual and non-visual experiences of educational environments.Design/methodology/approachThis study combines quantitative and qualitative analysis of data gathered through measurement and observation at three schools in Glasgow, with a total of 75 students, to identify key issues influencing child–nature multi-sensorial connections within indoor and outdoor environments and on building envelopes and layouts. It applies children's open-questions and diagrams to investigate children's discovery of nature, their feelings around natural attributes and their environmental preferences within school contexts.FindingsThis study's findings reveal that architectural features and landscape settings have significant influence on the quantitative and qualitative degrees of children's natural exploration through visual and non-visual sensorial modalities and environmental preferences.Research limitations/implicationsThe limitations of this study are that the data was gathered in the Spring season and with different groups of children from The Glasgow Academy who received the same educational curriculum. Thus, there is a need for further investigation on children's experiences of nature based on temporal and contextual differences, and varying educational-socio-cultural and economic factors.Practical implicationsThe findings suggest that applications of natural diversity, accessible and flexible pathways and indoor natural settings, are potential approaches to connect children with nature within their study and play environments.Originality/valueThe authors provide a deeper understanding of how nature-based settings, including indoor and outdoor environments, constructively benefit children's multi-sensorial experiences, knowledge and biophilic feelings toward nature.

1121-P: Association between Self-Monitored Blood Glucose and Continuous Glucose Monitor in Youth with Type 1 Diabetes and Medicaid

Background: In many states, patients with type 1 diabetes (T1D) and public insurance must demonstrate self-monitored blood glucose (SMBG) 3 times per day for continuous glucose monitor (CGM) approval. On January 2022, a policy change in California led to less stringent criteria for CGM approval, allowing for the evaluation of whether lower baseline SMBG leads to poor compliance and outcomes with CGM use. Method: We used electronical health record data of pediatric patients with T1D, Medicaid at UCLA who started CGM after January 2019. Patients were stratified by SMBG frequency (< 3 times per day vs ≥ 3 times per day). We used descriptive statistics to report baseline demographics, and chi-squared test, t-test and logistic regression to evaluate differences in compliance and change in A1c. Results: We found 52 patients who met the criteria - 52% with SMBG < 3 vs. 48% with SMBG ≥ 3. The patients were mostly male in both groups (63% vs. 60%). Patients with SMBG < 3 were older at time of T1D diagnosis (10 vs 6.2 years old), started CGM at older age (16.1 vs 11.7 years old), more likely to start CGM after January 2022 (82% vs 40%), and had higher baseline A1c (10.9% vs 9.0%). At 3 and 6 months after starting CGM, there was significantly greater reduction in A1c in those with SMBG <3 (1.6% vs 0.3%, p = 0.021, and 1.5% vs 0.23%, p = 0.01). There was no significant difference in CGM compliance (60% vs 72%, p = 0.21, and 69% vs 80%, p = 0.24, respectively) between the two groups. In adjusted models for 3 and 6 months, there were no significant association between CGM compliance (OR 1.04, 95%CI 0.68-1.60, and OR 1.06, 95%CI 0.76-1.28, respectively) and change in A1c. Conclusion: Patients with lower baseline SMBG had similar CGM compliance and greater improvement in A1c than patients with higher baseline SMBG. This suggests that restricting CGM approval to those who are adherent to SMBG ≥3 may exclude use in patients who would benefit the most from CGM technology. Larger studies are needed to confirm these findings. Disclosure J.Chan: None. J.K.Yee: None. T.Moin: None. E.M.Everett: None. Funding University of California, Los Angeles Children's Discovery and Innovation Institute (CDI-FRSA-07012022); National Center for Advancing Translational Sciences (UL1TR001881)

The Learning Development Process and Capacity Enhancement for Ethnic Children and Youth in The Northern

