The Safety and Efficacy of Early Enteral Nutrition After Paediatric Enterostomy Closure - The EPOC Study.

INTRODUCTION: Keeping children nil by mouth until return of bowel function after intestinal anastomosis surgery is said to reduce complications. Fasting may extend up to five days, risking malnourishment and usage of parenteral nutrition. This study aims to establish the efficacy and safety of early enteral nutrition in children undergoing intestinal stoma closure. METHODOLOGY: A retrospective cohort study of children aged three months to 16 years who underwent an intestinal stoma closure between 1/1/2019 and 31/12/2021 at two tertiary paediatric hospitals was undertaken. Children fed clear fluids within 24 h (EEN) were compared to those commencing feeds later (LEN). The primary outcome was length of post-operative stay (LOS) and secondary outcomes included: time to feeds; time to stool; and complications. RESULTS: Of the 129 children that underwent a stoma closure, 69 met inclusion criteria: 35 (51 %) in the LEN group and 34 (49 %) in the EEN group. Children in the EEN group had a significantly shorter LOS (92.6 h vs 121.7 h, p = 0.0045). Early feeding was also associated with a significantly decreased time to free fluids (p < 0.001) and full enteral intake (p = 0.007). There was no significant intergroup difference in complications. CONCLUSION: Commencing feeding within 24 h of stoma closure is efficacious and safe, with clear reductions in LOS, time to full feeds and time to stool, and no increase in complications. Further research is required to extrapolate these findings to other populations. LEVEL OF EVIDENCE: III.

A Case Report of Impacted Fecalith Within Mucosal Pouch: An Unusual Cause of Colocolic Intussusception.

Intussusception involving the colon is unusual in adults and when present is managed with resection due to the risk of malignancy. We present an unusual case where the intussusceptum was impacted stool in a mucosal pouch in the transverse colon. The patient presented with bleeding per rectum and abdominal pain and was found to have a colocolic intussusception on computed tomography. Colonoscopy showed an ulcerated mass in the transverse colon. A laparoscopic right hemicolectomy was performed. Histopathology demonstrated known chronic lymphocytic leukemia, but not solid malignancy. A large fecalith impacted within a mucosal pouch had acted as the lead point. This represents a highly unusual but benign cause of intussusception.

Low-flow vascular malformations of the hand and forearm: a multidisciplinary experience in a tertiary paediatric centre.

BACKGROUND: Vascular malformations (VMs) involving the hand and forearm in children provide management challenges due to complex anatomy, indispensable functionality and developmental implications. METHODS: The institution's Vascular Registry was searched for patients with hand and arm VMs, supplemented by chart review of included patients. RESULTS: Twenty-one patients were identified, 52% male, with mean presenting age 5.2 years. Venous malformations predominated (71%), followed by lymphatic-venous (19%), lymphatic (5%) and glomuvenous (5%). Symptoms included pain (76%), swelling (71%), cosmetic concerns (81%), functional compromise (29%) and stiffness (5%). Imaging modality was ultrasound (100%), and magnetic resonance imaging (71%). Treatment included compression (62%), sclerotherapy (62%) and surgery (24%). Post-sclerotherapy ultrasounds showed complete sclerosis (25%), near complete sclerosis (58%) and partial sclerosis (17%). Post-surgery, patients reported improved cosmesis (80%), size (100%), pain (60%) and function (40%). Complications occurred in 24%, including bleeding, digital ischaemia and thrombosis. Mean follow-up was 3.4 years. CONCLUSION: Children with low-flow VMs of the hand and forearm experience significant symptoms and functional limitations. A multidisciplinary approach to management ensures optimal outcomes.

Early enteral feeding after pediatric abdominal surgery: A systematic review of the literature.

