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The cannabinoid-type I (CB1) receptor functions as a double-edged sword to decide cell fate: apoptosis/survival. Elevated CB1 receptor expression is shown to cause acute ceramide accumulation to meet the energy requirements of fast-growing cancers. However, the flip side of continual CB1 activation is the initiation of a second ceramide peak that leads to cell death. In this study, we used ovarian cancer cells, PA1, which expressed CB1, which increased threefold when treated with a natural compound, bis(palmitoleic acid) ester of a glycerol (C2). This novel compound is isolated from a marine snail, Conus inscriptus, using hexane and the structural details are available in the public domain PubChem database (ID: 14275348). The compound induced two acute ceramide pools to cause G0/G1 arrest and killed cells by apoptosis. The compound increased intracellular ceramides (C:16 to 7 times and C:18 to 10 times), both of which are apoptotic inducers in response to CB1 signaling and thus the compound is a potent CB1 agonist. The compound is not genotoxic because it did not induce micronuclei formation in non-cancerous Chinese hamster ovarian (CHO) cells. Since the compound induced the cannabinoid pathway, we tested if there was a psychotropic effect in zebrafish models, however, it was evident that there were no observable neurobehavioral changes in the treatment groups. With the available data, we propose that this marine compound is safe to be used in non-cancerous cells as well as zebrafish. Thus, this anticancer compound is non-toxic and triggers the CB1 pathway without causing psychotropic effects. [ABSTRACT FROM AUTHOR]

Amritotharanam Kashyam, a specific Ayurvedic drug, was the focus of the current inquiry to evaluate its efficacy. For liver and digestive-related issues, this medication is suggested. This was obtained from a standard Ayurvedic vendor in Chennai (India), and GC-MS analysis was carried out according to the standard procedure. A few critical biomolecules include benzoic acid, hexadecanoic acid, 6,9-octadecadienoic acid, 9-octadecenoic acid, methyl ester (E)-, heptadecanoic acid, 16-methyl, methyl ester, methyl 18-methylnonadecanoate, tetracosanoic acid, distearin, hexadecanoic acid, and 1-(hydroxymethyl)-1,2-ethanediol ester. The obtained biomolecules exhibited some significant therapeutic functions, including acidification, inhibition of arachidonic acid formation, increase in the aromatic amino acid decarboxylase, suppression of uric acid generation, inhibitors of catechol-O-methyltransferase, urine acidifiers, etc. The anticancer and antiviral potential of these phytocompounds were investigated using molecular docking and dynamics. The phytocompounds pharmacokinetic characteristics were investigated using ADME analysis. Through docking and dynamics simulation, in silico tests demonstrated the phytocompounds' inhibitory efficiency against the target proteins. These functions reasonably relate to the medicinal function of Amritotharanam Kashyam. The MTT assay findings demonstrated this medication's anticancer effects. The ability to be an effective drug is demonstrated by its antioxidant, anti-inflammatory, and membrane-stabilizing properties. [ABSTRACT FROM AUTHOR]

Objectives: The following three studies examined if 4–5 year olds, 7–8 year olds and adults recognized the impact of physical and sedentary activities on weight. Methods: Study 1 examined if 4–5 year olds and adults recognized the impact of physical activities on weight. Study 2 investigated if all three age groups of participants recognized the difference that physical activities and sedentary activities would have on weight. Study 3 examined if participants recognized the short-term and long-term impact of active and sedentary activities on weight. Results: The results demonstrated that compared to 7 and 8 year olds, 4 and 5 year olds had a difficult time in making a clear distinction between the impact of physical and sedentary activities on weight. Conclusions: Preschoolers have an impoverished recognition of the impact of activities on weight compared to children in middle childhood. This suggests the need for parents and educators to further emphasize the importance of physical activities in maintaining a healthy lifestyle in early childhood. [ABSTRACT FROM AUTHOR]

The following three studies examined young children’s and adults’ recognition of the impact of healthy and unhealthy foods on height and weight. Study 1 examined the impact of foods on height and weight. Study 2 examined the role of foods on characters of different ethnicities. Study 3 controlled for participants’ prior knowledge about the impact of food by presenting fictitious alien characters. The results indicated that preschoolers recognized that healthy foods promoted an increase in height but only for African-American images. Adults recognized the impact of nutrition on both height and weight with a greater emphasis of nutrition for weight than height. These results demonstrate that preschoolers’ biological model is more sophisticated and differentiated than previously reported. [ABSTRACT FROM AUTHOR]

Abstract: Three studies were conducted to investigate if children think that physical growth is determined by inheritance. All three studies employed the “switched‐at‐birth” task. Study 1 investigated if children and adults thought that height and weight were determined by parentage. Study 2 examined preschoolers and elementary school children's and adults' understanding of the role of parentage and nutrition in determining weight. Study 2a examined children's and adults' understanding of the role of parentage and nutrition in determining height. Results indicate that overall, preschoolers and third graders have more of an inheritance bias for height than for weight. However, when nutrition was introduced, apart from third graders, all other grades reasoned that nutrition played a greater role in determining weight. Overall, these results indicate that even young children have a rudimentary but differentiated theory of the role of inheritance in determining height and weight. Highlights: Participants were presented with switched‐at‐birth tasks to determine if they thought that parentage and/or nutrition influences height and weight. Young children viewed height as determined more by parentage than weight, suggesting that they have a differentiated and autonomous theory for the determination of height. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal membrane oxygenation (ECMO) is a rapidly expanding, life-supporting therapy for critically ill patients with severe respiratory and/or cardiovascular failure. Cerebrovascular impairment can result in hemorrhagic and ischemic complications commonly seen in the patients supported on ECMO. The healthy brain is protected by cerebral autoregulation, which maintains an adequate cerebral blood flow in face of blood pressure changes.1 Pre-ECMO factors, such as hypoxia, hypercarbia, and hypertension, can disrupt blood flow regulation, leaving the brain vulnerable to changes in blood pressure.2 Cannulation of large blood vessels3 and alterations of pulsatile flow patterns during ECMO also play a role in altered cerebral autoregulation.4 A reliable methodology that can assess the status of cerebral autoregulation during ECMO and provide early indication of neurological injury is critical for optimization of bedside management to improve clinical outcomes. Wavelet transform coherence (WTC) is a time-frequency domain analysis that characterizes the cross-correlation and relative phase between spontaneous fluctuations in blood pressure and cerebral oxygenation measurement by oximetry. We implemented WTC5 to assess the degree of cerebral autoregulation impairment in neonatal and pediatric ECMO and evaluated its usefulness as an early predictor of acute neurological complications. Further, we examined cerebrovascular parameters, blood gas changes, and anticoagulation parameters as potential causes of autoregulation impairment during ECMO. Methods: Spontaneous fluctuations of mean arterial pressure (MAP) and cerebral tissue oxygen saturation (SctO2) were continuously measured during the ECMO run. The dynamic relationship between the MAP and SctO2 fluctuations were assessed based on wavelet transform coherence (WTC) to derive an index of cerebral autoregulation impairment. The Institutional Review Board at the University of Texas Southwestern Medical Center at Dallas approved the study. Results: A total of 25 neonatal (11) and pediatric (14) patients were studied. In-phase coherence between the MAP and SctO2 fluctuations was predominant in a time scale range of 8-32 min. Significant correlations between individual autoregulation indices and neuroimaging scores were found in both neonates and children. There was a significant association between individual blood pressure variations with autoregulation indices in the children, but not in the neonates (Figure 1). Discussion and conclusion: We found that intra- ECMO autoregulation impairments derived from WTC were apparent even before clinically observable changes occur at the bedside. Furthermore, these impairments correlated with the patients' neuroimaging abnormalities. This finding remained constant for both VA ECMO and VV ECMO in contrast to evidence of increased incidence of neurological complication with carotid artery cannulation in the literature. Blood pressure variability in ECMO patients appeared to be associated with impaired autoregulation in the nonneonatal population. Continuous assessment of cerebral autoregulation based onWTC has the potential to be a useful bedside tool to predict acute neurological events in patients on ECMO. Our study shows that high blood pressure viability, for which these patients are at risk, appears to be a cause of cerebral autoregulation impairment. This finding suggests a new approach to bedside management that may lead to a decrease in cerebral autoregulation impairment, thereby improving neurological outcomes in these patients. [ABSTRACT FROM AUTHOR]

