Contribution of Infant Food Pouches and Other Commercial Infant Foods to the Diets of Infants: A Cross-sectional Study.

BACKGROUND: Although considerable concern has been expressed about the nutritional implications of infant food pouches, how they impact infant diet has not been examined. OBJECTIVES: The objective of this study was to determine the contribution of infant food pouches specifically, and commercial infant foods generally, to nutrient intake from complementary foods in infants. METHODS: Two multiple-pass 24-h diet recall data were collected from 645 infants (6.0-11.9 mo) in the First Foods and Young Foods New Zealand studies. Detailed information was obtained on commercial infant food use, including pouches, and nutrient composition was calculated through recipe modeling. RESULTS: The diverse sample (46.1% female; 21.1% Maori, 14.1% Asian, and 54.6% European) was aged (SD) 8.4 (0.9) mo. More than one-quarter of households had high socioeconomic deprivation. Almost half (45.3%) of infants consumed an infant food pouch on ≥1 recall day [mean (SD), 1.3 (0.9) times/d], obtaining 218 (124) kJ of energy on each eating occasion. Comparable numbers for all commercial infant and toddler foods (CITFs) were 78.0%, contributing 2.2 (1.6) and 140 (118) kJ of energy. Infant food pouches provided 25.5% of the total energy from complementary foods in those infants who consumed pouches on the recall days but just 11% in all infants. Median percentage contribution of infant food pouches to nutrient intake from complementary foods in consumers ranged from <1% (added sugars and retinol) to >30% (carbohydrate, total sugars, fiber, vitamin A, and vitamin C). CITF contributed 21.4% of energy from complementary foods for infant consumers, with median percentage contribution ranging from 0.1% (retinol) to 40.3% (iron). CONCLUSIONS: Infant food pouches make relatively small contributions to energy intake in infants but are important sources of carbohydrates, fiber, and vitamins A, C, and B-6. Almost half of the total sugars consumed from complementary foods is provided by these pouches. This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12620000459921.

Local synaptic inhibition mediates cerebellar granule cell pattern separation and enables learned sensorimotor associations.

The cerebellar cortex has a key role in generating predictive sensorimotor associations. To do so, the granule cell layer is thought to establish unique sensorimotor representations for learning. However, how this is achieved and how granule cell population responses contribute to behavior have remained unclear. To address these questions, we have used in vivo calcium imaging and granule cell-specific pharmacological manipulation of synaptic inhibition in awake, behaving mice. These experiments indicate that inhibition sparsens and thresholds sensory responses, limiting overlap between sensory ensembles and preventing spiking in many granule cells that receive excitatory input. Moreover, inhibition can be recruited in a stimulus-specific manner to powerfully decorrelate multisensory ensembles. Consistent with these results, granule cell inhibition is required for accurate cerebellum-dependent sensorimotor behavior. These data thus reveal key mechanisms for granule cell layer pattern separation beyond those envisioned by classical models.

Bioassay-Driven, Fractionation-Empowered, Focused Metabolomics for Discovering Bacterial Activators of Aryl Hydrocarbon Receptor.

Aryl hydrocarbon receptor (AhR) is a transcription factor that regulates gene expression upon ligand activation, enabling microbiota-dependent induction, training, and function of the host immune system. A spectrum of metabolites, encompassing indole and tryptophan derivatives, have been recognized as activators. This work introduces an integrated, mass spectrometry-centric workflow that employs a bioassay-guided, fractionation-based methodology for the identification of AhR activators derived from human bacterial isolates. By leveraging the workflow efficiency, the complexities inherent in metabolomics profiling are significantly reduced, paving the way for an in-depth and focused mass spectrometry analysis of bioactive fractions isolated from bacterial culture supernatants. Validation of AhR activator candidates used multiple criteria─MS/MS of the synthetic reference compound, bioassay of AhR activity, and elution time confirmation using a C-13 isotopic reference─and was demonstrated for N-formylkynurenine (NFK). The workflow reported provides a roadmap update for improved efficiency of identifying bioactive metabolites using mass spectrometry-based metabolomics. Mass spectrometry datasets are accessible at the National Metabolomics Data Repository (PR001479, Project DOI: 10.21228/M8JM7Q).

