Interpretable prioritization of splice variants in diagnostic next-generation sequencing.

A critical challenge in genetic diagnostics is the computational assessment of candidate splice variants, specifically the interpretation of nucleotide changes located outside of the highly conserved dinucleotide sequences at the 5' and 3' ends of introns. To address this gap, we developed the Super Quick Information-content Random-forest Learning of Splice variants (SQUIRLS) algorithm. SQUIRLS generates a small set of interpretable features for machine learning by calculating the information-content of wild-type and variant sequences of canonical and cryptic splice sites, assessing changes in candidate splicing regulatory sequences, and incorporating characteristics of the sequence such as exon length, disruptions of the AG exclusion zone, and conservation. We curated a comprehensive collection of disease-associated splice-altering variants at positions outside of the highly conserved AG/GT dinucleotides at the termini of introns. SQUIRLS trains two random-forest classifiers for the donor and for the acceptor and combines their outputs by logistic regression to yield a final score. We show that SQUIRLS transcends previous state-of-the-art accuracy in classifying splice variants as assessed by rank analysis in simulated exomes, and is significantly faster than competing methods. SQUIRLS provides tabular output files for incorporation into diagnostic pipelines for exome and genome analysis, as well as visualizations that contextualize predicted effects of variants on splicing to make it easier to interpret splice variants in diagnostic settings.

Understanding sex differences and the translational value of models of persistent substance use despite negative consequences.

Persistent substance use despite negative consequences is a key facet of substance use disorder. The last decade has seen the preclinical field adopt the use of punishment to model adverse consequences associated with substance use. This has largely involved the pairing of drug use with either electric foot shock or quinine, a bitter tastant. Whilst at face value, these punishers may model aspects of the physical and psychological consequences of substance use, such models are yet to assist the development of approved medications for treatment. This review discusses progress made with animal models of punishment to understand the behavioral consequences of persistent substance use despite negative consequences. We highlight the importance of examining sex differences, especially when the behavioral response to punishment changes following drug exposure. Finally, we critique the translational value these models provide for the substance use disorder field.

Engines of change: Transposable element mutation rates are high and variable within Daphnia magna.

Transposable elements (TEs) represent a major portion of most eukaryotic genomes, yet little is known about their mutation rates or how their activity is shaped by other evolutionary forces. Here, we compare short- and long-term patterns of genome-wide mutation accumulation (MA) of TEs among 9 genotypes from three populations of Daphnia magna from across a latitudinal gradient. While the overall proportion of the genome comprised of TEs is highly similar among genotypes from Finland, Germany, and Israel, populations are distinguishable based on patterns of insertion site polymorphism. Our direct rate estimates indicate TE movement is highly variable (net rates ranging from -11.98 to 12.79 x 10-5 per copy per generation among genotypes), differing both among populations and TE families. Although gains outnumber losses when selection is minimized, both types of events appear to be highly deleterious based on their low frequency in control lines where propagation is not limited to random, single-progeny descent. With rate estimates 4 orders of magnitude higher than base substitutions, TEs clearly represent a highly mutagenic force in the genome. Quantifying patterns of intra- and interspecific variation in TE mobility with and without selection provides insight into a powerful mechanism generating genetic variation in the genome.

Patient comfort with sexual orientation and gender identity questions in adult congenital cardiology clinics.

BACKGROUND: Lack of sexual orientation and gender identity (SOGI) data creates barriers for lesbian, gay, bisexual, transgender, and queer (LGBTQ+) people in health care. Barriers to SOGI data collection include physician misperception that patients do not want to answer these questions and discomfort asking SOGI questions. This study aimed to assess patient comfort towards SOGI questions across five quaternary care adult congenital heart disease (ACHD) centres. METHODS: A survey administered to ACHD patients (≥18 years) asked (1) two-step gender identity and birth sex, (2) acceptance of SOGI data, and (3) the importance for ACHD physicians to know SOGI data. Chi-square tests were used to analyse differences among demographic groups and logistic regression modelled agreement with statement of patient disclosure of SOGI improving patient-physician communication. RESULTS: Among 322 ACHD patients, 82% identified as heterosexual and 16% identified as LGBTQ+, across the age ranges 18-29 years (39.4%), 30-49 years (47.8%), 50-64 years (8.7%), and > 65 years (4.0%). Respondents (90.4%) felt comfortable answering SOGI questions. Respondents with bachelor's/higher education were more likely to "agree" that disclosure of SOGI improves patient-physician communication compared to those with less than bachelor's education (OR = 2.45; 95% CI 1.41, 4.25; p = .0015). CONCLUSION: These findings suggest that in this largely heterosexual population, SOGI data collection is unlikely to cause patient discomfort. Respondents with higher education were twice as likely to agree that SOGI disclosure improves patient-physician communication. The inclusion of SOGI data in future studies will provide larger samples of underrepresented minorities (e.g. LGBTQ+ population), thereby reducing healthcare disparities within the field of cardiovascular research.

