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Objective: To describe differences in the frequency of small-for-gestational age (SGA) and large-for-gestational age (LGA) driven by different birth weight curves in assisted reproductive technology (ART)–conceived pregnancies. Design: Retrospective cohort study. Setting: Single academic medical center. Patients: Singleton live births between the gestational ages of 36 weeks and 0 days and 42 weeks and 6 days from fresh or frozen embryo transfer (ET). Intervention(s): None. Main Outcome Measure(s): SGA (90th percentile) classified by Fenton, INTERGROWTH-21, World Health Organization, Duryea, and Oken curves. Results: The median birth weight and gestational age at birth among fresh ET pregnancies were 3,289g (interquartile range [IQR], 2,977–3,600g) and 39.4 (IQR, 38.6–40.3) weeks, respectively, and those among frozen ET pregnancies were 3,399g (IQR, 3,065–3,685g) and 39.4 (IQR, 38.7–40.1) weeks, respectively. The frequencies of SGA neonates using each birth weight standard ranged from 5.8% to 13.4% for fresh ET and from 3.5% to 8.7% for frozen ET. Those of LGA neonates ranged from 5.3% to 14.3% for fresh ET and from 6.6% to 21.2% for frozen ET. Conclusion: The frequency of SGA and LGA neonates among ART-conceived gestations is partially driven by the birth weight standard. Selecting an appropriate standard that best reflects the patient population is critical to quantifying the risk of ART-conceived pregnancies.

Background: Ongoing debate remains regarding optimal antithrombotic therapy in patients with atrial fibrillation (AF) and coronary artery disease. Methods: We performed a systematic review and meta-analysis to synthesize randomized controlled trials (RCTs) comparing the following: (i) dual-pathway therapy (DPT; oral anticoagulant [OAC] plus antiplatelet) vs triple therapy (OAC and dual-antiplatelet therapy) after percutaneous coronary intervention (PCI) or acute coronary syndrome (ACS), and (iii) OAC monotherapy vs DPT at least 1 year after PCI or ACS. Following a 2-stage process, we identified systematic reviews published between 2019 and 2022 on these 2 clinical questions, and we updated the most comprehensive search for additional RCTs published up to October 2022. Outcomes of interest were major adverse cardiovascular events (MACE), death, stent thrombosis, and major bleeding. We estimated risk ratios (RRs) and 95% confidence intervals (CIs) using a random-effects model. Results: Based on 6 RCTs (n = 10,435), DPT reduced major bleeding (RR 0.62, 95% CI 0.52-0.73) and increased stent thrombosis (RR 1.55, 95% CI 1.02-2.36), vs triple therapy after PCI or medically-managed ACS, with no significant differences in MACE and death. In 2 RCTs (n = 2905), OAC monotherapy reduced major bleeding (RR 0.66, 95% CI 0.49-0.91) vs DPT in AF patients with remote PCI or ACS, with no significant differences in MACE or death. Conclusions: In patients with AF and coronary artery disease, using less-aggressive antithrombotic treatment (DPT after PCI or ACS, and OAC alone after remote PCI or ACS) reduced major bleeding, with an increase in stent thrombosis with recent PCI. These results support a minimalist yet personalized antithrombotic strategy for these patients. Résumé: Contexte: La question du traitement antithrombotique optimal chez les personnes présentant une fibrillation auriculaire (FA) et une coronaropathie demeure controversée. Méthodologie: Nous avons réalisé une revue systématique et une méta-analyse pour synthétiser les essais contrôlés randomisés ayant comparé i) la bithérapie (anticoagulant oral et antiplaquettaire) et la trithérapie (anticoagulant oral et bithérapie antiplaquettaire) après une intervention coronarienne percutanée (ICP) ou un syndrome coronarien aigu (SCA), et ii) un anticoagulant oral en monothérapie et la bithérapie au moins 1 an après une ICP ou un SCA. Nous avons procédé en 2 temps, d’abord en répertoriant les revues systématiques publiées entre 2019 et 2022 sur ces 2 questions cliniques, puis en effectuant la recherche la plus exhaustive possible pour trouver d’autres essais contrôlés randomisés publiés jusqu’en octobre 2022. Les paramètres qui nous intéressaient étaient les événements cardiovasculaires indésirables majeurs (ECIM), le décès, la thrombose de l’endoprothèse et l’hémorragie majeure. Nous avons estimé les rapports de risques (RR) et les intervalles de confiance (IC) à 95 % à l’aide d’un modèle à effets aléatoires. Résultats: D’après 6 essais contrôlés randomisés (n = 10 435), la bithérapie a réduit les hémorragies majeures (RR : 0,62; IC à 95 % : 0,52 à 0,73) et augmenté les thromboses de l’endoprothèse (RR : 1,55; IC à 95 % : 1,02 à 2,36), comparativement à la trithérapie après une ICP ou un SCA ayant fait l’objet d’une prise en charge médicale, tandis qu’aucune différence significative n’a été observée quant aux ECIM et aux décès. Dans 2 essais contrôlés randomisés (n = 2 905), un anticoagulant oral en monothérapie a réduit les hémorragies majeures (RR : 0,66; IC à 95 % : 0,49 à 0,91) comparativement à la bithérapie chez des patients présentant une FA après une ICP ou un SCA plus lointain, sans différence significative quant aux ECIM et aux décès. Conclusions: Chez les patients présentant une FA et une coronaropathie, l’utilisation d’un traitement antithrombotique moins agressif (bithérapie après un ICP ou un SCA, et anticoagulant oral en monothérapie après une ICP ou un SCA plus lointain) réduit les hémorragies majeures, mais s’accompagne d’une augmentation des thromboses de l’endoprothèse en cas d’ICP récente. Ces résultats plaident en faveur d’une stratégie antithrombotique minimaliste, mais personnalisée chez ces patients.