The research subject, The Learning Development Process and Capacity Enhancement for Ethnic Children and Youth in The Northern Region has the following objectives; 1. To promote and develop the learning process for children and youth, children and youth groups. 2. To support ethnic children and youth groups to have the opportunity to use their potential to create new activities to benefit the community. 3. To assess the implementation of learning management and capacity building for ethnic children and youth in the northern region. In this study, target groups were selected to study the learning development process of children and youth through the operation of 2 organizations, namely the Education for Life and Society Foundation and Ya Phraek Salawin group. The two organizations worked with school teachers, community leaders, children and youth. In this study, qualitative data were collected from interviews with teachers, staff of local organizations, community leaders and other stakeholders. The results showed that a child and youth work process was created through the management process by coaching in the learning development process and the use of empowerment methods is a process of developing capacity. There was an empowerment to see the creative power for youth and themselves. “Youth led, adults supported” and the assessment of the work found that both organizations focused on knowledge management that creates the power of change, discovery of children and youth as well as knowledge in working that creates change and solves problems for children and youth

A novel function for the CoQ10 biosynthetic complex in anti-pneumococcal macrophage function

Abstract Despite the recent introduction of pneumococcal polysaccharide and conjugate vaccines, Streptococcus pneumoniae infection remains a leading cause of illness and death worldwide. In particular, infants in Papua New Guinea are at increased risk of severe pneumococcal pneumonia compared to infants in similar countries. We sought to determine if a novel genetic variant could explain this increased susceptibility. Whole exome sequencing revealed a single nucleotide variant (D308Y) in the gene encoding COQ6 (COQ6DY), a monooxygenase required for CoQ10 biosynthesis. We have utilized both a Saccharomyces cerevisiae model and a mouse model of COQ6DY to show that despite adequate production of CoQ10, this variant directly causes increased susceptibility to S. pneumoniae. This variant represents a previously unknown function of the CoQ10 biosynthetic complex that does not exert its effects through CoQ10 deficiency but rather through alterations of mitochondrial function and metabolism. These mitochondrial deficits in COQ6DY macrophages are sufficient to abrogate macrophage killing of S. pneumoniae and alter the coordination of the downstream immune response. In conclusion, we have identified a novel susceptibility allele to S. pneumoniae infection that exerts its effects via alterations in macrophage mitochondrial function. Supported by NIH (R21 AI142723), SLCH Children's Discovery Institute (PD-II-2018-742)

Bclaf1 promotes hematopoietic stem cell repopulating capacity and self-renewal

Abstract Hematopoietic stem cells (HSC) balance differentiation and self-renewal to promote maintenance of mature blood cell lineages. The mechanisms that regulate HSC expansion during fetal hematopoietic development and adult HSC maintenance remain significant knowledge gaps. BCLAF1 (Bcl2-associated factor 1), a transcriptional regulator, is highly expressed in hematopoietic cells. We recently defined its function as a modulator of ETS-family transcription factor activity in developing B cells. Our objective in this study is to determine the molecular mechanism of BCLAF1 in regulation of fetal and adult HSCs. We used mouse models with selective deletion of Bclaf1 in hematopoietic cells to test whether BCLAF1 regulates HSC development and function. We find that loss of Bclaf1 results in significantly reduced numbers of fetal HSCs. The reduced HSC numbers persist in adult mice; but there is no additional decline or development of bone marrow failure with aging. In competitive transplant experiments, Bclaf1-deficient fetal and adult HSCs have defective repopulation and self-renewal capacity resulting in reduced reconstitution of all hematopoietic populations. Bclaf1-deficient HSCs do not have abnormalities in emergence, proliferation, cell death, or homing activity. Using single cell RNA-sequencing of fetal HSCs, we find that loss of BCLAF1 results in reduction of a subpopulation of HSCs and upregulation of the early response genes Jun, Fos, and Egr1. Collectively, these findings suggest BCLAF1 restrains activity of immediate early genes to preserve HSC self-renewal capacity and promote HSC expansion during both fetal development and repopulation of hematopoiesis after HSC transplant. Supported by grants from Children's Discovery Institute, St. Louis Children's Hospital Foundation, Siteman Cancer Center, and NIH (T32 AI007163).

