Krill body size drives particulate organic carbon export in West Antarctica.

The export of carbon from the ocean surface and storage in the ocean interior is important in the modulation of global climate1-4. The West Antarctic Peninsula experiences some of the largest summer particulate organic carbon (POC) export rates, and one of the fastest warming rates, in the world5,6. To understand how warming may alter carbon storage, it is necessary to first determine the patterns and ecological drivers of POC export7,8. Here we show that Antarctic krill (Euphausia superba) body size and life-history cycle, as opposed to their overall biomass or regional environmental factors, exert the dominant control on the POC flux. We measured POC fluxes over 21 years, the longest record in the Southern Ocean, and found a significant 5-year periodicity in the annual POC flux, which oscillated in synchrony with krill body size, peaking when the krill population was composed predominately of large individuals. Krill body size alters the POC flux through the production and export of size-varying faecal pellets9, which dominate the total flux. Decreases in winter sea ice10, an essential habitat for krill, are causing shifts in the krill population11, which may alter these export patterns of faecal pellets, leading to changes in ocean carbon storage.

Perinatal morbidity among women with a previous caesarean delivery (PRISMA trial): a cluster-randomised trial.

BACKGROUND: Women with a previous caesarean delivery face a difficult choice in their next pregnancy: planning another caesarean or attempting vaginal delivery, both of which are associated with potential maternal and perinatal complications. This trial aimed to assess whether a multifaceted intervention, which promoted person-centred decision making and best practices, would reduce the risk of major perinatal morbidity among women with one previous caesarean delivery. METHODS: We conducted an open, multicentre, cluster-randomised, controlled trial of a multifaceted 2-year intervention in 40 hospitals in Quebec among women with one previous caesarean delivery, in which hospitals were the units of randomisation and women the units of analysis. Randomisation was stratified according to level of care, using blocked randomisation. Hospitals were randomly assigned (1:1) to the intervention group (implementation of best practices and provision of tools that aimed to support decision making about mode of delivery, including an estimation of the probability of vaginal delivery and an ultrasound estimation of the risk of uterine rupture), or the control group (no intervention). The primary outcome was a composite risk of major perinatal morbidity. This trial was registered with ISRCTN, ISRCTN15346559. FINDINGS: 21 281 eligible women delivered during the study period, from April 1, 2016 to Dec 13, 2019 (10 514 in the intervention group and 10 767 in the control group). None were lost to follow-up. There was a significant reduction in the rate of major perinatal morbidity from the baseline period to the intervention period in the intervention group as compared with the control group (adjusted odds ratio [OR] for incremental change over time, 0·72 [95% CI 0·52-0·99]; p=0·042; adjusted risk difference -1·2% [95% CI -2·0 to -0·1]). Major maternal morbidity was significantly reduced in the intervention group as compared with the control group (adjusted OR 0·54 [95% CI 0·33-0·89]; p=0·016). Minor perinatal and maternal morbidity, caesarean delivery, and uterine rupture rates did not differ significantly between groups. INTERPRETATION: A multifaceted intervention supporting women in their choice of mode of delivery and promoting best practices resulted in a significant reduction in rates of major perinatal and maternal morbidity, without an increase in the rate of caesarean or uterine rupture. FUNDING: Canadian Institutes of Health Research (CIHR, MOP-142448).

Randomised trial of genetic testing and targeted intervention to prevent the development and progression of Paget's disease of bone.

INTRODUCTION: Paget's disease of bone (PDB) frequently presents at an advanced stage with irreversible skeletal damage. Clinical outcomes might be improved by earlier diagnosis and prophylactic treatment. METHODS: We randomised 222 individuals at increased risk of PDB because of pathogenic SQSTM1 variants to receive 5 mg zoledronic acid (ZA) or placebo. The primary outcome was new bone lesions assessed by radionuclide bone scan. Secondary outcomes included change in existing lesions, biochemical markers of bone turnover and skeletal events related to PDB. RESULTS: The median duration of follow-up was 84 months (range 0-127) and 180 participants (81%) completed the study. At baseline, 9 (8.1%) of the ZA group had PDB lesions vs 12 (10.8%) of the placebo group. Two of the placebo group developed new lesions versus none in the ZA group (OR 0.41, 95% CI 0.00 to 3.43, p=0.25). Eight of the placebo group had a poor outcome (lesions which were new, unchanged or progressing) compared with none of the ZA group (OR 0.08, 95% CI 0.00 to 0.42, p=0.003). At the study end, 1 participant in the ZA group had lesions compared with 11 in the placebo group. Biochemical markers of bone turnover were significantly reduced in the ZA group. One participant allocated to placebo required rescue therapy with ZA because of symptomatic disease. The number and severity of adverse events did not differ between groups. CONCLUSIONS: Genetic testing for pathogenic SQSTM1 variants coupled with intervention with ZA is well tolerated and has favourable effects on the progression of early PDB. TRIAL REGISTRATION NUMBER: ISRCTN11616770.

