Barriers and facilitators for recruiting and retaining male participants into longitudinal health research: a systematic review.

BACKGROUND: Successfully recruiting male participants to complete a healthcare related study is important for healthcare study completion and to advance our clinical knowledgebase. To date, most research studies have examined the barriers and facilitators of female participants in longitudinal healthcare-related studies with limited information available about the needs of males in longitudinal research. This systematic review examines the unique barriers and facilitators to male recruitment across longitudinal healthcare-related research studies. METHODS: Following PRIMSA guidelines, MEDLINE, Embase, CINAHL and Web of Science databases were systematically searched using the terms recruitment and/or retention, facilitators and/or barriers and longitudinal studies from 1900 to 2023 which contained separate data on males aged 17-59 years. Health studies or interventions were defined longitudinal if they were greater than or equal to 12 weeks in duration with 3 separate data collection visits. RESULTS: Twenty-four articles published from 1976-2023 met the criteria. One-third of the studies had a predominantly male sample and four studies recruited only male participants. Males appear disinterested towards participation in health research, however this lack of enthusiasm can be overcome by clear, non-directive communication, and studies that support the participants interests. Facilitating factors are diverse and may require substantial time from research teams. CONCLUSIONS: Future research should focus on the specific impact of these factors across the spectrum of longitudinal health-related studies. Based on the findings of this systematic review, researchers from longitudinal health-related clinical trials are encouraged to consider male-specific recruitment strategies to ensure successful recruitment and retention in their studies. REGISTRATION: This systemic review is registered with the PROSPERO database (CRD42021254696).

Dietary supplements, guideline alignment and biochemical nutrient status in pregnancy: Findings from the Queensland Family Cohort pilot study.

In high-income nations, multiple micronutrient (MMN) supplementation during pregnancy is a common practice. We aimed to describe maternal characteristics associated with supplement use and daily dose of supplemental nutrients consumed in pregnancy, and whether guideline alignment and nutrient status are related to supplement use. The Queensland Family Cohort is a prospective, Australian observational longitudinal study. Maternal characteristics, nutrient intake from food and supplements, and biochemical nutrient status were assessed in the second trimester (n = 127). Supplement use was reported by 89% of participants, of whom 91% reported taking an MMN supplement. Participants who received private obstetric care, had private health insurance and had greater alignment to meat/vegetarian alternatives recommendations were more likely to report MMN supplement use. Private obstetric care and general practitioner shared care were associated with higher daily dose of supplemental nutrients consumed compared with midwifery group practice. There was high reliance on supplements to meet nutrient reference values for folate, iodine and iron, but only plasma folate concentrations were higher in MMN supplement versus nonsupplement users. Exceeding the upper level of intake for folic acid and iron was more likely among combined MMN and individual supplement/s users, and associated with higher plasma concentrations of the respective nutrients. Given the low alignment with food group recommendations and potential risks associated with high MMN supplement use, whole food diets should be emphasized. This study confirms the need to define effective strategies for optimizing nutrient intake in pregnancy, especially among those most vulnerable where MMN supplement use may be appropriate.

The social predictors of paternal antenatal mental health and their associations with maternal mental health in the Queensland Family Cohort prospective study.

Antenatal depression (AND) affects 1 in 10 fathers, potentially negatively impacting maternal mental health and well-being during and after the transition to parenthood. However, few studies have assessed the social predictors of paternal AND or their possible associations with maternal mental health. We analysed data from 180 couples participating in the Queensland Family Cohort longitudinal study. Both parents completed surveys measuring mental health, relationship quality, social support, and sleep quality at 24 weeks of pregnancy. Mothers also completed the same surveys 6 weeks' postpartum. Antenatal depression, stress, and anxiety were highest among fathers reporting lower social support and higher sleep impairment. Maternal AND, stress, and anxiety were higher among mothers reporting higher physical pain and poor sleep quality. Postnatally, mothers reporting lower social support also reported higher depression, anxiety, stress, and psycho-social well-being. While there were no significant associations between AND among fathers and maternal antenatal or postnatal depression, an exploratory analysis revealed that mothers whose partners reported lower antenatal social support also reported lower postnatal social support and higher postnatal depression. Our findings highlight the importance of including data among fathers to achieve a whole family approach to well-being during the transition to parenthood.