Shared secrecy: teasing, attachment, and children's emotional management in rural southern Mongolia

AbstractIn recent decades, anthropologists have scrutinized psychologists’ claim that humans process information about others by imputing mental states. The debate remains open whether cross‐cultural variability in how people conceive of minds and inner states reflects differences in their folk theories only, or whether it engenders deep‐grained psychological differences. In this article, I look at the very onset of children's apprenticeship in emotional management to examine its cognitive consequences. In the context of rural Mongolia in the late 2000s, questions about homesickness prompted by adults raised children's awareness of the existence of a private self and by the very same process discouraged verbalization or public display of personal feelings. I start by presenting interactions where children were routinely teased about homesickness, and invited to deny that they missed their family. I contextualize this teasing routine within local conceptions about emotional control and linguistic ideology to unveil how it introduced children to the performative power of words while also making them face moral dilemmas. The irreconcilable tension between behaving according to expectations of self‐control and experiencing separation induced children's discovery of the possibility of disconnecting intimate feelings from public self‐presentation, thus transforming the experience of separation into an experience of secret connection. I speculate that the secrecy that hallows homesickness contributed to making it all the more poignant. The way adults constantly checked on whether children were missing their home prompted children to actually identify some emotional state or aspect of their experience as ‘missing home’. It gave a name to a personal experience which thus became social and guaranteed that it became a shared feeling, albeit a secret one.

THE IMPACT OF INFIDELITY ON FILIPINO FAMILY DYNAMICS AND YOUNG ADULT FILIPINO'S SELF-CONCEPT

Parental infidelity largely influences the quality of relationships in the family. In previous researches, the focus is mainly on the dyadic marital relationship of the couples, subsequently failing to consider how this influences the upbringing and well-being of their children. This study aims to explore how adult Filipino children's discovery of parental infidelity impacted their self-concept. Using purposive sampling, the study involved fourteen (14) participants, seven males, and seven females, who were aware of their parent's infidelity. The research used a semi-structured interview schedule to gather the necessary data. Thematic analysis was used to categorize the data into two major themes: (a) Pre-infidelity Family Dynamics and (b) Impacts of Parental Infidelity. The research utilized Dr. Murray Bowen's Family Systems Theory and Self-Concept Theory by Rogers to analyse the themes and to discuss the results of the study. The research helps explain the differences in the impacts of parental infidelity on the family and on the self-concept. Further implications are discussed in the study. Keywords: Parental infidelity; Family systems theory; Self-concept; Thematic analysis

“He Fell in and That's How He Became a Fossil!”: Engagement With a Storytelling Exhibit Predicts Families' Explanatory Science Talk During a Museum Visit

Parent-child conversations in everyday interactions may set the stage for children's interest and understanding about science. Studies of family conversations in museums have found links to children's engagement and learning. Stories and narratives about science may spark children's interest in science topics. This study asks whether a museum exhibit that provides opportunities for families to create narratives might encourage families' explanatory science talk throughout the rest of the exhibit. The project focused on the potential impact of a hands-on story-telling exhibit, the “spin browser” embedded within a larger exhibition focused on fossilized mammoth bones—Mammoth Discovery! at Children's Discovery Museum of San Jose. Participants were 83 families with children between 3 and 11 years (mean age 7 years). We coded families' narrative talk (telling stories about the living mammoth or the fossil discovery) and connecting talk (linking the story to other nearby exhibits) while families visited the spin browser, and we also coded families' explanatory science talk at the exhibits that contained authentic fossil bones and replica bones. The parents in families who visited the spin browser (n = 37) were more likely to engage in science talk at the fossil exhibits than those in families who did not visit the spin browser (n = 46). Further, a regression analysis showed that family science talk at the fossil exhibits was predicted by parents' connections talk and children's narrative talk at the spin browser. These findings suggest that families' narratives and stories may provide an entry point for science-related talk, and encourage future study about specific links between storytelling and science understanding.

