A systematic review and meta-analysis on the transcriptomic signatures in alcohol use disorder.

Currently available clinical treatments on alcohol use disorder (AUD) exhibit limited efficacy and new druggable targets are required. One promising approach to discover new molecular treatment targets involves the transcriptomic profiling of brain regions within the addiction neurocircuitry, utilizing animal models and postmortem brain tissue from deceased patients with AUD. Unfortunately, such studies suffer from large heterogeneity and small sample sizes. To address these limitations, we conducted a cross-species meta-analysis on transcriptome-wide data obtained from brain tissue of patients with AUD and animal models. We integrated 36 cross-species transcriptome-wide RNA-expression datasets with an alcohol-dependent phenotype vs. controls, following the PRISMA guidelines. In total, we meta-analyzed 964 samples - 502 samples from the prefrontal cortex (PFC), 282 nucleus accumbens (NAc) samples, and 180 from amygdala (AMY). The PFC had the highest number of differentially expressed genes (DEGs) across rodents, monkeys, and humans. Commonly dysregulated DEGs suggest conserved cross-species mechanisms for chronic alcohol consumption/AUD comprising MAPKs as well as STAT, IRF7, and TNF. Furthermore, we identified numerous unique gene sets that might contribute individually to these conserved mechanisms and also suggest novel molecular aspects of AUD. Validation of the transcriptomic alterations on the protein level revealed interesting targets for further investigation. Finally, we identified a combination of DEGs that are commonly regulated across different brain tissues as potential biomarkers for AUD. In summary, we provide a compendium of genes that are assessable via a shiny app, and describe signaling pathways, and physiological and cellular processes that are altered in AUD that require future studies for functional validation.

Clinical and preclinical insights into high-dose ambroxol therapy for Gaucher disease type 2 and 3: A comprehensive systematic review.

RATIONALE: Gaucher disease (GD), an autosomal recessive lysosomal storage disease, results from GBA1 variants causing glucocerebrosidase (GCase) deficiency. While enzyme replacement therapy (ERT) helps with systemic symptoms, neurological complications in GD2 and GD3 persist due to the blood-brain-barrier (BBB) limiting ERT efficacy. Ambroxol, a BBB-permeable chaperone, enhances GCase activity. Our review explores high-dose ambroxol's therapeutic potential, both preclinical and clinical, in GD2 and GD3. METHODS: PubMed was searched for studies published before March 2023, including clinical, animal, and in vitro studies focusing on the effect of high-dose ambroxol in GD2 and GD3. A narrative synthesis was performed. RESULTS: Nine in vitro, three animal, and eight clinical studies were included, demonstrating varied responses to ambroxol across diverse outcome measures. In vitro and animal studies demonstrated reduced endoplasmatic reticulum stress due to the relocation of GCase from the ER to the lysosomes. In vitro cell lines exhibited varying degrees of increased GCase activity. Clinical trials observed reduced lyso-GL1 levels in plasma (41-89%) and cerebrospinal fluid (CSF) (26-97%), alongside increased GCase activity in GD3 patients. Ambroxol exhibited varying effects on neurological outcomes and development. No severe adverse events were reported. CONCLUSION: High-dose ambroxol shows promise in managing neurological manifestations in GD3, albeit with uncertainties resulting from genetic heterogeneity and variable response. Further clinical trials, are essential for elucidating dosage-response relationships and refining treatment outcomes and strategies for neuronopathic GD.

Breaking the chains of lipoprotein lipase deficiency: A pediatric perspective on the efficacy and safety of Volanesorsen.

RATIONALE: Lipoprotein lipase (LPL) deficiency, a rare inherited metabolic disorder, is characterized by high triglyceride (TG) levels and life-threatening acute pancreatitis. Current treatment for pediatric patients involves a lifelong severely fat-restricted diet, posing adherence challenges. Volanesorsen, an EMA-approved RNA therapy for adults, effectively reduces TG levels by decreasing the production of apolipoprotein C-III. This 96-week observational open-label study explores Volanesorsen's safety and efficacy in a 13-year-old female with LPL deficiency. METHODS: The patient, with a history of severe TG elevations, 53 hospital admissions, and life-threatening recurrent pancreatitis despite dietary restrictions, received weekly subcutaneous Volanesorsen injections. We designed a protocol for this investigator-initiated study, primarily focusing on changes in fasting TG levels and hospital admissions. RESULTS: While the injections caused occasional pain and swelling, no other adverse events were observed. TG levels decreased during treatment, with more measurements below the pancreatitis risk threshold compared to pre-treatment. No hospital admissions occurred in the initial 14 months of treatment, contrasting with 21 admissions in the 96 weeks before. In the past 10 months, two pancreatitis episodes may have been linked to dietary noncompliance. Dietary restrictions were relaxed, increasing fat intake by 65% compared to baseline. While not fully reflected in the PedsQL, both parents and the patient narratively reported an improved quality of life. CONCLUSION: This study demonstrates, for the first time, that Volanesorsen is tolerated in a pediatric patient with severe LPL deficiency and effectively lowers TG levels, preventing life-threatening complications. This warrants consideration for expanded access in this population.