Bradley S Miller,1 Jo Blair,2 Reiko Horikawa,3 Agnès Linglart,4– 7 Kevin CJ Yuen8 1Division of Pediatric Endocrinology, University of Minnesota Medical School, MHealth Fairview Masonic Children’s Hospital, Minneapolis, MN, USA; 2Department of Paediatric Endocrinology, Alder Hey Children’s NHS Foundation Trust, Liverpool, UK; 3Division of Endocrinology and Metabolism, National Center for Child Health and Development, Tokyo, Japan; 4Department of Endocrinology and Diabetes for Children, Hospital Bicêtr Paris Saclay, AP-HP, Le Kremlin-Bicêtre, France; 5Unité 1185, INSERM, Paris, France; 6Reference Center for Rare Pituitary Disorders, Hospital Bicêtre Paris Saclay, AP-HP, Le Kremlin-Bicêtre, France; 7Platform of Expertise for Rare Diseases, OSCAR Network, Hospital Bicêtre Paris Saclay, AP-HP, Le Kremlin-Bicêtre, France; 8Departments of Neuroendocrinology and Neurosurgery, Barrow Neurological Institute, University of Arizona College of Medicine and Creighton School of Medicine, Phoenix, AZ, USACorrespondence: Bradley S Miller, Division of Pediatric Endocrinology, University of Minnesota Medical School, MHealth Fairview Masonic Children’s Hospital, Riverside Ave, Minneapolis, MN, 55455, USA, Tel +1 612-624-5409, Fax +1 612-626-5262, Email mille685@umn.eduAbstract: Growth hormone (GH) replacement therapy for growth hormone deficiency (GHD) in children and adults has for over 25 years, until recently, been administered as daily injections. This daily treatment regimen often incurs a burden to patients and caregivers, leading to high rates of non-adherence and, consequently, decreased treatment efficacy outcomes. To address this shortcoming, long-acting growth hormones (LAGHs) have been developed with the aim of reducing the burden of daily injections, thereby potentially improving treatment adherence and outcomes. Somapacitan (Sogroya®) (Novo Nordisk, Bagsværd, Denmark) is a LAGH currently approved for the treatment of adult and childhood GHD (AGHD and CGHD, respectively) in several countries. Other LAGHs, such as somatrogon (Ngenla®) (Pfizer, New York, United States) and lonapegsomatropin/TransCon GH (Skytrofa®) (Ascendis Pharma, Copenhagen, Denmark), are also currently approved and available for the treatment of CGHD in several countries. In this review, we will consider the method of protraction, pharmacokinetics (PK) and pharmacodynamics (PD), efficacy, and safety results of somapacitan in adult and pediatric trials and how these characteristics differ from those of the other aforementioned LAGHs. Additionally, the administration of somapacitan and timing of measurement of serum insulin-like growth factor-I (IGF-I) levels are summarized. Information on administration, advice on missed doses, and clinical guidelines are discussed, as well as identifying which patients are suitable for somapacitan therapy, and how to monitor and adjust dosing whilst on therapy.Keywords: (3– 6): growth hormone, long-acting growth hormone, adult growth hormone deficiency, pediatric growth hormone deficiency, adherence

Purpose Pregnancy and the postpartum period are increasingly recognised as sensitive windows for cardiometabolic disease risk. Growing evidence suggests environmental exposures, including endocrine-disrupting chemicals (EDCs), are associated with an increased risk of pregnancy complications that are associated with long-term cardiometabolic risk. However, the impact of perinatal EDC exposure on subsequent cardiometabolic risk post-pregnancy is less understood. The Environmental Reproductive and Glucose Outcomes (ERGO) Study was established to investigate the associations of environmental exposures during the perinatal period with post-pregnancy parental cardiometabolic health.Participants Pregnant individuals aged ≥18 years without pre-existing diabetes were recruited at

BackgroundRacial and ethnic disparities persist in preterm birth (PTB) and gestational age (GA) at delivery in the United States. It remains unclear whether exposure to environmental chemicals contributes to these disparities.ObjectivesWe applied recent methodologies incorporating environmental mixtures as mediators in causal mediation analysis to examine whether racial and ethnic disparities in GA at delivery and PTB may be partially explained by exposures to polybrominated diphenyl ethers (PBDEs), a class of chemicals used as flame retardants in the United States.MethodsData from a multiracial/ethnic US cohort of 2008 individuals with low-risk singleton pregnancies were utilized, with plasma PBDE concentrations measured during early pregnancy. We performed mediation analyses incorporating three forms of mediators: (1) reducing all PBDEs to a weighted index, (2) selecting a PBDE congener, or (3) including all congeners simultaneously as multiple mediators, to evaluate whether PBDEs may contribute to the racial and ethnic disparities in PTB and GA at delivery, adjusted for potential confounders.ResultsAmong the 2008 participants, 552 self-identified as non-Hispanic White, 504 self-identified as non-Hispanic Black, 568 self-identified as Hispanic, and 384 self-identified as Asian/Pacific Islander. The non-Hispanic Black individuals had the highest mean ∑PBDEs, the shortest mean GA at delivery, and the highest rate of PTB. Overall, the difference in GA at delivery comparing non-Hispanic Black to non-Hispanic White women was −0.30 (95% CI: −0.54, −0.05) weeks. This disparity reduced to −0.23 (95% CI: −0.49, 0.02) and −0.18 (95% CI: −0.46, 0.10) weeks if fixing everyone's weighted index of PBDEs to the median and the 25th percentile levels, respectively. The proportion of disparity mediated by the weighted index of PBDEs was 11.8%. No statistically significant mediation was found for PTB, other forms of mediator(s), or other racial and ethnic groups.ConclusionPBDE mixtures may partially mediate the Black vs. White disparity in GA at delivery. While further validations are needed, lowering the PBDEs at the population level might help reduce this disparity.