Sepsis Induced Red Cell Dysfunction (SiRD): Physiology and Mechanisms

BACKGROUND: In sepsis, many red blood cell (RBC) defects are described: ↑ oxygen (O2) affinity, ↓ deformability, ↑ aggregation & adhesion, and dysregulated RBC-based vasoregulation. We suggest these comprise a unique class of organ (RBC) failure, which we term sepsis-induced RBC dysfunction (SiRD). We propose SiRD arises from RBC metabolic failure and depowered antioxidant systems - resulting in impaired RBC physiology that disables O2 transport. We employed a murine cecal ligation and puncture (CLP) sepsis model to characterize SiRD features and explore mechanisms of SiRD initiation.METHODS: Mice underwent sham (Gcont), mild (Gmild: D1 mortality 10%), or severe CLP (Gsev: D1 mortality 50%); N=4-8/group. D1 RBCs were collected. SiRD phenotype was characterized by analyzing: (1) O2 affinity (p50, Bohr effect), (2) deformability (LORRCA - elongation index, EI), (3) osmotic fragility (LORRCA - ΔOsm resilience), (4) aggregation (LORRCA - syllectogram) and (5) vasoregulation (organ chamber bioassay - RBC hypoxic vasodilaton). Mechanistic explanation for the SiRD phenotype was explored by evaluating: (6) Ca+ accumulation (flow cytometry), (7) caspase3 activation (flow cytometry), (8) cdB3 proteolysis (western blot), (9) RBC metabolomic analysis (13C1,2,3-glucose based MS, +/- exogenous oxidant stress), (10) nitric oxide content (photolysis:chemiluminescence - total RBC NO, FeNO, and SNO content), and (11) eryptosis:phosphatidylserine (PS) exposure (flow cytometry). SiRD physiologic impact was evaluated by (12) quantifying tissue O2 delivery impairment in vivo (HIF-1a bioluminescent mouse, IVIS).RESULTS: RBCs from septic mice demonstrated the following physiologic Δs: (1) ↑ O2 affinity (L-shifted HbO2 dissociation) at 3 pHs (7.2, 7.4, and 7.6, with ↓ Bohr effect), with ↑ p50 (Gsev vs Gcont) (pH7.2: 47.8±1.2* vs. 53.3±0.9 Torr; pH7.4: 37.2±1.1** vs. 42.9±0.7 Torr; and pH7.6: 29.0±0.6*** vs. 34.2±0.8 Torr); (2) ↓ RBC deformability - with similar EImax, shear stress (SS)1/2 was ↑ in Gsev vs Gcont (0.92 vs. 0.65 Pa); (3) ↑ osmotic fragility - min & max tolerated osmolality (Omin & Omax): Omin in Gcont, Gmild, and Gsev were 166.1±8.9, 158.8±4.5, and 159.1±2.8 mOsm/kg; and Omax were 336.0±21.5, 315.3±9.1, and 314.0±8.5 mOsm/kg, respectively; (4) ↑ aggregation - syllectogram backscatter intensity (Isc): in Gsev, Isc ↓ from 32.5±5.0 to 12.5±2.8 Au; but in Gcont, Isc only changed from 31.1±3.4 to 23.6±4.6 Au; (5) hypoxic vasodilation response ↓ in Gsev RBCs vs Gcont (8.9±4.2% vs 10.2±4.0%*, respectively). Exploration of potential mechanisms for SiRD revealed: (6) ↑ RBC Ca+ (Fluo3-based flow cytometry): ↑ mean florescence intensity (MFI) with sepsis severity (Gcont: 61.3±11.6; Gmild: 73.4±14.6, and Gsev: 105±36.0); (7) MIF of active caspase3 probe (CaspGlow-DEVD-FMK) did not change following CLP; however, after incubation with 0.1mM H2O2, MIF for Gsev ↑ significantly (Gcont: 549.3±28.8 vs. Gsev: 3123±782.2*); (8) ↑ cdB3 proteolysis was observed, Gsev > Gmild; (9) principal component and pathway analysis of metabolomic data identified sepsis severity-based constraints in the hexose monophosphate shunt pathway & linked antioxidant systems (NADPH and GSH); (10) RBC SNOHb & membrane SNO ↓ in Gsev vs Gcont (0.08 ± 0.04* & 0.04 ± 0.02* vs 0.22 ± 0.08 & 0.17 ± 0.07 SNOHb (SNO:Hb molar ratio) and membrane SNO mol/mg protein, respectively; (11) ↑ %age of eryptotic RBCs after CLP (annexin V-based flow cytometry): Gsev annexin V positive sub-population was 5.3±2.9%**, compared to Gcont 1.3±0.6% - following oxidative stress (0.1mM H2O2), annexin V positive sub- population in Gcont ↑ further to 11.5±4.1%; whilst Gsev, ↑ to 31.0±9.2%***. (12) O2 delivery impairment was quantified by imaging (IVIS) HIF-bioluminescent mice (FVB/Gt(ROSA)26Sor tm2(HIF1A/luc)kael): D1 normalized luciferase activity in Gsev was ↑ 3.4±0.8* fold vs baseline; a similar difference was observed after washed RBC exchange from Gsev → Gcont mice. (NB: * P<0.05; ** P<0.01; *** P<0.001)CONCLUSIONS: In sepsis, RBCs undergo major biochemical & physiologic alterations that impair O2 delivery, which we term SiRD. We propose SiRD arises from acquired RBC metabolic constraints, oxidative RBC injuries and impaired physiology, comprising a distinct form of organ (RBC) failure that may influence sepsis outcome. This well characterized model will allow further characterization, mechanistic study, and therapeutic exploration. DisclosuresDoctor:KaloCyte, Inc.: Equity Ownership, Research Funding; Washington University in St. Louis: Patents & Royalties; NIH: Research Funding; DoD: Research Funding; Biogen: Consultancy; Children's Discovery Institute: Research Funding.