Four studies examined children's and adults' beliefs about the impact of nutrition on growth and mood states. In Studies 1 and 2, 271 participants (preschoolers through adults) judged the impact of healthy and unhealthy nutrition on height and weight. In Studies 3 and 4, 267 participants judged the impact of healthy and unhealthy nutrition on positive and negative mood states. The results suggest that young children demonstrate a co-existence of an ontologically distinct theory of biology as well as a theory of cross-domain interaction when reasoning about the impact of food on biological and psychological processes. [ABSTRACT FROM AUTHOR]

TEG values indicative of clot strength, including TEG-G, -angle, and TEG maximum amplitude (TEG-MA) were elevated in patients with cannula site bleeding, which is of unclear clinical significance. B Introduction/Hypothesis: b Bleeding and thrombosis cause significant morbidity and mortality in pediatric patients on extracorporeal membrane oxygenation (ECMO). [Extracted from the article]

Abstract: Brain injury is an important cause of morbidity in infants at risk for exposure to chronic hypoxia. Using a transgenic mouse that expresses green fluorescent protein (GFP) within this progenitor population we have previously shown that exposure to chronic hypoxia significantly decreases the progenitor stem cell pool in the dentate gyrus of the hippocampus that is in part mediated by inhibition of the mammalian target of rapamycin (mTOR) pathway. Hence we hypothesized that pharmacological inhibition of the mTOR pathway using rapamycin will alter the progenitor stem cell pool and impair the development of the dentate gyrus. We find that prolonged inhibition of the mTOR pathway causes a decrease in the early progenitor stem cell pool, demonstrated by decreased GFP-expressing progenitors, which persists long term. However there is a significant increase in proliferating progenitor cell pool, as seen by increased BrdU that is coupled with increased apoptosis thereby leading to fewer Neu N-expressing mature neurons. Further inhibition of the mTOR pathway leads to depletion of the astrocyte and microglial pool in the dentate gyrus as well. Overall our findings demonstrate that pharmacological inhibition of the mTOR pathway leads to impaired development of the DG, raising the concern that in young children could impair cognitive development. [Copyright &y& Elsevier]

In this study the author examined why children and adults think they need to eat. Preschoolers through adults were provided with physiological, social, psychological, and routine causes for eating breakfast, lunch, snack, and dinner, and were asked to either agree or disagree with the causal responses provided. A 4 Reason × 4 Meal repeated measures analysis of variance revealed significant main effects for meals and reasons, as well as significant Meal × Reason and Meal × Reason × Grade interactions. The effect sizes ranged from 0.1 to 0.7. Across all age groups, participants acknowledged physiological needs and desires (fulfilling hunger and needs to stay healthy) and routine (e.g., it is dinner time) as the primary causes for eating breakfast, lunch, and dinner. However, for snack physiological needs were the primary reason. Second-grade students onward spontaneously produced biological justifications such as the need for energy and nutrition as important reasons for food consumption. These results lend support to the developmental model that children's and adults’ understanding of eating changes in middle childhood. [ABSTRACT FROM AUTHOR]

The present set of studies examined the impact of intentionality (wanting/not wanting to get sick) on the transmission of contagious illness and injuries. Study I examined whether preschoolers and adults thought that a recipient of an illness is more likely to get sick if he/she wanted to. Studies 2, 2a, and 3 examined if the intentions of the transmitter would influence the transmission of illness to the recipient. Study 4 examined the influence of germs on intentionality. Both preschoolers and adults reasoned that the intentions of the recipient would play a significant role in the probability of contracting an illness but only adults reasoned that the recipient having knowledge of the transmitter's intentions would have an impact on illness. Moreover, preschoolers (but not adults) judged that biological contaminants such as germs would interact with the intentionality of the recipient to increase the chances of contracting an illness whereas adults reasoned that psychological states can have a direct influence on the manifestation of illness. These results suggest that preschoolers and adults entertain a highly sophisticated and selective process when assessing, the impact of psychological factors such as intentionality on biological processes such as the origins of illness. [ABSTRACT FROM AUTHOR]

The present studies examined beliefs concerning the impact of psychosocial factors in the transmission of contagious illness, injuries, and disgust. In Studies I and 2, participants ranging from preschoolers through adults judged the likelihood that a character would get sick (or injured) after being contaminated by another individual who was either of no stated relation to the character or who was a best friend, a disliked person, or a family member. Studies 3 and 4 examined effects of psychosocial relatedness on judgments of disgust (a psychological response). Study 5 examined the influence of germs on judgments of disgust. Overall, preschoolers through 2nd graders judged that any type of relatedness decreased the possibility of contracting illness from another person. However, for disgust, preschoolers judged that negative contagion would have a more powerful effect, particularly in the presence of germs. Relatedness had no effect on judgments of injury transmission. These results suggest that young children treat the psychological and biological domains as distinct but mutually interacting. [ABSTRACT FROM AUTHOR]