Development of a bioelectrical impedance analysis-based prediction equation for body composition of rural children aged 4-8 years in Myanmar.

Background: Reliable and accurate estimates of body composition are essential when studying the various health correlates of disease. Bioelectrical impedance analysis (BIA) is an affordable and feasible body composition assessment technique for clinical and field settings. Total body water (TBW) and hence fat-free mass is estimated by predictive regression algorithms using anthropometric measurements plus the resistance index. Aim: The study aimed to develop a BIA prediction equation for TBW in children in Myanmar using the deuterium dilution technique as the reference method. Methods: The study design was cross-sectional in a school setting with convenience sampling of participants. One hundred and two healthy children (57 boys and 45 girls) with aged 4 and 8 years participated; randomly divided into the prediction group (29 boys and 22 girls) and cross-validation group (28 boys and 23 girls). Whole-body impedance, anthropometric and TBW (by D2O dilution) measurements. The prediction equation was cross-validated using a split-group design and compared to published equations for contemporaneous populations. Results: TBW could be predicted by the following equation. TBW = 0.4597 * Weight (kg) + 0.1564 * Impedance index + 0.6075 (R2 = 0.891, P < 0.0001) with a correlation coefficient of 0.942 and limits of agreement of 0.98 kg TBW on cross-validation. Conclusions: This equation can be used to predict body composition in young (aged 4-8 years) children in Myanmar but because the age range of the participants in the present study was relatively narrow, more research in different age groups is required to establish its broader applicability.

Integrating risks and benefits: pretransplant assessment and patient selection for heart transplantation in adult congenital heart disease.

PURPOSE OF REVIEW: The number of adult congenital heart disease (ACHD) patients presenting for consideration of heart transplantation continues to grow. Comprehensive pretransplant assessment and thoughtful patient selection are of critical importance to mitigate perioperative and posttransplant morbidity and mortality in this population. RECENT FINDINGS: There is increasing evidence that patient outcomes after the onset of heart failure in the ACHD population are poor while overall transplant outcomes for ACHD patients have improved over time. Delineation of factors associated with better versus worse posttransplant outcomes is an area of ongoing research. Several studies have found that delayed patient referral, anatomic complexity and the presence of noncardiac organ dysfunction may increase peri-transplant and posttransplant risk. SUMMARY: Pretransplant assessment and patient selection in ACHD patients should focus on mitigating perioperative and early posttransplant risk. Anatomic complexity, noncardiac organ dysfunction, and referral timing after the onset of heart failure can contribute to poor posttransplant outcomes and should inform patient selection.

Interpretable Clinical Genomics with a Likelihood Ratio Paradigm.

Human Phenotype Ontology (HPO)-based analysis has become standard for genomic diagnostics of rare diseases. Current algorithms use a variety of semantic and statistical approaches to prioritize the typically long lists of genes with candidate pathogenic variants. These algorithms do not provide robust estimates of the strength of the predictions beyond the placement in a ranked list, nor do they provide measures of how much any individual phenotypic observation has contributed to the prioritization result. However, given that the overall success rate of genomic diagnostics is only around 25%-50% or less in many cohorts, a good ranking cannot be taken to imply that the gene or disease at rank one is necessarily a good candidate. Here, we present an approach to genomic diagnostics that exploits the likelihood ratio (LR) framework to provide an estimate of (1) the posttest probability of candidate diagnoses, (2) the LR for each observed HPO phenotype, and (3) the predicted pathogenicity of observed genotypes. LIkelihood Ratio Interpretation of Clinical AbnormaLities (LIRICAL) placed the correct diagnosis within the first three ranks in 92.9% of 384 case reports comprising 262 Mendelian diseases, and the correct diagnosis had a mean posttest probability of 67.3%. Simulations show that LIRICAL is robust to many typically encountered forms of genomic and phenomic noise. In summary, LIRICAL provides accurate, clinically interpretable results for phenotype-driven genomic diagnostics.