Extending diagnostic practices in gyrate atrophy: Enzymatic characterization and the development of an in vitro pyridoxine responsiveness assay.

Gyrate atrophy of the choroid and retina (GACR) is caused by pathogenic biallelic variants in the gene encoding ornithine-δ-aminotransferase (OAT), and is characterized by progressive vision loss leading to blindness. OAT is a pyridoxal-5'-phosphate (PLP) dependent enzyme that is mainly involved in ornithine catabolism, and patients with a deficiency develop profound hyperornithinemia. Therapy is aimed at lowering ornithine levels through dietary arginine restriction and, in some cases, through enhancement of OAT activity via supraphysiological dosages of pyridoxine. In this study, we aimed to extend diagnostic practices in GACR by extensively characterizing the consequences of pathogenic variants on the enzymatic function of OAT, both at the level of the enzyme itself as well as the flux through the ornithine degradative pathway. In addition, we developed an in vitro pyridoxine responsiveness assay. We identified 14 different pathogenic variants, of which one variant was present in all patients of Dutch ancestry (p.(Gly353Asp)). In most patients the enzymatic activity of OAT as well as the rate of [14C]-ornithine flux was below the limit of quantification (LOQ). Apart from our positive control, only one patient cell line showed responsiveness to pyridoxine in vitro, which is in line with the reported in vivo pyridoxine responsiveness in this patient. None of the patients harboring the p.(Gly353Asp) substitution were responsive to pyridoxine in vivo or in vitro. In silico analysis and small-scale expression experiments showed that this variant causes a folding defect, leading to increased aggregation properties that could not be rescued by PLP. Using these results, we developed a diagnostic pipeline for new patients suspected of having GACR. Adding OAT enzymatic analyses and in vitro pyridoxine responsiveness to diagnostic practices will not only increase knowledge on the consequences of pathogenic variants in OAT, but will also enable expectation management for therapeutic modalities, thus eventually improving clinical care.

Natural disease course of chronic visceral acid sphingomyelinase deficiency in adults: A first step toward treatment criteria.

Acid sphingomyelinase deficiency (ASMD) is an ultra-rare lysosomal storage disease with a broad spectrum of manifestations ranging from severe neuropathic forms to attenuated, chronic visceral forms. Manifestations of the chronic visceral subtype are variable and encompass different degrees of hepatosplenomegaly, pulmonary disease and dyslipidemia. The aim of this study was to provide insights into the natural course of adult patients with the chronic visceral subtype. Based on these insights, we proposed tentative criteria for initiation and follow-up of enzyme replacement therapy (ERT). The data of 23 adult patients were collected in a prospective study. Clinical, genetic and demographic data, plasma measurements, abdominal imaging, pulmonary imaging, pulmonary function tests and quality of life questionnaires were collected. Stability of disease based on several clinical, biochemical and radiological markers (i.e., spleen volume, platelet levels, liver volume, alanine aminotransferase [ALT] levels, diffusion capacity of the lungs for carbon monoxide [DLCO] chitotriosidase activity and lysosphingomyelin [LSM]) was assessed. Cardiovascular risk was estimated based on sex, age, smoking, systolic blood pressure and lipid profile. Quality of life was evaluated with the 36-Item Short Form Health Survey and the Health Assessment Questionnaire. Median follow-up was 6.1 years (range 1.3-19.5 years). The most common manifestations were splenomegaly (100%), decreased high-density lipoprotein cholesterol (HDL-C) plasma levels (83%), (signs of) steatosis measured with transient elastography (82%), thrombocytopenia (64%), hepatomegaly (52%) and decreased diffusion capacity (45%). The majority of markers remained stable during follow-up. Twelve patients showed progression of disease: four for spleen volume, two for liver volume, three for DLCO, seven for chitotriosidase activity and three for LSM. One patient showed progression of disease based on four markers, although this patient did not report any problems at the last visit. Cardiovascular risk was estimated and was increased in half of the patients older than 40 years. Patient-reported quality of life did not differ from the general population, but differences in median 36-Item Short Form Health Survey (SF-36) scores of patients with severe pulmonary involvement and those of patients without pulmonary involvement were observed. Tentative criteria for initiation and effect of therapy were proposed. In conclusion, the chronic visceral subtype of ASMD showed a predominantly stable disease course in this cohort. We propose that ERT should be initiated on an individual basis and only in case of progression or symptomatic disease. Collection and analysis of real world data are necessary to refine start, stop and follow-up criteria in the future.