Abstract: Chronic hypoxia (CH) present in infants with cyanotic congenital heart disease may be responsible for subsequent cognitive deficits seen in these children. In a rat model of CH [10% O2 between postnatal day (P) 3 and 28], we have demonstrated significant alterations in energy metabolism and excitatory neurotransmission in the developing hippocampus. These alterations may adversely affect dendritic morphology, which is a highly energy-dependent and excitatory neurotransmitter-mediated event, and hippocampus-mediated behaviors. We measured the apical segment length of dendrites in pyramidal neurons of the CA1 region of the hippocampus using microtubule-associated protein-2 (MAP-2) histochemistry on P28 while the animals were hypoxic (n =8 in CH and n =6 in control), and on P56 after the animals had been normoxic for 4 weeks (n =8/group). We also compared dorsal hippocampus-dependent trace fear conditioning and dorsal hippocampus-independent delay fear conditioning on P56. Developmental trajectory of the apical segment length was similar in CH and controls, decreasing between P28 and P56. However, when compared with the controls, the apical segment length was longer in the CH group on both P28 [55.11±2.30 μm (CH) vs. 40.52±1.20 μm (control), p <0.001] and P56 [44.01±1.56 μm (CH) vs. 31.75±1.31 μm (control), p <0.001], suggesting the persistence of an immature dendritic architecture. Both trace and delay fear conditioning were decreased in the CH group, suggesting functional abnormality beyond the dorsal hippocampus. These structural and functional alterations may contribute to the cognitive deficits seen in infants at risk for CH. [Copyright &y& Elsevier]

Generic noun phrases ("Birds lay eggs") are important for expressing knowledge about abstract kinds. The authors hypothesized that genericity would be part of gist memory, such that young children would appropriately recall whether sentences were presented as generic or specific. In 4 experiments, pre- schoolers and college students (N = 280) heard a series of sentences in either generic form (e.g., "Bears climb trees") or specific form (e.g., "This bear climbs trees") and were asked to recall the sentences following a 4-min distractor task. Participants in all age groups correctly distinguished between generic and specific noun phrases (NPs) in their recall, even when forgetting the details of the NP form. Memory for predicate content (e.g., "climb trees") was largely unaffected by genericity, although memory for category labels (e.g., "bear") was at times better for those who heard sentences with generic wording. Overall, these results suggest that generic form is maintained in long-term memory even for young children and thus may serve as the foundation for constructing knowledge about kinds. [ABSTRACT FROM AUTHOR]

The present set of studies examined children's and college students' recognition of the role of time in the manifestation of causes and cures for illnesses and injuries. In Study 1, participants ranging from 4-year-olds through college students were presented with biological, moral, psychological, and irrelevant causes for illness symptoms and were asked how much time elapsed between the cause and the symptom. They were also asked if medicine would make the person feel better and if so how much time elapsed between taking the medicine and feeling better. Study 2 replicated Study 1 with 4- and 5-year-olds. Study 3 examined whether 4- and 5-year-olds and college students could differentiate between physical and emotional reactions to illnesses and injuries, with regard to time course. Overall, young children underestimate how long it takes for illness symptoms to emerge (expecting them to result right away following exposure to contamination). Nonetheless, children generated longer timelines for biological cures than biological causes. Moreover, 4- and 5-year-olds expect physical and emotional reactions to follow different time courses. These results suggest that young children have a nascent expectation that biological events are distinct from non-biological events, in how they unfold over time. [ABSTRACT FROM AUTHOR]

Bronchopulmonary dysplasia is the most common pulmonary morbidity in preterm infants and is associated with chronic hypoxia. Animal studies have demonstrated structural, neurochemical and functional alterations due to chronic hypoxia in the developing brain. Long-term impairments in visual-motor, gross and fine motor, articulation, reading, mathematics, spatial memory and attention skills are prevalent in survivors of bronchopulmonary dysplasia, and impairments appear to correlate with the severity of hypoxia. However, due to the simultaneous occurrence of multiple neurodevelopmental risk factors, a primary or potentiating role for chronic hypoxia in these impairments has yet to be conclusively established. [ABSTRACT FROM AUTHOR]

Abstract: The cognitive deficits observed in children with cyanotic congenital heart disease suggest involvement of the developing hippocampus. Chronic postnatal hypoxia present during infancy in these children may play a role in these impairments. To understand the biochemical mechanisms of hippocampal injury in chronic hypoxia, a neurochemical profile consisting of 15 metabolite concentrations and 2 metabolite ratios in the hippocampus was evaluated in a rat model of chronic postnatal hypoxia using in vivo 1H NMR spectroscopy at 9.4 T. Chronic hypoxia was induced by continuously exposing rats (n = 23) to 10% O2 from postnatal day (P) 3 to P28. Fifteen metabolites were quantified from a volume of 9–11 μl centered on the left hippocampus on P14, P21, and P28 and were compared with normoxic controls (n = 14). The developmental trajectory of neurochemicals in chronic hypoxia was similar to that seen in normoxia. However, chronic hypoxia had an effect on the concentrations of the following neurochemicals: aspartate, creatine, phosphocreatine, GABA, glutamate, glutamine, glutathione, myo-inositol, N-acetylaspartate (NAA), phosphorylethanolamine, and phosphocreatine/creatine (PCr/Cr) and glutamate/glutamine (Glu/Gln) ratios (P &#60; 0.001 each, except glutamate, P = 0.04). The increased PCr/Cr ratio is consistent with decreased brain energy consumption. Given the well-established link between excitatory neurotransmission and brain energy metabolism, we postulate that elevated glutamate, Glu/Gln ratio, and GABA indicate suppressed excitatory neurotransmission in an energy-limited environment. Decreased NAA and phosphorylethanolamine suggest reduced neuronal integrity and phospholipid metabolism. The altered hippocampal neurochemistry during its development may underlie some of the cognitive deficits present in human infants at risk of chronic hypoxia. [Copyright &y& Elsevier]

The authors conducted 4 studies suggesting that children attribute different modes of transmission to genetic disorders and contagious illnesses. Study 1 presented preschoolers through 5th graders and adults with "switched-at-birth" scenarios for various disorders, Study 2 presented preschoolers with the same disorders but used contagion links in a contagion context; Studies 3 and 4 presented preschoolers and adults with novel (fictitious) illnesses to determine which cues participants would use to differentiate the modes of transmission. In the presence of kinship cues, children distinguished genetic disorders from contagious illnesses, but in the presence of contagion cues, preschoolers selectively applied contagious links primarily to contagious illnesses. With novel illnesses, preschoolers and adults inferred that permanent illnesses were more, likely to be transmitted by birth parents than by contagion. These results suggest that by the preschool years, children recognize that not all disorders are transmitted exclusively through germ contagion. [ABSTRACT FROM AUTHOR]

Forty-one Indian and American preschoolers, 48 first graders, 41 third graders, 43 fifth graders, and 48 college students were presented with vignettes that described symptoms of illnesses. Participants in both countries were presented with a biological, moral, psychological, and irrelevant choice for each of the illnesses. Results indicated that across all ages in both countries, the biological model was the most prominent. However, with increasing age Indian participants acknowledged significantly more moral and psychological causes than Americans. Participants' justifications revealed that Americans made explicit reference to germs whereas Indians primarily referred to contamination. This indicates that although the cultural backdrops between the two sets of populations are very different, there is a complex interaction of similarities and differences. [ABSTRACT FROM AUTHOR]

