Investigating Associations between Consumption of Unprocessed and Ultra Processed Foods and Maternal and Neonatal Health Outcomes—Secondary Outcomes of LIFT Trial

The ultra-processing of food has become a much more important aspect of dietary patterns and dietary quality in terms of its impact on body weight, diet related diseases, health, and well-being in the past decades. NOVA is a set of guidelines developed that classifies diet quality by degree of food processing. The NOVA guidelines distinguish four categories: unprocessed /minimally processed foods; culinary ingredients; processed foods; and ultra-processed foods. Numerous studies have found an association of ultra-processed foods and health conditions such as obesity and metabolic syndrome. This study analyzed the associations between maternal diet quality as measured by NOVA and maternal anthropometric and neonatal body composition outcomes. The optimal method of nutrition intervention and education for this special population remains unknown; using NOVA may provide researchers with a different lens to assess diet quality and health care professionals with additional vocabulary to convey more tailored messages regarding optimal nutrition strategies for mother and offspring. Using data collected from a large randomized controlled intervention trial at pre and post intervention, this study aimed to compare the NOVA guidelines assessment of maternal diet quality to the parent study assessment of diet quality, the Healthy Eating Index (HEI), using statistical correlations. Secondly, this study aimed to look at the relationship of ultra-processed food intake to the maternal gestational weight gain experience using a logistic regression. Thirdly, this dissertation aimed to explore the relationship between maternal ultra-processed food intake and neonatal lean mass as measured by quantitative magnetic resonance (QMR) and fat free mass as measured by air displacement plethysmography (ADP: PEAPOD). In terms of maternal outcomes, the study found that NOVA and HEI were significantly correlated at pre intervention but not at post intervention. The odds of gaining excessive gestational weight decreased as maternal ultra-processed food intake increased - which was not in the hypothesized direction - when using study participant data. However, the odds of gaining excessive gestational weight increased as maternal ultra-processed food intake increased - which was in the hypothesized direction - when using the Institute of Medicine weight gain recommendations. Also, while obesity did not predict excessive gestational weight gain, those with obesity ultra-processed food intake did predict gestational weight gain. These various inconsistencies are likely due to the instability of the dietary intake data because only one 24 -hour dietary recall was obtained from mother. In addition, the mothers’ diets were very healthy to begin with, where ultra-processed food intake formed about 45% of calories both pre and post intervention, when the national average is 57%. Race was also significant predictors of gestational weight gain for the mothers. Being non-white significantly increased the odds of gaining excessively as did the interaction of having obesity and eating more ultra-processed foods. In terms of neonatal outcomes, findings from this study suggest that length and fat mass are significant predictors of lean mass in neonates. In terms of the impact of maternal ultra-processed food intake, the higher the consumption of ultra-processed food, the greater the neonatal lean mass, which this was not in the hypothesized direction. However, the association was minimal with very small beta weights and regression line, when plotted was quite flat, so that the finding is not clinically meaningful. It remains important to know whether maternal ultra-processed food intake influences gestational weight gain and the body composition of the neonate. Thus, future research should include using similar data analyses on a population with a more nationally representative diet, a larger sample size, and a more robust measure of dietary intake such as three 24-hour recalls. Given that a similar recent study found ultra-processed food to be highly predictive of maternal and neonatal outcomes, and many other studies have demonstrated that ultra-processed food is related to several health conditions in many countries that this study did not measure, it seems prudent for healthcare providers to take advantage of prenatal visits as a window of opportunity to encourage the consumption of unprocessed and minimally foods and help women make informed decisions regarding ultra-processed foods

X-linked hypophosphatemia caused by the prevailing North American PHEX variant c.*231A\u3eG; exon 13–15 duplication is often misdiagnosed as ankylosing spondylitis and manifests in both men and women

Inactivating mutations of the gene coding for phosphate-regulating endopeptidase homolog X-linked (PHEX) cause X-linked hypophosphatemia (XLH). A nove

Analysis of continuous glucose tracking data in people with type 1 diabetes after COVID-19 vaccination reveals unexpected link between immune and metabolic response, augmented by adjunctive oral medication