Cross-sectional and longitudinal associations of magnesium intake and cognition in the Healthy Aging Longitudinal Study in Taiwan.

PURPOSE: Previous cross-sectional studies have shown that higher magnesium intake is associated with better cognitive function, particularly in individuals with sufficient vitamin D status. The aim of this study was to evaluate the longitudinal associations between magnesium intake and cognitive impairment in a community-based cohort study in Taiwan. METHODS: The study population included 5663 community-dwelling adults aged ≥ 55 years old recruited from 2009 to 2013 and followed up from 2013 to 2020. Magnesium intake was evaluated from a validated food frequency questionnaire at baseline. Cognitive performance was measured at baseline and follow-up for participants' Mini-Mental Status Examination (MMSE), Digit Symbol Substitution Test (DSST), and Clock-Drawing Test (CDT), and impairment was defined as MMSE < 24, DSST < 21, and CDT < 3, respectively. Multivariate logistic regression models were used to examine the associations and were stratified by sex and plasma vitamin D levels (≥ 50 or < 50 nmol/L). RESULTS: Higher baseline magnesium intake was associated with lower odds of a poor performance on the MMSE in both men and women (4th vs. 1st. quartile: OR = 0.43, 95% CI = 0.23-0.82, ptrend < 0.01 in men and OR = 0.53, 95% CI = 0.29-0.97, ptrend = 0.12 in women) and on the DSST in men (OR = 0.23, 95% CI = 0.09-0.61, ptrend < 0.01) at follow-up. Inverse associations between baseline magnesium intake and a poor performance on the MMSE or DSST were observed in men regardless of vitamin D status. CONCLUSION: Our study suggested that higher magnesium intake was associated with the development of cognitive impairment in men in a median follow-up period of 6 years.

A cohort study of 19 patients with gyrate atrophy of the choroid and retina (GACR).

PURPOSE: Gyrate atrophy of the choroid and retina (GACR) is an autosomal recessive inherited metabolic disorder (IMD) characterised by progressive retinal degeneration, leading to severe visual impairment. The rapid developments in ophthalmic genetic therapies warrant knowledge on clinical phenotype of eligible diseases such as GACR to define future therapeutic parameters in clinical trials. METHODS: Retrospective chart analysis was performed in nineteen patients. Data were analysed using IBM SPSS Statistics version 28.0.1.1. RESULTS: Nineteen patients were included with a mean age of 32.6 years (range 8-58). Mean age at onset of ophthalmic symptoms was 7.9 years (range 3-16). Median logMAR of visual acuity at inclusion was 0.26 (range -0.18-3.00). Mean age at cataract surgery was 28.8 years (n = 11 patients). Mean spherical equivalent of the refractive error was -8.96 (range -20.87 to -2.25). Cystoid maculopathy was present in 68% of patients, with a loss of integrity of the foveal ellipsoid zone (EZ) in 24/38 eyes. Of the 14 patients treated with dietary protein restriction, the four patients who started the diet before age 10 showed most benefit. CONCLUSION: This study demonstrates the severe ophthalmic disease course associated with GACR, as well as possible benefit of early dietary treatment. In addition to visual loss, patients experience severe myopia, early-onset cataract, and CME. There is a loss of foveal EZ integrity at a young age, emphasising the need for early diagnosis enabling current and future therapeutic interventions.

"I see it very much as an end-of-life food" - Barriers to oral nutritional supplement adherence, views from healthy older adults.