Three studies investigated developmental changes in immanent justice responding by asking participants to respond to vignettes in which a person's bad behaviour was followed by a negative consequence. Study 1 consisted of 152 sixth graders and 128 college students and presented participants with a vignette that examined the notion of bad people deserving to get ill. Study 2 consisted of 185 sixth graders and 154 college students and examined whether children and adults reasoned that that bad behaviour would actually cause the illness. Study 3 consisted of 96 third graders, 115 fifth graders, and 114 college students, and presented participants with vignettes that examined negative behaviours and consequences. Contrary to expectations based on traditional and contemporary developmental theories, all three studies demonstrated more evidence of immanent justice responding among adults than among elementary school children. These results call into question the comprehensiveness of traditional and contemporary developmental theories, and suggest the need to examine cognitive reasoning in adulthood when constructing developmental theories. [ABSTRACT FROM AUTHOR]

The authors investigated three seemingly contradictory views of the conception of illness: (a) the traditional, development "naive child" view; (b) a more contemporary, "sophisticated child" outlook; and (c) a largely social-psychological, "irrational adult" approach. They concluded that participants had a variety of views of the conception of illness and that they used different views in different experimental contexts. They found that, under certain conditions, children appeared to have sophisticated beliefs; under other conditions, children, and even adults, showed signs of folkloric and immanent justice reasoning. They also found that, with advancing grade level, children increasingly recognized psychological contributors to the cause of illness. [ABSTRACT FROM AUTHOR]

Though it was once known that upregulated Cannabinoid Receptor (CB1) and downregulated Fatty Acid Amide Hydrolase (FAAH1) are associated with tumour aggressiveness and metastasis, it is now clear that upregulated CB1 levels more than a certain point cause accumulation of ceramide and directs cells to apoptosis. Hence, CB1 analogues/FAAH1 blockers are explored widely as anticancer drugs. There are reports on CB1-agonists and FAAH1-blockers separately, however, dual activities along with ovarian cancer-specific links are not established for any natural compound. With this setting, we describe for the first time the isolation of 3-hydroxypropane-1,2-diyl dipalmitoleate (564.48 Da) from a marine snail, Conus inscriptus, which binds to both CB1 and FAAH1 (glide energies: −70.61 and −30.52 kcal/mol, respectively). MD simulations indicate stable compound–target interaction for a minimum of 50 nanoseconds with relative invariabilities in Rg. The compound inhibited ovarian cancer cell line, PA1 at 1.7 μM. Structural and chemical interpretation of the compound (C2) was done using FT-IR, GC-MS, ESI-MS, 1H and 13C-NMR (1 and 2D). Furthermore, a probable route for gram-scale synthesis of C2 is hinted herein. With the available preliminary data, molecular mechanisms involving dual roles for this potent molecule must be elucidated to understand the possibilities of usage as an anticancer drug. [ABSTRACT FROM AUTHOR]

Addresses the development of network management paradigm as part of open system interconnection (OSI) standards and emphasizes its three aspects. Advantages of the network management paradigm; Management functions; Management protocols; Prognosis and summary of the study.

Calcium channel blocker (CCB) toxicity is associated with refractory hypotension and can be fatal. A 13 year old young woman presented to the emergency department(ED) six hours after an intentional overdose of amlodipine, barbiturates, and alcohol. She remained extremely hypotensive despite the administration of normal saline and calcium chloride and despite infusions of norepinephrine, epinephrine, insulin, and dextrose. Due to increasing evidence of end organ dysfunction, Extracorporeal Life Support (ECLS) was initiated 9 hours after presentation to the ED. The patient's blood pressure and end organ function immediately improved after cannulation. She was successfully decannulated after 57 hours of ECLS and was neurologically intact. Patients with calcium channel blocker overdose who are resistant to medical interventions may respond favorably to early ECLS. [ABSTRACT FROM AUTHOR]

• Weight gain is due to unhealthy foods rather than engaging in unhealthy activities. • Three year olds do not make a food/activity distinction for height or weight. • Four and 5 year olds think foods primarily cause height and weight differences. • Results suggest that the role of foods tends to predominate in people's conceptions of body size. Despite the important ways that both food and physical activities influence body size, much prior research has focused exclusively on children's concepts of food. The present studies address this issue by comparing preschoolers' (N = 128) and adults' (N = 64) understanding of the causal consequences of different foods and activities on height and weight. Participants were asked to make predictions (Study 1) or provide explanations (Study 2). Three- to 5-year-olds predicted heavier weight more on the basis of unhealthy foods than unhealthy activities, but did not differentiate their predictions about height on the basis of food or activity. We also found that 4- and 5-year-olds, but not 3-year-olds, explained differences in weight and height more on the basis of food than on the basis of activity. Together, these results suggest that children's and adults' strongest links were between unhealthy food and greater weight, suggesting that the role of food tends to predominate in people's conceptions of body size. [ABSTRACT FROM AUTHOR]

Background: The high-quality evidence on managing COVID-19 patients requiring extracorporeal membrane oxygenation (ECMO) support is insufficient. Furthermore, there is little consensus on allocating ECMO resources when scarce. The paucity of evidence and the need for guidance on controversial topics required an international expert consensus statement to understand the role of ECMO in COVID-19 better. Twenty-two international ECMO experts worldwide work together to interpret the most recent findings of the evolving published research, statement formulation, and voting to achieve consensus. Objectives: To guide the next generation of ECMO practitioners during future pandemics on tackling controversial topics pertaining to using ECMO for patients with COVID-19-related severe ARDS. Methods: The scientific committee was assembled of five chairpersons with more than 5 years of ECMO experience and a critical care background. Their roles were modifying and restructuring the panel's questions and, assisting with statement formulation in addition to expert composition and literature review. Experts are identified based on their clinical experience with ECMO (minimum of 5 years) and previous academic activity on a global scale, with a focus on diversity in gender, geography, area of expertise, and level of seniority. We used the modified Delphi technique rounds and the nominal group technique (NGT) through three face-to-face meetings and the voting on the statement was conducted anonymously. The entire process was planned to be carried out in five phases: identifying the gap of knowledge, validation, statement formulation, voting, and drafting, respectively. Results: In phase I, the scientific committee obtained 52 questions on controversial topics in ECMO for COVID-19, further reviewed for duplication and redundancy in phase II, resulting in nine domains with 32 questions with a validation rate exceeding 75% (Fig. 1). In phase III, 25 questions were used to formulate 14 statements, and six questions achieved no consensus on the statements. In phase IV, two voting rounds resulted in 14 statements that reached a consensus are included in four domains which are: patient selection, ECMO clinical management, operational and logistics management, and ethics. Conclusion: Three years after the onset of COVID-19, our understanding of the role of ECMO has evolved. However, it is incomplete. Tota14 statements achieved consensus; included in four domains discussing patient selection, clinical ECMO management, operational and logistic ECMO management and ethics to guide next-generation ECMO providers during future pandemic situations. [ABSTRACT FROM AUTHOR]