A novel group of negative-sense RNA viruses associated with epizootics in managed and free-ranging freshwater turtles in Florida, USA.

Few aquatic animal negative-sense RNA viruses have been characterized, and their role in disease is poorly understood. Here, we describe a virus isolated from diseased freshwater turtles from a Florida farm in 2007 and from an ongoing epizootic among free-ranging populations of Florida softshell turtles (Apalone ferox), Florida red-bellied cooters (Pseudemys nelsoni), and peninsula cooters (Pseudemys peninsularis). Affected turtles presented with similar neurological signs, oral and genital ulceration, and secondary microbial infections. Microscopic lesions were most severe in the softshell turtles and included heterophilic/histiocytic meningoencephalitis, multi-organ vasculitis, and cytologic observation of leukocytic intracytoplasmic inclusions. The virus was isolated using Terrapene heart (TH-1) cells. Ultrastructurally, viral particles were round to pleomorphic and acquired an envelope with prominent surface projections by budding from the cell membrane. Viral genomes were sequenced from cDNA libraries of two nearly identical isolates and determined to be bi-segmented, with an ambisense coding arrangement. The larger segment encodes a predicted RNA-directed RNA polymerase (RdRP) and a putative zinc-binding matrix protein. The smaller segment encodes a putative nucleoprotein and an envelope glycoprotein precursor (GPC). Thus, the genome organization of this turtle virus resembles that of arenaviruses. Phylogenetic analysis shows that the RdRP of the turtle virus is highly diverged from the RdRPs of all known negative-sense RNA viruses and forms a deep branch within the phylum Negarnaviricota, that is not affiliated with any known group of viruses, even at the class level. In contrast, the GPC protein of the turtle virus is confidently affiliated with homologs from a distinct group of fish hantaviruses. Thus, the turtle virus is expected to become the founder of a new taxon of negative-sense RNA viruses, at least with a family rank, but likely, an order or even a class. These viruses probably evolved either by reassortment or by intrasegment recombination between a virus from a distinct branch of negarnaviruses distant from all known groups and a hanta-like aquatic virus. We suggest the provisional name Tosoviridae for the putative new family, with Turtle fraservirus 1 (TFV1) as the type species within the genus Fraservirus. A conventional RT-PCR assay, targeting the TFV1 RdRP, confirmed the presence of viral RNA in multiple tissues and exudates from diseased turtles. The systemic nature of the TFV1 infection was further supported by labeling of cells within lesions using in situ hybridization targeting the RNA of the TFV1 RdRP.

Sex differences in iron status during military training: a prospective cohort study of longitudinal changes and associations with endurance performance and musculoskeletal outcomes.

This study investigated sex differences in Fe status, and associations between Fe status and endurance and musculoskeletal outcomes, in military training. In total, 2277 British Army trainees (581 women) participated. Fe markers and endurance performance (2·4 km run) were measured at the start (week 1) and end (week 13) of training. Whole-body areal body mineral density (aBMD) and markers of bone metabolism were measured at week 1. Injuries during training were recorded. Training decreased Hb in men and women (mean change (-0·1 (95 % CI -0·2, -0·0) and -0·7 (95 % CI -0·9, -0·6) g/dl, both P < 0·001) but more so in women (P < 0·001). Ferritin decreased in men and women (-27 (95 % CI -28, -23) and -5 (95 % CI -8, -1) µg/l, both P ≤ 0·001) but more so in men (P < 0·001). Soluble transferrin receptor increased in men and women (2·9 (95 % CI 2·3, 3·6) and 3·8 (95 % CI 2·7, 4·9) nmol/l, both P < 0·001), with no difference between sexes (P = 0·872). Erythrocyte distribution width increased in men (0·3 (95 % CI 0·2, 0·4)%, P < 0·001) but not in women (0·1 (95 % CI -0·1, 0·2)%, P = 0·956). Mean corpuscular volume decreased in men (-1·5 (95 % CI -1·8, -1·1) fL, P < 0·001) but not in women (0·4 (95 % CI -0·4, 1·3) fL, P = 0·087). Lower ferritin was associated with slower 2·4 km run time (P = 0·018), sustaining a lower limb overuse injury (P = 0·048), lower aBMD (P = 0·021) and higher beta C-telopeptide cross-links of type 1 collagen and procollagen type 1 N-terminal propeptide (both P < 0·001) controlling for sex. Improving Fe stores before training may protect Hb in women and improve endurance and protect against injury.