Bioimpedance basics and phase angle fundamentals.

Measurement of phase angle using bioimpedance analysis (BIA) has become popular as an index of so-called "cellular health". What precisely is meant by this term is not always clear but strong relationships have been found between cellular water status (the relative amounts of extra- and intracellular water), cell membrane integrity and cellular mass. Much of the current research is empirical observation and frequently pays little regard to the underlying biophysical models that underpin the BIA technique or attempts to provide mechanistic explanations for the observations. This brief review seeks to provide a basic understanding of the electrical models frequently used to describe the passive electrical properties of tissues with particular focus on phase angle. In addition, it draws attention to some practical concerns in the measurement of phase angle and notes the additional understanding that can be gained when phase angle are obtained with bioimpedance spectroscopy (BIS) rather than single frequency BIA (SFBIA) along with the potential for simulation modelling.

Predicting eating disorder and anxiety symptoms using disorder-specific and transdiagnostic polygenic scores for anorexia nervosa and obsessive-compulsive disorder.

BACKGROUND: Clinical, epidemiological, and genetic findings support an overlap between eating disorders, obsessive-compulsive disorder (OCD), and anxiety symptoms. However, little research has examined the role of genetics in the expression of underlying phenotypes. We investigated whether the anorexia nervosa (AN), OCD, or AN/OCD transdiagnostic polygenic scores (PGS) predict eating disorder, OCD, and anxiety symptoms in a large developmental cohort in a sex-specific manner. METHODS: Using summary statistics from Psychiatric Genomics Consortium AN and OCD genome-wide association studies, we conducted an AN/OCD transdiagnostic genome-wide association meta-analysis. We then calculated AN, OCD, and AN/OCD PGS in participants from the Avon Longitudinal Study of Parents and Children to predict eating disorder, OCD, and anxiety symptoms, stratified by sex (combined N = 3212-5369 per phenotype). RESULTS: The PGS prediction of eating disorder, OCD, and anxiety phenotypes differed between sexes, although effect sizes were small. AN and AN/OCD PGS played a more prominent role in predicting eating disorder and anxiety risk than OCD PGS, especially in girls. AN/OCD PGS provided a small boost over AN PGS in the prediction of some anxiety symptoms. All three PGS predicted higher compulsive exercise across different developmental timepoints [ß = 0.03 (s.e. = 0.01) for AN and AN/OCD PGS at age 14; ß = 0.05 (s.e. = 0.02) for OCD PGS at age 16] in girls. CONCLUSIONS: Compulsive exercise may have a transdiagnostic genetic etiology, and AN genetic risk may play a role in the presence of anxiety symptoms. Converging with prior twin literature, our results also suggest that some of the contribution of genetic risk may be sex-specific.

The Human Phenotype Ontology in 2021.

The Human Phenotype Ontology (HPO, https://hpo.jax.org) was launched in 2008 to provide a comprehensive logical standard to describe and computationally analyze phenotypic abnormalities found in human disease. The HPO is now a worldwide standard for phenotype exchange. The HPO has grown steadily since its inception due to considerable contributions from clinical experts and researchers from a diverse range of disciplines. Here, we present recent major extensions of the HPO for neurology, nephrology, immunology, pulmonology, newborn screening, and other areas. For example, the seizure subontology now reflects the International League Against Epilepsy (ILAE) guidelines and these enhancements have already shown clinical validity. We present new efforts to harmonize computational definitions of phenotypic abnormalities across the HPO and multiple phenotype ontologies used for animal models of disease. These efforts will benefit software such as Exomiser by improving the accuracy and scope of cross-species phenotype matching. The computational modeling strategy used by the HPO to define disease entities and phenotypic features and distinguish between them is explained in detail.We also report on recent efforts to translate the HPO into indigenous languages. Finally, we summarize recent advances in the use of HPO in electronic health record systems.