Background: Children with congenital and acquired heart disease are at a higher risk of cardiac arrest compared to those without heart disease. Although the monitoring of cardiopulmonary resuscitation quality and extracorporeal resuscitation technologies have advanced, survival after cardiac arrest in this population has not improved. Cardiac arrest prevention, using predictive algorithms with machine learning, has the potential to reduce cardiac arrest rates. However, few studies have evaluated the use of these algorithms in predicting cardiac arrest in children with heart disease. Methods: We collected demographic, laboratory, and vital sign information from the electronic health records (EHR) of all the patients that were admitted to a single-center pediatric cardiac intensive care unit (CICU), between 2010 and 2019, who had a cardiac arrest during their CICU admission, as well as a comparator group of randomly selected non-cardiac-arrest controls. We compared traditional logistic regression modeling against a novel adaptation of a machine learning algorithm (functional gradient boosting), using time series data to predict the risk of cardiac arrest. Results: A total of 160 unique cardiac arrest events were matched to non-cardiac-arrest time periods. Using 11 different variables (vital signs and laboratory values) from the EHR, our algorithm's peak performance for the prediction of cardiac arrest was at one hour prior to the cardiac arrest (AUROC of 0.85 [0.79,0.90]), a performance that was similar to our previously published multivariable logistic regression model. Conclusions: Our novel machine learning predictive algorithm, which was developed using retrospective data that were collected from the EHR and predicted cardiac arrest in the children that were admitted to a single-center pediatric cardiac intensive care unit, demonstrated a performance that was similar to that of a traditional logistic regression model. While these results are encouraging, future research, including prospective validations with multicenter data, is warranted prior to the implementation of this algorithm as a real-time clinical decision support tool. [ABSTRACT FROM AUTHOR]

Impacted pediatric tracheobronchial thrombus is an uncommon diagnosis. There are no clearly proven therapeutic options for airway casts due to a similar process, plastic bronchitis. Cryotherapy, specifically cryoextraction, has shown potential as a therapeutic option in adults with tracheobronchial thrombus and cast. We describe the novel application of this method in a complex pediatric patient. [ABSTRACT FROM AUTHOR]

Objectives: This project aims to describe brain injuries on routine neuroimaging in a large single-center neonatal and pediatric cohort supported by extracorporeal membrane oxygenation. The study also aims to examine the association of these injuries with neurocognitive outcomes in survivors and identify laboratory findings associated with neurologic injury.Design: Retrospective observational single-center cohort study.Setting: Tertiary care PICU.Patients: Pediatric patients with noncardiac indications for extracorporeal membrane oxygenation supported by venoarterial or venovenous extracorporeal membrane oxygenation, with on-extracorporeal membrane oxygenation brain CT or postextracorporeal membrane oxygenation brain CT/MRI.Interventions: Extracorporeal membrane oxygenation support.Measurements and Main Results: Occurrence of brain injury on CT and MRI was reviewed; injuries were scored. Clinical and laboratory results associated with injury were identified. Survivor neurocognitive outcomes were obtained using the Pediatric Overall Performance Category scale and Pediatric Cerebral Performance Category scale. Of 132 imaged patients, 98 (74%) had radiological evidence of brain injury. Mean injury score was 6.5 (± 3.8). Head ultrasounds and clinician suspicion performed poorly in suspecting the presence of injury. Of 104 respondents to neurodevelopmental assessments, 61 (59%) had normal scores; 12.5%, 17%, and 11.5% had mild, moderate, or severe disability. A neuroimaging score greater than 10 was associated with an unfavorable outcome on the Pediatric Cerebral Performance Category (odds ratio, 3.4; p < 0.01) and Pediatric Overall Performance Category (odds ratio, 1.7; p < 0.05). Ischemic injury correlated with worse neurodevelopmental outcome. Preextracorporeal membrane oxygenation lactate, Vasoactive-Inotropic Scores, transaminitis, elevated bilirubin and creatinine levels, and thrombocytopenia were associated with injury occurrence.Conclusions: Brain injury is frequent in extracorporeal membrane oxygenation patients, although the majority of survivors have favorable neurocognitive outcomes. More research is needed in order to understand the etiology of such injuries. Head ultrasound and clinician suspicion are not sensitive in detecting extracorporeal membrane oxygenation-related brain injuries. Protocolizing postextracorporeal membrane oxygenation imaging with brain MRI allows the identification of injuries and provision of timely neurocognitive intervention. [ABSTRACT FROM AUTHOR]

Pre-arrest morbidity in adults who suffer out-of-hospital cardiac arrest (OHCA) is associated with increased mortality and poorer neurologic outcomes. The objective of this study was to determine if a similar association is seen in pediatric patients. We performed a secondary analysis of data from the Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital trial. Study sites included 36 pediatric intensive care units across the United States and Canada. The study enrolled children between the ages of 48 hours and 18 years following an OHCA between September 1, 2009 and December 31, 2012. For our analysis, patients with (N = 151) and without (N = 142) pre-arrest comorbidities were evaluated to assess morbidity, survival, and neurologic function following OHCA. No significant difference in 28-day survival was seen between groups. Dependence on technology and neurobehavioral outcomes were assessed among survivors using the Vineland Adaptive Behavior Scales-Second Edition (VABS-II), Pediatric Cerebral Performance Category (PCPC) and Pediatric Overall Performance Category (POPC). Children with pre-existing comorbidities maintained worse neurobehavioral function at twelve months, evidenced by poorer scores on POPC (p = 0.016), PCPC (p = 0.044), and VABS-II (p = 0.020). They were more likely to have a tracheostomy at hospital discharge (p = 0.034), require supplemental oxygen at three months (p = 0.039) and twelve months (p = 0.034), and be mechanically ventilated at twelve months (p = 0.041). There was no difference in survival to 28 days following OHCA in children with pre-existing comorbidity compared to previously healthy children. The group with pre-existing comorbidity was more reliant on technology following arrest and exhibited worse neurobehavioral outcomes. [ABSTRACT FROM AUTHOR]

Many languages distinguish generic utterances (e.g., 'Tigers are ferocious') from non-generic utterances (e.g., 'Those tigers are ferocious'). Two studies examined how generic language specially links properties and categories. We used a novel-word extension task to ask if 4- to 5-year-old children and adults distinguish between generic and specific language, and judge that predicating a property of a depicted novel animal using generic language (e.g., 'Bants have stripes'), rather than non-generic language (e.g., 'This bant has stripes') implies a more kind-relevant connection between category and property. Participants were asked to endorse an extension of the label taught to a novel animal matching the target instance on either overall similarity or the mentioned property. Wording was found to have a significant effect on responses for both age groups. Altogether, the results of these studies suggest that the generic may be a default interpretation for young children, who need to learn the semantics of specific and set-theoretic expressions. [ABSTRACT FROM AUTHOR]