Stress and anxiety during pregnancy and length of gestation: a federated study using data from five Canadian and European birth cohorts.

While its etiology is not fully elucidated, preterm birth represents a major public health concern as it is the leading cause of child mortality and morbidity. Stress is one of the most common perinatal conditions and may increase the risk of preterm birth. In this paper we aimed to investigate the association of maternal perceived stress and anxiety with length of gestation. We used harmonized data from five birth cohorts from Canada, France, and Norway. A total of 5297 pregnancies of singletons were included in the analysis of perceived stress and gestational duration, and 55,775 pregnancies for anxiety. Federated analyses were performed through the DataSHIELD platform using Cox regression models within intervals of gestational age. The models were fit for each cohort separately, and the cohort-specific results were combined using random effects study-level meta-analysis. Moderate and high levels of perceived stress during pregnancy were associated with a shorter length of gestation in the very/moderately preterm interval [moderate: hazard ratio (HR) 1.92 (95%CI 0.83, 4.48); high: 2.04 (95%CI 0.77, 5.37)], albeit not statistically significant. No association was found for the other intervals. Anxiety was associated with gestational duration in the very/moderately preterm interval [1.66 (95%CI 1.32, 2.08)], and in the early term interval [1.15 (95%CI 1.08, 1.23)]. Our findings suggest that perceived stress and anxiety are associated with an increased risk of earlier birth, but only in the earliest gestational ages. We also found an association in the early term period for anxiety, but the result was only driven by the largest cohort, which collected information the latest in pregnancy. This raised a potential issue of reverse causality as anxiety later in pregnancy could be due to concerns about early signs of a possible preterm birth.

Collagen peptide supplementation before bedtime reduces sleep fragmentation and improves cognitive function in physically active males with sleep complaints.

PURPOSE: The primary aim of this study was to examine whether a glycine-rich collagen peptides (CP) supplement could enhance sleep quality in physically active men with self-reported sleep complaints. METHODS: In a randomized, crossover design, 13 athletic males (age: 24 ± 4 years; training volume; 7 ± 3 h·wk1) with sleep complaints (Athens Insomnia Scale, 9 ± 2) consumed CP (15 g·day1) or a placebo control (CON) 1 h before bedtime for 7 nights. Sleep quality was measured with subjective sleep diaries and actigraphy for 7 nights; polysomnographic sleep and core temperature were recorded on night 7. Cognition, inflammation, and endocrine function were measured on night 7 and the following morning. Subjective sleepiness and fatigue were measured on all 7 nights. The intervention trials were separated by ≥ 7 days and preceded by a 7-night familiarisation trial. RESULTS: Polysomnography showed less awakenings with CP than CON (21.3 ± 9.7 vs. 29.3 ± 13.8 counts, respectively; P = 0.028). The 7-day average for subjective awakenings were less with CP vs. CON (1.3 ± 1.5 vs. 1.9 ± 0.6 counts, respectively; P = 0.023). The proportion of correct responses on the baseline Stroop cognitive test were higher with CP than CON (1.00 ± 0.00 vs. 0.97 ± 0.05 AU, respectively; P = 0.009) the morning after night 7. There were no trial differences in core temperature, endocrine function, inflammation, subjective sleepiness, fatigue and sleep quality, or other measures of cognitive function or sleep (P > 0.05). CONCLUSION: CP supplementation did not influence sleep quantity, latency, or efficiency, but reduced awakenings and improved cognitive function in physically active males with sleep complaints.

Alterations in regulators of the renal-bone axis, inflammation and iron status in older people with early renal impairment and the effect of vitamin D supplementation.

