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The objective of this study was to characterize biopsychosocial characteristics in children with failure to thrive with a focus on 4 domains: medical, nutrition, feeding skills, and psychosocial characteristics. A retrospective cross-sectional chart review was conducted of children assessed at the Infant and Toddler Growth and Feeding Clinic from 2015 to 2016. Descriptive statistics were used to analyze the data. One hundred thirty-eight children, 53.6% male, mean age 16.9 months (SD = 10.8), were included. Approximately one quarter of the children had complex medical conditions, medical comorbidities, and developmental delays. The mean weight-for-age percentile was 15.5 (SD = 23.9), and mean weight-for-length z score was −1.51 (SD = 1.4). A total of 22.5% of children had delayed oral-motor skills and 28.3% had oral aversion symptoms. Caregiver feeding strategies included force feeding (14.5%) and the use of distractions (47.1%). The multifactorial assessment of failure to thrive according to the 4 domains allowed for a better understanding of contributing factors and could facilitate multidisciplinary collaboration.

The development of adequate growth and healthy eating behaviors depends on nutritious food and responsive feeding practices. Our study examined (1) the relationship between maternal concern about child weight or perceived feeding difficulties and their feeding practices, and (2) the moderating role of child temperament and maternal mental health on their feeding practices. A cross-sessional study included mother–child dyads (n = 98) from a tertiary growth and feeding clinic. Children had a mean age of 12.7 ± 5.0 months and a mean weight-for-age z-score of −2.0 ± 1.3. Responsive and controlling feeding practices were measured with the Infant Feeding Styles Questionnaire. Spearman correlation and moderation analysis were performed. Maternal concern about child weight and perceived feeding difficulties were negatively correlated with responsive feeding (r = −0.40, −0.48, p < 0.001). A greater concern about child weight or perceived feeding difficulties was associated with greater use of pressure feeding practices when effortful control was low (B = 0.49, t = 2.47, p = 0.01; B = −0.27, p = 0.008). Maternal anxiety had a significant moderation effect on the relationship between feeding difficulty and pressure feeding (B = −0.04, p = 0.009). Higher maternal concern about child weight and perceived feeding difficulties were associated with less responsive satiety feeding beliefs and behaviors. Both child effortful control and maternal anxiety influenced the relationship between weight and feeding concerns and the use of pressure feeding practices.

Abstract Fellows in child maltreatment paediatrics (CMP) are at risk of secondary traumatic stress (STS). Contributing factors include inexperience, younger age, lack of mastery, high caseloads, and longer working hours. Literature has previously focused on individual resilience; as understanding about STS evolves, it has been recognized that organizational resilience is important in supporting healthcare professionals. Our objective was to develop, implement, and evaluate an innovative program to increase resilience to STS among fellows in a child maltreatment training program. A trauma-informed counsellor with expertise in both secondary-traumatic stress and medical education was identified through the University Wellness Office. The counsellor was not a member of the CMP team and facilitated a targeted program that included monthly, small group session for all CMP fellows. Sessions involved low-intensity activities that encouraged self-reflection and focused attention. The counsellor facilitated discussions around difficult cases with active listening, immersion into the affective experience of others, and avoidance of judgment, blame, or criticism. Fellows were encouraged to speak about their own experiences, rather than commenting on the experiences of others. This created a safe environment in which to explore and process difficult material. Evidence-based strategies were offered at the end of each session. An important component of the program was an iterative process of feedback and reflection on the session structure and process. Written reflections were collected from fellows and staff, which were qualitatively analyzed by two reviewers to identify key themes. Qualitative analysis of individual written reflections identified four major themes, including high satisfaction with program, strategies for prevention and management of STS, bonded fellowship peer group, and feelings of validation from one another. There was unanimous reporting of high levels of satisfaction with the program by both fellows and supervising staff. Fellows described excitedly anticipating sessions and experiencing renewed energy following group sessions. Supervising staff reported seeing fellows apply skills and strategies learned for prevention and management of STS. Between sessions, fellows reported improved STS symptoms and employing preventative self-care strategies. It was reported that the strategies learned assisted fellows in developing a reflection style that was intentional and individualized for their wellbeing. An unanticipated outcome that was unianimously reported by fellows and noted by staff was the fostering of a strongly bonded and supportive fellowship peer group, further increasing perceptions of wellbeing. Fellows reported feeling validation from one another during group sessions and utilizing approaches in real-time informal discussions with team members as difficult clinical cases arose. This targeted program for fellows was developed as an innovative approach to addressing secondary traumatic stress among new learners in the challenging field of child maltreatment paediatrics. It has demonstrated acceptability among fellows and supervising staff with reported improvement in STS symptoms. Future steps will address the broader goal of optimizing organizational resilience among other members of the child maltreatment team.