Malnutrition affects approximately one quarter of UK adults aged 65 years and over. As the global demographic shift continues, malnutrition is expected to increase. Oral nutritional supplements (ONS) are used both to prevent and to treat malnutrition. However, their effectiveness is compromised by poor adherence, and it is not well understood what contributes to this. Therefore, the current research was designed to explore ONS adherence from the parallel perspectives of ONS as a prescribed "medication" and as a food supplement/substitute. Eighteen older adults (13F, 5M; mean age = 73.4 yr; range: 70-80 yr) participated in focus groups (three in-person and one online), to investigate experiences of taking prescribed medications, including dietary supplements, and what should be factors to consider in supporting regular intake of ONS for trial development, as well as any potential improvements to products. Focus group sessions were recorded and then transcribed. Thematic Analysis was applied to the transcripts by the first author, and themes were discussed in depth, using exemplar quotes from participants. Five dominant themes were identified from the data: Disgust, Palatability and Acceptance; End-of-Life Care; Resistance to Medicines; Rituals and Reminders; and Real Food Displacement. Nutritional supplements were characterised as "disgusting", "manufactured", and associated with serious, chronic illness, as well as end-of-life care, in contrast to probiotics which were linked with health and wellness. The sweet taste of ONS was identified as a barrier to intake, given that it is generally associated with a signal to stop eating, and low hunger. As a group, participants tried to "avoid taking medicines", and viewed the need to have them negatively, yet most regularly took prescribed medication and/or vitamin supplements. Participants identified several, rituals and reminders to take medicines, including meal-based, or time-of-day-based prompts (e.g., before, with or after meals). To improve adherence, savoury products were suggested, as well as a more person-centred approach to individual nutritional needs and preferences. Overall, the group discussion mainly identified barriers to intake, but that improving taste, adding to "real food" (not replacing meals), and offering variety of flavour and form (e.g., savoury soups as well as sweet drinks) could be included in future trials to improve appeal and therefore intake. Future work should continue to explore how best to formulate, market and/or prescribe ONS, and how this might vary for malnutrition prevention vs treatment strategies.

Appetitive traits from childhood to adolescence: Analysis of their stability, derivation of trajectory profiles, and associated characteristics.

This study aimed to assess the potential stability of appetitive traits from childhood to early adolescence, identify groups of individuals with distinct trajectories for these traits, and explore their association with other child and family characteristics. Participants were 5040 children from the Generation XXI cohort. Appetitive traits were assessed with the Children's Eating Behaviour Questionnaire (CEBQ) at ages seven, 10, and 13 (eight subscales). Mixed-effect models estimated individual trajectories of appetitive traits and Gaussian mixture models identified groups following different trajectories (appetitive trait trajectory profiles). Appetitive traits showed moderate-to-high stability across the three ages (intra-class correlation coefficients:0.66-0.83); most of the variance observed across time were due to persistent individual differences rather than age-related changes. Six appetitive trait trajectory profiles were identified: 'Moderate appetite' (scores close to the average) (29% of children), 'Small to moderate appetite' (lowest food approach and emotional eating) (26%), 'Increasing appetite' (increasing food approach) (15%), 'Avid appetite' (highest food approach and lowest food avoidance) (12%), 'Smallest appetite' (highest food avoidance and low food approach) (10%), and 'Small appetite but increasing' (decreasing high food avoidance and Desire to Drink) (8%). In multinomial logistic regression, these profiles were associated with different child and family characteristics. Compared to children with a 'Moderate appetite' profile, those with higher BMI, who desired a thinner body, whose mothers were younger, had lower education, higher pre-pregnancy BMI (OR = 1.07; 95%CI:1.04,1.09), smoked during pregnancy (OR = 1.51; 95%CI:1.21,1.90), and used more restrictive feeding practices (OR = 1.79; 95%CI:1.57,2.03) had increased odds of belonging to the 'Avid Appetite'. In conclusion, distinct appetitive trait trajectory profiles emerged, differentiating individuals with avid and small appetites. These findings have implications for identifying children at higher risk for obesogenic profiles.

The impact of school-based cooking classes on vegetable intake, cooking skills and food literacy of children aged 4-12 years: A systematic review of the evidence 2001-2021.

BACKGROUND: Many children consume a poor quality diet with only a third of children aged 6-9 years eating vegetables daily. A high quality diet is important for good health in childhood; however, the prevalence of children living with obesity has doubled from 10% to 23% during primary school in the UK. Cooking lessons have the potential to improve diet quality and reduce obesity prevalence in childhood, both of which are associated with improved cardiometabolic outcomes in adulthood. The aim of this systematic review is to investigate the impact of school-based cooking classes on cooking skills, food literacy and vegetable intake of children aged 4-12 years. METHODS: We conducted a systematic review of OVID Medline, OVID Embase, EBSCO CINHAL and EBSCO ERIC for comparative studies that evaluated outcomes of children receiving cooking classes compared to a control group. Interventions included contained food preparation or a cooking activities and took place on school premises. Risk of bias was assessed using ROB2 and Robins-I. Outcomes were pooled in a meta-analysis using a random-effects model using standardised mean differences or reviewed using narrative synthesis. Certainty of evidence was assessed using GRADE. RESULTS: We included 21 studies, (6 randomised). Meta-analysis showed a small positive effect on cooking self-efficacy of 0.39 units (95% CI 0.05 to 0.54), and a small positive effect on vegetable intake of 0.25 units (95% CI 0.05 to 0.45). Programmes with more than 6 h of cooking showed the greatest effects. CONCLUSIONS: Children's cooking programmes result in small improvements in cooking efficacy and vegetable intake, particularly those with more than 6 h of classes. It is recommended that future interventions use consistent measurement for children's food literacy and cooking confidence.

