Search

RESEARCH QUESTION: To compare Anti-Mullerian hormone (AMH) concentrations in women with and without arthritis and determine association between AMH and arthritis drug regimen. DESIGN: In this prospective cohort study, AMH concentrations were measured at two time points (T(0) and T(1)) in 129 premenopausal women with arthritis. AMH at T(0) were compared to those from a separate bank of serum samples from 198 premenopausal women without arthritis. Primary outcomes were: (1) diminished ovarian reserve (DOR) (AMH < 1.1 ng/mL) and (2) annual rate of AMH decrease. Univariate, multivariable, and Firth logistic regression identified variables associated with annual AMH decrease in excess of the 75(th) percentile. RESULTS: The median time between T(0) and T(1) was 1.72 years (IQR 1.12–2.53). At time T(0), median age-adjusted AMH in women with arthritis was significantly lower than that of women without arthritis (median 2.21 ng/mL; 95% confidence interval [CI] 1.88–2.54, vs. 2.78 ng/mL, 95% CI 2.52–3.05; P = 0.009). Women with arthritis at highest risk for DOR had a history of tubal sterilization (odds ratio [OR] 2.30, 95% CI: 1.00–5.25) or were over age 35 years (OR 8.24, 95% CI: 1.40–41.47). Those with highest odds of having an annual AMH decrease in excess of the 75th percentile (over 28% decrease per year) were: those over age 35 (OR 4.75, 95% CI: 1.50–15.09) or who sought care for infertility (OR 3.02, 95% CI: 1.12–8.12). Women with arthritis who were taking methotrexate alone (OR 0.08, 95% CI: 0.01–0.67) or methotrexate plus TNFα-antagonists (OR 0.13, 95% CI: 0.02–0.89) were less likely to be in the highest quartile of annual AMH decrease than women with arthritis who were not taking medication. CONCLUSIONS: Women with arthritis had lower AMH than healthy controls. Long-term methotrexate use was not associated with an annual AMH decrease.

Objectives As the U.S. population ages, the prevalence of disability and functional limitations, and demand for long-term services and supports (LTSS), will increase. This study identified the distribution of older adults across different residential settings, and how their health characteristics have changed over time. Methods A cross-sectional analysis of older adults residing in traditional housing, community-based residential facilities (CBRFs), and nursing facilities using 3 data sources: the Medicare Current Beneficiary Survey (MCBS), 2008 and 2013; the Health and Retirement Study (HRS), 2008 and 2014; and the National Health and Aging Trends Study, 2011 and 2015. We calculated the age-standardized prevalence of older adults by setting, functional limitations, and comorbidities and tested for health characteristics changes relative to the baseline year (2002). Results The proportion of older adults in traditional housing increased over time, relative to baseline (p < .05), while the proportion of older adults in CBRFs was unchanged. The proportion of nursing facility residents declined from 2002 to 2013 in the MCBS (p < .05). The prevalence of dementia and functional limitations among traditional housing residents increased, relative to the baseline year in the HRS and MCBS (p < .05). Discussion The proportion of older adults residing in traditional housing is increasing, while the nursing facility population is decreasing. This change may not be due to better health; rather, older adults may be relying on noninstitutional LTSS.

Our objective was to determine if maternal first trimester urinary phthalate concentrations are associated with reduced penile length (PL) or width (PW) at birth in full term singletons. First trimester phthalate metabolite urinary concentrations were obtained from mothers participating in a Canadian pregnancy cohort study (MIREC). PL and PW were measured shortly after birth in the male offspring. Univariate and multivariable linear regressions were performed to study associations between maternal phthalate exposure and penile measurements, adjusting for confounders. On univariate analysis of 170 mother-infant pairs, PW showed an inverse relationship with the concentration of mono-3-carboxypropyl phthalate (MCPP-p = 0.016), which was not confirmed on multivariable analysis. On multivariable analysis controlling for infant’s size and other confounders, no statistically signficant associations between phthalate metabolite concentrations and PL or PW were identified. In this population of Canadian women, there was no strong evidence to suggest an association between maternal first trimester urinary phthalates with PL or PW in term singletons.

Objectives: To measure heavy metal concentrations among Kenyan youth and quantify associations with sociocultural, demographic, and health factors as well as anthropometry. Methods: Using data from a study of semi-nomadic pastoralists in Samburu County, Kenya, we measured blood concentrations of lead (Pb), mercury (Hg), and cadmium (Cd) in 161 adolescents. We identified sociocultural, demographic and health characteristics associated with each metal and quantified the association between metals and adolescent anthropometry. Results: Median blood concentrations of Pb, Cd, and Hg were 1.82 µg/dL, 0.24 µg/L and 0.16 µg/L, respectively. Place of residence (highlands vs lowlands) was a determinant of metal concentrations. Hg was inversely related to anemia, and metals were not associated with anthropometry. Conclusions: In this population of Samburu adolescents, median Pb and Cd blood concentrations were higher than other North American or European biomonitoring studies. These findings motivate further investigation into the environmental sources of metals in this community.

Background Chronic cough (CC) which is defined ≥8 weeks is a common condition in clinical practice. However, estimates of prevalence and associated comorbidities in German adults and key subgroups of age and gender are lacking. Methods Cross-sectional study based on a representative panel of 15 020 adult subjects of the general population who completed the German National Health and Wellness Survey, reporting CC and questions about comorbidities. Lifetime and 12-month prevalence are presented as unweighted estimates. Results The lifetime CC prevalence was 6.5% (range across age groups 5.1%–8.3%) and the 12-month prevalence was 4.9% (range 3.7–5.7%). The prevalence of diagnosed CC was 2.8% (range 0.9–4.1%) and the prevalence of persons currently on any prescription to treat CC was 0.6% (range 0.2–1.4%). Respondents who experienced CC were 52.0±17.0 years old, with a higher prevalence in those aged 50 years and older. Persons with CC had higher morbidity scores and were diagnosed with an increased number of comorbidities, most frequently diagnoses of the respiratory system (71.0%), followed by digestive tract disorders (34.0%) and sleep disorders (37.6%). Conclusions In a broadly representative sample of German adults, lifetime and 12-month prevalence of CC was greatest in current and former smokers and those older ≥50 years of age. Comorbidities are frequent and may complicate management of these patients., Chronic cough is a prevalent condition in Germany among all age groups, regardless of sex, with highest rates in those 18–29 and ≥50 years, and more frequent among current or prior smokers. Comorbidities are common in this population. https://bit.ly/3uiYj4w

Once a significant cause of morbidity and mortality, health care providers rarely see primary pellagra in developed countries where fortification of foods with niacin is commonplace and niacin-rich foods are generally widely available. We report a ten-year-old boy with autism spectrum disorder who presented with photosensitive dermatitis which resolved after vitamin supplementation and dietary changes. In this child, the pellagra developed as the result of a long-term pattern of selective eating. Restricted diets, even to the point of nutrient deficiencies, are well-documented among children with autism spectrum disorders (ASD).