CONTEXT: Chronic kidney disease (CKD) leads to alterations in fibroblast growth factor 23 (FGF23) and the renal-bone axis. This may be partly driven by altered inflammation and iron status. Vitamin D supplementation may reduce inflammation. OBJECTIVE AND METHODS: Older adults with early CKD (estimated glomerular filtration rate (eGFR) 30-60 ml/min/1.73 m2; CKDG3a/b; n = 35) or normal renal function (eGFR >90 ml/min/1.73 m2; CKDG1; n = 35) received 12,000, 24,000 or 48,000 IU D3/month for 1 year. Markers of the renal-bone axis, inflammation and iron status were investigated pre- and post-supplementation. Predictors of c-terminal and intact FGF23 (cFGF23; iFGF23) were identified by univariate and multivariate regression. RESULTS: Pre-supplementation, comparing CKDG3a/b to CKDG1, plasma cFGF23, iFGF23, PTH, sclerostin and TNFα were significantly higher and Klotho, 1,25-dihydroxyvitamin D and iron were lower. Post-supplementation, only cFGF23, 25(OH)D and IL6 differed between groups. The response to supplementation differed between eGFR groups. Only in the CKDG1 group, phosphate decreased, cFGF23, iFGF23 and procollagen type I N-propeptide increased. In the CKDG3a/b group, TNFα significantly decreased, and iron increased. Plasma 25(OH)D and IL10 increased, and carboxy-terminal collagen crosslinks decreased in both groups. In univariate models cFGF23 and iFGF23 were predicted by eGFR and regulators of calcium and phosphate metabolism at both time points; IL6 predicted cFGF23 (post-supplementation) and iFGF23 (pre-supplementation) in univariate models. Hepcidin predicted post-supplementation cFGF23 in multivariate models with eGFR. CONCLUSION: Alterations in regulators of the renal-bone axis, inflammation and iron status were found in early CKD. The response to vitamin D3 supplementation differed between eGFR groups. Plasma IL6 predicted both cFGF23 and iFGF23 and hepcidin predicted cFGF23.

Meta-analysis reveals the vaginal microbiome is a better predictor of earlier than later preterm birth.

BACKGROUND: High-throughput sequencing measurements of the vaginal microbiome have yielded intriguing potential relationships between the vaginal microbiome and preterm birth (PTB; live birth prior to 37 weeks of gestation). However, results across studies have been inconsistent. RESULTS: Here, we perform an integrated analysis of previously published datasets from 12 cohorts of pregnant women whose vaginal microbiomes were measured by 16S rRNA gene sequencing. Of 2039 women included in our analysis, 586 went on to deliver prematurely. Substantial variation between these datasets existed in their definition of preterm birth, characteristics of the study populations, and sequencing methodology. Nevertheless, a small group of taxa comprised a vast majority of the measured microbiome in all cohorts. We trained machine learning (ML) models to predict PTB from the composition of the vaginal microbiome, finding low to modest predictive accuracy (0.28-0.79). Predictive accuracy was typically lower when ML models trained in one dataset predicted PTB in another dataset. Earlier preterm birth (< 32 weeks, < 34 weeks) was more predictable from the vaginal microbiome than late preterm birth (34-37 weeks), both within and across datasets. Integrated differential abundance analysis revealed a highly significant negative association between L. crispatus and PTB that was consistent across almost all studies. The presence of the majority (18 out of 25) of genera was associated with a higher risk of PTB, with L. iners, Prevotella, and Gardnerella showing particularly consistent and significant associations. Some example discrepancies between studies could be attributed to specific methodological differences but not most study-to-study variations in the relationship between the vaginal microbiome and preterm birth. CONCLUSIONS: We believe future studies of the vaginal microbiome and PTB will benefit from a focus on earlier preterm births and improved reporting of specific patient metadata shown to influence the vaginal microbiome and/or birth outcomes.

Low-loss grating coupler based on inter-layer mode interference in a hybrid silicon nitride platform.

Surface grating couplers are an important component for interfacing photonic integrated circuits with optical fibers. However, conventional coupler designs typically provide limited performance due to low directionality and poor fiber-to-grating field overlap. The efficiency can be improved by using non-uniform grating structures at the expense of small critical dimensions complicating the fabrication process. While uniform gratings can alleviate this constraint, they produce an exponentially decaying near-field with the Gaussian fiber mode overlap limited to a theoretical maximum of 80%. In this work, we propose a uniform grating coupler that circumvents this field overlap limitation. This is achieved by leveraging inter-layer mode interference through a virtual directional coupler effect in a hybrid amorphous-silicon (α-Si) on silicon nitride (Si3N4) platform. By optimizing the inter-layer gap and grating geometry, a near-Gaussian profile of the out-radiated beam is achieved, resulting in an unprecedented grating-to-fiber overlap of 96%. The full three-dimensional (3D) finite-difference time-domain (FDTD) simulations show a high directionality of 84% and a record coupling loss of -1.27 dB with a 1-dB bandwidth of 20 nm for the uniform grating coupler design. Our device is designed for a wavelength of 950 nm aimed for use in hybrid quantum photonic integrated circuits using III-V quantum dot single photon sources.