Baby food pouches and Baby-Led Weaning: Associations with energy intake, eating behaviour and infant weight status.

Although concern is frequently expressed regarding the potential impact of baby food pouch use and Baby-Led Weaning (BLW) on infant health, research is scarce. Data on pouch use, BLW, energy intake, eating behaviour and body mass index (BMI) were obtained for 625 infants aged 7-10 months in the First Foods New Zealand study. Frequent pouch use was defined as ≥5 times/week during the past month. Traditional spoon-feeding (TSF), "partial" BLW and "full" BLW referred to the relative proportions of spoon-feeding versus infant self-feeding, assessed at 6 months (retrospectively) and current age. Daily energy intake was determined using two 24-h dietary recalls, and caregivers reported on a variety of eating behaviours. Researchers measured infant length and weight, and BMI z-scores were calculated (World Health Organization Child Growth Standards). In total, 28% of infants consumed food from pouches frequently. Frequent pouch use was not significantly related to BMI z-score (mean difference, 0.09; 95% CI -0.09, 0.27) or energy intake (92 kJ/day; -19, 202), but was associated with greater food responsiveness (standardised mean difference, 0.3; 95% CI 0.1, 0.4), food fussiness (0.3; 0.1, 0.4) and selective/restrictive eating (0.3; 0.2, 0.5). Compared to TSF, full BLW was associated with greater daily energy intake (BLW at 6 months: mean difference 150 kJ/day; 95% CI 4, 297; BLW at current age: 180 kJ/day; 62, 299) and with a range of eating behaviours, including greater satiety responsiveness, but not BMI z-score (6 months: 0.06 (-0.18, 0.30); current age: 0.06 (-0.13, 0.26)). In conclusion, neither feeding approach was associated with weight in infants, despite BLW being associated with greater energy intake compared with TSF. However, infants who consumed pouches frequently displayed higher food fussiness and more selective eating.

Adherence to Infant Feeding Guidelines in the First Foods New Zealand Study.

Infant feeding guidelines provide evidence-based recommendations to support optimal infant health, growth, and development, and exploring adherence to guidelines is a useful way of assessing diet quality. The aim of this study was to determine adherence to the recently updated Ministry of Health "Healthy Eating Guidelines for New Zealand Babies and Toddlers (0-2 years old)". Data were obtained from First Foods New Zealand, a multicentre observational study of 625 infants aged 7.0-10.0 months. Caregivers completed two 24-h diet recalls and a demographic and feeding questionnaire. Nearly all caregivers (97.9%) initiated breastfeeding, 37.8% exclusively breastfed to around six months of age, and 66.2% were currently breastfeeding (mean age 8.4 months). Most caregivers met recommendations for solid food introduction, including appropriate age (75.4%), iron-rich foods (88.3%), puréed textures (80.3%), and spoon-feeding (74.1%). Infants consumed vegetables (63.2%) and fruit (53.9%) more frequently than grain foods (49.5%), milk and milk products (38.6%), and meat and protein-rich foods (31.8%). Most caregivers avoided inappropriate beverages (93.9%) and adding salt (76.5%) and sugar (90.6%). Our findings indicated that while most infants met the recommendations for the introduction of appropriate solid foods, the prevalence of exclusive breastfeeding could be improved, indicating that New Zealand families may need more support.

High-throughput bioprinting of the nasal epithelium using patient-derived nasal epithelial cells.

Progenitor human nasal epithelial cells (hNECs) are an essential cell source for the reconstruction of the respiratory pseudostratified columnar epithelium composed of multiple cell types in the context of infection studies and disease modeling. Hitherto, manual seeding has been the dominant method for creating nasal epithelial tissue models through biofabrication. However, this approach has limitations in terms of achieving the intricate three-dimensional (3D) structure of the natural nasal epithelium. 3D bioprinting has been utilized to reconstruct various epithelial tissue models, such as cutaneous, intestinal, alveolar, and bronchial epithelium, but there has been no attempt to use of 3D bioprinting technologies for reconstruction of the nasal epithelium. In this study, for the first time, we demonstrate the reconstruction of the nasal epithelium with the use of primary hNECs deposited on Transwell inserts via droplet-based bioprinting (DBB), which enabled high-throughput fabrication of the nasal epithelium in Transwell inserts of 24-well plates. DBB of progenitor hNECs ranging from one-tenth to one-half of the cell seeding density employed during the conventional cell seeding approach enabled a high degree of differentiation with the presence of cilia and tight-junctions over a 4 weeks air-liquid interface culture. Single cell RNA sequencing of these cultures identified five major epithelial cells populations, including basal, suprabasal, goblet, club, and ciliated cells. These cultures recapitulated the pseudostratified columnar epithelial architecture present in the native nasal epithelium and were permissive to respiratory virus infection. These results denote the potential of 3D bioprinting for high-throughput fabrication of nasal epithelial tissue models not only for infection studies but also for other purposes, such as disease modeling, immunological studies, and drug screening.