Background: Epidemiological and toxicological evidence suggests that maternal total arsenic (As) levels are associated with an elevated risk of gestational diabetes (GDM). Uncertainty remains regarding the metabolic toxicity of specific arsenic species, comprised of both organic and inorganic sources of arsenic exposure. Objectives: We assessed associations between speciated As and GDM using data from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study. Methods: Concentrations of speciated As [(inorganic (trivalent, pentavalent)), methylated arsenic species metabolites (monomethylarsonic acid (MMA), dimethylarsinic acid (DMA)), and organic (arsenobetaine)] were measured in first trimester maternal urine samples. GDM cases were identified in accordance with Canadian guidelines. Multivariable regression models were used to estimate associations between speciated As and GDM, evaluate potential interaction between speciated As exposures, and assess fetal sex-specific findings. Results: Among 1243 women who had a live, singleton birth and no previous history of diabetes, 4% met the diagnostic criteria for GDM. Our analyses focused on DMA and arsenobetaine as these were the subtypes with detectable concentrations in at least 40% of samples. Compared to women in the lowest tertile of DMA (

Background: Medication errors at hospital admission, though preventable, continue to be common. The process of medication reconciliation has been identified as an important tool in reducing medication errors. The first step in medication reconciliation involves documenting a patient’s best possible medication history (BPMH); at the authors’ tertiary pediatric hospital, this step is completed at time of admission by resident physicians. Objectives: To describe and quantify the completeness of admission BPMH by resident physicians for pediatric inpatients with asthma. Methods: This single-centre, retrospective chart review evaluated documentation of admission medication reconciliation for pediatric inpatients with asthma who were admitted between January 2016 and December 2017. Medication reconciliation forms were deemed incomplete if records for asthma medications were missing drug name, inhaler strength or oral drug dose, directions for use, or evidence of reconciliation. Results: A total of 241 charts were evaluated, of which 97 (40%) had incomplete documentation for at least 1 medication; in particular, 48 (37%) of the 130 inhaled corticosteroid orders were missing inhaler strength. For most of the charts with incomplete medication history (68% [66/97]), no reason was documented; however, review of the medication reconciliation forms and physician notes revealed that families might have been unsure of a patient’s home medications or physicians might have left it to the pharmacy to clarify medication doses. Conclusions: Documentation of inhaler medications on admission medication reconciliation forms completed by resident physicians for pediatric patients with asthma was often incomplete. Future quality improvement interventions, including resident and patient education, are required at the study institution. Collaboration with pharmacy services is also likely to improve completeness of the medication reconciliation process. RÉSUMÉ Contexte : Bien qu’elles soient évitables, les erreurs de médication au moment de l’admission à l’hôpital sont encore répandues. Le processus du bilan comparatif des médicaments a été reconnu comme étant un outil important pour réduire ces erreurs. La première étape du bilan comparatif des médicaments vise à décrire le meilleur schéma thérapeutique possible (MSTP) du patient; dans l’hôpital pédiatrique tertiaire des auteurs, les médecins résidents se chargent de cette étape au moment de l’admission. Objectifs : Décrire et quantifier le degré d’exhaustivité du MSTP réalisé par les médecins résidents pour les patients en pédiatrie souffrant d’asthme. Méthodes : Cet examen rétrospectif unicentrique des dossiers a permis d’évaluer l’élaboration du bilan comparatif des médicaments à l’admission en pédiatrie des patients souffrant d’asthme entre janvier 2016 et décembre 2017. Les formulaires de bilan comparatif des médicaments étaient jugés incomplets si les dossiers relatifs aux médicaments contre l’asthme n’indiquaient pas le nom du médicament, la force de l’inhalateur ou la dose orale du médicament, le mode d’emploi ou les preuves de conciliation médicamenteuse. Résultats : L’évaluation portait sur 241 tableaux; au moins 1 médicament manquait dans la description de 97 d’entre eux (40 %); en particulier la force de l’inhalateur ne figurait pas dans 48 (37 %) des 130 ordonnances relatives aux corticostéroïdes administrés par inhalation. La plupart des tableaux dont l’histoire pharmacothérapeutique était incomplète (68 % [66/97]) n’en indiquaient pas la raison; cependant, l’examen des formulaires du bilan comparatif des médicaments et les notes des médecins ont révélé que les familles n’étaient peut-être pas certaines des médicaments que le patient prenait à domicile ou que les médecins auraient pu laisser aux pharmaciens le soin de clarifier les doses. Conclusions : La description des médicaments administrés au moyen d’inhalateurs au moment de l’admission, figurant sur les formulaires du bilan comparatif des médicaments remplis par les médecins résidents pour les patients en pédiatrie souffrant d’asthme, était souvent incomplète. De futures interventions sur l’amélioration de la qualité, y compris les instructions données au patient et au résident, sont nécessaires dans l’institution où s’est déroulée l’étude. Il est probable que la collaboration avec les services de pharmacie améliorerait l’exhaustivité du processus du bilan comparatif des médicaments.

Assessment of cardiac function is essential to conduct cardiovascular and pulmonary-vascular preclinical research. Pressure-volume loops (PV loops) generated by recording both pressure and volume during cardiac catheterization are vital when assessing both systolic and diastolic cardiac function. Left and right heart function are closely related, reflected in ventricular interdependence. Thus, recording biventricular function in the same animal is important to get a complete assessment of cardiac function. In this protocol, a closed chest approach to cardiac catheterization consistent with the way catheterization is performed in patients is adopted in mice. While challenging, the closed chest strategy is a more physiological approach, because opening the chest results in major changes in preload and afterload that create artifacts, most notably a fall in systemic blood pressure. While high-resolution echocardiography is used to assess rodents, cardiac catheterization is invaluable, particularly when assessing diastolic pressures in both ventricles. Described here is a procedure to perform invasive, closed chest, sequential left and right ventricular pressure-volume (PV) loops in the same animal. PV loops are acquired using admittance technology with a mouse pressure-volume catheter and pressure-volume system acquisition. The procedure is described, beginning with the neck dissection, which is required to access the right jugular vein and the right carotid artery, to the insertion and positioning of the catheter, and finally the data acquisition. Then, the criteria required to ensure the acquisition of high-quality PV loops are discussed. Finally, the analysis of the left and right ventricular PV loops and the different hemodynamic parameters available to quantify systolic and diastolic ventricular function are briefly described.

Background: Pulmonary arterial hypertension (PAH) is a lethal vasculopathy. Hereditary cases are associated with germline mutations in BMPR2 and 16 other genes; however, these mutations occur in TET2 ), a key enzyme in DNA demethylation, occur in cardiovascular disease and are associated with clonal hematopoiesis, inflammation, and adverse vascular remodeling. The role of TET2 in PAH is unknown. Methods: To test for a role of TET2 , we used a cohort of 2572 cases from the PAH Biobank. Within this cohort, gene-specific rare variant association tests were performed using 1832 unrelated European patients with PAH and 7509 non-Finnish European subjects from the Genome Aggregation Database (gnomAD) as control subjects. In an independent cohort of 140 patients, we quantified TET2 expression in peripheral blood mononuclear cells. To assess causality, we investigated hemodynamic and histological evidence of PAH in hematopoietic Tet2 -knockout mice. Results: We observed an increased burden of rare, predicted deleterious germline variants in TET2 in PAH patients of European ancestry (9/1832) compared with control subjects (6/7509; relative risk=6; P =0.00067). Assessing the whole cohort, 0.39% of patients (10/2572) had 12 TET2 mutations (75% predicted germline and 25% somatic). These patients had no mutations in other PAH-related genes. Patients with TET2 mutations were older (71±7 years versus 48±19 years; P P =0.02), and had increased inflammation (including elevation of interleukin-1β). Circulating TET2 expression did not correlate with age and was decreased in >86% of PAH patients. Tet2 -knockout mice spontaneously developed PAH, adverse pulmonary vascular remodeling, and inflammation, with elevated levels of cytokines, including interleukin-1β. Long-term therapy with an antibody targeting interleukin-1β blockade resulted in regression of PAH. Conclusions: PAH is the first human disease related to potential TET2 germline mutations. Inherited and acquired abnormalities of TET2 occur in 0.39% of PAH cases. Decreased TET2 expression is ubiquitous and has potential as a PAH biomarker.