Associations between COVID-19 lockdown and post-lockdown on the mental health of pregnant women, postpartum women and their partners from the Queensland family cohort prospective study.

BACKGROUND: There are very few developed countries where physical isolation and low community transmission has been reported for COVID-19 but this has been the experience of Australia. The impact of physical isolation combined with low disease transmission on the mental health of pregnant women is currently unknown and there have been no studies examining the psychological experience for partners of pregnant women during lockdown. The aim of the current study was to examine the impact of the first COVID-19 lockdown in March 2020 and post lockdown from August 2020 on the mental health of pregnant women or postpartum women and their partners. METHODS: Pregnant women and their partners were prospectively recruited to the study before 24 weeks gestation and completed various questionnaires related to mental health and general wellbeing at 24 weeks gestation and then again at 6 weeks postpartum. The Depression, Anxiety and Stress Scale (DASS-21) and the Edinburgh Postnatal Depression Scale (EPDS) were used as outcome measures for the assessment of mental health in women and DASS-21 was administered to their partners. This analysis encompasses 3 time points where families were recruited; before the pandemic (Aug 2018-Feb 2020), during lockdown (Mar-Aug 2020) and after the first lockdown was over (Sept-Dec 2020). RESULTS: There was no significant effect of COVID-19 lockdown and post lockdown on depression or postnatal depression in women when compared to a pre-COVID-19 subgroup. The odds of pregnant women or postpartum women experiencing severe anxiety was more than halved in women during lockdown relative to women in the pre-COVID-19 period (OR = 0.47; 95%CI: 0.27-0.81; P = 0.006). Following lockdown severe anxiety was comparable to the pre-COVID-19 women. Lockdown did not have any substantial effects on stress scores for pregnant and postpartum women. However, a substantial decrease of over 70% in the odds of severe stress was observed post-lockdown relative to pre-COVID-19 levels. Partner's depression, anxiety and stress did not change significantly with lockdown or post lockdown. CONCLUSION: A reproductive age population appear to be able to manage the impact of lockdown and the pandemic with some benefits related to reduced anxiety.

A decline in planned, but not spontaneous, preterm birth rates in a large Australian tertiary maternity centre during COVID-19 mitigation measures.

BACKGROUND: Reports from around the world suggest that rates of preterm birth decreased during COVID-19 lockdown measures. AIMS: To compare the prevalence of preterm birth and stillbirth rates during COVID-19 restriction measures with infants born at the same maternity centre during the same weeks in 2013-2019. MATERIALS AND METHODS: Deidentified data were extracted from the Mater Mothers' healthcare records database. This is a supra-regional tertiary perinatal centre. Logistic regressions were used to examine singleton live preterm birth rates during the beginning of COVID-19 restrictions (16 March-17 April; 'early'; 6955 births) and during the strictest part of COVID-19 restrictions (30 March-1 May; 'late'; 6953 births), according to gestational age subgroups and birth onset (planned or spontaneous). We adjusted for multiple covariates, including maternal age, body mass index, ethnicity, parity, socioeconomic status, maternal asthma, diabetes mellitus and/or hypertensive disorder. Singleton stillbirth rates were also examined between 16 March-1 May. RESULTS: Planned moderate/late preterm births declined by more than half during early COVID-19 restrictions compared with the previous seven years (29 vs an average of 64 per 1000 births; adjusted odds ratio 0.39, 95% CI 0.22-0.71). There was no effect on extremely or very preterm infants, spontaneous preterm births, or stillbirth rates. Rolling averages from January to June revealed a two-week non-significant spike in spontaneous preterm births from late April to early May, 2020. CONCLUSIONS: Together with evidence from other nations, the pandemic provides a unique opportunity to identify causal and preventative factors for preterm birth.

The effect of interleukin-22 treatment on autoimmune diabetes in the NOD mouse.