Attenuation hotspots in neurotropic human astroviruses.

During the last decade, the detection of neurotropic astroviruses has increased dramatically. The MLB genogroup of astroviruses represents a genetically distinct group of zoonotic astroviruses associated with gastroenteritis and severe neurological complications in young children, the immunocompromised, and the elderly. Using different virus evolution approaches, we identified dispensable regions in the 3' end of the capsid-coding region responsible for attenuation of MLB astroviruses in susceptible cell lines. To create recombinant viruses with identified deletions, MLB reverse genetics (RG) and replicon systems were developed. Recombinant truncated MLB viruses resulted in imbalanced RNA synthesis and strong attenuation in iPSC-derived neuronal cultures confirming the location of neurotropism determinants. This approach can be used for the development of vaccine candidates using attenuated astroviruses that infect humans, livestock animals, and poultry.

Gaudeamus Igitur at 40-A Tribute and Assessment.

This Arts and Medicine feature discusses the continuing relevance of the 1983 poem Gaudeamus Igitur by John Stone, which offers wisdom and guiding principles about the practice of medicine to newly graduated young physicians.

Skin microbiome attributes associate with biophysical skin ageing.

Two major arms of skin ageing are changes in the skin's biophysical conditions and alterations in the skin microbiome. This work partitioned both arms to study their interaction in detail. Leveraging the resolution provided by shotgun metagenomics, we explored how skin microbial species, strains and gene content interact with the biophysical traits of the skin during ageing. With a dataset well-controlled for confounding factors, we found that skin biophysical traits, especially the collagen diffusion coefficient, are associated with the composition and the functional potential of the skin microbiome, including the abundance of bacterial strains found in nosocomial infections and the abundance of antibiotic resistance genes. Our findings reveal important associations between skin biophysical features and ageing-related changes in the skin microbiome and generate testable hypotheses for the mechanisms of such associations.

High-Throughput Bioprinting of the Nasal Epithelium using Patient-derived Nasal Epithelial Cells.

Human nasal epithelial cells (hNECs) are an essential cell source for the reconstruction of the respiratory pseudostratified columnar epithelium composed of multiple cell types in the context of infection studies and disease modeling. Hitherto, manual seeding has been the dominant method for creating nasal epithelial tissue models. However, the manual approach is slow, low-throughput and has limitations in terms of achieving the intricate 3D structure of the natural nasal epithelium in a uniform manner. 3D Bioprinting has been utilized to reconstruct various epithelial tissue models, such as cutaneous, intestinal, alveolar, and bronchial epithelium, but there has been no attempt to use of 3D bioprinting technologies for reconstruction of the nasal epithelium. In this study, for the first time, we demonstrate the reconstruction of the nasal epithelium with the use of primary hNECs deposited on Transwell inserts via droplet-based bioprinting (DBB), which enabled high-throughput fabrication of the nasal epithelium in Transwell inserts of 24-well plates. DBB of nasal progenitor cells ranging from one-tenth to one-half of the cell seeding density employed during the conventional cell seeding approach enabled a high degree of differentiation with the presence of cilia and tight-junctions over a 4-week air-liquid interface culture. Single cell RNA sequencing of these cultures identified five major epithelial cells populations, including basal, suprabasal, goblet, club, and ciliated cells. These cultures recapitulated the pseudostratified columnar epithelial architecture present in the native nasal epithelium and were permissive to respiratory virus infection. These results denote the potential of 3D bioprinting for high-throughput fabrication of nasal epithelial tissue models not only for infection studies but also for other purposes such as disease modeling, immunological studies, and drug screening.

