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Background: Bereaved mothers describe positive experiences donating breast milk and negative experiences when not informed of opportunities to donate. Predictors of whether mothers donate milk are unknown, impairing efforts to optimize support in completing donation. Objective: To define circumstances associated with completing mother's milk (MM) donation during bereavement. Methods: A retrospective cohort study included dyads of bereaved mothers and their deceased children if a child's death occurred on-site at a quaternary care children's hospital during 2016-2020, the child had documentation of MM availability, and age at death <24 months. The primary outcome was the completion of MM donation to the milk bank. Multivariate logistic regression measured associations between clinical variables and odds of completion. Results: Of 124 deceased children with documented MM exposure, 34 mothers (28%) of 35 of those children completed MM donation, donating a mean of 13.7 liters (SD 16.8). The child's race/ethnicity documented in the medical record was White for 25 (71%), Black/African American (AA) for 1 (3%), Asian for 1 (3%), and Hispanic/Latino for 8 (23%). Referenced to mothers of White children, being a mother of an AA [OR 0.05 (95% CI: 0.01-0.43)] or Asian [0.08 (0.01-0.75)] child was associated with lower odds of donation. Referenced to mothers delivering full term (≥37 weeks'), mothers delivering <34 weeks showed higher odds [5.0 (1.5-17.5)] of donation. Conclusion: Relatively few bereaved mothers of children with indicators of MM exposure completed donation. The results suggest an opportunity to ensure bereaved mothers are uniformly informed and supported in donating.
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Lactancia Materna , Recien Nacido Prematuro , Humanos , Recién Nacido , Femenino , OptimismoAsunto(s)
Nutrición Enteral , Recien Nacido Prematuro , Lactante , Humanos , Recién Nacido , Estados Unidos , Nutrición ParenteralRESUMEN
Close attention to nutritional management is essential for optimizing growth and neurodevelopment of the preterm infant. Protein intake and the protein to energy ratio are the main determinants of growth and body composition. Yet large, multi-center, randomized controlled trials are lacking to guide protein delivery for the preterm infant. Until these studies are pursued, smaller trials must be used to inform clinical practice. This review summarizes the randomized controlled trials that have been performed to test the impact of higher vs. lower protein delivery to the preterm infant. We consider the trials that varied protein delivery rates during parenteral and enteral phases of nutrition. Considerable heterogeneity exists across study designs. Still, cumulative evidence from these trials provides a framework for current recommendations for protein intake in the preterm infant.
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Proteínas en la Dieta , Nutrición Enteral , Recien Nacido Prematuro , Nutrición Parenteral , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Nutrición Enteral/métodos , Recién Nacido , Nutrición Parenteral/métodos , Proteínas en la Dieta/administración & dosificación , Fenómenos Fisiológicos Nutricionales del LactanteRESUMEN
Free energy perturbation (FEP) remains an indispensable method for computationally assaying prospective compounds in advance of synthesis. However, before FEP can be deployed prospectively, it must demonstrate retrospective recapitulation of known experimental data where the subtle details of the atomic ligand-receptor model are consequential. An open question is whether AlphaFold models can serve as useful initial models for FEP in the regime where there exists a congeneric series of known chemical matter but where no experimental structures are available either of the target or of close homologues. As AlphaFold structures are provided without a bound ligand, we employ induced fit docking to refine the AlphaFold models in the presence of one or more congeneric ligands. In this work, we first validate the performance of our latest induced fit docking technology, IFD-MD, on a retrospective set of public experimental GPCR structures with 95% of cross-docks producing a pose with a ligand RMSD ≤ 2.5 Å in the top two predictions. We then apply IFD-MD and FEP on AlphaFold models of the somatostatin receptor family of GPCRs. We use AlphaFold models produced prior to the availability of any experimental structure from this family. We arrive at FEP-validated models for SSTR2, SSTR4, and SSTR5, with RMSE around 1 kcal/mol, and explore the challenges of model validation under scenarios of limited ligand data, ample ligand data, and categorical data.