The Collagen Synthesis Response to an Acute Bout of Resistance Exercise Is Greater when Ingesting 30 g Hydrolyzed Collagen Compared with 15 g and 0 g in Resistance-Trained Young Men.

BACKGROUND: Resistance exercise (RE) stimulates collagen synthesis in skeletal muscle and tendon but there is limited and equivocal evidence regarding an effect of collagen supplementation and exercise on collagen synthesis. Furthermore, it is not known if a dose-response exists regarding the effect of hydrolyzed collagen (HC) ingestion and RE on collagen synthesis. OBJECTIVE: To determine the HC dose-response effect on collagen synthesis after high-intensity RE in resistance-trained young men. METHODS: Using a double-blind, randomized crossover design, 10 resistance-trained males (age: 26 ± 3 y; height: 1.77 ± 0.04 m; mass: 79.7 ± 7.0 kg) ingested 0 g, 15 g, or 30 g HC with 50 mg vitamin C 1 h before performing 4 sets' barbell back squat RE at 10-repetition maximum load, after which they rested for 6 h. Blood samples were collected throughout each of the 3 interventions to analyze procollagen type Ⅰ N-terminal propeptide (PINP) and ß-isomerized C-terminal telopeptide of type I collagen (ß-CTX) concentration, and the concentration of 18 collagen amino acids. RESULTS: The serum PINP concentration × time area under the curve (AUC) was greater for 30 g (267 ± 79 µg·L-1·h) than for 15 g (235 ± 70 µg·L-1·h, P = 0.013) and 0 g HC (219 ± 88 µg·L-1·h, P = 0.002) but there was no difference between 0 and 15 g HC (P = 0.225). The AUCs of glycine and proline were greater for 30 g than for 15 and 0 g HC (P < 0.05). Plasma ß-CTX concentration decreased from -1 to +6 h (P < 0.05), with no differences between interventions. CONCLUSIONS: Ingesting 30 g HC before high-intensity RE augments whole-body collagen synthesis more than 15 g and 0 g HC in resistance-trained young males.

Distal Tibial Bone Properties and Bone Stress Injury Risk in Young Men Undergoing Arduous Physical Training.

Trabecular microarchitecture contributes to bone strength, but its role in bone stress injury (BSI) risk in young healthy adults is unclear. Tibial volumetric BMD (vBMD), geometry, and microarchitecture, whole-body areal BMD, lean and fat mass, biochemical markers of bone metabolism, aerobic fitness, and muscle strength and power were measured in 201 British Army male infantry recruits (age 20.7 [4.3] years, BMI 24.0 ± 2.7 kg·m2) in week one of basic training. Tibial scans were performed at the ultra-distal site, 22.5 mm from the distal endplate of the non-dominant leg using High Resolution Peripheral Quantitative Computed Tomography (XtremeCT, Scanco Medical AG, Switzerland). Binary logistic regression analysis was performed to identify associations with lower body BSI confirmed by MRI. 20 recruits (10.0%) were diagnosed with a lower body BSI. Pre-injured participants had lower cortical area, stiffness and estimated failure load (p = 0.029, 0.012 and 0.011 respectively) but tibial vBMD, geometry, and microarchitecture were not associated with BSI incidence when controlling for age, total body mass, lean body mass, height, total 25(OH)D, 2.4-km run time, peak power output and maximum dynamic lift strength. Infantry Regiment (OR 9.3 [95%CI, 2.6, 33.4]) Parachute versus Line Infantry, (p ≤ 0.001) and 2.4-km best effort run time (1.06 [95%CI, 1.02, 1.10], p < 0.033) were significant predictors. Intrinsic risk factors, including ultradistal tibial density, geometry, and microarchitecture, were not associated with lower body BSI during arduous infantry training. The ninefold increased risk of BSI in the Parachute Regiment compared with Line Infantry suggests that injury propensity is primarily a function of training load and risk factors are population-specific.

Second-trimester abortion and risk of live birth.