Children's use of everyday artifacts: Learning the hidden affordance of zipping.

The everyday world is populated with artifacts that require specific motor actions to use objects as their designers intended. But researchers know little about how children learn to use everyday artifacts. We encouraged forty-four 12- to 60-month-old children to unzip a vinyl pouch during a single 60-s trial. Although unzipping a pouch may seem simple, it is not. Unzipping requires precise role-differentiated bimanual actions-one hand must stabilize the pouch while the other hand applies a pulling force on the tab. Moreover, kinematic data from six adults showed that the tolerance limits for applying the forces are relatively narrow (pulling the tab within 63° of the zipper teeth while stabilizing the pouch within 4cm of the slider). Children showed an age-related progression for the unzipping action. The youngest children did not display the designed pulling action; children at intermediate ages pulled the tab but applied forces outside the tolerance limits (pulled in the wrong direction, failed to stabilize the pouch in the correct location), and the oldest children successfully implemented the designed action. Findings highlight the perceptual-motor requirements in children's discovery and implementation of the hidden affordances of everyday artifacts.

Longitudinal, strain-specific Staphylococcus aureus introduction and transmission events in households of children with community-associated meticillin-resistant S aureus skin and soft tissue infection: a prospective cohort study

Devising effective, targeted approaches to prevent recurrent meticillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infection requires an understanding of factors driving MRSA acquisition. We comprehensively defined household longitudinal, strain-level S aureus transmission dynamics in households of children with community-associated MRSA skin and soft tissue infection. From 2012-15, otherwise healthy paediatric patients with culture-confirmed, community-onset MRSA infections were recruited for the Household Observation of MRSA in the Environment (HOME) prospective cohort study from hospitals and community practices in metropolitan St Louis (MO, USA). Children with health-care-related risk factors were excluded, as determined by evidence of recent hospital admission, an invasive medical device, or residence in a long-term care facility. Household contacts (individuals sleeping in the home ≥four nights per week) and indoor dogs and cats were also enrolled. A baseline visit took place at the index patient's primary home, followed by four quarterly visits over 12 months. At each visit, interviews were done and serial cultures were collected, to detect S aureus from three anatomic sites of household members, two anatomic sites on dogs and cats, and 21 environmental surfaces. Molecular typing was done by repetitive-sequence PCR to define distinct S aureus strains within each household. Longitudinal, multivariable generalised mixed-effects logistic regression models identified factors associated with S aureus acquisition. Across household members, pets, and environmental surfaces, 1267 strain acquisition events were observed. Acquisitions were driven equally by 510 introductions of novel strains into households and 602 transmissions within households, each associated with distinct factors. Frequent handwashing decreased the likelihood of novel strain introduction into the household (odds ratio [OR] 0·86, credible interval [CrI] 0·74-1·01). Transmission recipients were less likely to own their homes (OR 0·77, CrI 0·63-0·94) and were more likely to share bedrooms with strain-colonised individuals (OR 1·33, CrI 1·12-1·58), live in homes with higher environmental S aureus contamination burden (OR 3·97, CrI 1·96-8·20), and report interval skin and soft tissue infection (OR 1·32, CrI 1·07-1·64). Transmission sources were more likely to share bath towels (OR 1·25, CrI 1·01-1·57). Pets were often transmission recipients, but rarely the sole transmission source. The household environment plays a key role in transmission, a factor associated with skin and soft tissue infection. Future interventions should inclusively target household members and the environment, focusing on straightforward changes in hand hygiene and household sharing behaviours. National Institutes of Health, Agency for Healthcare Research and Quality, Children's Discovery Institute, Burroughs Wellcome Foundation, Defense Advanced Research Projects Agency.