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Simulación de Dinámica Molecular , Sitios de Unión , Unión Proteica , Ligandos , Estudios Prospectivos , Estudios Retrospectivos , Simulación del Acoplamiento MolecularRESUMEN
BACKGROUND: The advent and continual improvement of high-throughput sequencing technologies has made immunoglobulin repertoire sequencing accessible and informative regardless of study species. However, to fully map dynamic changes in polyclonal responses precise framework and complementarity determining region annotation of rearranging genes is pivotal. Most sequence annotation tools are designed primarily for use with human and mouse antibody sequences which use databases with fixed species lists, applying very specific assumptions which select against unique structural characteristics. For this reason, data agnostic tools able to learn from presented data can be very useful with new species or with novel datasets. RESULTS: We have developed IgMAT, which utilises a reduced amino acid alphabet, that incorporates multiple HMM alignments into a single consensus to automatically annotate immunoglobulin sequences from most organisms. Additionally, the software allows the incorporation of user defined databases to better represent the species and/or antibody class of interest. To demonstrate the accuracy and utility of IgMAT, we present analysis of sequences extracted from structural data and immunoglobulin sequence datasets from several different species. CONCLUSIONS: IgMAT is fully open-sourced and freely available on GitHub ( https://github.com/TPI-Immunogenetics/igmat ) for download under GPLv3 license. It can be used as a CLI application or as a python module to be integrated in custom scripts.
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Inmunoglobulinas , Programas Informáticos , Animales , Ratones , Humanos , Inmunoglobulinas/genética , Bases de Datos FactualesRESUMEN
BACKGROUND: Neurofibromatosis type 1 (NF1) gives rise to a variety of spinal pathologies that include dural ectasia (DE), vertebral malalignments (VMA), spinal deformities (SD), syrinx, meningoceles, spinal nerve root tumours (SNRT), and spinal plexiform tumours (SPT). The relationship between these and the progression of these pathologies has not been explored before in detail and this paper aims to address this. METHODS: Data was retrospectively collected from adult NF1 multi-disciplinary team meetings from 2016 to 2022 involving a total of 593 patients with 20 distinct predictor variables. Data were analyzed utilizing; Chi-Square tests, binary logistic regression, and Kaplan-Meier analysis. RESULTS: SNRT (19.9%), SD (18.6%), and (17.7%) of VMA had the highest rates of progression. SD was significantly associated (p < 0.02) with the presence and progression of all spinal pathologies except for SPT. Statistically significant predictors of SD progression included the presence of DVA, VMA, syrinx, meningocele, and SNRT. Kaplan-Meier analysis revealed no statistically significant difference between the times to progression for SD (85 days), SNRT (1196 days), and VMA (2243 days). CONCLUSION: This paper explores for the first time in detail, the progression of various spinal pathologies in NF1. The presence and progression of SD is a key factor that correlated with the progression of different spinal pathologies. Early identification of SD may help support clinical decision-making and guide radiological follow-up protocols and treatment.
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Meningocele , Neurofibromatosis 1 , Neoplasias de la Médula Espinal , Neoplasias de la Columna Vertebral , Siringomielia , Adulto , Humanos , Neurofibromatosis 1/diagnóstico por imagen , Estudios Retrospectivos , Columna Vertebral/patología , Neoplasias de la Médula Espinal/patología , Radiografía , Neoplasias de la Columna Vertebral/patologíaRESUMEN
BACKGROUND: Parenteral nutrition (PN) is prescribed for preterm infants until nutrition needs are met via the enteral route, but unanswered questions remain regarding PN best practices in this population. METHODS: An interdisciplinary committee was assembled to answer 12 questions concerning the provision of PN to preterm infants. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) process was used. Questions addressed parenteral macronutrient doses, lipid injectable emulsion (ILE) composition, and clinically relevant outcomes, including PNALD, early childhood growth, and neurodevelopment. Preterm infants with congenital gastrointestinal disorders or infants already diagnosed with necrotizing enterocolitis or PN-associated liver disease (PNALD) at study entry were excluded. RESULTS: The committee reviewed 2460 citations published between 2001 and 2023 and evaluated 57 clinical trials. For most questions, quality of evidence was very low. Most analyses yielded no significant differences between comparison groups. A multicomponent oil ILE was associated with a reduction in stage 3 or higher retinopathy of prematurity (ROP) compared to an ILE containing 100% soybean oil. For all other questions, expert opinion was provided. CONCLUSION: Most clinical outcomes were not significantly different between comparison groups when evaluating timing of PN initiation, amino acid dose, and ILE composition. Future clinical trials should standardize outcome definitions to permit statistical conflation of data, thereby permitting more evidence based recommendations in future guidelines. This guideline has been approved by the ASPEN 2022-2023 Board of Directors.