BACKGROUND: Second-trimester abortion may result in a live birth, but the extent to which this outcome occurs is unknown. OBJECTIVE: This study aimed to examine rates of live birth after pregnancy termination in the second trimester and identify associated risk factors. STUDY DESIGN: We conducted a retrospective cohort study of 13,777 second-trimester abortions occurring in hospital settings between April 1, 1989 and March 31, 2021 in Quebec, Canada. The exposure was induced abortion between 15 and 29 weeks of gestation, including the indication for (fetal anomaly, maternal emergency, other) and use of feticidal injection (intracardiac/intrathoracic or intraamniotic). The primary outcome was live birth following abortion. We measured the rate of live birth per 100 abortions and used adjusted log-binomial regression models to estimate risk ratios and 95% confidence intervals for the association of fetal and maternal characteristics with the risk of live birth. We assessed the extent to which feticidal injection reduced the risk. RESULTS: Among 13,777 abortions between 15 and 29 weeks of gestation, 1541 (11.2%) led to live birth. Fetal anomaly was a common indication for termination (48.1%), and most abortions were by labor induction (72.2%). Compared with abortion between 15 and 19 weeks, abortion between 20 and 24 weeks was associated with 4.80 times the risk of live birth (95% confidence interval, 4.20-5.48), whereas abortion between 25 and 29 weeks was associated with 1.34 times the risk (95% confidence interval, 1.00-1.79). Feticidal injection reduced the risk of live birth by 57% compared with no injection (risk ratio, 0.43; 95% confidence interval, 0.36-0.51). Intracardiac or intrathoracic injection was particularly effective at preventing live birth (risk ratio, 0.02; 95% confidence interval, 0.01-0.07). CONCLUSION: Second-trimester abortion carries a risk of live birth, especially at 20 to 24 weeks of gestation, although feticidal injection may protect against this outcome.

New insights on labor progression: a systematic review.

The past 20 years witnessed an invigoration of research on labor progression and a change of thinking regarding normal labor. New evidence is emerging, and more advanced statistical methods are applied to labor progression analyses. Given the wide variations in the onset of active labor and the pattern of labor progression, there is an emerging consensus that the definition of abnormal labor may not be related to an idealized or average labor curve. Alternative approaches to guide labor management have been proposed; for example, using an upper limit of a distribution of labor duration to define abnormally slow labor. Nonetheless, the methods of labor assessment are still primitive and subject to error; more objective measures and more advanced instruments are needed to identify the onset of active labor, monitor labor progression, and define when labor duration is associated with maternal/child risk. Cervical dilation alone may be insufficient to define active labor, and incorporating more physical and biochemical measures may improve accuracy of diagnosing active labor onset and progression. Because the association between duration of labor and perinatal outcomes is rather complex and influenced by various underlying and iatrogenic conditions, future research must carefully explore how to integrate statistical cut-points with clinical outcomes to reach a practical definition of labor abnormalities. Finally, research regarding the complex labor process may benefit from new approaches, such as machine learning technologies and artificial intelligence to improve the predictability of successful vaginal delivery with normal perinatal outcomes.

Association between toxic metals, vitamin D and preterm birth in the Maternal-Infant research on environmental chemicals study.

BACKGROUND: Toxic metals, like lead, are risk factors for preterm birth (PTB), but few studies have examined low levels found in most Canadians. Vitamin D, which may have antioxidant activity, protects against PTB. OBJECTIVES: In this study, we investigated the impact of toxic metals (lead, mercury, cadmium and arsenic) on PTB and examined if maternal plasma vitamin D concentrations modify these associations. METHODS: We investigated whether concentrations of metals in whole blood measured in early and late pregnancy were associated with PTB (<37 weeks) and spontaneous PTB in 1851 live births from the Maternal-Infant Research on Environmental Chemicals Study using discrete time survival analysis. We also investigated whether the risk of PTB was modified by first-trimester plasma 25-hydroxyvitamin D (25OHD) concentrations. RESULTS: Of 1851 live births, 6.1% (n = 113) were PTBs and 4.9% (n = 89) were spontaneous PTB. A 1 µg/dL increase in blood lead concentrations during pregnancy was associated with an increased risk of PTB (relative risk [RR] 1.48, 95% confidence interval [CI] 1.00, 2.20) and spontaneous PTB (RR 1.71, 95% CI 1.13, 2.60). The risk was higher in women with insufficient vitamin D concentrations (25OHD <50 nmol/L) for both PTB (RR 2.42, 95% CI 1.01, 5.79) and spontaneous PTB (RR 3.04, 95% CI 1.15, 8.04). However, an interaction on the additive scale was not present. Arsenic was associated with a higher risk of PTB (RR 1.10, 95% CI 1.02, 1.19) and spontaneous PTB (RR 1.11, 95% CI 1.03, 1.20) per 1 µg/L. CONCLUSIONS: Gestational exposure to low levels of lead and arsenic may increase the risk of PTB and spontaneous PTB; individuals with insufficient vitamin D may be more susceptible to the adverse effects of lead. Given our relatively small number of cases, we encourage testing of this hypothesis in other cohorts, especially those with vitamin D-deficient populations.