Prenatal phenotyping: A community effort to enhance the Human Phenotype Ontology.

Technological advances in both genome sequencing and prenatal imaging are increasing our ability to accurately recognize and diagnose Mendelian conditions prenatally. Phenotype-driven early genetic diagnosis of fetal genetic disease can help to strategize treatment options and clinical preventive measures during the perinatal period, to plan in utero therapies, and to inform parental decision-making. Fetal phenotypes of genetic diseases are often unique and at present are not well understood; more comprehensive knowledge about prenatal phenotypes and computational resources have an enormous potential to improve diagnostics and translational research. The Human Phenotype Ontology (HPO) has been widely used to support diagnostics and translational research in human genetics. To better support prenatal usage, the HPO consortium conducted a series of workshops with a group of domain experts in a variety of medical specialties, diagnostic techniques, as well as diseases and phenotypes related to prenatal medicine, including perinatal pathology, musculoskeletal anomalies, neurology, medical genetics, hydrops fetalis, craniofacial malformations, cardiology, neonatal-perinatal medicine, fetal medicine, placental pathology, prenatal imaging, and bioinformatics. We expanded the representation of prenatal phenotypes in HPO by adding 95 new phenotype terms under the Abnormality of prenatal development or birth (HP:0001197) grouping term, and revised definitions, synonyms, and disease annotations for most of the 152 terms that existed before the beginning of this effort. The expansion of prenatal phenotypes in HPO will support phenotype-driven prenatal exome and genome sequencing for precision genetic diagnostics of rare diseases to support prenatal care.

Importance of health assessments for conservation in noncaptive wildlife.

Wildlife health assessments help identify populations at risk of starvation, disease, and decline from anthropogenic impacts on natural habitats. We conducted an overview of available health assessment studies in noncaptive vertebrates and devised a framework to strategically integrate health assessments in population monitoring. Using a systematic approach, we performed a thorough assessment of studies examining multiple health parameters of noncaptive vertebrate species from 1982 to 2020 (n = 261 studies). We quantified trends in study design and diagnostic methods across taxa with generalized linear models, bibliometric analyses, and visual representations of study location versus biodiversity hotspots. Only 35% of studies involved international or cross-border collaboration. Countries with both high and threatened biodiversity were greatly underrepresented. Species that were not listed as threatened on the International Union for Conservation of Nature Red List represented 49% of assessed species, a trend likely associated with the regional focus of most studies. We strongly suggest following wildlife health assessment protocols when planning a study and using statistically adequate sample sizes for studies establishing reference ranges. Across all taxa blood analysis (89%), body composition assessments (81%), physical examination (72%), and fecal analyses (24% of studies) were the most common methods. A conceptual framework to improve design and standardize wildlife health assessments includes guidelines on the experimental design, data acquisition and analysis, and species conservation planning and management implications. Integrating a physiological and ecological understanding of species resilience toward threatening processes will enable informed decision making regarding the conservation of threatened species.

Importancia de los exámenes diagnósticos para la conservación de fauna silvestre Resumen Los exámenes diagnósticos de fauna silvestre ayudan a identificar poblaciones en riesgo por desnutrición, enfermedades infecciosas y disminución poblacional, causadas por impactos antropogénicos. Revisamos los estudios disponibles que llevaron a cabo exámenes diagnósticos en fauna silvestre y diseñamos un marco de trabajo para integrar dichos exámenes en monitoreos poblacionales. Empleando un enfoque sistemático, evaluamos aquellos estudios que examinaban múltiples indicadores de salud en vertebrados no cautivos entre 1982 y 2020 (n = 261 estudios). Cuantificamos las tendencias estadísticas, clasificadas por taxones, del diseño del estudio y de los métodos diagnósticos usando modelos lineales generalizados, análisis bibliométricos y representaciones visuales del lugar de estudio versus los hotspots (puntos calientes) de biodiversidad. Sólo el 35% de los estudios incluían colaboraciones internacionales o transfronterizas, y los países ricos en biodiversidad y especies amenazadas estaban gravemente subrepresentados. Las especies no clasificadas como amenazadas en la Lista Roja de la Unión Internacional para la Conservación de la Naturaleza representaban el 49% de las especies examinadas; una tendencia posiblemente asociada al enfoque regional de la mayoría de los estudios. Recomendamos encarecidamente seguir protocolos diagnósticos y manuales de técnicas del estudio de la fauna silvestre, además de usar tamaños muestrales estadísticamente adecuados al establecer rangos de referencia. Los métodos diagnósticos más comunes para todos los taxones fueronanálisis sanguíneos (89%), evaluaciones de composición corporal (81%), exámenes físicos (72%) y análisis fecales (24% de los estudios). Presentamos un marco conceptual para mejorar y estandarizar los exámenes diagnósticos en estudios de fauna silvestre; dicho marco incluye guías para el diseño experimental, para la obtención y el análisis de datos, y para elaborar planes de acción para especies amenazadas. La combinación de conocimientos fisiológicos y ecológicos, relacionados con la resiliencia biológica de especies amenazadas, facilitará una toma de decisiones eficiente para el manejo y para la conservación de la biodiversidad.