Abstract Failure to thrive (FTT) is prevalent in 5% of the paediatric population and results from the interactions between the child's health, behaviour, development and social environment. A multi-disciplinary team approach to treat FTT is effective but resources are not always available. To characterize biopsychosocial factors and feeding behaviours in children presenting with failure to thrive in our clinic. A retrospective cross-sectional chart review of children referred to our academic growth and feeding clinic was performed. Children between the ages of 2 months and 5 years with a first clinic visit between 1st January 2015 and 31st of December 2016 were included. Data from the patient's first visit was included in the study. In a REDCAP database, anthropometric measures according to WHO growth curves, medical history and concurrent developmental delays were recorded. Factors important to the child's social environment (e.g. maternal mental health, financial problems) were identified. These factors were self-reported by parents to the clinic team or noted on the patient's referral. Specific attention was paid to the identification of feeding behaviours of children (e.g. vomiting, gagging) and parents (e.g. force feeding, use of distractions). Descriptive statistics were used to analyze the data. The study included n = 138 (53.6% male) children with a mean age of 16.9 (SD 10.8) months. The mean weight-for-age percentile was 16.0 (SD 24.3), mean height-for age percentile was 23.8 (SD 30.7), and mean weight-for-length percentile was 16.8 (SD 23.4). 88 (63.8%) children had both growth and feeding behaviour concerns. 26 (18.8%) children were born prematurely and 24 (17.4%) were small for gestational age. 57 (41.3%) children had a history of gastro-oesophageal reflux. In 10 (7.2 %) children, a genetic diagnosis was identified. Concurrent developmental delays were described in the gross motor (20.3%), fine motor (8.0%), speech and language (20.3%) and social domains (6.5%). Feeding developmental milestones that were delayed included not-self feeding (17.4%) and a diet inappropriate for age (20.3%). Important factors that were identified in the child's social environment were: maternal depression (5.1%), CAS involvement (10.1%) and financial problems (7.2 %). Maternal anxiety was reported but difficult to define. In more than half (50.7%) of the children, feeding behaviours of vomiting, gagging and/or crying and arching were described. Parents used force feeding (14.5%) and distractions (47.1%), and reported mealtimes longer than 30 minutes (70.3%). Most commonly used distractions were television (25.4%) and mobile screens (14.5%). In our academic population of children with FTT, there is a high incidence of concurrent developmental delays, delayed feeding milestones and feeding behaviour problems. Almost half of the parents used distractions and even more parents prolonged mealtimes to make their child eat. These results underscore the importance of a multi-disciplinary team approach to address feeding behaviours and child development in our population of children with FTT.

Understanding metabolism in the pathogen Candida glabrata is key to identifying new targets for antifungals. The thiamine biosynthetic (THI) pathway is partially defective in C . glabrata , but the transcription factor Cg Pdc2 upregulates some thiamine biosynthetic and transport genes. One of these genes encodes a recently evolved thiamine pyrophosphatase ( CgPMU3 ) that is critical for accessing external thiamine. Here, we demonstrate that Cg Pdc2 primarily regulates THI genes. In Saccharomyces cerevisiae , Pdc2 regulates both THI and pyruvate decarboxylase (PDC) genes, with PDC proteins being a major thiamine sink. Deletion of PDC2 is lethal in S . cerevisiae in standard growth conditions, but not in C . glabrata . We uncover cryptic cis elements in C . glabrata PDC promoters that still allow for regulation by Sc Pdc2, even when that regulation is not apparent in C . glabrata . C . glabrata lacks Thi2, and it is likely that inclusion of Thi2 into transcriptional regulation in S . cerevisiae allows for a more complex regulation pattern and regulation of THI and PDC genes. We present evidence that Pdc2 functions independent of Thi2 and Thi3 in both species. The C-terminal activation domain of Pdc2 is intrinsically disordered and critical for species differences. Truncation of the disordered domains leads to a gradual loss of activity. Through a series of cross species complementation assays of transcription, we suggest that there are multiple Pdc2-containing complexes, and C . glabrata appears to have the simplest requirement set for THI genes, except for CgPMU3 . CgPMU3 has different cis requirements, but still requires Pdc2 and Thi3 to be upregulated by thiamine starvation. We identify the minimal region sufficient for thiamine regulation in CgTHI20 , CgPMU3 , and ScPDC5 promoters. Defining the cis and trans requirements for THI promoters should lead to an understanding of how to interrupt their upregulation and provide targets in metabolism for antifungals.