This review examines the pharmacotherapy and lifestyle recommendations of the most recent iterations of the Canadian Cardiovascular Society (CCS) / Canadian Heart Failure Society (CHFS), the European Society of Cardiology (ESC), and the American Heart Association (AHA) / American College of Cardiology (ACC) / Heart Failure Society of America (HFSA) heart failure (HF) guidelines, which all have been updated in response to therapeutic developments across the spectrum of left ventricular ejection fraction. Identified areas of unanimity across these guidelines include the following: recommending quadruple therapy for patients with HF with reduced ejection fraction (HFrEF; although no guideline proposed an ideal sequence of initiation); intravenous iron administration for patients with HFrEF and iron deficiency; and sodium restriction for patients with HF. Recent evidence regarding the harms of HFrEF medication withdrawal in patients with HF with improved ejection fraction has prompted subsequent guidelines to recommend against withdrawal. Due to the lower quality of evidence, there are disagreements regarding management of HF with preserved ejection fraction and uncertainty regarding management of HF with mildly reduced ejection fraction. Practical guidance is provided to clinicians navigating these challenging areas. In addition to these clinically focused comparisons, we describe opportunities for guideline improvement and harmonization. Specifically, these include opportunities regarding HFrEF sequencing, the need for timely updates, shared decision-making, Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework adoption, and the creation of recommendations where high-quality evidence is lacking. Although these guidelines have broad agreement, key areas of controversy remain that may be addressed by emerging evidence and changes in guideline methodology. Résumé: Le présent examen porte sur les recommandations en matière de pharmacothérapie et d’habitudes de vie en présence d’insuffisance cardiaque (IC) des plus récentes lignes directrices sur l'IC de la Société cardiovasculaire du Canada (SCC) / Société canadienne d’insuffisance cardiaque (SCIC), de la Société européenne de cardiologie (ESC) et de l’American Heart Association (AHA) / American College of Cardiology (ACC) / Heart Failure Society of America (HFSA), qui ont toutes été mises à jour en réponse aux avancées thérapeutiques pour tout le spectre de fractions d’éjection du ventricule gauche. Voici certains des domaines qui font l’unanimité dans ces lignes directrices : quadrithérapie recommandée chez les patients atteints d’IC avec fraction d’éjection réduite (ICFER; toutefois, aucune ligne directrice ne comporte une proposition concernant la séquence idéale de l’instauration du traitement); administration de fer par voie intraveineuse aux patients atteints d’ICFER présentant une carence en fer; et restriction de l’apport sodique chez les patients aux prises avec une insuffisance cardiaque. Les données probantes récemment publiées sur les effets nocifs de l’abandon de médicaments contre l’ICFER chez les patients atteints d’insuffisance cardiaque dont la fraction d’éjection s’est améliorée ont incité les organismes à déconseiller de tels abandons dans leurs recommandations subséquentes. En raison de la faible qualité des données, il existe des différends en ce qui a trait à la prise en charge de l’IC avec fraction d’éjection préservée, ainsi qu’une incertitude quant à la prise en charge de l’IC avec fraction d’éjection légèrement réduite. Des conseils pratiques sont fournis afin d’aider les cliniciens à gérer ces domaines complexes. En plus de ces comparaisons axées sur la pratique clinique, nous décrivons des occasions d’amélioration et d’harmonisation des lignes directrices. Plus précisément, ces occasions touchent la séquence des traitements de l’ICFER, le besoin de mises à jour opportunes, la prise de décision conjointe, l’adoption du cadre GRADE (Grading of Recommendations, Assessment, Development and Evaluations, soit la classification des recommandations, des appréciations, du développement et des évaluations), ainsi que l’élaboration de recommandations dans les domaines où des données probantes de haute qualité sont lacunaires. Bien que ces lignes directrices obtiennent un vaste accord, d’importants domaines controversés demeurent. La publication de données probantes et la modification des méthodes d’élaboration des recommandations pourraient cependant y remédier.

The canonical target of the glucagon-like peptide-1 receptor (GLP-1R), Protein Kinase A (PKA), has been shown to stimulate mechanistic Target of Rapamycin Complex 1 (mTORC1) by phosphorylating the mTOR-regulating protein Raptor at Ser791 following β-adrenergic stimulation. The objective of these studies is to test whether GLP-1R agonists similarly stimulate mTORC1 via PKA phosphorylation of Raptor at Ser791 and whether this contributes to the weight loss effect of the therapeutic GLP-1R agonist liraglutide. We measured phosphorylation of the mTORC1 signaling target ribosomal protein S6 in Chinese Hamster Ovary cells expressing GLP-1R (CHO-Glp1r) treated with liraglutide in combination with PKA inhibitors. We also assessed liraglutide-mediated phosphorylation of the PKA substrate RRXS*/T* motif in CHO-Glp1r cells expressing Myc-tagged wild-type (WT) Raptor or a PKA-resistant (Ser791Ala) Raptor mutant. Finally, we measured the body weight response to liraglutide in WT mice and mice with a targeted knock-in of PKA-resistant Ser791Ala Raptor. Liraglutide increased phosphorylation of S6 and the PKA motif in WT Raptor in a PKA-dependent manner but failed to stimulate phosphorylation of the PKA motif in Ser791Ala Raptor in CHO-Glp1r cells. Lean Ser791Ala Raptor knock-in mice were resistant to liraglutide-induced weight loss but not setmelanotide-induced (melanocortin-4 receptor-dependent) weight loss. Diet-induced obese Ser791Ala Raptor knock-in mice were not resistant to liraglutide-induced weight loss; however, there was weight-dependent variation such that there was a tendency for obese Ser791Ala Raptor knock-in mice of lower relative body weight to be resistant to liraglutide-induced weight loss compared to weight-matched controls. Together, these findings suggest that PKA-mediated phosphorylation of Raptor at Ser791 contributes to liraglutide-induced weight loss.

Abstract Background Though anecdotal evidence suggests that smoke from HAP has a repellent effect on mosquitoes, very little work has been done to assess the effect of biomass smoke on malaria infection. The study, therefore, sought to investigate the hypothesis that interventions to reduce household biomass smoke may have an unintended consequence of increasing placental malaria or increase malaria infection in the first year of life. Methods This provides evidence from a randomized controlled trial among 1414 maternal-infant pairs in the Kintampo North and Kintampo South administrative areas of Ghana. Logistic regression was used to assess the association between study intervention assignment (LPG, Biolite or control) and placental malaria. Finally, an extended Cox model was used to assess the association between study interventions and all episodes of malaria parasitaemia in the first year of infant’s life. Results The prevalence of placental malaria was 24.6%. Out of this, 20.8% were acute infections, 18.7% chronic infections and 60.5% past infections. The study found no statistical significant association between the study interventions and all types of placental malaria (OR = 0.88; 95% CI 0.59–1.30). Of the 1165 infants, 44.6% experienced at least one episode of malaria parasitaemia in the first year of life. The incidence of first and/or only episode of malaria parasitaemia was however found to be similar among the study arms. Conclusion The findings suggest that cookstove interventions for pregnant women and infants, when combined with additional malaria prevention strategies, do not lead to an increased risk of malaria among pregnant women and infants.