The highly divergent spermatozoon of the Palawan spiny rat, Maxomys panglima has an extremely long tail.

CONTEXT: Sperm morphology varies greatly across mammalian species and this variability is especially evident in murid rodents with both sperm head shape and tail length being sexually selected traits. The Palawan spiny rat, Maxomys panglima has a longer sperm tail than that currently recorded for any other mammalian species. AIMS: The aim of the current study was to determine the sperm morphology of an individual Palawan spiny rat, M. panglima . METHODS: Light and transmission electron microscopy were carried out. KEY RESULTS: We found that the sperm tail of M. panglima has an average length of 380µm with the midpiece being approximately 185µm in length with comparatively small mitochondria but very large coarse fibres. Furthermore, the sperm head has a less acutely flexed apical hook than that of most other murid rodents including those of several other Maxomys species. CONCLUSIONS: The Palawan spiny rat has a highly divergent sperm morphology with an extremely long tail. It may turn out to be an important species for testing various hypotheses of sperm form and function in mammals. IMPLICATIONS: These findings suggest markedly different selective pressures may have resulted in this unique sperm morphology, the functional significance of which remains to be determined.

A balancing act: the role of pro- and anti-stress peptides within the central amygdala in anxiety and alcohol use disorders.

The central nucleus of the amygdala (CeA) is widely implicated as a structure that integrates both appetitive and aversive stimuli. While intrinsic CeA microcircuits primarily consist of GABAergic neurons that regulate amygdala output, a notable feature of the CeA is the heterogeneity of neuropeptides and neuropeptide/neuromodulator receptors that it expresses. There is growing interest in the role of the CeA in mediating psychopathologies, including stress and anxiety states and their interactions with alcohol use disorders. Within the CeA, neuropeptides and neuromodulators often exert pro- or anti- stress actions, which can influence anxiety and alcohol associated behaviours. In turn, alcohol use can cause adaptions within the CeA, which may render an individual more vulnerable to stress which is a major trigger of relapse to alcohol seeking. This review examines the neurocircuitry, neurochemical phenotypes and how pro- and anti-stress peptide systems act within the CeA to regulate anxiety and alcohol seeking, focusing on preclinical observations from animal models. Furthermore, literature exploring the targeting of genetically defined populations or neuronal ensembles and the role of the CeA in mediating sex differences in stress x alcohol interactions are explored.

High and Highly Variable Spontaneous Mutation Rates in Daphnia.