Aim -- Pulmonary arterial hypertension (PAH) results in right ventricular (RV) dysfunction owing, in part, to RV ischemia. The relative contribution of RV microvascular rarefaction vs reduced right coronary artery perfusion pressure (RCA-PP) to RV ischemia remains unknown. We hypothesize that increasing RCA-PP improves RV function in PAH by increasing RV systolic perfusion. Methods -- Supra-coronary aortic banding (SAB) or sham surgery was performed on male Sprague-Dawley rats. Seven to ten days later, rats received either monocrotaline (MCT; 60 mg/kg) or saline. After 1 month, echocardiography, cardiac catheterization, 99mTc-sestamibi single-photon emission computed tomography (SPECT) and microsphere infusion studies were performed. The RV was harvested for measurement of hypertrophy (RVH), fibrosis and immunoblotting, and the lung was harvested for pulmonary artery (PA) histology. Results -- Supra-coronary aortic banding increased systolic pressures in proximal aorta and systolic RCA-PP in SAB + MCT vs MCT rats (114 ± 12 vs 5 ± 9 mm Hg), without altering diastolic RCA-PP. SAB + MCT rats had improved RV function vs MCT rats, evident from their significantly increased cardiac output (CO), RV free wall (RVFW) thickening, tricuspid annular plane systolic excursion (TAPSE) and RV-PA coupling indices. RV-PA coupling indices and CO correlated directly with systolic RCA-PP. RV perfusion was increased in SAB + MCT vs MCT rats and correlated well with CO; whereas microvascular rarefaction was unaltered. SAB + MCT rats had less RVH and fibrosis and lower PA pressures vs MCT rats. SAB + MCT rats had significantly lower RV pyruvate kinase muscle isoform 2/1 ratios than MCT rats, consistent with restoration of oxidative metabolism. Conclusion -- A SAB-induced increase in systolic RCA-PP improves RV perfusion and function in MCT rats. Maintaining systolic RCA perfusion can preserve RV function in PAH.

Improvised Explosive Devices (IED) are the primary wounding mechanism for casualties in Operation Enduring Freedom. Patients can sustain devastating traumatic amputations, which are unlike injuries seen in the civilian trauma sector. This is a database analysis of the largest patient registry of multiple traumatic amputations.The Joint Theater Trauma Registry was queried for patients with a traumatic amputation from 2009 to 2012. Data obtained included the Injury Severity Score (ISS), Glasgow Coma Score (GCS), blood products, transfer from theatre, and complications including DVT, PE, infection (Acinetobacter and fungal), acute renal failure, and rhabdomyolysis. Comparisons were made between number of major amputations (1-4) and specific outcomes using χWe identified 720 military personnel with at least one traumatic amputation: 494 single, 191 double, 32 triple, and 3 quad amputees. Average age was 24.3 years (18-46), median ISS 24 (9-66), and GCS 15 (3-15). Tranexamic acid (TXA) was administered in 164 patients (23%) and tourniquets were used in 575 (80%). Both TXA and tourniquet use increased with increasing number of amputations (p0.001). Average transfusion requirements (in units) were packed red blood cells (PRBC) 18.6 (0-142), fresh frozen plasma (FFP) 17.3 (0-128), platelets 3.6 (0-26), and cryoprecipitate 5.6 (0-130). Transfusion of all blood products increased with the number of amputations (p0.001). All complications tested increased with the number of amputations except Acinetobacter infection, coagulopathy, and compartment syndrome. Transfer to higher acuity facilities was achieved in 676 patients (94%).Traumatic amputations from blast injuries require significant blood product transfusion, which increases with the number of amputations. Most complications also increase with the number of amputations. Despite high injury severity, 94% of traumatic amputation patients who are alive upon admission to a role II/III facility will survive to transfer to facilities with higher acuity care.

The objective of the present study was to examine the association between birth by Caesarean section (CS) and otitis media (OM) in childhood. We assembled a retrospective cohort of children born between 2003 and 2007 in Nova Scotia and followed them through to 2014. The cohort was derived through a linkage of the Nova Scotia Atlee Perinatal Database with provincial administrative health data. Cox proportional hazards, negative binomial regression and logistic regression were used to examine the association between CS and OM. Among the 36,318 children, 27% were born by CS, and 78% had at least one OM episode (median 2 episodes). Children born by CS were at a slightly higher risk of OM (hazard ratio 1.06, 95% confidence interval (CI) 1.03, 1.09), had more OM episodes in the first 7 years of life (incidence rate ratio 1.04, 95% CI 1.01, 1.07), and were more likely to be above the 95th percentile for OM episodes than children born vaginally (odds ratio 1.10, 95% CI 0.99, 1.23). Our study shows that birth by CS is weakly associated with OM in childhood, but the clinical and public health impact of these findings is small.

Background The negative impact of exposures such as maternal obesity, excessive gestational weight gain, and hypertension in pregnancy on the health of the next generation has been well studied. Evidence from animal studies suggests that the effects of in utero exposures may persist into the second generation, but the epidemiological literature on the influence of pregnancy-related exposures across three generations in humans is sparse. Objectives This cohort was established to investigate associations between antenatal and perinatal exposures and health outcomes in women and their offspring. Population The cohort includes women who were born and subsequently had their own pregnancies in the Canadian province of Nova Scotia from 1980 onward. Design Intergenerational linkage of data in the Nova Scotia Atlee Perinatal Database was used to establish a population-based dynamic retrospective cohort. Methods The cohort has prospectively collected information on sociodemographics, maternal health and health behaviours, pregnancy health and complications, and obstetrical and neonatal outcomes for two generations of women and their offspring. Preliminary results As of October 2018, the 3G cohort included 14 978 grandmothers (born 1939-1986), 16 766 mothers or cohort women (born 1981-2003), and 28 638 children (born 1996-2018). The cohort women were generally younger than Nova Scotian women born after 1980, and as a result, characteristics associated with pregnancy at a younger age were more frequently seen in the cohort women; sampling weights will be created to account for this design effect. The cohort will be updated annually to capture future deliveries to women who are already in the cohort and women who become eligible for inclusion when they deliver their first child. Conclusions The 3G Multigenerational Cohort is a population-based cohort of women and their mothers and offspring, spanning a time period of 38 years, and provides the opportunity to study inter- and transgenerational associations across the maternal line.

Fetal exposure to some toxic metals has been associated with reduced fetal growth, but the impact of contemporary, low-level metals on anthropometric measures in childhood is not well understood. Our primary objective was to quantify associations between childhood levels of toxic metals and concurrently measured body mass index (BMI) in a population of Canadian preschool-aged children. We collected biomonitoring data and anthropometric measures on 480 children between the ages of two and five years in the Maternal-Infant Research on Environmental Chemicals (MIREC) Child Development Plus study. Concentrations of four toxic metals (lead, arsenic, cadmium, and mercury) were measured in whole blood collected from pregnant women and their children. Blood levels of key essential elements were also measured in children. Children's weight, height, and BMI z-scores were calculated using the World Health Organization growth standards. We used a series of linear regression models, adjusted for potential parental confounders, concurrently measured metals and elements, and prenatal blood metal levels, to evaluate associations between tertiles of each toxic metal and anthropometric measures. We tested for effect modification by sex. Of the 480 children, 449 (94%) were singleton births and had complete biomonitoring and anthropometric data. The majority of children had detectable concentrations of metals. In the adjusted models, girls with blood lead concentrations in the highest tertile (>0.82 μg/dL) had, on average, 0.26 (95% Cl: -0.55, 0.03) lower BMI z-scores than those in the referent category. In contrast, boys with lead levels in the highest tertile had, on average, 0.14 higher BMI z-scores (95% Cl: -0.14, 0.41) (p-value heterogeneity = 0.04). In this population of Canadian preschool-aged children with low-level blood lead concentrations, we observed effect modification by sex in the association between Pb and BMI but no statistically significant associations in the sex-specific strata. Child blood levels of As, Cd, and Hg were not associated with childhood BMI, weight, or height in boys or girls.