Background: Pharmacologic management of heart failure with reduced ejection fraction (HFrEF) involves several medications. Decision aids informed by patient decisional needs and treatment preferences could assist in making HFrEF medication choices; however, these are largely unknown. Methods: We searched MEDLINE, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), without language restriction, for qualitative, quantitative, and mixed-method studies that included patients with HFrEF or clinicians providing HFrEF care, and reported data on decisional needs or treatment preferences applicable to HFrEF medications. We classified decisional needs using a modified version of the Ottawa Decision Support Framework (ODSF). Results: From 3996 records, we included 16 reports describing 13 studies (n = 854). No study explicitly assessed ODSF decisional needs; however, 11 studies reported ODSF-classifiable data. Patients commonly reported having inadequate knowledge or information, and difficult decisional roles. No study systematically assessed treatment preferences, but 6 studies reported on attribute preferences. Reducing mortality and improving symptoms frequently were ranked as being important, whereas cost importance rankings varied, and adverse events generally were ranked as being less important. Conclusion: This scoping review identified key decisional needs regarding HFrEF medications, notably inadequate knowledge or information, and difficult decisional roles, which can readily be addressed by decision aids. Future studies should systematically explore the full scope of ODSF-based decisional needs in patients with HFrEF, along with relative preferences among treatment attributes to further inform development of individualized decision aids. Résumé: Contexte: La prise en charge pharmacologique de l’insuffisance cardiaque avec fraction d’éjection réduite (ICFER) peut être réalisée à l’aide de plusieurs médicaments. Des outils d’aide à la décision reposant sur les besoins décisionnels et les préférences thérapeutiques des patients pourraient faciliter le choix des médicaments dans les cas d’ICFER. Malheureusement, ce type d’outils demeure largement inconnu. Méthodologie: Nous avons interrogé les bases de données MEDLINE, Embase et Cumulative Index to Nursing and Allied Health Literature (CINAHL), sans restriction quant à la langue, pour trouver des études qualitatives, quantitatives et mixtes incluant des patients atteints d’ICFER ou des cliniciens prodiguant des soins aux personnes atteintes d’ICFER. Nous avons recueilli les données sur les besoins décisionnels ou les préférences thérapeutiques qui s’appliquaient aux médicaments contre l’ICFER, puis avons classé les besoins décisionnels à l’aide d’une version modifiée du Modèle d’aide à la décision d’Ottawa (MADO). Résultats: Sur un total de 3996 résultats, nous avons retenu 16 rapports décrivant 13 études (n = 854). Aucune étude n’évaluait explicitement les besoins décisionnels selon le MADO, mais 11 études faisaient état de données qu’il était possible de classer selon ce modèle. Les patients ont fréquemment mentionné avoir des connaissances ou des informations inadéquates et un rôle décisionnel difficile. Aucune étude n’évaluait systématiquement les préférences de traitement, mais six études ont rapporté des préférences quant aux attributs du traitement. La réduction de la mortalité et l’atténuation des symptômes étaient souvent classées comme importantes, les coûts faisaient l’objet d’un classement variable et les événements indésirables étaient généralement classés comme étant peu importants. Conclusion: Cette revue exploratoire a permis de relever des besoins décisionnels clés concernant les médicaments contre l’ICFER, notamment des connaissances et des informations inadéquates, et un rôle décisionnel difficile, besoins qui peuvent facilement être comblés par des outils d’aide à la décision. De futures études devraient explorer de manière systématique la portée complète des besoins décisionnels des patients atteints d’ICFER selon le MADO, ainsi que les préférences relatives quant aux attributs du traitement pour orienter l’élaboration d’outils personnalisés d’aide à la décision.

Background: Prenatal household air pollution impairs birth weight and increases pneumonia risk however time-varying associations have not been elucidated and may have implications for the timing of public health interventions. Methods: The Ghana Randomized Air Pollution and Health Study (GRAPHS) enrolled 1,414 pregnant women from Kintampo, Ghana and measured personal carbon monoxide (CO) exposure four times over pregnancy. Birth weight was measured within 72-hours of birth. Fieldworkers performed weekly pneumonia surveillance and referred sick children to study physicians. The primary pneumonia outcome was one or more physician-diagnosed severe pneumonia episode in the first year of life. We employed reverse distributed lag models to examine time-varying associations between prenatal CO exposure and birth weight and infant pneumonia risk. Results: Analyses included n = 1,196 mother-infant pairs. In models adjusting for child sex; maternal age, body mass index (BMI), ethnicity and parity at enrollment; household wealth index; number of antenatal visits; and evidence of placental malaria, prenatal CO exposures from 15 to 20 weeks gestation were inversely associated with birth weight. Sex-stratified models identified a similar sensitive window in males and a window at 10-weeks gestation in females. In models adjusting for child sex, maternal age, BMI and ethnicity, household wealth index, gestational age at delivery and average postnatal child CO exposure, CO exposure during 34–39 weeks gestation were positively associated with severe pneumonia risk, especially in females. Conclusions: Household air pollution exposures in mid- and late- gestation are associated with lower birth weight and higher pneumonia risk, respectively. These findings support the urgent need for deployment of clean fuel stove interventions beginning in early pregnancy.

The effect of supplemental lighting on strawberry growth and anthracnose disease response of three strawberry (Fragaria ×ananassa) cultivars was evaluated in two greenhouse trials, and the effect on strawberry anthracnose pathogens (Colletotrichum sp.) was evaluated in the laboratory. The objective of the greenhouse trials was to determine the effect of various intensities of the red and blue light emitting diode (LED) light treatment on strawberry plant vigor, injury, and disease development. In these trials, the duration of supplemental light treatments was split into two 4-hour periods: dawn and dusk. The intensity of the red and blue LED bulbs was set using an adjustable dial at 1 or 3 in trial 1 and at 1, 5, or 10 in trial 2. Illuminance and photosynthetic photon flux densities of the light treatments ranged from lows of 402 lx and 5 μmol⋅m–2⋅s–1 (blue LED 1) to highs of 575 lx and 25 μmol⋅m–2⋅s–1 (red LED 1 + blue LED 3) in trial 1, and from lows of 4213 lx and 81 μmol⋅m–2⋅s–1 (red LED 1) to highs of 7051 lx (red LED 5) and 194 μmol⋅m–2⋅s–1 (red LED 10) in trial 2. Lower light intensities in trial 1 resulted in no significant differences as a result of light treatments in relative chlorophyll content, plant vigor ratings, or disease severity ratings (DSRs). However, plant injury ratings were significantly greater in plants in the wide-spectrum fluorescent (WSF) plus ultraviolet B (UVB) light treatment compared with the other treatments. Under the higher light intensities in trial 2, there were more significant effects among light treatments. Relative chlorophyll content of plants in the WSF + UVB, WSF, and red LED 1 treatments was significantly greater than that of plants in the red LED 10 treatment; however, plants in the red LED 10 treatment had the greatest injury ratings. Detached leaves from plants in the red 5 LED and red 10 LED treatments inoculated with Colletotrichum gloeosporioides received the greatest DSRs, and leaves from plants in the red LED 1 and WSF treatments received the lowest DSRs. In the laboratory, five days of exposure to supplemental lights did not prevent the growth of isolates of three species of Colletotrichum pathogens even though the intensity of the LED lights was set at their highest intensity. However, growth of isolates exposed to the WSF + UVB light treatment was slowed.