The effect of modest changes in sleep on dietary intake and eating behavior in children: secondary outcomes of a randomized crossover trial.

BACKGROUND: Insufficient sleep duration increases obesity risk in children, but the mechanisms remain unclear. OBJECTIVES: This study seeks to determine how changes in sleep influence energy intake and eating behavior. METHODS: Sleep was experimentally manipulated in a randomized, crossover study in 105 children (8-12 y) who met current sleep guidelines (8-11 h/night). Participants went to bed 1 h earlier (sleep extension condition) and 1 h later (sleep restriction condition) than their usual bedtime for 7 consecutive nights, separated by a 1-wk washout. Sleep was measured via waist-worn actigraphy. Dietary intake (2 24-h recalls/wk), eating behaviors (Child Eating Behavior Questionnaire), and the desire to eat different foods (questionnaire) were measured during or at the end of both sleep conditions. The type of food was classified by the level of processing (NOVA) and as core or noncore (typically energy-dense foods) foods. Data were analyzed according to 'intention to treat' and 'per protocol,' an a priori difference in sleep duration between intervention conditions of ≥30 min. RESULTS: The intention to treat analysis (n = 100) showed a mean difference (95% CI) in daily energy intake of 233 kJ (-42, 509), with significantly more energy from noncore foods (416 kJ; 6.5, 826) during sleep restriction. Differences were magnified in the per-protocol analysis, with differences in daily energy of 361 kJ (20, 702), noncore foods of 504 kJ (25, 984), and ultraprocessed foods of 523 kJ (93, 952). Differences in eating behaviors were also observed, with greater emotional overeating (0.12; 0.01, 0.24) and undereating (0.15; 0.03, 0.27), but not satiety responsiveness (-0.06; -0.17, 0.04) with sleep restriction. CONCLUSIONS: Mild sleep deprivation may play a role in pediatric obesity by increasing caloric intake, particularly from noncore and ultraprocessed foods. Eating in response to emotions rather than perceived hunger may partly explain why children engage in unhealthy dietary behaviors when tired. This trial was registered at Australian New Zealand Clinical Trials Registry; ANZCTR as CTRN12618001671257.

Multi-'omics of gut microbiome-host interactions in short- and long-term myalgic encephalomyelitis/chronic fatigue syndrome patients.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, debilitating disorder manifesting as severe fatigue and post-exertional malaise. The etiology of ME/CFS remains elusive. Here, we present a deep metagenomic analysis of stool combined with plasma metabolomics and clinical phenotyping of two ME/CFS cohorts with short-term (<4 years, n = 75) or long-term disease (>10 years, n = 79) compared with healthy controls (n = 79). First, we describe microbial and metabolomic dysbiosis in ME/CFS patients. Short-term patients showed significant microbial dysbiosis, while long-term patients had largely resolved microbial dysbiosis but had metabolic and clinical aberrations. Second, we identified phenotypic, microbial, and metabolic biomarkers specific to patient cohorts. These revealed potential functional mechanisms underlying disease onset and duration, including reduced microbial butyrate biosynthesis and a reduction in plasma butyrate, bile acids, and benzoate. In addition to the insights derived, our data represent an important resource to facilitate mechanistic hypotheses of host-microbiome interactions in ME/CFS.

Engineering a "detect and destroy" skin probiotic to combat methicillin-resistant Staphylococcus aureus.

The prevalence and virulence of pathogens such as methicillin-resistant Staphylococcus (S.) aureus (MRSA), which can cause recurrent skin infections, are of significant clinical concern. Prolonged antibiotic exposure to treat or decolonize S. aureus contributes to development of antibiotic resistance, as well as depletion of the microbiome, and its numerous beneficial functions. We hypothesized an engineered skin probiotic with the ability to selectively deliver antimicrobials only in the presence of the target organism could provide local bioremediation of pathogen colonization. We constructed a biosensing S. epidermidis capable of detecting the presence of S. aureus quorum sensing autoinducer peptide and producing lysostaphin in response. Here, we demonstrate in vitro activity of this biosensor and present and discuss challenges to deployment of this and other engineered topical skin probiotics.