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Enterocolitis Necrotizante , Recien Nacido Prematuro , Preescolar , Lactante , Humanos , Recién Nacido , Nutrición Enteral , Aminoácidos , HígadoRESUMEN
Use of parenteral nutrition (PN) in the neonatal intensive care unit (NICU) requires evaluating the need for central venous catheters, potential drug incompatibilities, unintentional exposures, and suboptimal energy and nutrient intake during the transition to full enteral nutrition. Risks of photooxidation reactions in PN components, refeeding syndrome, and excess early amino acid intake should prompt the reevaluation of routine practices. The goal of this paper is to review the practicalities, challenges, and conundrums of administering PN in the NICU.
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Unidades de Cuidado Intensivo Neonatal , Nutrición Parenteral , Recién Nacido , Humanos , Nutrición Enteral , Ingestión de EnergíaRESUMEN
We examine challenges with measuring 'success' in access and benefit-sharing (ABS) of biological resources. We note a lack of indicators and draw on Pacific patent landscaping, ABS case studies, and research permit figures to highlight that ABS systems are functioning somewhat, although they are often not meeting expectations.
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Studying the antibody response to infection or vaccination is essential for developing more effective vaccines and therapeutics. Advances in high-throughput antibody sequencing technologies and immunoinformatic tools now allow the fast and comprehensive analysis of antibody repertoires at high resolution in any species. Here, we detail a flexible and customizable suite of methods from flow cytometry, single cell sorting, heavy and light chain amplification to antibody sequencing in cattle. These methods were used successfully, including adaptation to the 10x Genomics platform, to isolate native heavy-light chain pairs. When combined with the Ig-Sequence Multi-Species Annotation Tool, this suite represents a powerful toolkit for studying the cattle antibody response with high resolution and precision. Using three workflows, we processed 84, 96, and 8313 cattle B cells from which we sequenced 24, 31, and 4756 antibody heavy-light chain pairs, respectively. Each method has strengths and limitations in terms of the throughput, timeline, specialist equipment, and cost that are each discussed. Moreover, the principles outlined here can be applied to study antibody responses in other mammalian species.
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Introduction: Although school communities may be required to provide physical education opportunities for all students-including for those with disabilities-the same is not generally true with respect to school sport (i.e., participation in interscholastic or intramural sport programs). Hence, opportunities for inclusive school sport participation are consequently limited. Recognizing the need for continued attention and action in this area, we recently developed and piloted Game Changers-a participatory action research project. Together, 27 students with various cognitive and/or intellectual disabilities (i.e., student-participants), their schools' six physical education teachers and learning support teachers (i.e., champion-participants), four university researchers (i.e., researcher-participants), and two community partners [i.e., Physical and Health Education (PHE) Canada, Special Olympics Nova Scotia] engaged in the Game Changers project with three idealized goals: (a) to bring to the fore para/adapted/inclusive sport opportunities for all students; (b) to provide an empowering opportunity for students with disabilities to participate, make choices, and act as leaders in the development of sport programming; and (c) to engage youth with disabilities in sport as participants, leaders, mentors, and role models. Methods: Utilizing a mixed-methods design, data were collected from a variety of sources before the implementation of the Game Changers program, during its implementation, and once it was complete. These four data sources included the following: pre- and post-program survey for student-participants, pre- and post-program focus group interviews for student-participants, pre- and post-program focus group interviews for champion-participants, and school/sport observations. Results: The first cycle of this participatory action research project has yielded positive and informative findings. Strictly positive findings, among others, relate to the following: improving upon students' perceived competence and autonomy, inviting student voice, identifying and responding to sport participation barriers, and creating genuine sport opportunities within school settings. More undesirable yet informative findings, among others, relate to the following: unachieved intrinsic motivation and belonging, (un)sustainability of sport programs without "interventions" like Game Changers, recreation/leisure as "substitutes" for sport, and a continued want for authentic leadership and mentorship opportunities. Discussion: With these findings, we offer insights for future iterations of Game Changers (and programs like it) in similar school communities.