Strategies for scaling up pre-ART advanced HIV disease screening at a secondary referral hospital-Malawi: a qualitative study.

BACKGROUND: Implementation of the World Health Organization (WHO) recommended Advanced HIV Disease screening package, remains poor in most settings with limited resources. More than 50% of newly diagnosed-HIV clients are missed on screening as a result of implementation barriers. It is important to mitigate the existing barriers and leverage enablers' inorder to maximize uptake of the advanced HIV disease screening. This study aimed to identify strategies for scaling up implementation of advanced HIV disease screening among newly HIV-diagnosed clients in pre-ART phase using a Consolidated Framework for Implementation Research-Expert Recommendation for Implementing Change (CFIR-ERIC) guiding tool. METHODS: A qualitative study was conducted at Rumphi district hospital in Malawi (August - September, 2023). Two sessions of Focus group discussions (FDGs) involving key stakeholders were facilitated to identify specific strategies following the initial study on exploration of barriers and facilitators of advanced HIV disease screening package. Participants comprised healthcare providers, purposively selected from key hospital departments. A deductive approach was used to analyze FDG transcripts where emerging themes were mapped with ERIC list of strategies. CFIR-ERIC Matching tool version 1.0, was used to generate an output of the most to least expert-endorsed Level 1 and Level 2 strategies. FINDINGS: About 25 key healthcare workers participated in FDGs. Overall, 6 Level 1 strategies (≥ 50% expert endorsement score) and 4 Level 2 strategies (≥ 20%, ≤ 49% expert endorsement score) were identified, targeting barriers associated with availability of resources, intervention complexity, access to knowledge and information, communication; and implementation leads. Most of the reported strategies were cross-cutting and aimed at enhancing clinical knowledge of the intervention (distributing training materials, educational meetings), developing stakeholders' interrelations (network weaving) as well as improving clinical workflow (environmental restructuring). Use of evaluative and iterative strategies such as monthly data collection for evaluation were also recommended as part of continuous improvement while an AHD coordinator was recommended to be formally appointed inorder to spearhead coordination of AHD screening services. CONCLUSION: Through the involvement of key stakeholders and the use of CFIR-ERIC matching tool, this study has identified cross-cutting strategies that if well implemented, can help to mitigate contextual barriers and leverage enablers for an improved delivery of AHD screening package.

Glycoprotein non-metastatic protein B (GPNMB) plasma values in patients with chronic visceral acid sphingomyelinase deficiency.

Acid sphingomyelinase deficiency (ASMD) is a rare LSD characterized by lysosomal accumulation of sphingomyelin, primarily in macrophages. With the recent availability of enzyme replacement therapy, the need for biomarkers to assess severity of disease has increased. Glycoprotein non-metastatic protein B (GPNMB) plasma levels were demonstrated to be elevated in Gaucher disease. Given the similarities between Gaucher disease and ASMD, the hypothesis was that GPNMB might be a potential biochemical marker for ASMD as well. Plasma samples of ASMD patients were analyzed and GPNMB plasma levels were compared to those of healthy volunteers. Visceral disease severity was classified as severe when splenic, hepatic and pulmonary manifestations were all present and as mild to moderate if this was not the case. Median GPNMB levels in 67 samples of 19 ASMD patients were 185 ng/ml (range 70-811 ng/ml) and were increased compared to 10 healthy controls (median 36 ng/ml, range 9-175 ng/ml, p < 0.001). Median plasma GPNMB levels of ASMD patients with mild to moderate visceral disease compared to patients with severe visceral disease differed significantly and did not overlap (respectively 109 ng/ml, range 70-304 ng/ml and 325 ng/ml, range 165-811 ng/ml, p < 0.001). Correlations with other biochemical markers of ASMD (i.e. chitotriosidase activity, CCL18 and lysosphingomyelin, respectively R = 0.28, p = 0.270; R = 0.34, p = 0.180; R = 0.39, p = 0.100) and clinical parameters (i.e. spleen volume, liver volume, diffusion capacity and forced vital capacity, respectively R = 0.59, p = 0.061, R = 0.5, p = 0.100, R = 0.065, p = 0.810, R = -0.38, p = 0.160) could not be established within this study. The results of this study suggest that GPNMB might be suitable as a biomarker of visceral disease severity in ASMD. Correlations between GPNMB and biochemical or clinical markers of ASMD and response to therapy have to be studied in a larger cohort.