Dramatización y literatura infantil: un binomio innovador para el desarrollo de la expresión oral y corporal en Educación Infantil

Este artículo se centra en los beneficios de la dramatización, como práctica vinculada a la literatura infantil, para el desarrollo de las habilidades comunicativas —de expresión oral y corporal— en el segundo ciclo de infantil.

Reflections of Play and Toys on Impressionist Painting Children and Play as a Pictorial Expression

Play is a significant event and opportunity for experience and discovery for children to find their place in the society, to search for themselves and their identity. This study aimed to analyze how the images of children and play were reflected on impressionist painting in Europe in the 19th century. First, the works of impressionist painters were analyzed because they contain concrete and understandable images. According to the impressionist movement, the artist should give prominence to their personal interpretations and the emotions and the thoughts evoked by what they see instead of being objective and directly reflecting the reality. Children play in such a way. This qualitative study examined the images of children and play in 35 works of 10 impressionist painters within the context of the cultural play. Results indicated that, in the 35 paintings studied, children were depicted mostly in open, natural enviroments or social settings. Most of the children were depicted as girls of high socio-economical appearance and alone. Dolls, sensory toys, hoops, and animal toys were observed frequently. The most common type of play was symbolic. The findings suggest that arts also reflect the child play as a cultural value under the conditions of a certain period. This study traces the historical marks of children and play in art and offers insights for today’s early education.

Isabelle Rapin (1927–2017)

Isabelle Rapin (1927–2017)

Erythromer (EM), a Nanoscale Bio-Synthetic Artificial Red Cell: Proof of Concept and In Vivo Efficacy Results

▪BACKGROUND: There is need for an artificial oxygen (O2) carrier for use when: stored blood is unavailable or undesirable. To date, efforts to develop hemoglobin (Hb) based oxygen carriers (HBOCs) have failed, because of design flaws which do not preserve physiologic interactions of Hb with: O2 (they capture O2 in lungs, but do not release O2 effectively to tissue) and nitric oxide (NO) (they trap NO, causing vasoconstriction). EM design surmounts these weaknesses by: encapsulating Hb, controlling O2 capture/release with a novel 2,3-DPG shuttle and attenuating NO uptake through shell properties.METHODS: The EM prototype and its lyophilized form were analyzed: (1) structurally (dynamic light scattering (DLS), transmission electron microscopy (TEM) and atomic force microscopy (AFM)), as well as for: (2) payload retention (Drabkin), (3) biocompatibility (ex vivo complement activation), (4) O2 affinity (p50, Hill n, Adair), (5) rheology (cone and plate viscometer in rabbit plasma), (6) NO consumption (chemiluminescence), (7) pharmacokinetic (PK) profile (tracking 99mTc-labeled EM in rats), and (8) in vivo O2 delivery (two rodent models: hemorrhagic shock [rats, instrumented for tissue pO2] and hemodilution [bioluminescent HIF-1α reporter mice]).RESULTS: EM was structurally stable (size: 175±10 nm; polydispersity: 0.26±0.0 by DLS, confirmed by TEM and AFM; zeta potential: 12±2 mV). After 3 months storage, we observed nominal change (<10%) in size, zeta potential, or polydispersity. CH50 (complement activation) results were indistinguishable from negative controls and we observed no impact on plasma viscosity (1:10 and 1:5 dilution). p50 was calculated to be 21.46±2.75 Torr (control RBC p50: 23.63±1.84); EM Hill & Adair also similar to control RBC. Two compartment PK modeling in rats resulted in good fit, with distribution t1/2=26.2±3.6 min and elimination t1/2=300±12 min (R2>0.96); which is likely to translate to a t1/2 in humans of ~ 3h. EM NO sequestration varied as a function of shell crosslinking and was below the rate observed for RBCs. In our hemorrhagic shock model in fully instrumented SD Rats (400g), 40% blood volume was removed; animals were then resuscitated with an equal volume of EM (N=6) or normal saline (N=6). EM was suspended at 40 wt/vol%, [Hb]=4mM. EM infusion rapidly stabilized hemodynamics. During the 1st hour, we observed resolution of both lactic acidosis (3.2±1.5 v 8.2±2.1 mM) [for EM and NS, respectively, throughout] and elevated AV O2 difference (24±11 v 67±23%) as well as improved brain pO2 (30.5±1.4 v 17.2±1.3 Torr); p<0.05, RMANOVA, for all. Hemodilution model:Un-instrumented, HIF-1α (ODD) luciferase mice underwent hemodilution (70% v/v) with pentastarch, fresh blood (autotransfusion controls), or EM [N=6, all groups];Hb target nadir was reached (5 mg/dL). To detect whole body luciferase expression, D-luciferin (50 mg/kg, IP) was injected, then serial images were obtained (IVIS, Living Image). HIF-luc radiance was significantly higher in the HES group than in autotransfusion and EM groups, which did not differ (p<0.01, RMANOVA).CONCLUSIONS: The ErythroMer prototype has passed rigorous initial ex vivo and in vivo "proof of concept" testing and bench testing, which suggests this design surmounts prior challenges (by HBOCs) in emulating normal RBC physiologic interactions with O2 and NO. In models of major bleeding/anemia, EM reconstitutes normal hemodynamics and O2 delivery, observed at the system, tissue, and cellular level. EM potential for extended ambient dry storage has significant implications for portability and use. Next steps include formulation scaling, detailed study of pharmacokinetics, biodistribution and safety, as well as evaluation in large animal models of hemorrhagic shock. DisclosuresPan:KaloCyte, Inc.: Equity Ownership; Children's Discovery Institute: Research Funding; National Institutes of Health: Research Funding. Spinella:KaloCyte, Inc.: Equity Ownership; Children's Discovery Institute: Research Funding; National Institutes of Health: Research Funding. Hare:Children's Discovery Institute: Research Funding. Lanza:KaloCyte, Inc.: Membership on an entity's Board of Directors or advisory committees; National Institutes of Health: Research Funding. Doctor:KaloCyte, Inc.: Equity Ownership; Children's Discovery Institute: Research Funding; National Institutes of Health: Research Funding.