Objective: Glucagon-like peptide-1 receptor (GLP-1R) agonists (GLP-1RA) and fibroblast growth factor-21 (FGF21) confer similar metabolic benefits. GLP-1RA induce FGF21, leading us to investigate mechanisms engaged by the GLP-1RA liraglutide to increase FGF21 levels and the metabolic relevance of liraglutide-induced FGF21. Methods: Circulating FGF21 levels were measured in fasted male C57BL/6J, neuronal GLP-1R knockout, β-cell GLP-1R knockout, and liver peroxisome proliferator-activated receptor alpha knockout mice treated acutely with liraglutide. To test the metabolic relevance of liver FGF21 in response to liraglutide, chow-fed control and liver Fgf21 knockout (LivFgf21−/−) mice were treated with vehicle or liraglutide in metabolic chambers. Body weight and composition, food intake, and energy expenditure were measured. Since FGF21 reduces carbohydrate intake, we measured body weight in mice fed matched diets with low- (LC) or high-carbohydrate (HC) content and in mice fed a high-fat, high-sugar (HFHS) diet. This was done in control and LivFgf21−/− mice and in mice lacking neuronal β-klotho (Klb) expression to disrupt brain FGF21 signaling. Results: Liraglutide increases FGF21 levels independently of decreased food intake via neuronal GLP-1R activation. Lack of liver Fgf21 expression confers resistance to liraglutide-induced weight loss due to attenuated reduction of food intake in chow-fed mice. Liraglutide-induced weight loss was impaired in LivFgf21−/− mice when fed HC and HFHS diets but not when fed a LC diet. Loss of neuronal Klb also attenuated liraglutide-induced weight loss in mice fed HC or HFHS diets. Conclusions: Our findings support a novel role for a GLP-1R-FGF21 axis in regulating body weight in a dietary carbohydrate-dependent manner.

BACKGROUND: Hypertension is a key contributor to the global epidemic of cardiovascular disease and is responsible for more deaths worldwide than any other cardiovascular risk factor. Hypertensive disorders of pregnancy, of which preeclampsia and eclampsia are the most common forms, have been shown to be a female-specific risk factor for chronic hypertension. OBJECTIVE: This study aimed to determine the proportion and risk factors for persistent hypertension at 3 months after delivery among women with hypertensive disorders of pregnancy in Southwestern Uganda. STUDY DESIGN: This was a prospective cohort study of pregnant women with hypertensive disorders of pregnancy admitted for delivery at Mbarara Regional Referral Hospital in Southwestern Uganda from January 2019 to December 2019; however, women with chronic hypertension were excluded from the study. The participants were followed up for 3 months after delivery. Participants with a systolic blood pressure of ≥140 mm Hg or a diastolic blood pressure of ≥90 mm Hg or receiving antihypertension therapy at 3 months after delivery were considered to have persistent hypertension. Multivariable logistic regression was used to determine independent risk factors associated with persistent hypertension. RESULTS: A total of 111 participants with hypertensive disorders of pregnancy diagnosed at hospital admission were enrolled with a follow-up rate of 49% (54/111) at 3 months after delivery. Of these women, 21 of 54 (39%) had persistent hypertension 3 months after delivery. In the adjusted analyses, an elevated serum creatinine level (>106.08 µmol/L [≤1.2 mg/dL]) at admission for delivery was the only independent risk factor for persistent hypertension at 3 months after delivery (adjusted relative risk, 1.93; 95% confidence interval, 1.08–3.46; P=.03), controlling for age, gravidity, and eclampsia. CONCLUSION: Approximately 4 of 10 women presenting with hypertensive disorders of pregnancy at our institution remained hypertensive 3 months after delivery. Innovative strategies are needed to identify these women and provide long-term care to optimize blood pressure control and reduce future cardiovascular disease after hypertensive disorders of pregnancy.

Introduction Dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) reduces major adverse cardiovascular events (MACE) and stent thrombosis. However, DAPT duration is a concern in high bleeding risk (HBR) patients. We evaluated the effect of short DAPT (1–3 months) compared to standard DAPT (6–12 months) on bleeding and ischemic events in HBR PCI. Methods We searched MEDLINE, Embase and CENTRAL up to August 18, 2022. Randomized controlled trials (RCTs) comparing short DAPT (1–3 months) versus standard DAPT in HBR PCI were included. We assessed risk of bias (RoB) using the Cochrane RoB2 tool, and certainty of evidence using GRADE criteria. Outcomes included MACE, all-cause death, stent thrombosis, major bleeding, and the composite of major or clinically-relevant non-major bleeding. We estimated risk ratios (RR) and 95% confidence intervals (CI) using a random-effects model. Results From 503 articles, we included five RCTs (n = 7,242) at overall low risk of bias with median follow-up of 12-months. Compared to standard DAPT, short DAPT did not increase MACE (RR 1.02, 95% CI 0.84–1.23), all-cause death (RR 0.92, 95% CI 0.71–1.20) or stent thrombosis (RR 1.47, 95% CI 0.73–2.93). Short DAPT reduced major bleeding (RR 0.34, 95% CI 0.13–0.90) and the composite of major or clinically-relevant non-major bleeding (RR 0.60, 95% CI 0.44–0.81), translating to 21 and 34 fewer events, respectively, per 1000 patients. Conclusions In HBR PCI, DAPT for 1–3 months compared to 6–12 months reduced clinically-relevant bleeding events without jeopardizing ischemic risk. Short DAPT should be considered in HBR patients receiving PCI.