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In the United States, 10% of infants are born preterm (PT; <37 weeks gestational age) each year and are at higher risk of complications compared to full term infants. The burden of PT birth is borne disproportionately by Black versus non-Black families, with Black mothers significantly more likely to give birth to a PT infant. One proven strategy to improve short- and long-term health outcomes in PT infants is to feed mother's own milk (MOM; breast milk from the mother). However, mothers must make decisions about work and MOM provision following PT birth, and more time spent in paid work may reduce time spent in unpaid activities, including MOM provision. Non-Black PT infants are substantially more likely than Black PT infants to receive MOM during the birth hospitalization, and this disparity is likely to be influenced by the complex decisions mothers of PT infants make about allocating their time between paid and unpaid work. Work is a social determinant of health that provides a source of income and health insurance coverage, and at the same time, has been shown to create disparities through poorer job quality, lower earnings, and more precarious employment in racial and ethnic minority populations. However, little is known about the relationship between work and disparities in MOM provision by mothers of PT infants. This State of the Science review synthesizes the literature on paid and unpaid work and MOM provision, including: (1) the complex decisions that mothers of PT infants make about returning to work, (2) racial and ethnic disparities in paid and unpaid workloads of mothers, and (3) the relationship between components of job quality and duration of MOM provision. Important gaps in the literature and opportunities for future research are summarized, including the generalizability of findings to other countries.
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BACKGROUND: Several studies show that emergency medicine (EM) physicians are less comfortable caring for pediatric patients than adults. The state of pediatric training has not been comprehensively evaluated since 2000. OBJECTIVES: We sought to describe current pediatric education in EM residencies and to evaluate EM Program Director (PD) confidence in graduating trainees' abilities to care for pediatric patients. METHODS: We conducted an anonymous, cross-sectional survey study of EM PDs in August 2020. We collected program demographics, clinical rotations, and didactic methods. We used Likert scales to measure PD confidence in graduating residents' competence to care for pediatric and adult patients. RESULTS: We found e-mail addresses for 249 (93%) of 268 EM programs. One hundred nineteen (48%) PDs completed the survey. We include denominators to account for unanswered questions. Sixty-eight (59%) of 116 programs spend 10% to 20% of clinical time seeing pediatric patients. One hundred ten (91%) of 119 require a pediatric emergency medicine (PEM) rotation, 88/119 (83%) require pediatric intensive care, and 34/119 (29%) require neonatal intensive care. Seventy (62%) of 113 have curricula designed by PEM-trained faculty, 96/113 (85%) have PEM attendings teach lectures, and 77/113 (68%) spend 10% to 20% of didactic time on pediatric topics. Twenty-three (23%) of 106 PDs stated not all residents graduate with competence in pediatric resuscitation compared with 2/106 (2%) for adult resuscitation ( P < 0.05). CONCLUSIONS: Program directors report less confidence in graduating residents' competence in caring for pediatric patients compared with adult patients. We propose ideas to strengthen the quality of pediatric education in EM residencies.
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Medicina de Emergencia , Internado y Residencia , Medicina de Urgencia Pediátrica , Adulto , Recién Nacido , Humanos , Niño , Medicina de Urgencia Pediátrica/educación , Estudios Transversales , Medicina de Emergencia/educación , Curriculum , Encuestas y CuestionariosRESUMEN
Refeeding syndrome (RS) in preterm infants is a scenario of fetal malnutrition, primarily resulting from placental insufficiency, followed by a postnatal physiologic adaptation and response to an imbalance of nutrients provided parenterally. Growth restriction and small gestational age status are common findings in infants at risk of developing RS. Adverse clinical outcomes associated with RS may be severe and life-threatening. The biochemical abnormalities that occur in RS may be mitigated through careful monitoring and adaptation of the clinical management of parenteral and enteral nutrition. This perspective reviews the physiology and metabolism in infants with RS and provides suggested approaches to their clinical monitoring and nutritional management.