Gesture and intonation are “sister systems” of infant communication: Evidence from regression patterns of language development

This study investigates infants' transition from nonverbal to verbal communication using evidence from regression patterns. As an example of regressions, prelinguistic infants learning American Sign Language (ASL) use pointing gestures to communicate. At the onset of single signs, however, these gestures disappear. Petitto (1987) attributed the regression to the children's discovery that pointing has two functions, namely, deixis and linguistic pronouns. The 1:2 relation (1 form, 2 functions) violates the simple 1:1 pattern that infants are believed to expect. This kind of conflict, Petitto argued, explains the regression. Based on the additional observation that the regression coincided with the boundary between prelinguistic and linguistic communication, Petitto concluded that the prelinguistic and linguistic periods are autonomous. The purpose of the present study was to evaluate the 1:1 model and to determine whether it explains a previously reported regression of intonation in English. Background research showed that gestures and intonation have different forms but the same pragmatic meanings, a 2:1 form–function pattern that plausibly precipitates the regression. The hypothesis of the study was that gestures and intonation are closely related. Moreover, because gestures and intonation change in the opposite direction, the negative correlation between them indicates a robust inverse relationship. To test this prediction, speech samples of 29 infants (8–16 months) were analyzed acoustically and compared to parent-report data on several verbal and gestural scales. In support of the hypothesis, gestures alone were inversely correlated with intonation. In addition, the regression model explains nonlinearities stemming from different form–function configurations. However, the results failed to support the claim that regressions linked to early words or signs reflect autonomy. The discussion ends with a focus on the special role of intonation in children's transition from “prelinguistic” communication to language.

Visual sign phonology: insights into human reading and language from a natural soundless phonology.