In the setting of acute coronary syndrome, right-ventricular (RV) infarction, which has significant clinical implications, can occur in conjunction with inferior left-ventricular (LV) infarction. In rare cases, RV infarction is isolated. We describe a case of isolated RV infarction identified based on previously described electrocardiogram findings in the absence of hemodynamic or imaging evidence of RV dysfunction. This case highlights the fact that RV transmural ischemia can exist in the absence of the clinical syndrome associated with RV infarction, which we hypothesize is related to the proportion of RV myocardium involved in the infarct, or conversely, the amount of myocardium protected through various mechanisms. Résumé: Dans le cadre du syndrome coronarien aigu, l’infarctus du ventricule droit, qui a des répercussions cliniques importantes, peut survenir conjointement avec un infarctus inférieur du ventricule gauche. Dans de rares cas, l’infarctus du ventricule droit est isolé. Nous décrivons un cas d’infarctus du ventricule droit isolé décelé à l’aide des résultats précédemment décrits d’un électrocardiogramme faute de résultats hémodynamiques ou d’imagerie indiquant une dysfonction ventriculaire droite. Ce cas souligne le fait qu'une ischémie transmurale du ventricule droit peut survenir même sans syndrome clinique associé à l’infarctus du ventricule droit, ce qui s’explique, selon notre hypothèse, par la proportion de myocarde ventriculaire droit touché par l’infarctus ou, à l’inverse, la quantité de myocarde protégé par divers mécanismes.

Abstract Background Hypertensive disorders of pregnancy are important causes of maternal morbidity and mortality, as well as preterm birth, the leading cause of death for children under 5 years globally. The World Health Organization currently recommends that pregnant women receive high-dose calcium supplementation (1500–2000 mg elemental calcium) for prevention of preeclampsia in populations with low dietary calcium intake. Trials of low-dose calcium supplementation (

Introduction The WHO Nutrition Target aims to reduce the global prevalence of low birth weight by 30% by the year 2025. The Enhancing Nutrition and Antenatal Infection Treatment (ENAT) study will test the impact of packages of pregnancy interventions to enhance maternal nutrition and infection management on birth outcomes in rural Ethiopia.Methods and analysis ENAT is a pragmatic, open-label, 2×2 factorial, randomised clinical effectiveness study implemented in 12 rural health centres in Amhara, Ethiopia. Eligible pregnant women presenting at antenatal care (ANC) visits at

Joanne Blair, 1 Kelly Warth, 2 Yashasvi Suvarna, 3 Marco Cappa 4 1Department of Endocrinology, Alder Hey Children’s NHS Foundation Trust, Liverpool, UK; 2Instar, London, UK; 3Global Medical Affairs, Novo Nordisk Global Business Services (GBS), Bangalore, India; 4Endocrinology Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyCorrespondence: Joanne BlairDepartment of Endocrinology, Alder Hey Children’s NHS Foundation Trust, Liverpool, L12 2AP, UKTel +44 151 252 5335 Fax +44 151 282 4606Email Jo.Blair@alderhey.nhs.ukPurpose: This study investigated why some clinicians switched growth hormone (GH) brands in pediatric patients with GH-related disorders to Norditropin® since the start of the COVID-19 pandemic, the clinicians’ perceptions of the results, and whether observations from this period of disruption could inform clinical practice in the future.Patients and Methods: Clinicians (N=106) from the UK, France, Italy, and Japan who had switched at least one patient to Norditropin® from a GH therapy manufactured by a different pharmaceutical company between February and November 2020 participated. They completed an online survey and submitted patient report forms for up to three switched patients.Results: Since the start of COVID-19, 39– 54% of the reported consultations were virtual (ie, via telephone or online means) in the UK, France, and Italy. Overall, 17% of patients seen by respondents in the survey were switched to a different GH brand; approximately two-thirds of switches were to Norditropin®. Clinicians’ top considerations in choosing a GH brand were patient/carer feedback, patient support programs, and the need for easy-to-use therapies in the context of virtual consultations. The top reasons for switching patients to Norditropin® included ease of use, device features and benefits, better patient/carer feedback, and ease of training in device use via virtual consultations. Norditropin® was considered suitable for use in virtual or in-person consultations or a mixture of both. Based on patient/carer feedback, 66% of clinicians believed that patients preferred Norditropin® to their previous therapy in terms of overall satisfaction.Conclusion: In this survey, key considerations in prescribing GH therapy were ease of use and acceptability to patients and carers. If virtual consultations increasingly replace in-person ones, ease in training patients/carers in device use will be particularly important. A majority of clinicians considered that their patients preferred Norditropin® to their previous therapy.Keywords: growth disorders, somatropin, virtual consultations, ease of use, Norditropin®

Abstract Background Low birthweight (LBW) (

Abstract Background Prenatal endocrine disrupting chemical (EDC) exposure has been associated with increased risk of preterm birth. Non-Hispanic Black women have higher incidence of preterm birth compared to other racial/ethnic groups and may be disproportionately exposed to EDCs through EDC-containing hair products. However, research on the use of EDC-associated hair products during pregnancy and risk of preterm birth is lacking. Therefore, the objective of this pilot study was to estimate associations of prenatal hair product use with gestational age at delivery in a Boston, Massachusetts area pregnancy cohort. Methods The study population consisted of a subset of participants enrolled in the Environmental Reproductive and Glucose Outcomes (ERGO) Study between 2018 and 2020. We collected self-reported data on demographics and hair product use using a previously validated questionnaire at four prenatal visits (median: 12, 19, 26, 36 weeks’ gestation) and abstracted gestational age at delivery from medical records. We compared gestational age and hair product use by race/ethnicity and used linear regression to estimate covariate-adjusted associations of product use and frequency of use at each study visit with gestational age at delivery. Primary models were adjusted for maternal age at enrollment and delivery method. Results Of the 154 study participants, 7% delivered preterm. Non-Hispanic Black participants had lower mean gestational age at delivery compared to non-Hispanic White participants (38.2 vs. 39.2 weeks) and were more likely to report ever and more frequent use of hair products. In regression models, participants reporting daily use of hair oils at visit 4 had lower mean gestational age at delivery compared to non-users (β: -8.3 days; 95% confidence interval: -14.9, -1.6). We did not find evidence of associations at earlier visits or with other products. Conclusions Frequent use of hair oils during late pregnancy may be associated with shorter gestational duration. As hair oils are more commonly used by non-Hispanic Black women and represent potentially modifiable EDC exposure sources, this may have important implications for the known racial disparity in preterm birth.