INTRODUCTION: Traditionally enteral nutrition has been delayed following abdominal surgery in children, to prevent complications. However, recent evidence in the adult literature refutes the supposed benefits of fasting and suggests decreased complications with early enteral nutrition (EEN). This review aimed to compile the evidence for EEN in children in this setting. METHODS: Databases Pubmed, EmBase, Medline and reference lists were searched for articles containing relevant search terms according to PRISMA guidelines. First and second authors reviewed abstracts. Studies containing patients less than 18 years undergoing abdominal surgery, with feeding initiated earlier than standard practice, were included. Studies including pyloromyotomy were excluded. Primary outcome was length of stay (LOS). Secondary outcomes included time to full enteral nutrition, time to stool and postoperative complications. RESULTS: Fourteen articles met inclusion criteria - five on neonatal abdominal surgery, three on gastrostomy formation and six on intestinal anastomoses. There were three randomized control trials (RCTs), five cohort studies, four historical control trials, one nonrandomized trial and one case series. Nine studies showed a decreased LOS with EEN. Most studies which reported time to full enteral nutrition showed improvement with EEN; however, time to stool was similar in most studies. Postoperative complications were either decreased or not statistically different in EEN groups in all studies. CONCLUSION: Studies to date in a limited number of procedures suggest EEN appears safe and effective in children undergoing abdominal surgery. Although robust evidence is lacking, there are clear benefits in LOS and time to full feeds, and no increase in complications. LEVEL OF EVIDENCE: IV.

Lymphopaenia in the diagnosis of paediatric appendicitis: a false sense of security?

BACKGROUND: Appendicitis is a common indication for emergent surgery in children; however, it is a small proportion of presentations with abdominal pain. As viral illness is a common differential diagnosis, lymphopaenia is used by some as a predictor against appendicitis. Furthermore, neutrophil-lymphocyte ratio (NLR) has been found to predict appendicitis. We aimed to verify if lymphopaenia predicted against appendicitis in children. METHODS: Retrospective review was conducted for all patients aged 15 years and under presenting with abdominal pain to our institution in 2017, and data including age, white cell count, neutrophil and lymphocyte count, NLR, C-reactive protein and diagnosis of appendicitis were recorded. Statistical analysis was performed using Stata©. Receiver operating characteristic curves for various tests were formed and areas under curve (AUC) compared using regression, P < 0.05 was considered significant. RESULTS: A total of 1263 patients were presented, of whom 546 had their blood performed and were included, 86 had appendicitis and 460 did not. Neutrophilia was the best predictor for appendicitis (AUC = 0.86), significantly higher than NLR (0.81), P < 0.05. Lymphopaenia was a poor negative predictor of appendicitis (AUC = 0.46), and while isolated lymphopaenia was more predictive (AUC = 0.23) this was inferior to the positive prediction of neutrophilia, P < 0.05. CONCLUSION: The value of isolated lymphopaenia to predict against appendicitis is largely accounted for inherently normal neutrophils, independently lymphopaenia has little value. NLR, while predictive, is a weaker predictor than neutrophilia.

Is 14 the new 40: trends in gallstone disease and cholecystectomy in Australian children.

BACKGROUNDS: Gallstone disease and cholecystectomy have been uncommon in paediatric patients and associated with haemolytic disease and prematurity. Many countries have observed an increase in the prevalence of paediatric gallstones and cholecystectomy with increasing childhood obesity. The purpose of this study was to determine any trend in prevalence in Australian children and the role of obesity. METHODS: Chart review was conducted for patients undergoing cholecystectomy under 18 in 25 years between 1992 and 2016. Patients were grouped based on year of operation into five groups of 5 years each. Patient demographics including age and gender were noted, as were weight, height, and percentiles. Also noted were comorbidities, indication for surgery, whether elective or emergent, and procedure performed. Statistical analysis was performed using logistic regression on R-Studio®. RESULTS: Seventy-nine patients were included, 9, 15, 18, 18, and 19 in Groups 1-5, respectively. A trend was noted of increasing frequency which did not reach statistical significance. Nineteen patients had alternative explanations for gallstone disease, decreasing over time, coefficient - 10.5. A trend was also noted of increasing proportion of patients in higher percentiles for weight, which was statistically significant for those above the 98th percentile. CONCLUSIONS: The changing profile of paediatric cholecystectomy is a little recognised aspect of the 'obesity epidemic'. This has implications when considering the impact of childhood overweight and obesity, and for clinicians involved in the diagnosis and management of these children.