AIMS/HYPOTHESIS: The aim of this study was to determine whether therapy with the cytokine IL-22 could be used to prevent the development of, or treat, autoimmune diabetes in the NOD mouse. METHODS: Six-week-old NOD mice were administered bi-weekly either recombinant mouse IL-22 (200 ng/g) or PBS (vehicle control) intraperitoneally until overt diabetes was diagnosed as two consecutive measurements of non-fasting blood glucose ≥ 11 mmol/l. At this time, NOD mice in the control arm were treated with LinBit insulin pellets and randomised to bi-weekly therapeutic injections of either PBS or IL-22 (200 ng/g) and followed until overt diabetes was diagnosed, as defined above. RESULTS: IL-22 therapy did not delay the onset of diabetes in comparison with the vehicle-treated mice. We did not observe an improvement in islet area, glycaemic control, beta cell residual function, endoplasmic reticulum stress, insulitis or macrophage and neutrophil infiltration as determined by non-fasting blood glucose, C-peptide and histological scoring. Therapeutic administration of IL-22 did not reduce circulating lipopolysaccharide, a marker of impaired gut mucosal integrity. CONCLUSIONS/INTERPRETATION: Our study suggests that, at this dosing regimen introduced either prior to overt diabetes or at diagnosis of diabetes, recombinant mouse IL-22 therapy cannot prevent autoimmune diabetes, or prolong the honeymoon period in the NOD mouse.

Targeting advanced glycation with pharmaceutical agents: where are we now?

Advanced glycation end products (AGEs) are the final products of the Maillard reaction, a complex process that has been studied by food chemists for a century. Over the past 30 years, the biological significance of advanced glycation has also been discovered. There is mounting evidence that advanced glycation plays a homeostatic role within the body and that food-related Maillard products, intermediates such as reactive α-dicarbonyl compounds and AGEs, may influence this process. It remains to be understood, at what point AGEs and their intermediates become pathogenic and contribute to the pathogenesis of chronic diseases that inflict current society. Diabetes and its complications have been a major focus of AGE biology due to the abundance of excess sugar and α-dicarbonyls in this family of diseases. While further temporal information is required, a number of pharmacological agents that inhibit components of the advanced glycation pathway have already showed promising results in preclinical models. These therapies appear to have a wide range of mechanistic actions to reduce AGE load. Some of these agents including Alagebrium, have translated successfully to clinical trials, while others such as aminoguanidine, have had undesirable side-effect profiles. This review will discuss different pharmacological agents that have been used to reduce AGE burden in preclinical models of disease with a focus on diabetes and its complications, compare outcomes of those therapies that have reached clinical trials, and provide further rationale for the use of inhibitors of the glycation pathway in chronic diseases.

Receptor for Advanced Glycation End Products (RAGE) in Type 1 Diabetes Pathogenesis.

The receptor for advanced glycation end products (RAGE) is a novel protein increasingly studied in the pathogenesis of type 1 diabetes (T1D). RAGE is expressed by several immune cell types, including T cells, antigen-presenting cells, endothelial cells, and the endocrine cells of the pancreatic islets. RAGE binds various ligands including advanced glycation end products (AGEs), high-mobility group box protein 1 (HMGB1), S100 proteins, ß-amyloid, ß-sheet fibrils, and lipopolysaccharide. AGEs are a particularly interesting ligand because their exogenous introduction into the body can be accelerated by the consumption of AGE-rich processed foods. This review will detail RAGE isoforms and its ligands and discuss how RAGE binding on the aforementioned cells could be linked to T1D pathogenesis.

Mesenchymal stromal cells improve transplanted islet survival and islet function in a syngeneic mouse model.