Abstract Background Exposure to ionizing radiation has been associated with insulin resistance and type 2 diabetes. In light of recent work showing an association between ambient particulate matter (PM) gross β-activity and gestational diabetes mellitus (GDM) among pregnant women, we examined pregnancy glucose levels in relation to PM gross β-activity to better understand this pathway. Methods Our study included 103 participants receiving prenatal care at Beth Israel Deaconess Medical Center in Boston, MA. PM gross β-activity was obtained from US Environmental Protection Agency’s RadNet program monitors, and blood glucose levels were obtained from the non-fasting glucose challenge test performed clinically as the first step of the 2-step GDM screening test. For each exposure window we examined (i.e., moving average same-day, one-week, first-trimester, and second-trimester PM gross β-activity), we fitted generalized additive models and adjusted for clinical characteristics, socio-demographic factors, temporal variables, and PM with an aerodynamic diameter ≤ 2.5 μm (PM2.5). Subgroup analyses by maternal age and by body mass index were also conducted. Results An interquartile range increase in average PM gross β-activity during the second trimester of pregnancy was associated with an increase of 17.5 (95% CI: 0.8, 34.3) mg/dL in glucose concentration. Associations were stronger among younger and overweight/obese participants. Our findings also suggest that the highest compared to the lowest quartile of one-week exposure was associated with 17.0 (95% CI: − 4.0, 38.0) mg/dL higher glucose levels. No associations of glucose were observed with PM gross β-activity during same-day and first-trimester exposure windows. PM2.5 was not associated with glucose levels during any exposure window in our data. Conclusions Exposure to higher levels of ambient PM gross β-activity was associated with higher blood glucose levels in pregnant patients, with implications for how this novel environmental factor could impact pregnancy health.

Abstract Background Women in sub-Saharan Africa have the highest rates of morbidity and mortality during childbirth globally. Despite increases in facility-based childbirth, gaps in quality of care at facilities have limited reductions in maternal deaths. Infrequent physiologic monitoring of women around childbirth is a major gap in care that leads to delays in life-saving interventions for women experiencing complications. Methods We will conduct a type-2 hybrid effectiveness-implementation study over 12 months to evaluate using a wireless physiologic monitoring system to detect and alert clinicians of abnormal vital signs in women for 24 h after undergoing emergency cesarean delivery at a tertiary care facility in Uganda. We will provide physiologic data (heart rate, respiratory rate, temperature and blood pressure) to clinicians via a smartphone-based application with alert notifications if monitored women develop predefined abnormalities in monitored physiologic signs. We will alternate two-week intervention and control time periods where women and clinicians use the wireless monitoring system during intervention periods and current standard of care (i.e., manual vital sign measurement when clinically indicated) during control periods. Our primary outcome for effectiveness is a composite of severe maternal outcomes per World Health Organization criteria (e.g. death, cardiac arrest, jaundice, shock, prolonged unconsciousness, paralysis, hysterectomy). Secondary outcomes include maternal mortality rate, and case fatality rates for postpartum hemorrhage, hypertensive disorders, and sepsis. We will use the RE-AIM implementation framework to measure implementation metrics of the wireless physiologic system including Reach (proportion of eligible women monitored, length of time women monitored), Efficacy (proportion of women with monitoring according to Uganda Ministry of Health guidelines, number of appropriate alerts sent), Adoption (proportion of clinicians utilizing physiologic data per shift, clinical actions in response to alerts), Implementation (fidelity to monitoring protocol), Maintenance (sustainability of implementation over time). We will also perform in-depth qualitative interviews with up to 30 women and 30 clinicians participating in the study. Discussion This is the first hybrid-effectiveness study of wireless physiologic monitoring in an obstetric population. This study offers insights into use of wireless monitoring systems in low resource-settings, as well as normal and abnormal physiologic parameters among women delivering by cesarean. Trial registration ClinicalTrials.gov , NCT04060667 . Registered on 08/01/2019.

Helianthus verticillatus Small (whorled sunflower) is a federally endangered plant species found only in the southeastern United States that has potential horticultural value. Evidence suggests that H. verticillatus is self-incompatible and reliant on insect pollination for seed production. However, the identity of probable pollinators is unknown. Floral visitors were collected and identified during Sept. 2017 and Sept. 2018. Thirty-six species of visitors, including 25 hymenopterans, 7 dipterans, 2 lepidopterans, and 2 other insect species, were captured during 7 collection days at a site in Georgia (1 day) and 2 locations in Tennessee (6 days). Within a collection day (0745–1815 hr), there were either five or six discrete half-hour collection periods when insects were captured. Insect visitor activity peaked during the 1145–1215 and 1345–1415 hr periods, and activity was least during the 0745–0845 and 0945–1015 hr periods at all three locations. Visitors were identified by genus and/or species with morphological keys and sequences of the cox-1 mitochondrial gene. The most frequent visitors at all sites were Bombus spp. (bumblebees); Ceratina calcarata (a small carpenter bee species) and members of the halictid bee tribe Augochlorini were the second and third most common visitors at the two Tennessee locations. Helianthus pollen on visitors was identified by microscopic observations and via direct polymerase chain reaction of DNA using Helianthus-specific microsatellites primers. Pollen grains were collected from the most frequent visitors and Apis mellifera (honeybee) and counted using a hemocytometer. Based on the frequency of the insects collected across the three sites and on the mean number of pollen grains carried on the body of the insects, Bombus spp., Halictus ligatus (sweat bee), Agapostemon spp., and Lasioglossum/Dialictus spp., collectively, are the most probable primary pollinators of H. verticillatus.