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Recien Nacido Prematuro , Síndrome de Realimentación , Recién Nacido , Lactante , Femenino , Humanos , Embarazo , Síndrome de Realimentación/prevención & control , Placenta , Estado Nutricional , Nutrición Parenteral/efectos adversos , Nutrición Parenteral/métodosRESUMEN
Sustainable modern poultry production depends on effective protection against infectious diseases and a diverse range of antibodies is key for an effective immune response. In the domestic chicken, somatic gene conversion is the dominant process in which the antibody immunoglobulin genes are diversified. Affinity maturation by somatic hypermutation (SHM) also occurs, but the relative contribution of gene conversion versus somatic hypermutation to immunoglobulin (Ig) gene diversity is poorly understood. In this study, we use high throughput long-read sequencing to study immunoglobulin diversity in multiple immune-associated tissues in Rhode Island Red chickens. To better understand the impact of genetic diversification in the chicken, a novel gene conversion identification software was developed (BrepConvert). In this study, BrepConvert enabled the identification of over 1 million gene conversion events. Mapping the occurrence of putative somatic gene conversion (SGC) events throughout the variable gene region revealed repetitive and highly restricted patterns of genetic insertions in both the antibody heavy and light chains. These patterns coincided with the locations of genetic variability in available pseudogenes and align with antigen binding sites, predominately the complementary determining regions (CDRs). We found biased usage of pseudogenes during gene conversion, as well as immunoglobulin heavy chain diversity gene (IGHD) preferences during V(D)J gene rearrangement, suggesting that antibody diversification in chickens is more focused than the genetic potential for diversity would suggest.
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Introduction: Clinical faculty may have limited knowledge of education theories and best practices in health professions education. Many faculty development programs focus on passive learning with limited application to practice. There is a need for more active engagement for early career educators. Methods: We created an apprenticeship-based electronic book series focused on translating education theories into practical applications for clinician educators. Chapters were authored by teams of two to four geographically separated early career educators, who were tasked with explaining an education theory and relating it to their educational practice. The chapters underwent internal peer review, followed by open peer review as a blog post and eventual publication. Usage data were collected, and surveys were sent to authors and end-users. Results: Six volumes (60 total chapters) have been created to date by 180 unique authors and 17 editors over a 6-year period. There have been 65,571 total blog page views and 17,180 total book downloads across the five published volumes. Authors reported an increase in their perceived knowledge (pre 2.6 ± 1.7 vs. post 7.2 ± 1.1, mean difference 4.5/9.0, 95% confidence interval [CI] 4.0-5.0, p < 0.001) after writing their chapter. Authors also reported career benefits including authorship for academic advancement/promotion and developing an area of education theory expertise. End-users also reported a mean increase in their perceived knowledge (pre 4.4 ± 2.5 vs. post 7.3 ± 1.4, mean difference 2.9/9.0, 95% CI 2.1-3.8, p < 0.001) after reading a chapter. Conclusion: The Education Theory Made Practical electronic book series represents a proof of concept for an apprenticeship-based model to teach education theory, while also creating scholarship and open access resources for the broader community.
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Background: Rotavirus infection is a significant cause of gastroenteritis in developing countries and, in severe cases even leads to death. The impact of rotavirus vaccine introduction in reducing the rotavirus disease burden in children was well known. The study was aimed to determine the prevalence and clinical characteristics of rotavirus gastroenteritis before the introduction of rotavirus vaccine into Nigeria's routine immunization program. Materials and Methods: We conducted a cross-sectional hospital-based study involving 735 children aged 0-59 months with acute gastroenteritis hospitalized at the Ahmadu Bello University Teaching Hospital Zaria from September 2017 to August 2020. Relevant sociodemographic and clinical data were obtained and entered into the World Health Organization standardized case investigation forms. Stool specimens were tested for rotavirus Group A antigen using the ProSpecT™ Rotavirus Microplate Assay by Thermoscientific Oxoid Microbiology UK. Results: One hundred and fifty-three stool samples tested positive for rotavirus giving a prevalence of 20.8%. One hundred and two (66.7%) children with rotavirus gastroenteritis were infants. There were 87 males and 66 females with M: F ratio of 1.3:1. Only 30 (19.6%) children with rotavirus-associated diarrhea presented with severe dehydration. The presence of vomiting was significantly associated with rotavirus diarrhea (P = 0.001). More cases of rotavirus diarrhea occurred in September through February. None of the studied children were vaccinated against rotavirus. Conclusion: The prevalence of rotavirus diarrhea remains high in this study. Infants were recognized as a high-risk group, and none of them were vaccinated against rotavirus and this underscores the urgent need for implementing the rotavirus vaccine in the national vaccination program to reduce the disease burden in the country.