Dietary Inflammatory Patterns Are Associated With Serum TGs and Insulin in Adults: A Community-Based Study in Taiwan.

BACKGROUND: Dietary patterns related to inflammation have become a focus of disease prevention but the patterns may vary among populations. OBJECTIVES: The study was conducted to determine Taiwanese dietary inflammatory patterns and evaluate their associations with biomarkers of lipid and glucose. METHODS: Data were taken from 5664 community-dwelling individuals aged ≥55 y recruited in 2009-2013 in the Healthy Aging Longitudinal Study in Taiwan (HALST). Dietary data were obtained from an FFQ. An empirical dietary inflammatory pattern (EDIP) was derived from reduced rank regression models that explained the serum high-sensitivity CRP, plasma IL-6, and TNF receptor 1. Cross-sectional associations between dietary scores and biomarkers of total cholesterol (TC); HDL cholesterol; LDL cholesterol; TG; and ratios of TG/HDL cholesterol, TG/TC, fasting glucose, insulin, and HbA1c were analyzed via multiple linear regression and adjusted for major confounders. The false-discovery rate (FDR)-adjusted P < 0.05 was considered statistically significant. Abdominal obesity was defined as a waist circumference of ≥90 cm for men and ≥80 cm for women. RESULTS: Higher EDIP-HALST scores were associated with higher TG (per score increment: 1.62%, 95% CI: 0.58%, 2.76%; PFDR = 0.01), TG/HDL cholesterol (2.01%, 95% CI: 0.67%, 3.37%; PFDR = 0.01), and TG/TC (1.42%, 95% CI: 0.41%, 2.43%; PFDR = 0.01) and nonlinearly associated with insulin, with those in the middle tertile had the highest serum insulin concentrations (means: 5.12 µIU/mL, 95% CI: 4.78, 5.78; PFDR = 0.04) in men, but not in women. No heterogeneity was detected between sexes. The associations with TG (1.23%, 95% CI: 0.19, 2.23%; Ptrend = 0.02), TG/HDL cholesterol (1.62%, 95% CI: 0.30%, 2.96%; Ptrend = 0.02), and TG/TC (1.11%, 95% CI: 0.11%, 2.13%; Ptrend = 0.03) were stronger in participants with abdominal obesity, but were borderline associated in participants with normal abdominal circumferences (all Ptrend = 0.05). CONCLUSIONS: Inflammatory diets, as measured via EDIP-HALST, are associated with serum TG concentration, particularly in participants with abdominal obesity. These findings may suggest that developing disease prevention strategies using dietary inflammatory patterns may be different by populations. J Nutr 20xx;x:xx.

Oral sialic acid supplementation in NANS-CDG: Results of a single center, open-label, observational pilot study.

NANS-CDG is a congenital disorder of glycosylation (CDG) caused by biallelic variants in NANS, encoding an essential enzyme in de novo sialic acid synthesis. It presents with intellectual developmental disorder (IDD), skeletal dysplasia, neurologic impairment, and gastrointestinal dysfunction. Some patients suffer progressive intellectual neurologic deterioration (PIND), emphasizing the need for a therapy. In a previous study, sialic acid supplementation in knockout nansa zebrafish partially rescued skeletal abnormalities. Here, we performed the first in-human pre- and postnatal sialic-acid study in NANS-CDG. In this open-label observational study, 5 patients with NANS-CDG (range 0-28 years) were treated with oral sialic acid for 15 months. The primary outcome was safety. Secondary outcomes were psychomotor/cognitive testing, height and weight, seizure control, bone health, gastrointestinal symptoms, and biochemical and hematological parameters. Sialic acid was well tolerated. In postnatally treated patients, there was no significant improvement. For the prenatally treated patient, psychomotor and neurologic development was better than two other genotypically identical patients (one treated postnatally, one untreated). The effect of sialic acid treatment may depend on the timing, with prenatal treatment potentially benefiting neurodevelopmental outcomes. Evidence is limited, however, and longer-term follow-up in a larger number of prenatally treated patients is required.

Management and monitoring of pediatric inflammatory bowel disease in the Asia-Pacific region: A position paper by the Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology, and Nutrition (APPSPGHAN) PIBD Working Group: Surgical management, disease monitoring, and special considerations.