Ecological applications of compound-specific stable isotope analysis (CSIA) of amino acids (AAs) include 1) tracking carbon pathways in food webs using essential AA (AA ESS ) δ 13 C values, and 2) estimating consumer trophic position (TP) by comparing relative differences of ‘trophic’ and ‘source’ AA δ 15 N values. Despite the significance of these applications, few studies have examined AA-specific SI patterns among tissues with different AA compositions and metabolism/turnover rates, which could cause differential drawdown of body AA pools and impart tissue-specific isotopic fractionation. To address this knowledge gap, especially in the absence of controlled diet studies examining this issue in captive marine mammals, we used a paired-sample design to compare δ 13 C and δ 15 N values of 11 AAs in commonly sampled tissues (skin, muscle, and dentine) from wild beluga whales ( Delphinapterus leucas ). δ 13 C of two AAs, glutamic acid/glutamine (Glx, a non-essential AA) and, notably, threonine (an essential AA), differed between skin and muscle. Furthermore, δ 15 N of three AAs (alanine, glycine, and proline) differed significantly among the three tissues, with glycine δ 15 N differences of approximately 10 ‰ among tissues supporting recent findings it is unsuitable as a source AA. Significant δ 15 N differences in AAs such as proline, a trophic AA used as an alternative to Glx in TP estimation, highlight tissue selection as a potential source of error in ecological applications of CSIA-AA. Amino acids that differed among tissues play key roles in metabolic pathways (e.g., ketogenic and gluconeogenic AAs), pointing to potential physiological applications of CSIA-AA in studies of free-ranging animals. These findings underscore the complexity of isotopic dynamics within tissues and emphasize the need for a nuanced approach when applying CSIA-AA in ecological research.

CRISPR/Cas9 screening has proven to be a versatile tool for genomics research. Based on unexpected results from a genome-wide screen, we developed a CRISPR/Cas9-mediated approach to mutagenesis, exploiting the allelic diversity generated by error-prone non-homologous end-joining (NHEJ) to identify novel gain-of-function and drug resistant alleles of the MAPK signaling pathway genes MEK1 and BRAF. We define the parameters of a scalable technique to easily generate cell populations containing thousands of endogenous allelic variants to map gene functions. Further, these results highlight an unexpected but important phenomenon, that Cas9-induced gain-of-function alleles are an inherent by-product of normal Cas9 loss-of-function screens and should be investigated during analysis of data from large-scale positive selection screens.

The difficulty in obtaining as well as maintaining weight loss, together with the impairment of metabolic control in conditions like diabetes and cardiovascular disease, may represent pathological situations of inadequate neural communication between the brain and peripheral organs and tissues. Innervation of adipose tissues by peripheral nerves provides a means of communication between the master metabolic regulator in the brain (chiefly the hypothalamus), and energy-expending and energy-storing cells in the body (primarily adipocytes). Although chemical and surgical denervation studies have clearly demonstrated how crucial adipose tissue neural innervation is for maintaining proper metabolic health, we have uncovered that adipose tissue becomes neuropathic (ie: reduction in neurites) in various conditions of metabolic dysregulation. Here, utilizing both human and mouse adipose tissues, we present evidence of adipose tissue neuropathy, or loss of proper innervation, under pathophysiological conditions such as obesity, diabetes, and aging, all of which are concomitant with insult to the adipose organ as well as metabolic dysfunction. Neuropathy is indicated by loss of nerve fiber protein expression, reduction in synaptic markers, and lower neurotrophic factor expression in adipose tissue. Aging-related adipose neuropathy particularly results in loss of innervation around the tissue vasculature, which cannot be reversed by exercise. Together with indications of neuropathy in muscle and bone, these findings underscore that peripheral neuropathy is not restricted to classic tissues like the skin of distal extremities, and that loss of innervation to adipose may trigger or exacerbate metabolic diseases. In addition, we have demonstrated stimulation of adipose tissue neural plasticity with cold exposure, which may ameliorate adipose neuropathy and be a potential therapeutic option to re-innervate adipose and restore metabolic health.