Background Though the physiological roles of adipokines in metabolism, insulin resistance and satiety are clear, literature regarding associations between cord blood adipokine levels and childhood adiposity is equivocal. Objectives To determine whether cord blood levels of leptin and adiponectin are associated with adiposity in children 2 to 5 years of age, and whether such associations are modified by sex. Methods Leptin and adiponectin levels were measured in cord blood and anthropometric measures were completed on 550 children enrolled in the Maternal-Infant Research on Environmental Chemicals Child Development Plus study (MIREC-CD Plus). We used multivariable linear and Poisson regression models to determine associations between cord blood adipokine levels and child body mass index (BMI), triceps and subscapular skinfold thickness and risk of overweight/obesity and to assess effect modification by child sex. Results Cord blood adiponectin was significantly associated with modest increases in BMI and the sum of triceps and subscapular skinfold z-scores in boys but not girls. A doubling of adiponectin levels was associated with a 30% increased risk of overweight/obesity in boys (RR = 1.30; 95% CI: 1.02, 1.64). Leptin was not associated with anthropometric measures in either sex. Conclusions The observed associations between adiponectin and adiposity in boys were statistically significant, of moderate magnitude, and underscore the value of considering sex-specific patterns.

Introduction: Group 2 pulmonary hypertension (PH), defined as a mean pulmonary arterial pressure ≥25 mmHg with elevated pulmonary capillary wedge pressure >15 mmHg, has no approved therapy and patients often die from right ventricular failure (RVF). Alterations in mitochondrial metabolism, notably impaired glucose oxidation, and increased mitochondrial fission, contribute to right ventricle (RV) dysfunction in PH. We hypothesized that the impairment of RV and left ventricular (LV) function in group 2 PH results in part from a proglycolytic isoform switch from pyruvate kinase muscle (PKM) isoform 1 to 2 and from increased mitochondrial fission, due either to upregulation of expression of dynamin-related protein 1 (Drp1) or its binding partners, mitochondrial dynamics protein of 49 or 51 kDa (MiD49 or 51).Methods and Results: Group 2 PH was induced by supra-coronary aortic banding (SAB) in 5-week old male Sprague Dawley rats. Four weeks post SAB, echocardiography showed marked reduction of tricuspid annular plane systolic excursion (2.9 ± 0.1 vs. 4.0 ± 0.1 mm) and pulmonary artery acceleration time (24.3 ± 0.9 vs. 35.4 ± 1.8 ms) in SAB vs. sham rats. Nine weeks post SAB, left and right heart catheterization showed significant biventricular increases in end systolic and diastolic pressure in SAB vs. sham rats (LV: 226 ± 15 vs. 103 ± 5 mmHg, 34 ± 5 vs. 7 ± 1 mmHg; RV: 40 ± 4 vs. 22 ± 1 mmHg, and 4.7 ± 1.5 vs. 0.9 ± 0.5 mmHg, respectively). Picrosirius red staining showed marked biventricular fibrosis in SAB rats. There was increased muscularization of small pulmonary arteries in SAB rats. Confocal microscopy showed biventricular mitochondrial depolarization and fragmentation in SAB vs. sham cardiomyocytes. Transmission electron microscopy confirmed a marked biventricular reduction in mitochondria size in SAB hearts. Immunoblot showed marked biventricular increase in PKM2/PKM1 and MiD51 expression. Mitofusin 2 and mitochondrial pyruvate carrier 1 were increased in SAB LVs.Conclusions: SAB caused group 2 PH. Impaired RV function and RV fibrosis were associated with increases in mitochondrial fission and expression of MiD51 and PKM2. While these changes would be expected to promote increased production of reactive oxygen species and a glycolytic shift in metabolism, further study is required to determine the functional consequences of these newly described mitochondrial abnormalities.

Childhood exposure to phthalates, a class of chemicals with known reproductive and developmental effects, has been hypothesized to increase the risk of obesity, but this association is not well understood in preschool children. We examined the association between urinary concentrations of phthalate metabolites and concurrently measured body mass index (BMI) and skinfolds among children between the ages of two and five years. We collected anthropometric measures and biomonitoring data on approximately 200 children enrolled in the Maternal-Infant Research on Environmental Chemicals Child Development Plus study. We measured 22 phthalate metabolites in children's urine and used the 19 metabolites detected in at least 40% of samples. Our primary outcome was BMI z-scores calculated using the World Health Organization growth standards. Skinfold z-scores were secondary outcomes. We used multivariable linear regression to evaluate the association between tertiles of phthalate concentrations and each anthropometric measure. We also used weighted quantile sum regression to identify priority exposures of concern. Our analytic sample included 189 singleton-born children with complete anthropometric data. Children with concentrations of the parent compound di-n-butyl phthalate (∑DnBP) in the third tertile had 0.475 (95% CI: 0.068, 0.883) higher BMI z-scores than those in the lower tertile. ∑DnBP was identified as a priority exposure in the weighted quantile sum regression BMI model. In this population of Canadian preschool aged children, we identified DnBP as a potential chemical of concern in regard to childhood obesity. Future research with serial phthalate measurements and anthropometric measurements in young children will help confirm these findings.

ObjectiveTo model the development of the tri-ponderal mass index (TMI, kg/m3) throughout childhood and adolescence and to compare the utility of the TMI with that of the body mass index (BMI, kg/m2) to predict cardiometabolic risk in a population-based sample of Canadian children and youth.MethodsWe used data from the Canadian Health Measures Survey to model TMI from 6 to 19 years of age. Percentile curves were developed using the LMS method. Logistic regression was used to predict abnormal levels of cardiometabolic markers; predictive accuracy was assessed using the area under the ROC curve (AUC).ResultsMean TMI was relatively stable from ages 6 to 19 years for both sexes, but variability increased with age. There was no notable difference in AUC values for prediction models based on BMI z-score compared with TMI for any of the outcomes. For both BMI z-score and TMI, prediction accuracy was good for homeostasis model assessment insulin resistance and having ≥3 abnormal tests (AUC>0.80), fair for C-reactive protein and poor for the remainder of the outcomes.ConclusionsThe use of a single sex-specific TMI cut-off for overweight or obesity is hampered by the increasing variability of the measure with age. Weight-for-height indices likely have only limited ability to predict cardiometabolic marker levels, and changing the scaling power of height is unlikely to improve predictive accuracy.