Objective: The goal of this work is to provide insight into survival and neurologic outcomes of pediatric patients supported with extracorporeal cardiopulmonary resuscitation.Data Sources: A systematic search of Embase, PubMed, Cochrane, Scopus, Google Scholar, and Web of Science was performed from January 1990 to May 2020.Study Selection: A comprehensive list of nonregistry studies with pediatric patients managed with extracorporeal cardiopulmonary resuscitation was included.Data Extraction: Study characteristics and outcome estimates were extracted from each article.Data Synthesis: Estimates were pooled using random-effects meta-analysis. Differences were estimated using subgroup meta-analysis and meta-regression. The Meta-analyses Of Observational Studies in Epidemiology guideline was followed and the certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation system. Twenty-eight studies (1,348 patients) were included. There was a steady increase in extracorporeal cardiopulmonary resuscitation occurrence rate from the 1990s until 2020. There were 32, 338, and 1,094 patients' articles published between 1990 and 2000, 2001 and 2010, and 2010 and 2020, respectively. More than 70% were cannulated for a primary cardiac arrest. Pediatric extracorporeal cardiopulmonary resuscitation patients had a 46% (CI 95% = 43-48%; p < 0.01) overall survival rate. The rate of survival with favorable neurologic outcome was 30% (CI 95% = 27-33%; p < 0.01).Conclusions: The use of extracorporeal cardiopulmonary resuscitation is rapidly expanding, particularly for children with underlying cardiac disease. An overall survival of 46% and favorable neurologic outcomes add credence to this emerging therapy. [ABSTRACT FROM AUTHOR]

Recently DNA sequencing analysis has played a vital role in the unambiguous diagnosis of clinically suspected patients with Duchenne Muscular Dystrophy (DMD). DMD is a monogenic, X-linked, recessive, degenerative pediatric neuromuscular disorder affecting males, invariably leading to fatal cardiopulmonary failure. Early and precise diagnosis of the disease is an essential part of an effective disease management strategy as care guidelines and prevention through counseling need to be initiated at the earliest particularly since therapies are now available for a subset of patients. In this manuscript we report the DMD gene mutational profiles of 961 clinically suspected male DMD patients, 99% of whom were unrelated. We utilized a molecular diagnostic approach which is cost-effective for most patients and follows a systematic process that sequentially involves identification of hotspot deletions using mPCR, large deletions and duplications using MLPA and small insertions/ deletions and point mutations using an NGS muscular dystrophy gene panel. Pathogenic DMD gene mutations were identified in 84% of patients. Our data compared well with the frequencies and distribution of deletions and duplications reported in the DMD gene in other published studies. We also describe a number of rare in-frame mutations, which appeared to be enriched in the 5' proximal hotspot region of the DMD gene. Furthermore, we identified a family with a rare non-contiguous deletion mutation in the DMD gene where three males were affected and two females were deemed carriers. A subset of patients with mutations in the DMD gene who are likely to benefit therapeutically from new FDA and EMA approved drugs were found in our cohort. Given that the burden of care for DMD patients invariably falls on the mothers, particularly in rural India, effective genetic counseling followed by carrier screening is crucial for prevention of this disorder. We analyzed the carrier status of consented female relatives of 463 probands to gauge the percentage of patients with familial disease. Our analysis revealed 43.7% of mothers with DMD gene mutations. Our comprehensive efforts, involving complete genetic testing coupled with compassionate genetic counseling provided to DMD patients and their families, are intended to improve the quality of life of DMD patients and to empower carrier females to make informed reproductive choices to impede the propagation of this deadly disease. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this position paper is two-fold: first, to describe the state of extracorporeal membrane oxygenation education worldwide, noting current limitations and challenges; and second, to put forth an educational agenda regarding opportunities for an international collaborative approach toward standardization.Design: Relevant medical literature was reviewed through literature search, and materials from national organizations were accessed through the Internet. Taskforce members generated a consensus statement using an iterative consensus process through teleconferences and electronic communication.Setting: In 2018, the Extracorporeal Life Support Organization convened the ECMOed Taskforce at two structured, face-to-face meetings of 40 healthcare practitioners and educators with expertise in caring for the extracorporeal membrane oxygenation patient and in extracorporeal membrane oxygenation education.Patients: None.Interventions: None.Measurements and Main Results: The ECMOed Taskforce identified seven educational domains that would benefit from international collaborative efforts. Of primary importance, the Taskforce outlined actionable items regarding 1) the creation of a standardized extracorporeal membrane oxygenation curriculum; 2) defining criteria for an extracorporeal membrane oxygenation course as a vehicle for delivering the curriculum; 3) outlining a mechanism for evaluating the quality of educational offerings; 4) utilizing validated assessment tools in the development of extracorporeal membrane oxygenation practitioner certification; and 5) promoting high-quality educational research to guide ongoing educational and competency assessment development.Conclusions: Significant variability and limitations in global extracorporeal membrane oxygenation education exist. In this position paper, we outline a road map for standardizing international extracorporeal membrane oxygenation education and practitioner certification. Ongoing high-quality educational research is needed to evaluate the impact of these initiatives. [ABSTRACT FROM AUTHOR]

Background: Foreign body aspiration (FBA) is a common cause of morbidity and mortality in children < 3 years of age. Guidelines recommend performing a bronchoscopy in any suspected or confirmed FBA. Extracorporeal membrane oxygenation (ECMO) can be used as a rescue mode of support in children with life-threatening FBA for stabilization before, during, and after removal.Case Report: We present a series of children with life-threatening FBA who were placed on ECMO for stabilization before or after FB removal and a review of the literature and the Extracorporeal Life Support Organization database. Foreign bodies were removed without complications, and all patients survived ECMO support and were promptly discharged home. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: ECMO can be safely used in the stabilization of children with life-threatening FBA before, during, and after bronchoscopic removal. ECMO should be considered in the stabilization of children presenting with FBA to facilitate removal. [ABSTRACT FROM AUTHOR]