Universal Relationship between Molecular Structure and Crystal Structure in Peptoid Polymers and Prevalence of the cis Backbone Conformation.

Peptoid polymers are often crystalline in the solid-state as examined by X-ray scattering, but thus far, there has been no attempt to identify a common structural motif among them. In order to probe the relationship between molecular structure and crystal structure, we synthesized and analyzed a series of crystalline peptoid copolymers, systematically varying peptoid side-chain length (S) and main-chain length (N). We also examined X-ray scattering data from 18 previously reported peptoid polymers. In all peptoids, we found that the unit cell dimensions, a, b, and c, are simple functions of S and N: a (Å) = 4.55, b (Å) = [2.98]N + 0.35, and c (Å) = [1.86]S + 5.5. These relationships, which apply to both bulk crystals and self-assembled nanosheets in water, indicate that the molecules adopt extended, planar conformations. Furthermore, we performed molecular dynamics simulations (MD) of peptoid polymer lattices, which indicate that all backbone amides adopt the cis conformation. This is a surprising conclusion, because previous studies on isolated molecules indicated an energetic preference for the trans conformer. This study demonstrates that when packed into supramolecular lattices or crystals, peptoid polymers prefer to adopt a regular, extended, all-cis secondary structure.

Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects.

Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (odds ratio (OR) = 1.11, P = 5.7 × 10-15), which persisted after excluding loci implicated in previous studies (OR = 1.07, P = 1.7 × 10-6). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 × 10-11) and neurobehavioral phenotypes in mouse (OR = 1.18, P = 7.3 × 10-5). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by nonallelic homologous recombination.

Whole-genome sequencing in autism identifies hot spots for de novo germline mutation.

De novo mutation plays an important role in autism spectrum disorders (ASDs). Notably, pathogenic copy number variants (CNVs) are characterized by high mutation rates. We hypothesize that hypermutability is a property of ASD genes and may also include nucleotide-substitution hot spots. We investigated global patterns of germline mutation by whole-genome sequencing of monozygotic twins concordant for ASD and their parents. Mutation rates varied widely throughout the genome (by 100-fold) and could be explained by intrinsic characteristics of DNA sequence and chromatin structure. Dense clusters of mutations within individual genomes were attributable to compound mutation or gene conversion. Hypermutability was a characteristic of genes involved in ASD and other diseases. In addition, genes impacted by mutations in this study were associated with ASD in independent exome-sequencing data sets. Our findings suggest that regional hypermutation is a significant factor shaping patterns of genetic variation and disease risk in humans.

Virus pathogen database and analysis resource (ViPR): a comprehensive bioinformatics database and analysis resource for the coronavirus research community.

Several viruses within the Coronaviridae family have been categorized as either emerging or re-emerging human pathogens, with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) being the most well known. The NIAID-sponsored Virus Pathogen Database and Analysis Resource (ViPR, www.viprbrc.org) supports bioinformatics workflows for a broad range of human virus pathogens and other related viruses, including the entire Coronaviridae family. ViPR provides access to sequence records, gene and protein annotations, immune epitopes, 3D structures, host factor data, and other data types through an intuitive web-based search interface. Records returned from these queries can then be subjected to web-based analyses including: multiple sequence alignment, phylogenetic inference, sequence variation determination, BLAST comparison, and metadata-driven comparative genomics statistical analysis. Additional tools exist to display multiple sequence alignments, view phylogenetic trees, visualize 3D protein structures, transfer existing reference genome annotations to new genomes, and store or share results from any search or analysis within personal private 'Workbench' spaces for future access. All of the data and integrated analysis and visualization tools in ViPR are made available without charge as a service to the Coronaviridae research community to facilitate the research and development of diagnostics, prophylactics, vaccines and therapeutics against these human pathogens.