AIMS/HYPOTHESIS: Islet transplantation is used therapeutically in a minority of patients with type 1 diabetes. Successful outcomes are hampered by early islet beta cell loss. The adjuvant co-transplantation of mesenchymal stromal cells (MSCs) has the promise to improve islet transplant outcome. METHODS: We used a syngeneic marginal islet mass transplantation model in a mouse model of diabetes. Mice received islets or islets plus 250,000 MSCs. Kidney subcapsule, intra-hepatic and intra-ocular islet transplantation sites were used. Apoptosis, vascularisation, beta cell proliferation, MSC differentiation and laminin levels were determined by immunohistochemical analysis and image quantification post-transplant. RESULTS: Glucose homeostasis after the transplantation of syngeneic islets was improved by the co-transplantation of MSCs together with islets under the kidney capsule (p = 0.01) and by intravenous infusion of MSCs after intra-hepatic islet transplantation (p = 0.05). MSC co-transplantation resulted in reduced islet apoptosis, with reduced numbers of islet cells positive for cleaved caspase 3 being observed 14 days post-transplant. In kidney subcapsule, but not in intra-ocular islet transplant models, we observed increased re-vascularisation rates, but not increased blood vessel density in and around islets co-transplanted with MSCs compared with islets that were transplanted alone. Co-transplantation of MSCs did not increase beta cell proliferation, extracellular matrix protein laminin production or alpha cell numbers, and there was negligible MSC transdifferentiation into beta cells. CONCLUSIONS/INTERPRETATION: Co-transplantation of MSCs may lead to improved islet function and survival in the early post-transplantation period in humans receiving islet transplantation.

Deletion of bone-marrow-derived receptor for AGEs (RAGE) improves renal function in an experimental mouse model of diabetes.

AIMS/HYPOTHESIS: The AGEs and the receptor for AGEs (RAGE) are known contributors to diabetic complications. RAGE also has a physiological role in innate and adaptive immunity and is expressed on immune cells. The aim of this study was to determine whether deletion of RAGE from bone-marrow-derived cells influences the pathogenesis of experimental diabetic nephropathy. METHODS: Groups (n = 8/group) of lethally irradiated 8 week old wild-type (WT) mice were reconstituted with bone marrow from WT (WT → WT) or RAGE-deficient (RG) mice (RG → WT). Diabetes was induced using multiple low doses of streptozotocin after 8 weeks of bone marrow reconstitution and mice were followed for a further 24 weeks. RESULTS: Compared with diabetic WT mice reconstituted with WT bone marrow, diabetic WT mice reconstituted with RG bone marrow had lower urinary albumin excretion and podocyte loss, more normal creatinine clearance and less tubulo-interstitial injury and fibrosis. However, glomerular collagen IV deposition, glomerulosclerosis and cortical levels of TGF-ß were not different among diabetic mouse groups. The renal tubulo-interstitium of diabetic RG → WT mice also contained fewer infiltrating CD68(+) macrophages that were activated. Diabetic RG → WT mice had lower renal cortical concentrations of CC chemokine ligand 2 (CCL2), macrophage inhibitory factor (MIF) and IL-6 than diabetic WT → WT mice. Renal cortical RAGE ligands S100 calgranulin (S100A)8/9 and AGEs, but not high mobility box protein B-1 (HMGB-1) were also decreased in diabetic RG → WT compared with diabetic WT → WT mice. In vitro, bone-marrow-derived macrophages from WT but not RG mice stimulated collagen IV production in cultured proximal tubule cells. CONCLUSIONS/INTERPRETATION: These studies suggest that RAGE expression on haemopoietically derived immune cells contributes to the functional changes seen in diabetic nephropathy by promoting macrophage infiltration and renal tubulo-interstitial damage.

Maternal physical activity and sitting time and its association with placental morphology and blood flow during gestation: Findings from the Queensland Family Cohort study.

OBJECTIVES: Antenatal exercise is associated with placental morphological alterations, however research in this area is limited. Given the emphasis on the beneficial effects of antenatal exercise, it is important to understand its effect on placental function and the relationship to foetal development. The aim of this study was to investigate the association between physical activity, sitting time, and placental outcomes measured during gestation. DESIGN: Prospective cohort study. METHODS: Pregnant women in the Queensland Family Cohort study self-reported physical activity at 24 and 36 weeks of gestation (n = 203) and were categorised into physical activity volume groups of nil-low (0-<500 metabolic equivalent of task·minutes/week), moderate (500-<1000 metabolic equivalent of task·minutes/week), or high-volume activity (≥1000 metabolic equivalent of task·minutes/week). Participants reported average daily sitting time, whereby excessive sitting time was considered as ≥8h/day. Placental stiffness, thickness, and uteroplacental blood flow resistance were measured by ultrasound imaging at each timepoint. RESULTS: Physical activity volume was not associated with changes to placental morphometrics or uteroplacental blood flow resistance at 24 or 36 weeks of gestation. Excessive sitting time at 36 weeks was associated with greater placental stiffness (p = 0.046), and a lower umbilical artery pulsatility index (p = 0.001). CONCLUSIONS: Placental tissue stiffness and umbilical artery resistance were altered in late gestation with higher maternal sitting time but not with physical activity volume. Overall, excessive sitting time may be a risk for suboptimal placental function and could be an important focus for antenatal care.