Objectives: Extracorporeal membrane oxygenation provides short-term cardiopulmonary life support, but is associated with peripheral innate inflammation, disruptions in cerebral autoregulation, and acquired brain injury. We tested the hypothesis that extracorporeal membrane oxygenation also induces CNS-directed adaptive immune responses which may exacerbate extracorporeal membrane oxygenation-associated brain injury.Design: A single center prospective observational study.Setting: Pediatric and cardiac ICUs at a single tertiary care, academic center.Patients: Twenty pediatric extracorporeal membrane oxygenation patients (0-14 yr; 13 females, 7 males) and five nonextracorporeal membrane oxygenation Pediatric Logistic Organ Dysfunction score matched patients INTERVENTIONS:: None.Measurements and Main Results: Venous blood samples were collected from the extracorporeal membrane oxygenation circuit at day 1 (10-23 hr), day 3, and day 7 of extracorporeal membrane oxygenation. Flow cytometry quantified circulating innate and adaptive immune cells, and CNS-directed autoreactivity was detected using an in vitro recall response assay. Disruption of cerebral autoregulation was determined using continuous bedside near-infrared spectroscopy and acquired brain injury confirmed by MRI. Extracorporeal membrane oxygenation patients with acquired brain injury (n = 9) presented with a 10-fold increase in interleukin-8 over extracorporeal membrane oxygenation patients without brain injury (p < 0.01). Furthermore, brain injury within extracorporeal membrane oxygenation patients potentiated an inflammatory phenotype in adaptive immune cells and selective autoreactivity to brain peptides in circulating B cell and cytotoxic T cell populations. Correlation analysis revealed a significant relationship between adaptive immune responses of extracorporeal membrane oxygenation patients with acquired brain injury and loss of cerebral autoregulation.Conclusions: We show that pediatric extracorporeal membrane oxygenation patients with acquired brain injury exhibit an induction of pro-inflammatory cell signaling, a robust activation of adaptive immune cells, and CNS-targeting adaptive immune responses. As these patients experience developmental delays for years after extracorporeal membrane oxygenation, it is critical to identify and characterize adaptive immune cell mechanisms that target the developing CNS. [ABSTRACT FROM AUTHOR]

Objective: To evaluate risk factors for hemolysis in pediatric extracorporeal life support. Design: Retrospective, single-center study. Setting: Pediatric intensive care unit. Patients: Two hundred thirty-six children who received extracorporeal membrane oxygenation. Interventions: None. Measurements and Main Results: Risk factors for hemolysis were retrospectively analyzed from a single center in a total of 236 neonatal and pediatric patients who received extracorporeal membrane oxygenation support (ECMO). There was no difference in the incidence of hemolysis between centrifugal (127 patients) and roller head (109 patients) pump type or between venoarterial and venovenous ECMO. High hemoglobin (Hb) was found to be an independent risk factor for hemolysis in both pump types. The Hb level >12 g/dL was significant in the roller group and the Hb level >13 g/dL was significant in the centrifugal group for the development of hemolysis for the cumulative ECMO run. The presence of high Hb levels on any given day increased the risk of hemolysis for that day of the ECMO run regardless of ECMO pump type. Higher revolutions per minute (RPMs) and higher inlet pressures on any given day increased the risk for the development of hemolysis in the centrifugal pump. Lower inlet venous pressures and RPMs were not associated with hemolysis in the roller group. Conclusions: An Hb level greater than 13 g/dL was associated with an increased risk of hemolysis, and a high Hb on a given day was associated with a significantly higher risk of hemolysis on the same day. Higher RPMs and lower inlet venous pressures were associated with an increased risk of hemolysis in the centrifugal pump only. [ABSTRACT FROM AUTHOR]

To analyze the association between hypothermia and neurologic complications among children who were treated with extracorporeal cardiopulmonary resuscitation (ECPR) using the Extracorporeal Life Support Organization (ELSO) international registry. We conducted a retrospective, multicenter, database study utilizing ELSO data for ECPR encounters from January 1, 2011, through December 31, 2019. Exclusion criteria included multiple ECMO runs and lack of variable data. The primary exposure was hypothermia under 34 °C for greater than 24 hours. The primary outcome, determined a priori, was a composite of neurologic complications defined by ELSO registry including brain death, seizures, infarction, hemorrhage, diffuse ischemia. Secondary outcomes were mortality on ECMO and mortality prior to hospital discharge. Multivariable logistic regression determined the odds of neurologic complications, mortality on ECMO or prior to hospital discharge associated with hypothermia after adjustment for available pertinent covariables. Of the 2,289 ECPR encounters, no difference in odds of neurologic complications were found between the hypothermia and non-hypothermia groups (AOR 1.10, 95% CI 0.80–1.51). However, hypothermia exposure was associated with decreased odds of mortality on ECMO (AOR 0.76, 95% CI 0.59–0.97), but no difference in mortality prior to hospital discharge (AOR 0.96, 95% CI 0.76–1.21) Analysis of a large, multicenter, international dataset demonstrates that hypothermia for greater than 24 hours among children who undergo ECPR is not associated with decreased neurologic complications or mortality benefit at time of hospital discharge. [ABSTRACT FROM AUTHOR]

Chronic hypoxia (CH), a disease state that accounts for significant morbidity and mortality in pediatrics, occurs in many children during critical periods of hippocampal development and cortical myelination. Hippocampal neurogenesis occurs throughout postnatal life and is important for normal development, thus impairment results in long-term cognitive deficits. Erythropoietin (EPO), a drug commonly known for its role in erythrogenesis, has recently been evaluated in neuroprotection in neonatal injury models and preterm brain injury. However, the effects of EPO therapy on hippocampal neurogenesis and myelination in pediatric CH are unknown. We show that CH decreases hippocampal neurogenesis in a pediatric mouse model. This decrease in early and late progenitors, and actively dividing cells is rescued with EPO treatment. Furthermore, we show that CH during this critical time decreases oligodendrocyte progenitor (OPC) populations in the cortex, leading to defective myelination. However, EPO therapy is only able to rescue the OPC but not the loss of mature myelin. Overall, our findings demonstrate that CH in developing mice has significant effects on hippocampal neurogenesis and OPCs, which can be rescued with EPO treatment. Future studies should confirm the role of this FDA-approved therapy in neuroprotection in at-risk pediatric populations. [ABSTRACT FROM AUTHOR]

Background: Marine sponges are important sources of bioactive compounds. Objective: This study investigated the anticancer properties of Hyattella cribriformis ethyl acetate (EA) fraction in various cancer and normal cell lines. Materials and Methods: anticancer assay was carried out in 15 cell lines to evaluate the anticancer potential of the EA fraction. Impact on cell cycle distribution was determined using flow cytometry. The fraction was investigated for interfering microtubules assembly in both in vitro and cellular assay. Further studies were conducted to determine the fraction induced cell death (apoptosis) using calcein/propidium iodide dual staining, activated caspase-3 and phosphorylation of Bcl-2 protein at Ser70. DNA fragmentation assay was performed to confirm the apoptosis. Results: EA fraction exhibited potent inhibition of cancer cell growth and resulted in 50% growth inhibition (GI50) of 0.27 μg/mL in A673 cell line. Sarcoma (MG-63, Saos-2) and ovarian (SK-OV-3 and OVCAR-3) cancer cell lines also showed superior anticancer activity GI50 of 1.0 μg/mL. Colon and breast cancer cell lines exhibited moderate GI compare other cancer cell lines and normal human lung fibroblast showed GI50 of 15.6 μg/mL. EA fraction showed potent G2/M phase arrest in A673 cell line and induced apoptosis at 48 h exposure. EA fraction promoted microtubule polymerization in tubulin polymerization assay and increased level of polymerized tubulin in the HeLa cells. Fraction induced the activation of caspase-3 and phosphorylation of Bcl-2 anti-apoptotic protein. Fraction induced DNA fragmentation in HeLa cells as evidence of apoptosis. Conclusion: Marine sponge H. cribriformis EA fraction exhibited potent anticancer activity through tubulin polymerization and induction of apoptosis. [ABSTRACT FROM AUTHOR]

Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency due to mutations in the WAS gene expressed in hematopoietic cells. Hematopoietic stem cell transplantation (HSCT) is the treatment of choice when an appropriate human leukocyte antigen-matched donor is available. The use of the extracorporeal membrane oxygenation (ECMO) circuit to infuse donor cells for HSCT has not been previously published in the literature. We describe a case of a child who had successful engraftment after HSCT with infusion of the donor stem cells through the ECMO circuit. [ABSTRACT FROM AUTHOR]

Generic noun phrases (e.g., "Bats live in caves") are important for expressing knowledge about abstract kinds. Past work has found that parents frequently use generic noun phrases in their speech to young children. However, little is known regarding how children understand these expressions, nor which cues signal generic meaning. The present set of 5 studies examined the influence of linguistic form class (e.g., "What color are dogs?" [generic] versus "What color are the dogs?" [nongeneric]) and of pragmatic context (e.g., "What color are they?" in the presence of either a single exemplar [generic] or multiple exemplars [nongeneric]). Participants were 2-year-olds (N = 42), 3-year-olds (N = 40), 4-year-olds (N = 40), and adults (N = 51). The data indicate that by 2 years of age, children use linguistic form class, and by 3 years of age, children use pragmatic context. These findings demonstrate that young children have begun to understand the distinction between generic and nongeneric noun phrases from a very young age, and that identification of generics is signaled not by formal or pragmatic cues alone, but by a combination of information from both language form and pragmatic context. It is suggested that children make use of multiple linguistic and conceptual cues to acquire and interpret generics. [ABSTRACT FROM AUTHOR]

The transition from control modes to spontaneous modes is ubiquitous for mechanically ventilated patients yet there is little data describing the changes and patterns that occur to breathing during this transition for patients on ECMO. We identified high fidelity data among a diverse cohort of 419 mechanically ventilated patients on ECMO. We examined every ventilator change, describing the differences in >30,000 sets of original ventilator observations, focused around the time of transition from control modes to spontaneous modes. We performed multivariate regression with mixed effects, clustered by patient, to examine changes in ventilator characteristics within patients, including a subset among patients with low compliance (<30 milliliters (mL)/centimeters water (cmH2O)). We found that during the transition to spontaneous modes among patients with low compliance, patients exhibited greater tidal volumes (471 mL (364,585) vs. 425 mL (320,527); p < 0.0001), higher respiratory rate (23 breaths per minute (bpm) (18,28) vs. 18 bpm (14,23); p = 0.003), greater mechanical power (elastic component) (0.08 mL/(cmH2O × minute) (0.05,0.12) vs. 0.05 mL/(cmH2O × minute) (0.02,0.09); p < 0.0001) (range 0 to 1.4), and lower positive end expiratory pressure (PEEP) (6 cmH2O (5,8) vs. 10 cmH2O (8,11); p < 0.0001). For patients on control modes, the combination of increased tidal volume and increased respiratory rate was temporally associated with significantly low partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio (p < 0.0001). These changes in ventilator parameters warrant prospective study, as they may be associated with worsened lung injury. [ABSTRACT FROM AUTHOR]

Post-cardiotomy extracorporeal life support (PC-ECLS) has seen a substantial increase in use over the past 10 years. PC-ECLS can be a life-saving procedure and is mostly applied in the presence of unexpected, severe cardio-respiratory complication. Despite PC-ECLS being critical in allowing for organ recovery, it is unfortunately closely connected with an unpredictable outcomes, high morbidity, and, even in the case of cardiac function improvement, potential sustained disabilities that have a life-changing impact for the patient and his or her family. Since the decision to start PC-ECLS is made in an acute setting, there is often only limited or no time for self-determined choices. Due to the major impact of the intervention, it would be highly desirable to obtain informed consent before starting PC-ECLS, since the autonomy of the patient and shared-decision making are two of the most important ethical values in modern medicine. Recent developments regarding awareness of the impacts of a prolonged intensive care stay make this a particularly relevant topic. Therefore, it would be desirable to develop a structural strategy that takes into account the likelihood of such an intervention and the wishes and preferences of the patient, and thus the related autonomy of the patient. This article proposes key points for such a strategy in the form of a PC-ECLS informed consent, a do-(not-)mechanical-circulatory-support order (D(N)MCS), and specific guidelines to determine the extent of the shared decision making. The concept presented in this article could be a starting point for improved and ethical PC-ECLS treatment and application. [ABSTRACT FROM AUTHOR]

Brain injury is a significant source of morbidity and mortality for pediatric patients treated with Extracorporeal Membrane Oxygenation (ECMO). Our objective was to utilize neural networks to predict radiographic evidence of brain injury in pediatric ECMO-supported patients and identify specific variables that can be explored for future research. Data from 174 ECMO-supported patients were collected up to 24 h prior to, and for the duration of, the ECMO course. Thirty-five variables were collected, including physiological data, markers of end-organ perfusion, acid-base homeostasis, vasoactive infusions, markers of coagulation, and ECMO-machine factors. The primary outcome was the presence of radiologic evidence of moderate to severe brain injury as established by brain CT or MRI. This information was analyzed by a neural network, and results were compared to a logistic regression model as well as clinician judgement. The neural network model was able to predict brain injury with an Area Under the Curve (AUC) of 0.76, 73% sensitivity, and 80% specificity. Logistic regression had 62% sensitivity and 61% specificity. Clinician judgment had 39% sensitivity and 69% specificity. Sequential feature group masking demonstrated a relatively greater contribution of physiological data and minor contribution of coagulation factors to the model's performance. These findings lay the foundation for further areas of research directions. [ABSTRACT FROM AUTHOR]

The goal of this project was to evaluate if severity of electroencephalogram (EEG) during or shortly after being placed on extracorporeal membrane oxygenation (ECMO) would correlate with neuroimaging abnormalities, and if that could be used as an early indicator of neurologic injury. This was a retrospective chart review spanning November 2009 to May 2018. Patients who had an EEG recording during ECMO or within 48 hours after being decannulated (early group) or within 3 months of being on ECMO (late group) were included if they also had ECMO-related neuroimaging. In the early EEG group, severity of the EEG findings of mild, moderate, and severe EEG correlated to mild, moderate, and severe neuroimaging scores. Patients on venoarterial (VA) ECMO were noted to have higher EEG and neuroimaging severity; this was statistically significant. There was no association in the late EEG group to neuroimaging abnormalities. Our study highlights that EEG severity can be an early predictor for neuroimaging abnormalities that can be identified by computed tomography (CT) and or magnetic resonance imaging (MRI). This can provide guidance for both the medical team and families, allowing for a better understanding of overall prognosis. [ABSTRACT FROM AUTHOR]