Large-Scale CRISPRi and Transcriptomics of Staphylococcus epidermidis Identify Genetic Factors Implicated in Lifestyle Versatility.

Staphylococcus epidermidis is a ubiquitous human commensal skin bacterium that is also one of the most prevalent nosocomial pathogens. The genetic factors underlying this remarkable lifestyle plasticity are incompletely understood, mainly due to the difficulties of genetic manipulation, precluding high-throughput functional profiling of this species. To probe the versatility of S. epidermidis to survive across a diversity of environmental conditions, we developed a large-scale CRISPR interference (CRISPRi) screen complemented by transcriptional profiling (RNA sequencing) across 24 diverse conditions and piloted a droplet-based CRISPRi approach to enhance throughput and sensitivity. We identified putative essential genes, importantly revealing amino acid metabolism as crucial to survival across diverse environments, and demonstrated the importance of trace metal uptake for survival under multiple stress conditions. We identified pathways significantly enriched and repressed across our range of stress and nutrient-limited conditions, demonstrating the considerable plasticity of S. epidermidis in responding to environmental stressors. Additionally, we postulate a mechanism by which nitrogen metabolism is linked to lifestyle versatility in response to hyperosmotic challenges, such as those encountered on human skin. Finally, we examined the survival of S. epidermidis under acid stress and hypothesize a role for cell wall modification as a vital component of the survival response under acidic conditions. Taken together, this study integrates large-scale CRISPRi and transcriptomics data across multiple environments to provide insights into a keystone member of the human skin microbiome. Our results additionally provide a valuable benchmarking analysis for CRISPRi screens and are a rich resource for other staphylococcal researchers. IMPORTANCE Staphylococcus epidermidis is a bacteria that broadly inhabits healthy human skin, yet it is also a common cause of skin infections and bloodstream infections associated with implanted medical devices. Because human skin has many different types of S. epidermidis, each containing different genes, our goal is to determine how these different genes allow S. epidermidis to switch from healthy growth in the skin to being an infectious pathogen. Understanding this switch is critical to developing new strategies to prevent and treat S. epidermidis infections.

Associations of the skin, oral and gut microbiome with aging, frailty and infection risk reservoirs in older adults.

Older adults represent a vulnerable population with elevated risk for numerous morbidities. To explore the association of the microbiome with aging and age-related susceptibilities including frailty and infectious disease risk, we conducted a longitudinal study of the skin, oral, and gut microbiota in 47 community- or skilled nursing facility-dwelling older adults vs. younger adults. We found that microbiome changes were not associated with chronological age so much as frailty: we identified prominent changes in microbiome features associated with susceptibility to pathogen colonization and disease risk, including diversity, stability, heterogeneity, and biogeographic determinism, which were moreover associated with a loss of Cutibacterium (C.) acnes in the skin microbiome. Strikingly, the skin microbiota were also the primary reservoir for antimicrobial resistance, clinically important pathobionts, and nosocomial strains, suggesting a potential role particularly for the skin microbiome in disease risk and dissemination of multidrug resistant pathogens.

Notes on Healing After a Missed Diagnosis.

In this narrative medicine essay, a family physician maintains her patient's trust despite missing what could have been a catastrophic diagnosis because she apologized for her oversight.

Embryonic exposure to benzo[a]pyrene causes age-dependent behavioral alterations and long-term metabolic dysfunction in zebrafish.