Toma de perspectiva y teoría de la mente: aspectos conceptuales y empíricos. Una propuesta complementaria y pragmática

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Abstract: The present work completes an exhaustive revisión of the delimitation of the ability of perspective taking from different points of view. First, perspective taking is defined as the ability of an individual to interpret his/hers emotional and mental states and those of others. Additionally, the term has also been used in medical settings to refer to a tactic intended to stop certain limiting feeling and/or thoughts and instead move feelings and thoughts towards a different direction. At the same time, perspective taking is considered to be at the heart of psychological phenomena such as empathy, that is, the capacity to distinguish what individuals know about themselves in a certain situation (how someone thinks, feels and behaves), self-awareness, interpersonal relations, and various social skills deficits. Second, this ability is conceptualized as a metacognition and it is assumed that the object of study is the theory of the mind. Third, from a developmental perspective, data have shown that children four to five years old, without any psychological disabilities, have the ability to take somebody else's perspective. We reviewed different studies regarding the development of the abilities to express and interpret emotions as precursors to perspective taking. Subsequently, we revised and analyzed the tests or strategies most commonly used to evaluate the ability of perspective taking. Typically, the capacity of an individual to have "a theory of the mind" is determined through tests of false beliefs (such as the classic test of Sally-Anne, the "Smarties" test, "M&M's", and the "Maxi's" Test). Múltiple variations of the tests of false beliefs have been conducted with flashcards or photographs, with characters in oral stories, and through the use of games. Additionally, over the last few years the focus of this body of research has evolved towards the elaboration and validation instruments to measure empathy. Among them are the tests of Empathy Quotient (EQ), the Friendship Questionnaire (FQ), and reading the "mind" in the eyes. It is important to note that these efforts have been focused mostly on individuals with Asperger" s Syndrome or those with higher verbal capabilities. From this latter perspective, we propose empirical evidence that points out to differences in the ability of perspective taking between children with or without autism. This is also shown in the results of previous studies, in which different levels of perspective taking skills were seen between children diagnosed with autism, and those diagnosed with Down Syndrome. It is important to note that this was not true when their verbal skills were not considered as a variable. Likewise, other studies showed that children with autism were not the only ones that failed the theory of the mind tests, but that these tests were also failed by those children with deficits in language and cognitive skills. In this article, we present the results of a study that replicates previous findings which show that typical developing children per-form better in perspective taking tests, followed by children diag-nosed with Down Syndrome, and subsequently by children with autism. It was also noted that the typical developing children showed the highest level of verbal discrimination, followed by the children diagnosed with Down Syndrome, and finally the children diagnosed with autism. One important finding in this study is that all children benefited from the use of contextual prompts, which improved the number of correct responses across all the theory of the mind tests. Additionally, the data varied depending on the type of tests utilized to measure perspective taking skills. In this article, we have also reviewed the different explanations for the origins and development of perspective taking, among which the theory of the mind prevails. The ability to take some-one else's perspective is explained by the development or matura-tion of an innate and specialized module of representations and knowledge, and the formation of conceptual structures of a higher order or meta-representations. Additionally, the ability to ignore perceptual information, salient or not, and to combine simultaneously various contexts are considered prerequisites. In other words, perspective taking speaks to the relationship between psychological constructs such as perception and knowledge. Additionally, it has been hypothesized that shared, joint, or independent attention can be a prerequisite for conversation, and may be the basis of a theory of the mind. In any case, the origins of the development of such a theory have been especially ubiquitous in terms of the executive function and possible relations with cerebral lesions or alterations. However, some authors consider that the process of central coherence may be relatively independent of a theory of the mind. The research of Baron-Cohen et al. has concentrated on