Zika virus (ZIKV) infection during pregnancy in humans is associated with an increased incidence of congenital anomalies including microcephaly as well as fetal death and miscarriage and collectively has been referred to as Congenital Zika Syndrome (CZS). Animal models for ZIKV infection in pregnancy have been developed including mice and non-human primates (NHPs). In macaques, fetal CZS outcomes from maternal ZIKV infection range from none to significant. In the present study we develop the olive baboon (Papio anubis), as a model for vertical transfer of ZIKV during pregnancy. Four mid-gestation, timed-pregnant baboons were inoculated with the French Polynesian ZIKV isolate (104 ffu). This study specifically focused on the acute phase of vertical transfer. Dams were terminated at 7 days post infection (dpi; n = 1), 14 dpi (n = 2) and 21 dpi (n = 1). All dams exhibited mild to moderate rash and conjunctivitis. Viremia peaked at 5–7 dpi with only one of three dams remaining mildly viremic at 14 dpi. An anti-ZIKV IgM response was observed by 14 dpi in all three dams studied to this stage, and two dams developed a neutralizing IgG response by either 14 dpi or 21 dpi, the latter included transfer of the IgG to the fetus (cord blood). A systemic inflammatory response (increased IL2, IL6, IL7, IL15, IL16) was observed in three of four dams. Vertical transfer of ZIKV to the placenta was observed in three pregnancies (n = 2 at 14 dpi and n = 1 at 21 dpi) and ZIKV was detected in fetal tissues in two pregnancies: one associated with fetal death at ~14 dpi, and the other in a viable fetus at 21 dpi. ZIKV RNA was detected in the fetal cerebral cortex and other tissues of both of these fetuses. In the fetus studied at 21 dpi with vertical transfer of virus to the CNS, the frontal cerebral cortex exhibited notable defects in radial glia, radial glial fibers, disorganized migration of immature neurons to the cortical layers, and signs of pathology in immature oligodendrocytes. In addition, indices of pronounced neuroinflammation were observed including astrogliosis, increased microglia and IL6 expression. Of interest, in one fetus examined at 14 dpi without detection of ZIKV RNA in brain and other fetal tissues, increased neuroinflammation (IL6 and microglia) was observed in the cortex. Although the placenta of the 14 dpi dam with fetal death showed considerable pathology, only minor pathology was noted in the other three placentas. ZIKV was detected immunohistochemically in two placentas (14 dpi) and one placenta at 21 dpi but not at 7 dpi. This is the first study to examine the early events of vertical transfer of ZIKV in a NHP infected at mid-gestation. The baboon thus represents an additional NHP as a model for ZIKV induced brain pathologies to contrast and compare to humans as well as other NHPs., Author summary Zika virus is endemic in the Americas, primarily spread through mosquitos and sexual contact. Zika virus infection during pregnancy in women is associated with a variety of fetal pathologies now referred to as Congenital Zika Syndrome (CZS), with the most severe pathology being fetal microcephaly. Developing model organisms that faithfully recreate Zika infection in humans is critical for future development of treatments and preventions. In our present study, we infected Olive baboons at mid-gestation with Zika virus and studied the acute period of viremia and transfer of Zika virus to the fetus during the first three weeks after infection to better understand the timing and mechanisms of transfer of ZIKV across the placenta, leading to CZS. We observed Zika virus transfer to fetuses resulting in fetal death in one pregnancy and in a second pregnancy, significant damage to the frontal cortex of the fetal brain at a critical period of neurodevelopment in primates. Thus, the baboon provides a promising new non-human primate model to further compare and contrast the consequences of Zika virus infection in pregnancy to humans and other non-human primates.

Dually eligible individuals (i.e., eligible for Medicare and Medicaid) often have worse health and greater functional limitations than patients eligible for Medicare only. For dually eligible patients receiving inpatient rehabilitation services following a major illness or injury, improvement in function may be lower than for Medicare-only patients. To our knowledge, this is the first study to examine the relationship of dual eligibility on improvement in mobility for inpatient rehabilitation facility (IRF) patients by 13 primary diagnosis groups (e.g., Stroke, Amputation). Data was collected on the IRF-Patient Assessment Instrument at admission and discharge for all IRF patients discharged during 2017 (N = 428,631). A generalized linear model was run for each primary diagnosis group to examine the effect of dual eligibility on change in mobility during an IRF stay, adjusting for sociodemographic factors, clinical factors, and comorbidities. The proportion of patients who were dually eligible varied among primary diagnosis groups (9.6% for Hip/Knee Replacements, Fractures and Multiple Trauma to 21.7% for Amputation). Compared to patients who were non-dually eligible, dually eligible patients had lower improvement in mobility across all 13 diagnostic groups. The strongest effect of dual eligibility on lower improvement in mobility was among patients with hip and/or knee replacements (β: -1.99, p

BACKGROUND: Medication errors at admission and discharge to hospital continue to be common and preventable. Medication discrepancies occur in 22–73% of hospitalized pediatric patients and are mostly related to admissions. The process of medication reconciliation (MedRec) has been identified as an important tool in reducing medication errors and is a patient safety standard in Canadian hospitals at transitions of care. Resident physicians in our tertiary pediatric hospital are responsible for completing the MedRec form at hospital admission. We hypothesized based on clinical observation that the strength of asthma inhalers is frequently omitted on the admission MedRec. Asthma is the leading cause of hospitalization in children, and incomplete information on patient’s home controller medications could impact the medical team’s ability to make an appropriate discharge plan. OBJECTIVES: To describe and quantify the completeness of admission medication reconciliation documentation by resident physicians for pediatric asthma patients. DESIGN/METHODS: This study was a single-centre, retrospective chart review of admission MedRec documentation for pediatric asthma patients from January 2016 – December 2017. Charts with an admitting diagnosis of asthma and home asthma medications on the admission MedRec were included for review. MedRec forms were deemed incomplete if asthma medications were missing drug name, strength, dose/frequency or not reconciled. Charts with an incomplete MedRec were further reviewed to determine if the reason for the incomplete medication history was documented, and if home medications were clarified prior to hospital discharge. RESULTS: A total of 241 charts of pediatric asthma admissions from the review period included home asthma medications on the admission MedRec. 40% of all MedRec forms reviewed had at least one medication incompletely documented. Inhaled corticosteroids were the most frequent with 40% incomplete for any reason, 37% missing the inhaler strength, 14% missing the dose/frequency, 2% not reconciled and 1% missing the drug name. Documentation of other inhalers were also more likely to be incomplete than oral asthma medications with 27% of short-acting bronchodilators and 24% of combination inhalers incomplete for any reason. No cause for the incomplete medication history was documented in 68% of charts, and 36% had no clarification order written for home asthma medications prior to hospital discharge. CONCLUSION: Documentation of inhalers on admission MedRec forms by resident physicians for pediatric asthma patients is often incomplete. Missing information on patient’s home asthma medications could result in medication errors at discharge. Future quality improvement interventions in our institution are required.

Epidemiological studies have hypothesized that both insufficient and excess blood manganese (Mn) levels during pregnancy are associated with reduced fetal growth. This literature is characterized by inconsistent results and a limited focus on women with exposures representative of the general North American population. We examined the relationship between maternal and cord blood Mn levels and fetal growth among women enrolled in the Maternal-Infant Research on Environmental Chemicals Study (MIREC). Mothers with singleton, term infants and complete maternal first and third trimester blood Mn data were eligible for inclusion in the present study (n = 1519). Mean birth weight and odds ratios of small for gestational age (SGA) births according to maternal and cord blood Mn levels (low (10), referent (10-90), high (≥90) percentiles) were estimated. We also evaluated the association between the ratio of cord and maternal blood Mn and birth weight. Women with low (0.82 μg/dL) maternal blood third trimester Mn levels had infants that weighed an average of 64.7 g (95% CI: -142.3,12.8) less than infants born to women in the referent exposure group. This association was strengthened and became statistically significant when adjusted for toxic metals (lead, mercury, arsenic, and cadmium) [-83.3 g (95% CI: -162.4, -4.1)]. No statistically significant associations were observed in models of maternal first trimester or cord blood Mn. A one unit increase in the cord/maternal blood Mn ratio was associated with a 29.4 g (95% CI: -50.2, -8.7), when adjusted for maternal and neonatal characteristics. Our findings motivate additional research regarding the relation between Mn exposure and fetal growth. Further inquiry is necessary to determine whether an exposure threshold exists, how growth related effects of maternal and fetal Mn may differ, and how concurrent exposure to other toxic metals may impact the association between Mn and growth.