Liver and pancreatic-targeted interleukin-22 as a therapeutic for metabolic dysfunction-associated steatohepatitis.

Metabolic dysfunction-associated steatohepatitis (MASH) is the most prevalent cause of liver disease worldwide, with a single approved therapeutic. Previous research has shown that interleukin-22 (IL-22) can suppress ß-cell stress, reduce local islet inflammation, restore appropriate insulin production, reverse hyperglycemia, and ameliorate insulin resistance in preclinical models of diabetes. In clinical trials long-acting forms of IL-22 have led to increased proliferation in the skin and intestine, where the IL-22RA1 receptor is highly expressed. To maximise beneficial effects whilst reducing the risk of epithelial proliferation and cancer, we designed short-acting IL-22-bispecific biologic drugs that successfully targeted the liver and pancreas. Here we show 10-fold lower doses of these bispecific biologics exceed the beneficial effects of native IL-22 in multiple preclinical models of MASH, without off-target effects. Treatment restores glycemic control, markedly reduces hepatic steatosis, inflammation, and fibrogenesis. These short-acting IL-22-bispecific targeted biologics are a promising new therapeutic approach for MASH.

Shear wave velocity measurement of the placenta is not limited by placental location.

INTRODUCTION: Ultrasound elastography shows diagnostic promise via the non-invasive determination of placental elastic properties. A limitation is a potential for inadequate measurements from posterior placentae. This study aimed to analyse placental position's influence on measures of shear wave elastography (SWV). METHODS: SWV elastography measurements were obtained via ultrasound at 24, 28 and 36 weeks gestation from 238 pregnancies. . The placental position was labelled as either anterior, posterior or fundal/lateral. Average SWV measurements (m/s) and the corresponding standard deviations (SD) were used for data analysis. RESULTS: There was a statistically significant difference between SWV recorded from anterior (1.33 ± 0.19)m/s and posterior (1.39 ± 0.18)m/s placentae (p < 0.001). However, the average sampling depth between these groups was significantly different (3.98 cm vs. 5.38 cm, p < 0.001). There was no statistically significant difference between SWV when measurements were compared at similar depths, regardless of placental location. The addition of placental position to a previously developed mixed-effects model confirmed placental position did not result in improved SWV measurements. In this model, sampling depth remained the best predictor for SWV. CONCLUSIONS: This study showed that placental position does not influence the accuracy or reliability of SWV.

Insufficient Evidence of a Breastmilk Microbiota at Six-Weeks Postpartum: A Pilot Study.

Breastmilk is thought to influence the infant gut by supplying prebiotics in the form of human milk oligosaccharides and potentially seeding the gut with breastmilk microbes. However, the presence of a breastmilk microbiota and origins of these microbes are still debated. As a pilot study, we assessed the microbes present in expressed breastmilk at six-weeks postpartum using shotgun metagenomic sequencing in a heterogenous cohort of women who delivered by vaginal (n = 8) and caesarean delivery (n = 8). In addition, we estimated the microbial load of breastmilk at six-weeks post-partum with quantitative PCR targeting the 16S rRNA gene. Breastmilk at six-weeks postpartum had a low microbial mass, comparable with PCR no-template and extraction controls. Microbes identified through metagenomic sequencing were largely consistent with skin and oral microbes, with four samples returning no identifiable bacterial sequences. Our results do not provide convincing evidence for the existence of a breastmilk microbiota at six-weeks postpartum. It is more likely that microbes present in breastmilk are sourced by ejection from the infant's mouth and from surrounding skin, as well as contamination during sampling and processing.