Cohort profile update: The Canadian Maternal-Infant Research on Environmental Chemicals Child Development study (MIREC-CD PLUS).

BACKGROUND: The pan-Canadian Maternal-Infant Research on Environmental Chemicals (MIREC) study was established to determine whether maternal environmental chemical exposures were associated with adverse pregnancy outcomes in 2001 pregnant women. OBJECTIVES: The MIREC-Child Development (CD PLUS) study followed this cohort with the goal of assessing the potential effects of prenatal exposures on anthropometry and neurodevelopment in early childhood. POPULATION: MIREC families with children between the ages of 15 months and 5 years who had agreed to be contacted for future research (n = 1459) were invited to participate in MIREC-CD PLUS which combines data collected from an online Maternal Self-Administered Questionnaire with biomonitoring and neurodevelopment data collected from two in-person visits. PRELIMINARY RESULTS: Between April 2013 and March 2015, 803 children participated in the Biomonitoring visit where we collected anthropometric measures, blood, and urine from the children. The Behavioural Assessment System for Children-2, Behaviour Rating Inventory of Executive Function, MacArthur-Bates Communicative Development Inventories and the Communication subscale of the Adaptive Behaviour Scale from the Bayley Scales of Infant and Toddler Development-III are available on close to 900 children. There were 610 singleton children who completed in-person visits for neurodevelopment assessments including the Social Responsiveness Scale, Wechsler Preschool Primary Scale of Intelligence-III and NEuroPSYchological assessments (NEPSY). Currently, we are following the cohort into early adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO). CONCLUSIONS: Data collection for the MIREC-CD PLUS study is complete and analysis of the data continues. We are now extending the follow-up of the cohort into adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO). MIREC-CD PLUS is limited by loss to follow-up and the fact that mothers are predominately of higher socioeconomic status and 'White' ethnicity, which limits our generalizability. However, the depth of biomonitoring and clinical measures in MIREC provides a platform to examine associations of prenatal, infancy and childhood exposures with child growth and development.

The effects of collagen peptides on exercise-induced gastrointestinal stress: a randomized, controlled trial.

PURPOSE: We examined the effects of collagen peptides (CP) supplementation on exercise-induced gastrointestinal (GI) stress. METHODS: In a randomized, crossover design, 20 volunteers (16 males: [Formula: see text]O2max, 53.4 ± 5.9 ml·kg-1) completed 3 trials: a non-exercise rest trial, with no supplement (REST) and then an exercise trial with CP (10 g·day-1) or placebo control (CON) supplements, which were consumed for 7 days prior to, and 45 min before, a 70 min run at 70-90% of [Formula: see text]O2max. Outcome measures included urinary lactulose and rhamnose (L/R), intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), anti-LPS antibody, monocyte-chemoattractant protein-1 (MCP-1), interleukin (IL) 6 and 8, cortisol, alkaline phosphatase (ALP) (measured pre, 10 min post and 2 h post) and subjective GI symptoms. RESULTS: There were no differences in heart rate, perceived exertion, thermal comfort, or core temperature during exercise in the CP and CON trials (all P > 0.05). I-FABP was higher in CP (2538 ± 1221 pg/ml) and CON (2541 ± 766 pg/ml) vs. REST 2 h post (1893 ± 1941 pg/ml) (both P < 0.05). LPS increased in CON vs. REST 2 h post (+ 71.8 pg/ml; P < 0.05). Anti-LPS antibody decreased in CON and CP vs. REST at post (both P < 0.05). There were no differences in MCP-1, IL-6, and IL-8 between the CP and CON trials (all P > 0.05), and no differences in L/R or GI symptoms between CON and CP (all P > 0.05). CONCLUSION: Collagen peptides did not modify exercise-induced changes in inflammation, GI integrity or subjective GI symptoms but LPS was higher in CON 2 h post-exercise and thus future studies may be warranted.

A harmonized analysis of five Canadian pregnancy cohort studies: exploring the characteristics and pregnancy outcomes associated with prenatal alcohol exposure.