Introduction: The COVID-19 vaccination programme is under way worldwide. Anecdotal evidence is increasing that some people with type 1 diabetes mellitus (T1DM) experience temporary instability of blood glucose (BG) levels post-vaccination which normally settles within 2-3 days. We report an analysis of BG profiles of 20 individuals before/after vaccination. Methods: We examined the BG profile of 20 consecutive adults (18 years of age or more) with T1DM using the FreeStyle Libre flash glucose monitor in the period immediately before and after COVID-19 vaccination. The primary outcome measure was percentage (%) BG readings in the designated target range 3.9-10 mmmol/L as reported on the LibreView portal for 7 days prior to the vaccination (week −1) and the 7 days after the vaccination (week +1). Results: There was a significant decrease in the %BG on target following the COVID-vaccination for the 7 days following vaccination (mean 45.2% ± SE 4.2%) vs pre-COVID-19 vaccination (mean 52.6% ± SE 4.5%). This was mirrored by an increase in the proportion of readings in other BG categories 10.1%-13.9%/≥14%. There was no significant change in BG variability in the 7days post-COVID-19 vaccination. This change in BG proportion on target in the week following vaccination was most pronounced for people taking Metformin/Dapagliflozin+basal-bolus insulin (−23%) vs no oral hypoglycaemic agents (−4%), and median age <53 vs ≥53 years (greater reduction in %BG in target for older individuals (−18% vs −9%)). Conclusion: In T1DM, we have shown that COVID-19 vaccination can cause temporary perturbation of BG, with this effect more pronounced in patients talking oral hypoglycaemic medication plus insulin, and in older individuals. This may also have consequences for patients with T2DM who are currently not supported by flash glucose monitoring

Monitoring guidance for patients with hypophosphatasia treated with asfotase alfa.

Hypophosphatasia (HPP) is a rare, inherited, systemic, metabolic disorder caused by autosomal recessive mutations or a single dominant-negative mutation in the gene encoding tissue-nonspecific alkaline phosphatase (TNSALP). The disease is associated with a broad range of signs, symptoms, and complications, including impaired skeletal mineralization, altered calcium and phosphate metabolism, recurrent fractures, pain, respiratory problems, impaired growth and mobility, premature tooth loss, developmental delay, and seizures. Asfotase alfa is a human, recombinant enzyme replacement therapy that is approved in many countries for the treatment of patients with HPP. To address the unmet need for guidance in the monitoring of patients receiving asfotase alfa, an international panel of physicians with experience in diagnosing and managing HPP convened in May 2016 to discuss treatment monitoring parameters. The panel discussions focused on recommendations for assessing and monitoring patients after the decision to treat with asfotase alfa had been made and did not include recommendations for whom to treat. Based on the consensus of panel members, this review provides guidance on the monitoring of patients with HPP during treatment with asfotase alfa, including recommendations for laboratory, efficacy, and safety assessments and the frequency with which these should be performed during the course of treatment. Recommended assessments are based on patient age and include regular monitoring of biochemistry, skeletal radiographs, respiratory function, growth, pain, mobility and motor function, and quality of life. Because of the systemic presentation of HPP, a coordinated, multidisciplinary, team-based, patient-focused approach is recommended in the management of patients receiving asfotase alfa. Monitoring of efficacy and safety outcomes must be tailored to the individual patient, depending on medical history, clinical manifestations, availability of resources in the clinical setting, and the clinician's professional judgment

A Secondary Analysis of Maternal Ultra-Processed Food Intake in Women with Overweight or Obesity and Associations with Gestational Weight Gain and Neonatal Body Composition Outcomes