The rate and spectrum of spontaneous mutations are critical parameters in basic and applied biology because they dictate the pace and character of genetic variation introduced into populations, which is a prerequisite for evolution. We use a mutation-accumulation approach to estimate mutation parameters from whole-genome sequence data from multiple genotypes from multiple populations of Daphnia magna, an ecological and evolutionary model system. We report extremely high base substitution mutation rates (µ-n,bs = 8.96 × 10-9/bp/generation [95% CI: 6.66-11.97 × 10-9/bp/generation] in the nuclear genome and µ-m,bs = 8.7 × 10-7/bp/generation [95% CI: 4.40-15.12 × 10-7/bp/generation] in the mtDNA), the highest of any eukaryote examined using this approach. Levels of intraspecific variation based on the range of estimates from the nine genotypes collected from three populations (Finland, Germany, and Israel) span 1 and 3 orders of magnitude, respectively, resulting in up to a ∼300-fold difference in rates among genomic partitions within the same lineage. In contrast, mutation spectra exhibit very consistent patterns across genotypes and populations, suggesting the mechanisms underlying the mutational process may be similar, even when the rates at which they occur differ. We discuss the implications of high levels of intraspecific variation in rates, the importance of estimating gene conversion rates using a mutation-accumulation approach, and the interacting factors influencing the evolution of mutation parameters. Our findings deepen our knowledge about mutation and provide both challenges to and support for current theories aimed at explaining the evolution of the mutation rate, as a trait, across taxa.

Assessing ablation margins of FDG-avid liver tumors during PET/CT-guided thermal ablation procedures: a retrospective study.

BACKGROUND: To retrospectively assess liver tumor ablation margins using intraprocedural PET/CT images from FDG PET/CT-guided microwave or cryoablation procedures and to correlate minimum margin measurements with local progression outcomes. METHODS: Fifty-six patients (ages 36 to 85, median 62; 32 females) with 77 FDG-avid liver tumors underwent 60 FDG PET/CT guided, percutaneous microwave, or cryoablation procedures. Single breath-hold PET/CT images were used for intraprocedural assessment of the tumor ablation margin: liver tumors remained visible on PET immediately following ablation; microwave ablation zones were visible using contrast-enhanced CT; cryoablation zones (ice balls) were visible using unenhanced CT. Two readers retrospectively determined ablation margin assessability and measured the minimum ablation margin on intraprocedural PET/CT (n = 77) and postprocedural MRI (n = 56). Local tumor progression was assessed on all available follow-up imaging (1-49 months, mean 15). Local tumor progression was correlated with PET/CT minimum margin measurements using clustered survival models for 61 tumors. RESULTS: Minimum ablation margins were more often assessable using intraprocedural PET/CT (≥ 73/77 tumors, 95%) than postprocedural MRI (≤ 35/56 tumors, 63%). In 61 tumors with PET/CT-assessable margins (excluding tumors with overlapping ablations after PET/CT), there was a 6-fold increased risk of local tumor progression [hazard ratio (HR) 6.05; P = 0.004] for minimum ablation margins < 5 mm. CONCLUSION: Breath-hold PET/CT scans, during PET/CT-guided microwave or cryoablation procedures for FDG-avid liver tumors, enable reliable intraprocedural assessment of the entire tumor ablation margin; a minimum PET/CT ablation margin threshold of 5 mm correlates well with local tumor progression outcomes.

Standardization of lower extremity quantitative lymphedema measurements and associated patient-reported outcomes in gynecologic cancers.

Practice changing standardization of lower extremity lymphedema quantitative measurements with integrated patient reported outcomes will likely refine and redefine the optimal risk-reduction strategies to diminish the devastating limb-related dysfunction and morbidity associated with treatment of gynecologic cancers. The National Cancer Institute (NCI), Division of Cancer Prevention brought together a diverse group of cancer treatment, therapy and patient reported outcomes experts to discuss the current state-of-the-science in lymphedema evaluation with the potential goal of incorporating new strategies for optimal evaluation of lymphedema in future developing gynecologic clinical trials.

Human milk immunomodulatory proteins are related to development of infant body composition during the first year of lactation.