Alpha cell receptor for advanced glycation end products associate with glucagon expression in type 1 diabetes.

Hypoglycemia in type 1 diabetes associates with changes in the pancreatic islet α cells, where the receptor for advanced glycation end products (RAGE) is highly expressed. This study compared islet RAGE expression in donors without diabetes, those at risk of, and those with type 1 diabetes. Laser-dissected islets were subject to RNA bioinformatics and adjacent pancreatic tissue were assessed by confocal microscopy. We found that islets from type 1 diabetes donors had differential expression of the RAGE gene (AGER) and its correlated genes, based on glucagon expression. Random forest machine learning revealed that AGER was the most important predictor for islet glucagon levels. Conversely, a generalized linear model identified that glucagon expression could be predicted by expression of RAGE signaling molecules, its ligands and enzymes that create or clear RAGE ligands. Confocal imaging co-localized RAGE, its ligands and signaling molecules to the α cells. Half of the type 1 diabetes cohort comprised of adolescents and a patient with history of hypoglycemia-all showed an inverse relationship between glucagon and RAGE. These data confirm an association between glucagon and islet RAGE, its ligands and signaling pathways in type 1 diabetes, which warrants functional investigation into a role for RAGE in hypoglycemia.

Advanced Glycation End Products (AGEs) and Chronic Kidney Disease: Does the Modern Diet AGE the Kidney?

Since the 1980s, chronic kidney disease (CKD) affecting all ages has increased by almost 25%. This increase may be partially attributable to lifestyle changes and increased global consumption of a "western" diet, which is typically energy dense, low in fruits and vegetables, and high in animal protein and ultra-processed foods. These modern food trends have led to an increase in the consumption of advanced glycation end products (AGEs) in conjunction with increased metabolic dysfunction, obesity and diabetes, which facilitates production of endogenous AGEs within the body. When in excess, AGEs can be pathological via both receptor-mediated and non-receptor-mediated pathways. The kidney, as a major site for AGE clearance, is particularly vulnerable to AGE-mediated damage and increases in circulating AGEs align with risk of CKD and all-cause mortality. Furthermore, individuals with significant loss of renal function show increased AGE burden, particularly with uraemia, and there is some evidence that AGE lowering via diet or pharmacological inhibition may be beneficial for CKD. This review discusses the pathways that drive AGE formation and regulation within the body. This includes AGE receptor interactions and pathways of AGE-mediated pathology with a focus on the contribution of diet on endogenous AGE production and dietary AGE consumption to these processes. We then analyse the contribution of AGEs to kidney disease, the evidence for dietary AGEs and endogenously produced AGEs in driving pathogenesis in diabetic and non-diabetic kidney disease and the potential for AGE targeted therapies in kidney disease.

Relationship between placental elastography, maternal pre-pregnancy body mass index and gestational weight gain.

INTRODUCTION: Maternal obesity is a significant risk factor for poor pregnancy outcomes. Obesity is linked to abnormalities in placental tissue at term. The purpose of this study was to correlate changes in placental stiffness, measured via ultrasound elastography, with maternal pre-pregnancy body mass index and gestational weight gain. METHODS: Body Mass Index and gestation weight gain data was collected from 238 women. Elastography measurements were obtained via ultrasound at 24-, 28- and 36-weeks' gestation. An analysis using a linear mixed regression model assessed for the statistical significance of pre-pregnancy BMI, pregnancy weight gain and placental SWV (Shear Wave Velocity). RESULTS: Pre-pregnancy weight status has a significant impact on placental tissue stiffness detectable via ultrasound elastography. Placental tissue stiffness was highest in obese women, followed by overweight women. Obese women, on average, had a MeanSWV 0.11 m/s (95% CI (0.061-0.15) m/s, p < 0.001) above the healthy group throughout the 3rd trimester. Weight gain during pregnancy had a small impact on placental stiffness at the end of pregnancy. MeanSWV was 0.06 m/s (95% CI (0.03-0.10) m/s, p < 0.001) higher in the excessive weight gain group. DISCUSSION: Structural changes of the placenta detected via ultrasound elastography techniques are not exclusive to placental dysfunction conditions (pre-eclampsia and growth restriction) but are also associated with maternal obesity.