Résumé L'infection à rotavirus est une cause importante de gastro-entérite dans les pays en développement et, dans les cas graves, entraîne même la mort. L'impact de l'introduction du vaccin antirotavirus pour réduire le fardeau de la maladie à rotavirus chez les enfants était bien connue. L'étude visait à déterminer la prévalence et les caractéristiques cliniques de la gastro-entérite à rotavirus avant l'introduction du vaccin antirotavirus dans le programme de vaccination systématique du Nigéria. Matériels et méthodesNous avons mené une étude hospitalière transversale portant sur 735 enfants âgés de 0 à 59 mois atteints de gastro-entérite aiguë. hospitalisé à l'hôpital universitaire Ahmadu Bello Zaria de septembre 2017 à août 2020. Données sociodémographiques et cliniques pertinentes les données ont été obtenues et saisies dans les formulaires normalisés d'investigation de cas de l'Organisation mondiale de la santé. Des échantillons de selles ont été testés pour le rotavirus Antigène du groupe A utilisant le test sur microplaque ProSpecT™ Rotavirus par Thermoscientific Oxoid Microbiology UK. Résultatscent cinquante trois les échantillons de selles ont été testés positifs pour le rotavirus donnant une prévalence de 20,8 %. Cent deux (66,7 %) enfants atteints de gastro-entérite à rotavirus ont été nourrissons. Il y avait 87 hommes et 66 femmes avec un rapport M:F de 1,3:1. Seuls 30 (19,6 %) enfants atteints de diarrhée à rotavirus ont présenté déshydratation sévère. La présence de vomissements était significativement associée à la diarrhée à rotavirus (P = 0,001). Plus de cas de diarrhée à rotavirus se sont produits de septembre à février. Aucun des enfants étudiés n'a été vacciné contre le rotavirus. ConclusionLa prévalence de la diarrhée à rotavirus reste élevé dans cette étude. Les nourrissons ont été reconnus comme un groupe à haut risque et aucun d'entre eux n'a été vacciné contre le rotavirus, ce qui souligne la nécessité urgente de mettre en Åuvre le vaccin antirotavirus dans le programme national de vaccination afin de réduire la charge de morbidité dans le pays. Mots-clésGastro-entérite aiguë, diarrhée à rotavirus, vaccin à rotavirus, Zaria.
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Gastroenteritis , Infecciones por Rotavirus , Vacunas contra Rotavirus , Rotavirus , Niño , Estudios Transversales , Diarrea/epidemiología , Heces , Femenino , Gastroenteritis/epidemiología , Hospitalización , Hospitales de Enseñanza , Humanos , Lactante , Masculino , Nigeria/epidemiología , Prevalencia , Infecciones por Rotavirus/epidemiología , Infecciones por Rotavirus/prevención & control , UniversidadesRESUMEN
Body composition analysis to distinguish between fat mass and fat-free mass is an established research approach to assess nutritional status. Within neonatal medicine, preterm infant body composition is linked with later health outcomes including neurodevelopment and cardiometabolic health. Mounting evidence establishing fat-free mass as an indicator of nutritional status, coupled with the availability of testing approaches that are feasible to use in preterm infants, have enhanced interest in measuring body composition in the neonatal intensive care unit (NICU) setting. In this paper, we use the concept of clinical utility-the added value of a new methodology over current standard care-as a framework for assessing several existing body composition methodologies with potential for clinical application to preterm neonates. We also use this framework to identify remaining knowledge gaps and prioritize efforts to advance our understanding of clinically-oriented body composition testing in the NICU.