This study is an observational secondary analysis of the Lifestyle Intervention for Two (LIFT) randomised controlled trial data. There is a paucity of data related to mechanisms of health effects and dietary intake of ultra-processed foods (UPF). Earlier studies demonstrate associations between greater UPF intake and weight gain. The purpose of the study was to describe associations among maternal UPF intake with gestational weight gain (GWG) and neonatal body composition. Women with overweight or obesity (n=156) and offspring (n=126) with complete energy intake, anthropometrics and body composition measures were selected. Maternal weights and diet recalls (Automated Self-Administered 24) were measured at weeks 14 and 35 gestational age (GA). Body composition was assessed by infant quantitative magnetic resonance (infant-QMR) and air displacement plethysmography (ADP) at birth. Dependent variables were GWG and neonatal fat mass, fat-free mass, and lean mass at birth; covariates were dietary, socioeconomic and biological. Stepwise linear regressions were used to test associations. Highest quartile of percentage of energy intake from UPF (PEI-UPF) was not significantly correlated with maternal GWG (p=0.215), infant QMR fat (p=0.816) and lean mass (p=0.423) or ADP fat (p=0.482) or fat-free mass (p=0.835). While no significant associations with UPF were observed in this smaller size cohort, further investigations would be justified in larger cohorts on the relationships of maternal UPF intake and GWG and offspring outcomes. Clinical Trial NCT0161614

People of the British Isles: preliminary analysis of genotypes and surnames in a UK control population

There is a great deal of interest in fine scale population structure in the UK, both as a signature of historical immigration events and because of the effect population structure may have on disease association studies. Although population structure appears to have a minor impact on the current generation of genome-wide association studies, it is likely to play a significant part in the next generation of studies designed to search for rare variants. A powerful way of detecting such structure is to control and document carefully the provenance of the samples involved. Here we describe the collection of a cohort of rural UK samples (The People of the British Isles), aimed at providing a well-characterised UK control population that can be used as a resource by the research community as well as providing fine scale genetic information on the British population. So far, some 4,000 samples have been collected, the majority of which fit the criteria of coming from a rural area and having all four grandparents from approximately the same area. Analysis of the first 3,865 samples that have been geocoded indicates that 75% have a mean distance between grandparental places of birth of 37.3km, and that about 70% of grandparental places of birth can be classed as rural. Preliminary genotyping of 1,057 samples demonstrates the value of these samples for investigating fine scale population structure within the UK, and shows how this can be enhanced by the use of surnames

Roles of neutrophils in the regulation of the extent of human inflammation through delivery of IL-1 and clearance of chemokines

This study examined the establishment of neutrophilic inflammation in humans. We tested the hypotheses that neutrophil recruitment was associated with local CXCL8 production and that neutrophils themselves might contribute to the regulation of the size of the inflammatory response. Humans were challenged i.d. with endotoxin. Biopsies of these sites were examined for cytokine production and leukocyte recruitment by qPCR and IHC. Additional in vitro models of inflammation examined the ability of neutrophils to produce and sequester cytokines relevant to neutrophilic inflammation. i.d. challenge with 15 ng of a TLR4-selective endotoxin caused a local inflammatory response, in which 1% of the total biopsy area stained positive for neutrophils at 6 h, correlating with 100-fold up-regulation in local CXCL8 mRNA generation. Neutrophils themselves were the major source of the early cytokine IL-1β. In vitro, neutrophils mediated CXCL8 but not IL-1β clearance (>90% clearance of ≤2 nM CXCL8 over 24 h). CXCL8 clearance was at least partially receptor-dependent and modified by inflammatory context, preserved in models of viral infection but reduced in models of bacterial infection. In conclusion, in a human inflammatory model, neutrophils are rapidly recruited and may regulate the size and outcome of the inflammatory response through the uptake and release of cytokines and chemokines in patterns dependent on the underlying inflammatory stimulus

Hypoxia shapes the immune landscape in lung injury and promotes the persistence of inflammation

Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. In the present study, we have shown that ARDS patients were hypoxemic and monocytopenic within the first 48 h of ventilation. Monocytopenia was also observed in mouse models of hypoxic acute lung injury, in which hypoxemia drove the suppression of type I interferon signaling in the bone marrow. This impaired monopoiesis resulted in reduced accumulation of monocyte-derived macrophages and enhanced neutrophil-mediated inflammation in the lung. Administration of colony-stimulating factor 1 in mice with hypoxic lung injury rescued the monocytopenia, altered the phenotype of circulating monocytes, increased monocyte-derived macrophages in the lung and limited injury. Thus, tissue hypoxia altered the dynamics of the immune response to the detriment of the host and interventions to address the aberrant response offer new therapeutic strategies for ARDS