identifying existing neurological deficits or organic changes such as bilateral lesions or the role of testosterone on the quality of social interactions and the restrictive social interests of individuals with autism. A similar interest exists in researching the difference in perspective taking and empathy abilities exhibited by members of the opposite sex. Continuing with the neurological foundations of the empathy is of full present time the discoveries regarding «mirror neurons¼ and this recent study with monkeys proposes a specific cerebral area for the formation of the meta-representation. These neurons discharge both when the individual performs an action and when the individual observes another person performing the same action. Finally, even in the light of all the above, other sources point toward the social root of perspective taking skills. Additionally, as indicated by the research of Howlin, Baron-Cohen & Hadwin, it is considered perspective taking includes five different levels: a) simple visual perspective taking, b) the knowl-edge that different individuals can have separately the same thoughts, and c) understanding that "seeing leads to learning," followed by d) the ability to predict actions based on valid beliefs, and finally e) the ability to predict false beliefs. In the light of all of the above, once the radical conclusions of these investigations are viewed critically, the theory of the mind is viewed as a disputable theory of the delimitation of the cause and development of such skills. In addition, to the perspective taking tests themselves, the pre-requisite skills of perspective taking need to be extensively ana-lyzed. In fact, it has been shown that, in order to have an adequate performance on these tests of false beliefs, individuals should be able: 1. to remember and adequately retell their own past desires, thoughts, and past actions; 2. to retain an object in their mind, perceive a second object, and form a relationship between the two, as in a "symbolic function"; 3. to demonstrate the ability to pretend; and 4. to identify the role of age and verbal abilities in children as pre-requisites for an accurate performance on tests of false beliefs, and interpretations of the world. Lastly, we propose a pragmatic and complementary analysis the Theory of Mind based in the functional-contextual analysis of behavior. First, it is considered that perspective taking requires or is closely related to other social behaviors (such as taking turns when talking, initiating verbal responses in interpersonal relations, and the capacity for empathy). In the same manner, theory of mind requires an adequate level of simple and complex conditional discriminations, and these should be analyzed in terms of stimulus control and equivalence relations. In other words, this ability to infer thoughts, feeling, and emotions of others exists if the following prerequisites are present: 1. the processes of the classical conditioning of the emotions, 2. a generalized imitation, and 3. the development of functional classes. Without these experiences or the capability to be affected by them, children (i.e. children with generalized autism) do not develop language adequately. Second, perspective taking implies that an observer's previous experiences and observations with certain events determine his/ her reaction to responses emitted by others in similar circumstances. Finally, from a contextual perspective, it is considered that a speaker's relational frames play a role in this process (for the discriminations I/you, here/there, now/later). These relational properties are abstracted through multiple exemplars or multiple learning opportunities to speak from one's own perspective in relation to others.

An ontology driven architecture for derived representations of macromolecular structure.

UNLABELLED: An object metamodel based on a standard scientific ontology has been developed and used to generate a CORBA interface, an SQL schema and an XML representation for macromolecular structure (MMS) data. In addition to the interface and schema definitions, the metamodel was also used to generate the core elements of a CORBA reference server and a JDBC database loader. The Java source code which implements this metamodel, the CORBA server, database loader and XML converter along with detailed documentation and code examples are available as part of the OpenMMS toolkit. AVAILABILITY: http://openmms.sdsc.edu CONTACT: dsg@sdsc.edu

The Protein Data Bank: unifying the archive.

The Protein Data Bank (PDB; http://www.pdb.org/) is the single worldwide archive of structural data of biological macromolecules. This paper describes the progress that has been made in validating all data in the PDB archive and in releasing a uniform archive for the community. We have now produced a collection of mmCIF data files for the PDB archive (ftp://beta.rcsb.org/pub/pdb/uniformity/data/mmCIF/). A utility application that converts the mmCIF data files to the PDB format (called CIFTr) has also been released to provide support for existing software.