BACKGROUND: As a teratogen, alcohol exposure during pregnancy can impact fetal development and result in adverse birth outcomes. Despite the clinical and social importance of prenatal alcohol use, limited routinely collected information or epidemiological data exists in Canada. The aim of this study was to pool data from multiple Canadian cohort studies to identify sociodemographic characteristics before and during pregnancy that were associated with alcohol consumption during pregnancy and to assess the impact of different patterns of alcohol use on birth outcomes. METHODS: We harmonized information collected (e.g., pregnant women's alcohol intake, infants' gestational age and birth weight) from five Canadian pregnancy cohort studies to consolidate a large sample (n = 11,448). Risk factors for any alcohol use during pregnancy, including any alcohol use prior to pregnancy recognition, and binge drinking, were estimated using binomial regressions including fixed effects of pregnancy cohort membership and multiple maternal risk factors. Impacts of alcohol use during pregnancy on birth outcomes (preterm birth and low birth weight for gestational) were also estimated using binomial regression models. RESULTS: In analyses adjusting for multiple risk factors, women's alcohol use during pregnancy, both any use and any binge drinking, was associated with drinking prior to pregnancy, smoking during pregnancy, and white ethnicity. Higher income level was associated with any drinking during pregnancy. Neither drinking during pregnancy nor binge drinking during pregnancy was significantly associated with preterm delivery or low birth weight for gestational age in our sample. CONCLUSIONS: Pooling data across pregnancy cohort studies allowed us to create a large sample of Canadian women and investigate the risk factors for alcohol consumption during pregnancy. We suggest that future pregnancy and birth cohorts should always include questions related to the frequency and amount of alcohol consumed before and during pregnancy that are prospectively harmonized to support data reusability and collaborative research.

Vitamin D and acute and severe illness - a mechanistic and pharmacokinetic perspective.

The coronavirus disease 2019 (COVID-19) pandemic has generated high interest in factors modulating risk of infection, disease severity and recovery. Vitamin D has garnered interest since it is known to modulate immune function and vitamin D deficiency is associated with increased risk of respiratory infections and adverse health outcomes in severely ill patients. There are no population representative data on the direct relationship between vitamin D status and severe acute respiratory syndrome coronavirus 2 infection risk and severity of COVID-19. Data from intervention studies are limited to four studies. Here we summarise findings regarding vitamin D status and metabolism and their alterations during severe illness, relevant to COVID-19 patients. Further, we summarise vitamin D intervention studies with respiratory disease outcomes and in critically ill patients and provide an overview of relevant patient and population guidelines. Vitamin D deficiency is highly prevalent in hospitalised patients, particularly when critically ill, including those with COVID-19. Acute and critical illness leads to pronounced changes in vitamin D metabolism and status, suggestive of increased requirements. This needs to be considered in the interpretation of potential links between vitamin D status and disease risk and severity and for patient management. There is some evidence that vitamin D supplementation decreases the risk of respiratory tract infections, while supplementation of intensive care unit patients has shown little effect on disease severity or length of treatment. Considering the high prevalence of deficiency and low risks associated with supplementation, pro-actively applying current population and patient management guidelines to prevent, monitor and correct vitamin D deficiency is appropriate.

Small-for-gestational-age and predictors of HOMA indices, leptin and adiponectin in infancy.

AIM: To assess whether small-for-gestational-age (SGA) - an indicator of poor fetal growth, may affect metabolic health biomarkers in infancy and explore the predictors. METHODS: This was a nested matched (1:2) prospective observational study of 65 SGA (birth weight < 10th percentile) and 130 optimal-for-gestational-age (OGA, birth weight 25th-75th percentiles, control) infants in the 3D birth cohort with subjects recruited in Canada from 1 May 2010 to 31 August 2012. The outcomes included homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-ß), circulating leptin and adiponectin concentrations at age 2 years. RESULTS: HOMA-IR, HOMA-ß, leptin and adiponectin concentrations were similar in SGA versus OGA infants. Female sex and accelerated growth in length during mid-infancy (3-12 months) were associated with higher HOMA-IR. Caucasian ethnicity and decelerated growth in weight during late infancy (12-24 months) were associated with lower HOMA-IR. Current BMI was positively associated with circulating adiponectin in SGA infants only (+13.4% [4.0%-23.7%] per BMI z score increment). CONCLUSION: Insulin resistance and secretion, circulating leptin and adiponectin levels were normal in SGA subjects in infancy at age 2 years. The novel observation in SGA-specific positive association between current BMI and circulating adiponectin suggests dysfunctional adiposity-adiponectin negative feedback loop development during infancy in SGA subjects.