Increased plant growth under elevated carbon dioxide (CO2) slows the pace of climate warming and underlies projections of terrestrial carbon (C) and climate dynamics. However, this important ecosystem service may be diminished by concurrent changes to vegetation carbon‐to‐nitrogen (C:N) ratios. Despite clear observational evidence of increasing foliar C:N under elevated CO2, our understanding of potential ecological consequences of foliar stoichiometric flexibility is incomplete. Here, we illustrate that when we incorporated CO2‐driven increases in foliar stoichiometry into the Community Land Model the projected land C sink decreased two‐fold by the end of the century compared to simulations with fixed foliar chemistry. Further, CO2‐driven increases in foliar C:N profoundly altered Earth's hydrologic cycle, reducing evapotranspiration and increasing runoff, and reduced belowground N cycling rates. These findings underscore the urgency of further research to examine both the direct and indirect effects of changing foliar stoichiometry on soil N cycling and plant productivity. Plain Language Summary As atmospheric carbon dioxide (CO2) increases, plants grow more and take up more CO2, which could slow the pace of climate change. However, higher CO2 dilutes leaf nutrient concentrations, which could ultimately limit plant growth as CO2 continues to rise. The change in leaf chemistry in response to rising CO2 is not well represented in models used to predict future productivity and the land carbon sink. By simulating CO2‐driven changes in leaf chemistry in the Community Land Model, we quantified potential effects of shifting leaf chemistry on future vegetation growth and global C, nutrient, and hydrologic cycles. The new model simulation reduced the strength of the land C sink 2‐fold compared to simulations where foliar chemistry does not change in response to atmospheric CO2. The reduction in plant growth also produced large hydrologic changes, including reduced global evapotranspiration and increased runoff. Nitrogen cycling rates were reduced in the flexible simulation but highlighted a gap in our understanding of aboveground‐belowground feedbacks that warrants further research. Thus, the ways we represent foliar chemistry in models are important for understanding the future conditions of the planet and our capacity to respond to climate change. Key Points A flexible, CO2‐driven parameterization of foliar C:N in the Community Land Model produced a 2‐fold reduction in the projected land C sink The flexible foliar C:N parameterization also had large effects on the hydrologic cycle, reducing evapotranspiration and increasing runoff N cycling rates were reduced under the flexible C:N scenario but highlight the need for additional research on modeled plant‐soil feedbacks

ObjectiveIgG4-related disease (IgG4-RD) is a heterogeneous, multiorgan condition of unclear aetiology that can cause organ failure. Difficulty recognising IgG4-RD contributes to diagnostic delays. We sought to identify key IgG4-RD phenotypes.MethodsWe used two cross-sectional studies assembled by an international, multispecialty network of IgG4-RD specialists who submitted 765 cases to derive and replicate phenotypic groups. Phenotype groups of disease manifestations and key covariate distributions across the identified groups were measured using latent class analysis.ResultsIn the derivation cohort (n=493), we identified four groups with distinct manifestations: Group 1 (31%), Pancreato-Hepato-Biliary disease; Group 2 (24%), Retroperitoneal Fibrosis and/or Aortitis; Group 3 (24%), Head and Neck-Limited disease and Group 4 (22%), classic Mikulicz syndrome with systemic involvement. We replicated the identification of four phenotype groups in the replication cohort. Compared with cases in Groups 1, 2 and 4, respectively, cases in Group 3 were more likely to be female (OR 11.60 (95% CI 5.39 to 24.98), 10.35 (95% CI 4.63 to 23.15) and 9.24 (95% CI 3.53 to 24.20)) and Asian (OR 6.68 (95% CI 2.82 to 15.79), 7.43 (95% CI 2.97 to 18.56) and 6.27 (95% CI 2.27 to 17.29)). Cases in Group 4 had a higher median serum IgG4 concentration (1170 mg/dL) compared with groups 1–3 (316, 178 and 445 mg/dL, respectively, p<0.001).ConclusionWe identified four distinctive IgG4-RD phenotypes according to organ involvement. Being Asian or female may predispose individuals to head and neck-limited disease. These phenotypes serve as a framework for identifying IgG4-RD and studying its aetiology and optimal treatment.