Among the most prevailing assumptions in science and society about the human reading process is that sound and sound-based phonology are critical to young readers. The child's sound-to-letter decoding is viewed as universal and vital to deriving meaning from print. We offer a different view. The crucial link for early reading success is not between segmental sounds and print. Instead the human brain's capacity to segment, categorize, and discern linguistic patterning makes possible the capacity to segment all languages. This biological process includes the segmentation of languages on the hands in signed languages. Exposure to natural sign language in early life equally affords the child's discovery of silent segmental units in visual sign phonology (VSP) that can also facilitate segmental decoding of print. We consider powerful biological evidence about the brain, how it builds sound and sign phonology, and why sound and sign phonology are equally important in language learning and reading. We offer a testable theoretical account, reading model, and predictions about how VSP can facilitate segmentation and mapping between print and meaning. We explain how VSP can be a powerful facilitator of all children's reading success (deaf and hearing)-an account with profound transformative impact on learning to read in deaf children with different language backgrounds. The existence of VSP has important implications for understanding core properties of all human language and reading, challenges assumptions about language and reading as being tied to sound, and provides novel insight into a remarkable biological equivalence in signed and spoken languages. WIREs Cogn Sci 2016, 7:366-381. doi: 10.1002/wcs.1404 For further resources related to this article, please visit the WIREs website.

Gut bacteria dysbiosis and necrotising enterocolitis in very low birthweight infants: a prospective case-control study.

Gut bacteria might predispose to or protect from necrotising enterocolitis, a severe illness linked to prematurity. In this observational prospective study we aimed to assess whether one or more bacterial taxa in the gut differ between infants who subsequently develop necrotising enterocolitis (cases) and those who do not (controls). We enrolled very low birthweight (1500 g and lower) infants in the primary cohort (St Louis Children's Hospital) between July 7, 2009, and Sept 16, 2013, and in the secondary cohorts (Kosair Children's Hospital and Children's Hospital at Oklahoma University) between Sept 12, 2011 and May 25, 2013. We prospectively collected and then froze stool samples for all infants. Cases were defined as infants whose clinical courses were consistent with necrotising enterocolitis and whose radiographs fulfilled criteria for Bell's stage 2 or 3 necrotising enterocolitis. Control infants (one to four per case; not fixed ratios) with similar gestational ages, birthweight, and birth dates were selected from the population after cases were identified. Using primers specific for bacterial 16S rRNA genes, we amplified and then pyrosequenced faecal DNA from stool samples. With use of Dirichlet multinomial analysis and mixed models to account for repeated measures, we identified host factors, including development of necrotising enterocolitis, associated with gut bacterial populations. We studied 2492 stool samples from 122 infants in the primary cohort, of whom 28 developed necrotising enterocolitis; 94 infants were used as controls. The microbial community structure in case stools differed significantly from those in control stools. These differences emerged only after the first month of age. In mixed models, the time-by-necrotising-enterocolitis interaction was positively associated with Gammaproteobacteria (p=0·0010) and negatively associated with strictly anaerobic bacteria, especially Negativicutes (p=0·0019). We studied 1094 stool samples from 44 infants in the secondary cohorts. 18 infants developed necrotising enterocolitis (cases) and 26 were controls. After combining data from all cohorts (166 infants, 3586 stools, 46 cases of necrotising enterocolitis), there were increased proportions of Gammaproteobacteria (p=0·0011) and lower proportions of both Negativicutes (p=0·0013) and the combined Clostridia-Negativicutes class (p=0·0051) in infants who went on to develop necrotising enterocolitis compared with controls. These associations were strongest in both the primary cohort and the overall cohort for infants born at less than 27 weeks' gestation. A relative abundance of Gammaproteobacteria (ie, Gram-negative facultative bacilli) and relative paucity of strict anaerobic bacteria (especially Negativicutes) precede necrotising enterocolitis in very low birthweight infants. These data offer candidate targets for interventions to prevent necrotising enterocolitis, at least among infants born at less than 27 weeks' gestation. National Institutes of Health (NIH), Foundation for the NIH, the Children's Discovery Institute.

The Relationship between Parental Treatment Styles and Early Discovery of Learning Difficulties among Pre-school Children

This study aimed to explore the relationship between the parenting style and discovery of learning disabilities in early childhood education. The study used a sample of Egyptian parents to investigate the parenting style followed in the family. Also, the study investigated the family awareness and interest in the discovery and treatment of learning difficulties. The results indicated that there was a significant relationship between parenting style and discovery of child’s learning difficulties in the early stages. The results also showed that there was a significant relationship between positive parenting styles and discovering of learning difficulties. However, there was a negative relationship between negative parenting styles and discovery of learning difficulties in early childhood. The study recommended the need to provide appropriate training and guidance programs of positive parenting and avoid the negative methods of raising children.