Exploring the diets of mothers and their partners during pregnancy: Findings from the Queensland Family Cohort pilot study.

AIM: Modifiable behaviours during the first 1000 days of life influence developmental trajectories of adult chronic diseases. Despite this, sub-optimal dietary intakes during pregnancy and excessive gestational weight gain are common. Very little is known about partners' dietary patterns and the influence on women's pregnancy dietary patterns. We aimed to examine dietary intake during pregnancy among women and their partners, and gestational weight gain patterns in the Queensland Family Cohort pilot study. METHODS: The Queensland Family Cohort is a prospective, observational study piloted at a Brisbane (Australia) tertiary maternity hospital from 2018 to 2021. Participant characteristics, weight gain, dietary and nutrient intake were assessed. RESULTS: Data were available for 194 pregnant women and their partners. Poor alignment with Australian Guide to Healthy Eating recommendations was observed. Highest alignment was for fruit (40% women) and meat/alternatives (38% partners) and lowest for breads/cereals (<1% women) and milk/alternatives (13% partners). Fewer women (4.4%-60.3%) than their partners (5.4%-92.3%) met guidelines for all micronutrient intakes from food alone, particularly folic acid, iodine, and iron. Women were more likely to meet daily recommendations for fruit, vegetables, dairy, bread/cereals, and meat/alternatives when their partners also met recommendations. Women with a higher pre-pregnancy body mass index were more likely to gain above recommended weight gain ranges. CONCLUSIONS: In this contemporary cohort of pregnant women and their partners, sub-optimal dietary patterns and deficits in some nutrients were common. There is an urgent need for evidence-informed public health policy and programs to improve diet quality during pregnancy due to intergenerational effects.

Soluble RAGE Prevents Type 1 Diabetes Expanding Functional Regulatory T Cells.

Type 1 diabetes is an autoimmune disease with no cure, where clinical translation of promising therapeutics has been hampered by the reproducibility crisis. Here, short-term administration of an antagonist to the receptor for advanced glycation end products (sRAGE) protected against murine diabetes at two independent research centers. Treatment with sRAGE increased regulatory T cells (Tregs) within the islets, pancreatic lymph nodes, and spleen, increasing islet insulin expression and function. Diabetes protection was abrogated by Treg depletion and shown to be dependent on antagonizing RAGE with use of knockout mice. Human Tregs treated with a RAGE ligand downregulated genes for suppression, migration, and Treg homeostasis (FOXP3, IL7R, TIGIT, JAK1, STAT3, STAT5b, CCR4). Loss of suppressive function was reversed by sRAGE, where Tregs increased proliferation and suppressed conventional T-cell division, confirming that sRAGE expands functional human Tregs. These results highlight sRAGE as an attractive treatment to prevent diabetes, showing efficacy and reproducibility at multiple research centers and in human T cells.

Mesenchymal cells appearing in pancreatic tissue culture are bone marrow-derived stem cells with the capacity to improve transplanted islet function.

Adherent fibroblast-like cells have been reported to appear in cultures of human endocrine or exocrine pancreatic tissue during attempts to differentiate human beta cells from pancreatic precursors. A thorough characterization of these mesenchymal cells has not yet been completed, and there are no conclusive data about their origin.We demonstrated that the human mesenchymal cells outgrowing from cultured human pancreatic endocrine or exocrine tissue are pancreatic mesenchymal stem cells (pMSC) that propagate from contaminating pMSC. The origin of pMSC is partly extrapancreatic both in humans and mice, and by using green fluorescent protein (GFP(+)) bone marrow transplantation in the mouse model, we were able to demonstrate that these cells derive from the CD45(+) component of bone marrow. The pMSC express negligible levels of islet-specific genes both in basal conditions and after serum deprivation or exogenous growth factor exposure, and might not represent optimal candidates for generation of physiologically competent beta-cells. On the other hand, when cotransplanted with a minimal pancreatic islet mass, pMSC facilitate the restoration of normoglycemia and the neovascularization of the graft. These results suggest that pMSCs could exert an indirect role of "helper" cells in tissue repair processes.