Background: Studies from several countries report increases in rates of gestational diabetes mellitus (GDM) over recent decades. Exposure to environmental chemicals could contribute to this trend. Objectives: To determine the associations between plasticisers and metals measured in early pregnancy with impaired glucose tolerance (IGT) and GDM in a Canadian pregnancy cohort. Methods: Women enrolled in the Maternal–Infant Research on Environmental Chemicals (MIREC) Study were included if they had a singleton delivery and did not have pre-existing diabetes. Eleven phthalate metabolites and total bisphenol A (BPA) were measured in first-trimester urine samples, and four metals (lead, cadmium, mercury and arsenic) were measured in first-trimester blood samples. IGT and GDM were assessed in accordance with standard guidelines by chart review. Chemical concentrations were grouped by quartiles, and associations with outcomes were examined using logistic regression with adjustment for maternal age, race, pre-pregnancy BMI, and education. Restricted cubic spline analysis was performed to help assess linearity and nature of any dose–response relationships. Results: Of 2001 women recruited into the MIREC cohort, 1274 met the inclusion criteria and had outcome data and biomonitoring data measured for at least one of the chemicals we examined. Elevated odds of GDM were observed in the highest quartile of arsenic exposure (OR = 3.7, 95% CI = 1.4–9.6) in the adjusted analyses. A significant dose–response relationship was observed in a cubic spline model between arsenic and odds of GDM (p

This study examined the levels of Latino mothers’ and fathers’ involvement in their school-age children’s care and the relationships between parents’ socio-economic status (SES) variables, sense of community, community provisions, and marital satisfaction with their involvement in children’s routine and demand care. Mothers and fathers from 159 intact Latino families participated in the study. Multivariate analyses revealed that mothers spent significantly more time in providing child care than fathers did. The gender of the child did not make a difference in the amount of time mothers and fathers invested in children’s care. Whereas community provisions and marital satisfaction predicted mothers’ involvement in routine care, sense of community and community provisions predicted mothers’ involvement in demand care. None of the predictors were related to fathers’ involvement in routine or demand care. Findings are discussed in light of gender role differences in parental involvement with children within Latino families.

Background The fetal immune system is a critical window of development. The epithelial cell-derived cytokines, thymic stromal lymphopoietin (TSLP), and interleukin-33 (IL-33) have received attention for their role in allergic responses but not been studied during this critical window. The objectives were to assess correlations among IL-33, TSLP, and IgE in umbilical cord blood samples and identify prenatal predictors of these biomarkers. Methods This study utilized data and banked cord blood collected in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a trans-Canada cohort study of 2001 pregnant women. Our analytic sample comprised the 1254 women with a singleton, term birth with a cord blood sample. Spearman correlation coefficients (SCC) and logistic regression models were used to examine associations between biomarkers and identify potential predictors of elevated biomarker levels. Results Thymic stromal lymphopoietin and IL-33 were more strongly correlated with each other (SCC = 0.75, p

Background Triclosan is a phenolic biocide used in a multitude of consumer products and in health care settings. It is widely detected in the American and Canadian populations and has been shown in animal models to act as an endocrine disrupting agent. However, there has been little examination to date of the effects of triclosan exposure in pregnancy on perinatal metabolic outcomes in human populations. Methods Using data from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a Canadian pregnancy cohort, we measured associations of first-trimester urinary triclosan concentrations with total gestational weight gain, gestational diabetes mellitus and impaired glucose tolerance in pregnancy, and fetal markers of metabolic function. Leptin and adiponectin were measured in plasma from umbilical cord blood samples in term neonates and categorized into low ( 90th percentile) levels. Triclosan concentrations were grouped into quartiles and associations with study outcomes were examined using logistic regression models with adjustment for maternal age, race/ethnicity, pre-pregnancy BMI, education and urinary specific gravity. Restricted cubic spline analysis was performed to help assess linearity and shape of any dose-response relationships. All analyses for leptin and adiponectin levels were performed on the entire cohort as well as stratified by fetal sex. Results Triclosan measures were available for 1795 MIREC participants with a live born singleton birth. Regression analyses showed a non-significant inverse association between triclosan concentrations and leptin levels above the 90th percentile that was restricted to female fetuses (OR for highest quartile of triclosan compared to lowest quartile = 0.4 (95% CI 0.2–1.1), p-value for trend across quartiles = 0.02). Triclosan concentrations in the second quartile were associated with elevated odds of adiponectin below the 10th percentile in male fetuses (OR for Q2 compared to Q1 = 2.5, 95% CI 1.1–5.9, p-value for trend across quartiles = 0.93). No significant linear associations between triclosan concentrations and leptin or adiponectin levels in overall or sex-specific analyses were observed from restricted cubic spline analyses. No significant associations were observed in adjusted analyses between triclosan concentrations and gestational diabetes mellitus, impaired glucose tolerance or gestational weight gain. Conclusions This study does not support an association between triclosan concentrations in pregnancy and fetal metabolic markers, glucose disorders of pregnancy, or excessive gestational weight gain.

Perfluoroalkyl substances (PFAS) are ubiquitous, persistent chemicals that have been widely used in the production of common household and consumer goods for their nonflammable, lipophobic, and hydrophobic properties. Inverse associations between maternal or umbilical cord blood concentrations of perfluorooctanoic acid and perfluorooctanesulfonate and birth weight have been identified. This literature has primarily examined each PFAS individually without consideration of the potential influence of correlated exposures. Further, the association between PFAS exposures and indicators of metabolic function (i.e., leptin and adiponectin) has received limited attention. We examined associations between first-trimester maternal plasma PFAS concentrations and birth weight and cord blood concentrations of leptin and adiponectin using data on 1,705 mother-infant pairs from the Maternal Infant Research on Environmental Chemicals (MIREC) Study, a trans-Canada birth cohort study that recruited women between 2008 and 2011. Bayesian hierarchical models were used to quantify associations and calculate credible intervals. Maternal perfluorooctanoic acid concentrations were inversely associated with birth weight z score, though the null value was included in all credible intervals (log10 β = −0.10, 95% credible interval: −0.34, 0.13). All associations between maternal PFAS concentrations and cord blood adipocytokine concentrations were of small magnitude and centered around the null value. Follow-up in a cohort of children is required to determine how the observed associations manifest in childhood.

Excess gestational weight gain (GWG) may predispose mothers to becoming overweight or obese. The aim of this study was to investigate the association between GWG, according to the American Institute of Medicine (IOM) guidelines, and postpartum weight retention (PPWR). A cohort of 12,875 women from Nova Scotia, Canada with at least two consecutively recorded pregnancies was identified through a population-based perinatal database between 1993 and 2010. GWG was calculated as the difference between delivery and prepregnancy weights. PPWR, analyzed as a continuous variable in linear regression models, was calculated via interpregnancy weight change. Fifty eight percent of the total study population gained in excess of the IOM guidelines. Mean PPWR, adjusted for age and prepregnancy body mass index (BMI) among women with excess GWG was 5.0 kg (95 % CI 4.9-5.2), greater than women with adequate (2.1 kg, 95 % CI 1.8-2.3) or inadequate GWG (0.3 kg, 95 % CI 0-0.7). Effect modification by prepregnancy BMI was observed; the relationship between excess GWG and increased PPWR was observed in all prepregnancy BMI categories, yet was greatest among underweight women (7.5 kg, 95 % CI 6.6-8.3). Effect modification by parity was also observed; in contrast to multiparous women, primiparous women who gained in excess of GWG guidelines retained more postpartum weight (5.3 kg, 95 % CI 5.1-5.5 vs. 4.3 kg, 95 % CI 4.0-4.7). This study demonstrates that excess GWG is associated with an increase in the amount of weight retained after pregnancy. Interventions targeted to promote optimal GWG are warranted.

Glucose control in the acute setting has long been a debate among leaders in the fields of diabetes and acute care. Providers struggle to maintain euglycemia in critically ill patients and simultaneously prevent hypoglycemia. Intravenous insulin infusions are frequently preferred in the critical care setting to control glucose, because they can be titrated for changing insulin requirements and can be cleared from the system rapidly. This article discusses the basics of the insulin drip, common insulin drips, and the role of the nurse in managing an insulin drip.