Polycyclic aromatic hydrocarbons (PAH) are products of incomplete combustion which are ubiquitous pollutants and constituents of harmful mixtures such as tobacco smoke, petroleum and creosote. Animal studies have shown that these compounds exert developmental toxicity in multiple organ systems, including the nervous system. The relative persistence of or recovery from these effects across the lifespan remain poorly characterized. These studies tested for persistence of neurobehavioral effects in AB* zebrafish exposed 5-120 h post-fertilization to a typical PAH, benzo[a]pyrene (BAP). Study 1 evaluated the neurobehavioral effects of a wide concentration range of BAP (0.02-10 µM) exposures from 5 to 120 hpf during larval (6 days) and adult (6 months) stages of development, while study 2 evaluated neurobehavioral effects of BAP (0.3-3 µM) from 5 to 120 hpf across four stages of development: larval (6 days), adolescence (2.5 months), adulthood (8 months) and late adulthood (14 months). Embryonic BAP exposure caused minimal effects on larval motility, but did cause neurobehavioral changes at later points in life. Embryonic BAP exposure led to nonmonotonic effects on adolescent activity (0.3 µM hyperactive, Study 2), which attenuated with age, as well as startle responses (0.2 µM enhanced, Study 1) at 6 months of age. Similar startle changes were also detected in Study 2 (1.0 µM), though it was observed that the phenotype shifted from reduced pretap activity to enhanced posttap activity from 8 to 14 months of age. Changes in the avoidance (0.02-10 µM, Study 1) and approach (reduced, 0.3 µM, Study 2) of aversive/social cues were also detected, with the latter attenuating from 8 to 14 months of age. Fish from study 2 were maintained into aging (18 months) and evaluated for overall and tissue-specific oxygen consumption to determine whether metabolic processes in the brain and other target organs show altered function in late life based on embryonic PAH toxicity. BAP reduced whole animal oxygen consumption, and overall reductions in total basal, mitochondrial basal, and mitochondrial maximum respiration in target organs, including the brain, liver and heart. The present data show that embryonic BAP exposure can lead to neurobehavioral impairment across the life-span, but that these long-term risks differentially emerge or attenuate as development progresses.

Selenium intakes and plasma selenium of New Zealand toddlers: secondary analysis of a randomised controlled trial.

Little is known about Se intakes and status in very young New Zealand children. However, Se intakes below recommendations and lower Se status compared with international studies have been reported in New Zealand (particularly South Island) adults. The Baby-Led Introduction to SolidS (BLISS) randomised controlled trial compared a modified version of baby-led weaning (infants feed themselves rather than being spoon-fed), with traditional spoon-feeding (Control). Weighed 3-d diet records were collected and plasma Se concentration measured using inductively coupled plasma mass spectrometry (ICP-MS). In total, 101 (BLISS n 50, Control n 51) 12-month-old toddlers provided complete data. The OR of Se intakes below the estimated average requirement (EAR) was no different between BLISS and Control (OR: 0·89; 95 % CI 0·39, 2·03), and there was no difference in mean plasma Se concentration between groups (0·04 µmol/l; 95 % CI -0·03, 0·11). In an adjusted model, consuming breast milk was associated with lower plasma Se concentrations (-0·12 µmol/l; 95 % CI -0·19, -0·04). Of the food groups other than infant milk (breast milk or infant formula), 'breads and cereals' contributed the most to Se intakes (12 % of intake). In conclusion, Se intakes and plasma Se concentrations of 12-month-old New Zealand toddlers were no different between those who had followed a baby-led approach to complementary feeding and those who followed traditional spoon-feeding. However, more than half of toddlers had Se intakes below the EAR.

Skin Microbiome Variation with Cancer Progression in Human Cutaneous Squamous Cell Carcinoma.

The skin microbiome plays a critical role in skin homeostasis and disorders. UVR is the major cause of nonmelanoma skin cancer, but other risk factors, including immune suppression, chronic inflammation, and antibiotic usage, suggest the microbiome as an additional, unexplored risk factor and potential disease biomarker. The overarching goal was to study the skin microbiome in squamous cell carcinoma (SCC) and premalignant actinic keratosis compared with that in healthy skin to identify skin cancer‒associated changes in the skin microbiome. We performed a high-resolution analysis of shotgun metagenomes of actinic keratosis and SCC in healthy skin, revealing the microbial community shifts specific to actinic keratosis and SCC. Most prominently, the relative abundance of pathobiont Staphylococcus aureus was increased at the expense of commensal Cutibacterium acnes in SCC compared with that in healthy skin, and enrichment of functional pathways in SCC reflected this shift. Notably, C. acnes associated with lesional versus healthy skin differed at the strain level, suggesting the specific functional changes associated with its depletion in SCC. Our study revealed a transitional microbial dysbiosis from healthy skin to actinic keratosis to SCC, supporting further investigation of the skin microbiome for use as a biomarker and providing hypotheses for studies investigating how these microbes might influence skin cancer progression.