Disease phenotype of pediatric inflammatory bowel disease (PIBD) in children from the Asia-Pacific region differs from that of children from the West. Many parts of Asia are endemic for tuberculosis, making diagnosis and management of pediatric Crohn's disease a challenge. Current available guidelines, mainly from Europe and North America, may not be completely applicable to clinicians caring for children with PIBD in Asia due to differences in disease characteristics and regional resource constraints. This position paper is an initiative from the Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology and Nutrition (APPSPGHAN) that aims to provide an up-to-date, evidence-based approach to PIBD in the Asia-Pacific region. A group of pediatric gastroenterologists with a special interest in PIBD performed an extensive literature search covering epidemiology, disease characteristics and natural history, management, and monitoring. Attention was paid to publications from the region with special consideration to a resource-limited setting. This current position paper deals with surgical management, disease monitoring, immunization, bone health, and nutritional issues of PIBD in Asia. A special section on differentiating pediatric Crohn's disease from tuberculosis in children is included. This position paper provides a useful guide to clinicians in the surgical management, disease monitoring, and various health issues in children with IBD in Asia-Pacific region.

A Scoping Review of the Oral Microbiome in Preterm Infants.

The purpose of this scoping review was to examine the oral microbiome composition in preterm infants, sampling and collection methods, as well as exposures associated with oral microbiome composition and health implications. We conducted a scoping review of the literature using the Arskey and O'Malley framework. We identified a total of 13 articles which met our inclusion criteria and purpose of this scoping review. Articles included in this review compared the oral microbiome in preterm infants to term infants, examined alterations to the oral microbiome over time, compared the oral microbiome to different body site microbiomes, and explored associations with clinically relevant covariates and outcomes. Exposures associated with the diversity and composition of the oral microbiome in preterm infants included delivery mode, oral feeding, oropharyngeal care, skin-to-skin care, and antibiotics. Day of life and birth weight were also associated with oral microbiome composition. The oral microbiome may be associated with the composition of the tracheal and gut microbiomes, likely due to their proximity. Alpha and beta diversity findings varied across studies as well as the relative abundance of taxa. This is likely due to the different sampling techniques and timing of collection, as well as the wide range of infant clinical characteristics. Multiple factors may influence the composition of the oral microbiome in preterm infants. However, given the heterogeneity of sampling techniques and results within this review, the evidence is not conclusive on the development as well as short- and long-term implications of the oral microbiome in preterm infants and needs to be explored in future research studies. KEY POINTS: · Day of life is a critical factor in oral microbiome development in preterm infants.. · The oral microbiome may be associated with tracheal and gut microbiome colonization.. · Future research should examine sampling methodology for examining the oral microbiome.. · Future research should explore associations with the oral microbiome and adverse health outcomes..

Nonpharmacologic Factors Affecting Milk Production in Pump-Dependent Mothers of Critically Ill Infants: State of the Science.

BACKGROUND: Improved health outcomes for critically ill infants including neurodevelopmental, immunological, and cost benefits are dependent upon the dose and duration of mother's own milk feedings. However, mothers of infants admitted to the neonatal intensive care unit (NICU) must express their milk (pump-dependent) and often struggle with milk production. PURPOSE: To examine the state of the science on nonpharmacologic modifiable expression factors that may influence milk production in pump-dependent mothers of critically ill infants admitted to the NICU. DATA SOURCES: PubMed, Embase, and CINAHL databases from 2005 to 2020. SEARCH STRATEGY: Guided by the lactation conceptual model, the authors searched for peer-reviewed studies with terms related to milk volume, pump dependency, critically ill infants, and modifiable factors, which may influence milk volume and assessed 46 eligible studies. DATA EXTRACTION: Data were extracted by 3 reviewers with a systematic staged review approach. RESULTS: Evidence from 26 articles found expressed milk volume may be influenced by multiple potentially modifiable factors. Simultaneous expression with a hospital-grade electric pump at least 5 times per day beginning 3 to 6 hours after delivery, and adding complementary techniques including hand expression, hands-on-pumping, music, breast massage, warm compresses, skin-to-skin care, and the mother expressing near her infant may promote increased milk volume. IMPLICATIONS FOR PRACTICE AND RESEARCH: Healthcare providers should assist pump-dependent mothers with early initiation and frequent milk removal with a hospital-grade breast pump. Further research is needed to explore optimal frequency of expressions, dose and timing of skin-to-skin care, and other targeted strategies to improve expressed milk volume.

Maternal perception, concern and dissatisfaction with child weight and their association with feeding practices in the Generation XXI birth cohort.