Objectives We aimed to determine whether average and trimester-specific exposures to ambient measures of nitrogen dioxide (NO2) and particular matter (PM2.5) were associated with elevated cord blood concentrations of immunoglobulin E (IgE) and two epithelial cell produced cytokines: interleukin-33 (IL-33) and thymic stromal lymphopoietin (TSLP). Methods This study utilized data and biospecimens from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study. There were 2001 pregnant women recruited between 2008 and 2011 from 10 Canadian cities. Maternal exposure to NO2 and PM2.5 was estimated using land use regression and satellite-derived models. Results We observed statistically significant associations between maternal NO2 exposure and elevated cord blood concentrations of both IL-33 and TSLP among girls but not boys. Conclusions Maternal NO2 exposure may impact the development of the newborn immune system as measured by cord blood concentrations of two cytokines.

Study Objective To examine the association between gestational weight gain (GWG) and interpregnancy weight change (IPWC) in adolescent mothers (younger than 20 years), and to determine if this association differs from adult women (aged 20-35 years). Design Retrospective cohort study. Setting and Participants We included 3055 adolescents and 17,090 adult women with singleton pregnancies recorded in the Nova Scotia Atlee Perinatal Database with a subsequent pregnancy occurring between 2003 and 2014. Interventions and Main Outcome Measures GWG in the first pregnancy was categorized as below, within, or above the current Institute of Medicine recommendations. IPWC was defined as the difference between the prepregnancy weights of the 2 pregnancies. Analyses were adjusted for parity, body mass index in the first pregnancy, and time between pregnancies. Results Relative to adolescents with GWG within the recommendations, those who gained below had a 2.7 kg (95% confidence interval [CI], 1.4-3.9) lower mean IPWC whereas those who gained above had a 4.2 kg (95% CI, 3.3-5.1) higher mean IPWC. Smaller differences in IPWC between GWG categories were observed in adult women; relative to those with GWG within the recommendations, adults who gained below had a 1.3 kg (95% CI, 0.9-1.7) lower mean IPWC and those who gained above had a 2.9 kg (95% CI, 2.6-3.2) higher mean IPWC. Conclusion Mean IPWC differed across GWG categories and the differences were greater in adolescents than in adult women. This difference should be considered when assessing whether specific GWG recommendations are needed for adolescents.

Background.Skinfold thickness (SFT) measurements are a reliable and feasible method for assessing body fat in children but their use and interpretation is hindered by the scarcity of reference values in representative populations of children. The objective of the present study was to develop age- and sex-specific percentile curves for five SFT measures (biceps, triceps, subscapular, suprailiac, medial calf) in a representative population of Canadian children and youth.Methods.We analyzed data from 3,938 children and adolescents between 6 and 19 years of age who participated in the Canadian Health Measures Survey cycles 1 (2007/2009) and 2 (2009/2011). Standardized procedures were used to measure SFT. Age- and sex-specific centiles for SFT were calculated using the GAMLSS method.Results.Percentile curves were materially different in absolute value and shape for boys and girls. Percentile girls in girls steadily increased with age whereas percentile curves in boys were characterized by a pubertal centered peak.Conclusions.The current study has presented for the first time percentile curves for five SFT measures in a representative sample of Canadian children and youth.

Iron, vitamin D, and calcium intakes in the prenatal period are important determinants of maternal and fetal health. The objective of this study was to examine iron, vitamin D, and calcium intakes from diet and supplements in relation to maternal characteristics. Data were collected in a subsample of 1186 pregnant women from the Maternal–Infant Research on Environmental Chemicals (MIREC) Study, a cohort study including pregnant women recruited from 10 Canadian sites between 2008 and 2011. A food frequency questionnaire was administered to obtain rankings of iron, calcium, and vitamin D intake (16–21 weeks of pregnancy). Intakes from supplements were obtained from a separate questionnaire (6–13 weeks of pregnancy). Women were divided into 2 groups according to the median total intake of each nutrient. Supplement intake was an important contributor to total iron intake (median 74%, interquartile range (IQR) 0%–81%) and total vitamin D intake (median 60%, IQR 0%–73%), while the opposite was observed for calcium (median 18%, IQR 0%–27%). Being born outside of Canada was significantly associated with lower total intakes of iron, vitamin D, and calcium (p ≤ 0.01 for all). Consistent positive indicators of supplement use (iron, vitamin D, and calcium) were maternal age over 30 years and holding a university degree. In conclusion, among Canadian women, the probability of having lower iron, vitamin D, and calcium intakes is higher among those born outside Canada; supplement intake is a major contributor to total iron and vitamin D intakes; and higher education level and age over 30 years are associated with supplement intake.

Background: Skinfold thickness (SFT) measurements are a reliable and feasible method for assessing body fat in children but their use and interpretation is hindered by the scarcity of reference values in representative populations of children. The objectives of the present study were to develop age- and sex-specific percentile curves for five SFT measures (biceps, triceps, subscapular, suprailiac, medial calf) and to describe body fat composition in a representative population of Canadian children and youth. Methods: We analyzed data from 3938 children and adolescents between 6 and 19 years of age who participated in the Canadian Health Measures Survey cycles 1 (2007/2009) and 2 (2009/2011). Standardized procedures were used to measure SFT. Age- and sex-specific centiles for skinfolds and body fat were calculated using the GAMLSS method. Results: Percentile curves were materially different in absolute value and shape for boys and girls. Percentile girls in girls steadily increased with age whereas percentile curves in boys were characterized by a pubertal centered peak. Median body fat percentage at age 18 was 13.2 and 25.4% among boys and girls, respectively. Conclusions: The current study has presented for the first time percentile curves for five SFT measures and body fat in a representative sample of Canadian children and youth.

The primary objective was to determine the rate of breastfeeding by gestational age reported by new mothers 1 month postpartum, with particular focus on early term newborns (37-38(6)/7 weeks).Three thousand six primiparous women aged 18-36 years were interviewed during their third trimester and again 1 month postpartum. Logistic regression analysis was used to model the association between gestational age and breastfeeding 1 month postpartum among those who reported that they planned to breastfeed, controlling for potentially confounding variables.Two thousand seven hundred seventy-two women planned to breastfeed (92.2%), among whom 116 (4.2%) delivered late preterm (34-36(6)/7 weeks), 519 (18.7%) early term (37-38(6)/7 weeks), and 2,137 (77.1%) term or postterm (39+ weeks). Among those who delivered late preterm, 63.8% were breastfeeding 1 month postpartum, early term 72.6%, and term or postterm 76.5%. This relationship was verified by a multivariate logistic regression analysis; late preterm newborns were significantly less likely to be breastfeeding 1 month postpartum than the term or postterm newborns (odds ratio [OR] 0.44; 95% confidence interval [CI] 0.28-0.69; p ≤ 0.0001), as were early term newborns (OR 0.77; 95% CI 0.60-0.99; p = 0.038).In this large prospective study of first-time mothers and newborns, gestational age was significantly associated with breastfeeding 1 month postpartum; highlighting late preterm and early term infants as populations at risk for shortened breastfeeding duration and the need to create specific breastfeeding support and education.