BACKGROUND: To investigate relationships between infant body composition (BC) and human milk (HM) immunomodulatory proteins (IMPs) during the first 12 months of lactation. METHODS: BC of breastfeeding dyads (n = 20) was measured with ultrasound skinfolds (infants) and bioimpedance spectroscopy (infants/mothers) at 2, 5, 9, and/or 12 months post partum. Breastfeeding frequency, 24-h milk intake, and IMP concentrations (lactoferrin, lysozyme, secretory immunoglobulin A (sIgA)) were measured, and calculated daily intakes (CDIs) were determined. We used linear regression/mixed-effects models and adjusted results for multiple comparisons. RESULTS: No associations were seen between maternal characteristics and IMP concentrations/CDIs or between IMP concentrations and infant BC. Lactoferrin CDI was negatively associated with infant fat-free mass index (P = 0.002); lysozyme CDI was positively associated with infant fat mass (P = 0.004) and fat mass index (P = 0.004) measured with ultrasound skinfolds. CONCLUSION: In this small cohort of infants breastfed on demand during first year of life, we report differential associations of HM IMPs with infant BC, showing that in addition to their critical role in shaping infant immunity, lactoferrin, and lysozyme also influence development of infant BC, highlighting the importance of breastfeeding for 12 months and beyond. IMPACT: HM IMPs (concentrations and, most importantly, daily intakes) time-dependently and differentially associate with development of infant lean mass and adiposity during first 12 months of lactation. There is no information on how intakes and concentrations of these components affect development of infant BC. HM contains IMPs-lactoferrin, lysozyme, and sIgA, which not only play a critical role in shaping infant's immunity, but also influence infant growth and development of BC, highlighting the importance of breastfeeding for 12 months and beyond and warranting careful consideration of the dose effects of supplemented formula.

Comparison of segmental lean tissue mass in individuals with spinal cord injury measured by dual energy X-ray absorptiometry and predicted by bioimpedance spectroscopy.

STUDY DESIGN: Observational. OBJECTIVES: To compare two methods for predicting segmental (arms, legs, trunk) lean tissue mass (LTM: non-bone fat-free mass) from bioimpedance spectroscopy (BIS) against LTM measured from dual energy X-ray absorptiometry (DXA) in individuals with acute spinal cord injury (SCI). SETTING: Austin Health Victorian Spinal Cord Service, Victoria, Australia. METHODS: Fourteen participants (two female), within 8 weeks of traumatic SCI had BIS measured following an overnight fast and within 24 h of DXA scanning. Total body fat-free mass (FFM, body weight minus fat mass) and segmental LTM were predicted from BIS using manufacturer's proprietary software and a previously established SCI-specific prediction method. Appendicular LTM (ALM) was calculated from the sum of the LTM of the arms and legs. Agreement and strength of relationships with DXA for predicted LTM measures using both approaches were assessed using Lin's concordance coefficient and limits of agreement analysis (LOA). RESULTS: The BIS proprietary method performed better than the SCI-specific prediction method in predicting DXA LTM, demonstrating substantial concordance for total body FFM (rc = 0.80), ALM (rc = 0.78), arm (rc = 0.76) and leg LTM (rc = 0.65) and a smaller bias and LOA for ALM (+0.8 vs. -3.4 kg; LOA -4.9-6.4 vs. -11.9-5.1 kg), arm (+0.02 vs. -0.3 kg; LOA -1.1-1.1 kg vs. -2.2-1.6 kg) and leg (+0.4 vs. -1.4 kg; LOA -2.0-2.8 vs. -5.6-2.8) LTM. CONCLUSIONS: BIS can be used to accurately predict total body FFM, segmental LTM and ALM in individuals with acute SCI.

Social appearance anxiety moderates the relationship between thin-ideal internalization and eating disorder symptoms cross-sectionally and prospectively in adolescent girls.

PURPOSE: The sociocultural theory of eating disorders (EDs) posits that thin-ideal internalization may interact with social risk factors to influence ED development. Social appearance anxiety (SAA) is a potential social risk factor for EDs that may influence the relationship between thin-ideal internalization and EDs. METHODS: The current study (N = 525 adolescent females) examined whether SAA moderated the relationship between thin-ideal internalization and ED symptoms cross-sectionally and prospectively across one month. RESULTS: The interaction between thin-ideal internalization and SAA on ED symptoms was significant in both models, such that when SAA was higher, there was a significantly stronger relationship between thin-ideal internalization and ED symptoms. We also found that SAA uniquely, prospectively predicted ED symptoms. CONCLUSION: These results suggest that adolescents with high SAA and high thin-ideal internalization are more likely to exhibit higher ED symptoms. SAA both prospectively predicts ED symptoms and may amplify the relationship between thin-ideal internalization and EDs. This research highlights SAA as a social risk factor for ED development in adolescents. Interventions focused on SAA may optimize ED prevention in this population. LEVEL OF EVIDENCE: Level IV, evidence obtained from multiple time series with or without the intervention.