What a mother thinks about her child's weight status might influence what and how she feeds her child. We examined the association between maternal perception, concern and dissatisfaction with child weight alongside feeding practices. Participants were from the Generation XXI birth cohort (n = 3233). A validated version of the Child Feeding Questionnaire and the Overt/Covert Control scale were used. Associations were evaluated by linear regression models (ß coefficients and 95 % confidence intervals (95 % CI) with Bonferroni correction). Perceived underweight was associated with practices promoting food intake, such as higher pressure to eat at ages 4 and 7 years (ß = 0·229; 95 % CI: 0·059, 0·398 and ß = 0·190; 95 % CI:0·005, 0·376, respectively) and lower restriction at age 4 (ß = -0·175; 95 % CI: -0·0310, -0·039). At age 7, perceived overweight was associated with higher covert control (ß = 0·203; 95 % CI: 0·029, 0·376). Mothers who were concerned about child weight reported higher restriction (ß = 0·226; 95 % CI: 0·142, 0·310 at 4 years and ß = 0·261; 95 % CI: 0·169, 0·353 at 7 years) and covert control (ß = 0·183; 95 % CI: 0·083, 0·282 at 4 years and ß = 0·171; 95 % CI: 0·073, 0·269 at 7 years). Maternal desire for a heavier child was associated with higher pressure to eat at both ages (ß = 0·285; 95 % CI: 0·163, 0·406 and ß = 0·393; 95 % CI: 0·266, 0·520), while the desire for a thinner child was related to higher covert control at 7 years of age (ß = 0·158; 95 % CI: 0·001, 0·316). Maternal perceptions and concern for child weight status are associated with feeding practices independently of actual weight status.

Medical Management of Pediatric Inflammatory Bowel Disease (PIBD) in the Asia Pacific Region: A Position Paper by the Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology, and Nutrition (APPSPGHAN) PIBD Working Group.

Pediatric inflammatory bowel disease (PIBD) is rising rapidly in many industrialised and affluent areas in the Asia Pacific region. Current available guidelines, mainly from Europe and North America, may not be completely applicable to clinicians caring for children with PIBD in this region due to differences in disease characteristics and regional resources constraints. This position paper is an initiative from the Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology and Nutrition (APPSPGHAN) with the aim of providing an up-to-date, evidence-based approach to PIBD in the Asia Pacific region, taking into consideration the unique disease characteristics and financial resources available in this region. A group of pediatric gastroenterologists with special interest in PIBD performed an extensive literature search covering epidemiology, disease characteristics and natural history, management and monitoring. Gastrointestinal infections, including tuberculosis, need to be excluded before diagnosing IBD. In some populations in Asia, the Nudix Hydrolase 15 (NUD15) gene is a better predictor of leukopenia induced by azathioprine than thiopurine-S-methyltransferase (TPMT). The main considerations in the use of biologics in the Asia Pacific region are high cost, ease of access, and potential infectious risk, especially tuberculosis. Conclusion: This position paper provides a useful guide to clinicians in the medical management of children with PIBD in the Asia Pacific region.

From food preference development to responsive feeding - Selective studies to commemorate the life and work of Dr Leann Birch.

Dr Leann Birch was a pioneer in conducting research on infant and child eating behaviour. At the beginning of her research career, Leann recognised a significant gap in the developmental psychology literature, namely that few studies had been conducted to understand infant eating and feeding behaviours. This seems an unusual omission given that food intake is essential and that developmental milestones from milk to solids, and from being fed to becoming an autonomous eater, are obvious to most caregivers. Leann paved the way for interdisciplinary research from psychology, paediatrics and public health to explore and apply this knowledge to infant and child appetite, eating behaviour, dietary patterns, food preferences, and obesity risk. Early studies in her laboratory demonstrated that children form food preferences through experience and socialisation. Experiments published in 1979 tested the role of familiarisation through repeat exposure, and the impact of instrumental and social learning on the acquisition of food preferences. In 1984, a presentation given to the British Feeding and Drinking Group (BFDG) in Brighton set out three organising principles for understanding how children acquire food preferences: genetically pre-programmed behavioural propensities; social constraints on experience with food; and social transmission resulting from direct social interaction. Building on these three organising principles, research on child eating behaviour has flourished, including the intersection between individual differences, food experience and environmental influences on children's food preferences, energy regulation, and weight outcomes. In this review, the initial groundwork set out by Leann Birch on food preference development in children is considered followed by a discussion of how this has since inspired an interdisciplinary, international and expanding field of research on children's food intake, appetite and body weight regulation.