Combining MS-based proteomic data with network and topological features of such network would identify more clinically relevant molecules and meaningfully expand the repertoire of proteins derived from MS analysis. The integrative topological indexes representing 95.96% information of seven individual topological measures of node proteins were calculated within a protein-protein interaction (PPI) network, built using 244 differentially expressed proteins (DEPs) identified by iTRAQ 2D-LC-MS/MS. Compared with DEPs, differentially expressed genes (DEGs) and comprehensive features (CFs), structurally dominant nodes (SDNs) based on integrative topological index distribution produced comparable classification performance in three different clinical settings using five independent gene expression data sets. The signature molecules of SDN-based classifier for distinction of early from late clinical TNM stages were enriched in biological traits of protein synthesis, intracellular localization and ribosome biogenesis, which suggests that ribosome biogenesis represents a promising therapeutic target for treating ESCC. In addition, ITGB1 expression selected exclusively by integrative topological measures correlated with clinical stages and prognosis, which was further validated with two independent cohorts of ESCC samples. Thus the integrative topological analysis of PPI networks proposed in this study provides an alternative approach to identify potential biomarkers and therapeutic targets from MS/MS data with functional insights in ESCC.

Perfluoroalkyl substances (PFASs) are ubiquitous, persistent pollutants widely used in the production of common household and consumer goods. There is a limited body of literature suggesting that these chemicals may alter metabolic pathways and growth trajectories. The relationship between prenatal exposures to these chemicals and gestational weight gain (GWG) has received limited attention. One objective was to analyze the associations among maternal plasma levels of three common perfluoroalkyl substances (perfluorooctanoate (PFOA), perfluorooctanesulfonate (PFOS), perfluorohexanesulfanoate (PFHxS)) and GWG. Additionally, we explored whether GWG was associated with cord blood PFAS levels. This study utilized data collected in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a trans-Canada cohort study of 2001 pregnant women. Our analysis quantified associations between (1) maternal PFAS concentrations and GWG and (2) GWG and cord blood PFAS concentrations. Maternal PFOS concentrations were positively associated with GWG (β = 0.39 95% CI: 0.02, 0.75). Interquartile increases in GWG were significantly associated with elevated cord blood PFOA (OR = 1.33; 95% CI: 1.13 to 1.56) and PFOS (OR = 1.20; 95% CI: 1.03 to 1.40) concentrations. No statistically significant associations were observed between GWG and either measure of PFHxS. These findings warrant elucidation of the potential underlying mechanisms.

Functional status is tied to important health outcomes, yet the collection of functional status data has not been standardized across post-acute care (PAC). The IMPACT Act of 2014 required the submission of standardized assessment data by PAC providers, including data related to function. Previously, functional assessment data collected in skilled nursing facilities (SNFs), inpatient rehabilitation facilities (IRFs), and long-term care hospitals (LTCHs) consisted of different assessment instruments, scales, and items. Standardization of functional data across PAC settings has the potential to improve care coordination. We present a preliminary review of recently implemented standardized self-care and mobility data by examining the cross-setting quality measure, Application of Percent of Long-Term Care Hospital (LTCH) Patients with an Admission and Discharge Functional Assessment and a Care Plan That Addresses Function.

BACKGROUND Patients with colorectal cancer often present with advanced disease and concomitant poor prognosis. The best known serum biomarker, carcinoembryonic antigen (CEA) is not recommended for screening because of its limited specificity and sensitivity. A number of other circulating proteins have been suggested to be diagnostically useful but individually none of these has proved to be of sufficient sensitivity or specificity to establish a role in routine clinical practice. Here, we test the hypothesis that combining several of these biomarkers will improve diagnostic efficacy. METHODS To select the markers for our model we screened CEA and 26 other candidate biomarkers. Four candidates were selected and their concentrations determined in the serum of 239 patients (106 colorectal cancer patients and 133 non-cancer subjects). RESULTS Class prediction models based on CEA, DR-70 and sCD26 produced a modest increase in detection accuracy over CEA alone, particularly for early stage cancers. The sensitivity and specificity required for a clinically useful test was not reached. CONCLUSION It is unlikely that a biomarker panel comprised of the currently available serum markers will generate a clinically useful diagnostic test for colorectal cancer. Our findings reiterate the urgent need to discover novel biomarkers for the detection of colorectal cancer.

There is an urgent need for biomarkers to detect pancreatic cancer in the early, potentially curable, stages.We have used SELDI profiling to analyze serum from 75 patients with pancreatic cancer and 61 patients with nonmalignant pancreaticobiliary diseases.A peak in the SELDI spectra corresponding to a 53 residue fragment of the α-chain of fibrinogen is remarkably elevated in approximately 50% of the cancer patients. In addition, fibrinogen degradation products were measured using the DR-70 assay. The areas under the receiver operating characteristic curves for the SELDI-detected fibrinogen fragment, DR-70 and CA19-9 were 0.65, 0.75 and 0.86, respectively. Class prediction models using combinations of these markers did not increase the area under the receiver operating characteristic curve compared with CA19-9. The novel fibrinogen fragment was not elevated to the same extent in other malignancies but was elevated in some patients with benign pancreatic disease.Both the SELDI-detected fragment of fibrinogen and DR-70 are significantly elevated in the serum of pancreatic cancer patients. However, they do not seem to improve pancreatic cancer detection over CA19-9 alone.

IntroductionLung cancer is the leading cause of cancer-related death worldwide. The discovery of new biomarkers could aid early diagnosis and monitoring of recurrence following tumor resection.MethodsWe have prospectively collected serum from 97 lung cancer patients undergoing surgery with curative intent and compared their serum proteomes with those of 100 noncancer controls (59 disease-free and 41 with a range of nonmalignant lung conditions). We initially analyzed serum from 67 lung cancer patients and 73 noncancer control subjects by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry using immobilized metal affinity capture ProteinChip arrays and subsequently validated our findings with an independent analysis of 30 lung cancer patients and 27 noncancer subjects.ResultsThe data from both experiments show many significant differences between the serum proteomes of lung cancer patients and nondiseased control subjects, and a number of these polypeptides have been identified. However, the profiles of patients with benign lung diseases resembled those of lung cancer patients such that very few significant differences were found when these cohorts were compared.ConclusionsThis report provides clear evidence of the need to account for the confounding effects of benign diseases when designing lung cancer serum biomarker discovery projects.

Background Cholangiocarcinoma has a high mortality and morbidity. Median survival is less than 6 months. Surgical resection is appropriate in certain circumstances. Because distal cholangiocarcinoma is difficult to distinguish from pancreatic cancers, patients might not receive optimum therapy. Proteomics is the study of complex cellular proteins using mass spectrometry. The aim of this study was to determine the constituent proteins on the cell surface of a model of cholangiocarcinoma. Methods A sample preparation technique to enrich for cell surface proteins of the intrahepatic cholangiocarcinoma cell line CC-SW-1 was developed by modifying a NeutrAvidin-biotin system. After isolation, trypsin digestion, and purification, peptides were fractionated for tandem mass spectrometry before being analysed with the NCBInr database and the Mascot search algorithm. Results were confirmed by immunohistochemistry using a peroxidase detection technique on paraffin-embedded sections from resected specimens. Findings Peptide enrichment was confirmed by electrophoresis. 862 proteins were consistently expressed between samples (n=3). 271 of these proteins were attributed only to the cell surface. They included proteins used clinically for staging disease (cytokeratin 19 [CK19]), identifying cancer stem cells (epithelial cell adhesion molecule [EpCAM], neural cell adhesion molecule [NCAM], epithelial growth factor receptor [EGFR]), and indicating potential for differentiation (Frozzled receptor, Notch pathway). Novel markers from the tumour necrosis factor (TNF) receptor superfamily were also identified. Immunohistochemistry confirmed these findings. Interpretation The results from this surface proteomic profiling could help to identify novel therapeutic targets in cholangiocarcinoma. Further development of this technique could be translated to distinguish between distal cholangiocarcinoma and pancreatic cancers. Funding UK Medical Research Council.

Introduction Concerns have been raised that exposure to outdoor air pollution during pregnancy could alter fetal metabolic function which could increase the risk of obesity in childhood. However, n...