In low- and middle-income countries (LMIC), measurement of symphysis fundal height (SFH) is often the only available method of estimating gestational age (GA) in pregnancy. This systematic review aims to summarize methods of SFH measurement and assess the accuracy of SFH for the purpose of GA estimation. We searched PubMed, EMBASE, Cochrane, Web of Science, POPLINE, and WHO Global Health Libraries from January 1980 through November 2021. For SFH accuracy, we pooled the variance of the mean difference between GA confirmed by ultrasound versus SFH. Of 1,003 studies identified, 37 studies were included. Nineteen different SFH measurement techniques and 13 SFH-to-GA conversion methods were identified. In pooled analysis of five studies (n = 5838 pregnancies), 71% (95% CI: 66-77%) of pregnancies dated by SFH were within ±14 days of ultrasound confirmed dating. Using the 1 cm SFH = 1wk assumption, SFH underestimated GA compared with ultrasound-confirmed GA (mean bias: -14.0 days) with poor accuracy (95% limits of agreement [LOA]: ±42.8 days; n = 3 studies, 2447 pregnancies). Statistical modeling of three serial SFH measurements performed better, but accuracy was still poor (95% LOA ±33 days; n = 4 studies, 4391 pregnancies). In conclusion, there is wide variation in SFH measurement and SFH-to-GA conversion techniques. SFH is inaccurate for estimating GA and should not be used for GA dating. Increasing access to quality ultrasonography early in pregnancy should be prioritized to improve gestational age assessment in LMIC.

Abstract Background In developed countries, prenatal maternal stress has been associated with poor fetal growth, however this has not been evaluated in rural sub-Saharan Africa. We evaluated the effect of prenatal maternal stress on fetal growth and birth outcomes in rural Ghana. Methods Leveraging a prospective, rural Ghanaian birth cohort, we ascertained prenatal maternal negative life events, categorized scores as 0-2 (low stress; referent), 3-5 (moderate), and > 5 (high) among 353 pregnant women in the Kintampo North Municipality and Kintampo South District located within the middle belt of Ghana. We employed linear regression to determine associations between prenatal maternal stress and infant birth weight, head circumference, and length. We additionally examined associations between prenatal maternal stress and adverse birth outcome, including low birth weight, small for gestational age, or stillbirth. Effect modification by infant sex was examined. Results In all children, high prenatal maternal stress was associated with reduced birth length (β = − 0.91, p = 0.04; p-value for trend = 0.04). Among girls, moderate and high prenatal maternal stress was associated with reduced birth weight (β = − 0.16, p = 0.02; β = − 0.18, p = 0.04 respectively; p-value for trend = 0.04) and head circumference (β = − 0.66, p = 0.05; β = − 1.02, p = 0.01 respectively; p-value for trend = 0.01). In girls, high prenatal stress increased odds of any adverse birth outcome (OR 2.41, 95% CI 1.01-5.75; p for interaction = 0.04). Sex-specific analyses did not demonstrate significant effects in boys. Conclusions All infants, but especially girls, were vulnerable to effects of prenatal maternal stress on birth outcomes. Understanding risk factors for impaired fetal growth may help develop preventative public health strategies. Trial registration NCT01335490 (prospective registration). Date of Registration: April 14, 2011. Status of Registration: Completed.

ڐ: This survey study was conducted to better consider ways that the Society of Maternal-Fetal Medicine (SMFM) can increase their international outreach. Most survey respondents indicated that international representation could be improved and cited barriers of cost and physical distance to annual meetings. This study highlights support for continuation of virtual conferencing to improve international representation and proposes a hybrid model of scientific engagement moving forward.

Background: Low birth weight and prematurity are important risk factors for death and disability, and may be affected by prenatal exposure to household air pollution (HAP). Methods: We investigate associations between maternal exposure to carbon monoxide (CO) during pregnancy and birth outcomes (birth weight, birth length, head circumference, gestational age, low birth weight, small for gestational age, and preterm birth) among 1288 live-born infants in the Ghana Randomized Air Pollution and Health Study (GRAPHS). We evaluate whether evidence of malaria during pregnancy, as determined by placental histopathology, modifies these associations. Results: We observed effects of CO on birth weight, birth length, and gestational age that were modified by placental malarial status. Among infants from pregnancies without evidence of placental malaria, each 1 ppm increase in CO was associated with reduced birth weight (−53.4 g [95% CI: −84.8, −21.9 g]), birth length (−0.3 cm [−0.6, −0.1 cm]), gestational age (−1.0 days [−1.8, −0.2 days]), and weight-for-age Z score (−0.08 standard deviations [−0.16, −0.01 standard deviations]). These associations were not observed in pregnancies with evidence of placental malaria. Each 1 ppm increase in maternal exposure to CO was associated with elevated odds of low birth weight (LBW, OR 1.14 [0.97, 1.33]) and small for gestational age (SGA, OR 1.14 [0.98, 1.32]) among all infants. Conclusions: Even modest reductions in exposure to HAP among pregnant women could yield substantial public health benefits, underscoring a need for interventions to effectively reduce exposure. Adverse associations with HAP were discernible only among those without evidence of placental malaria, a key driver of impaired fetal growth in this malaria-endemic area.

Background: Parental preconception exposure to select phenols and phthalates was previously associated with increased risk of preterm birth in single chemical analyses. However, the joint effect of phenol and phthalate mixtures on preterm birth is unknown. Methods: We included 384 female and 211 male (203 couples) participants seeking infertility treatment in the Environment and Reproductive Health (EARTH) Study who gave birth to 384 singleton infants between 2005 and 2018. Mean preconception urinary concentrations of bisphenol A (BPA), parabens, and eleven phthalate biomarkers, including di(2-ethylhexyl) phthalate (DEHP) metabolites, were examined. We used principal component analysis (PCA) with log-Poisson regression and Probit Bayesian Kernel Machine Regression (BKMR) with hierarchical variable selection to examine maternal and paternal phenol and phthalate mixtures in relation to preterm birth. Couple-based BKMR model was fit to assess couples’ joint mixtures in relation to preterm birth. Results: PCA identified the same four factors for maternal and paternal preconception mixtures. Each unit increase in PCA scores of maternal (adjusted Risk Ratio (aRR): 1.36, 95%CI: 1.00, 1.84) and paternal (aRR: 1.47, 95%CI: 0.90, 2.42) preconception DEHP-BPA factor was positively associated with preterm birth. Maternal and paternal BKMR models consistently presented the DEHP-BPA factor with the highest group Posterior Inclusion Probability (PIP). BKMR models further showed that maternal preconception BPA and mono(2-ethyl-5-hydroxyhexyl) phthalate, and paternal preconception mono(2-ethylhexyl) phthalate were positively associated with preterm birth when the remaining mixture components were held at their median concentrations. Couple-based BKMR models showed a similar relative contribution of paternal (PIP: 61%) and maternal (PIP: 77%) preconception mixtures on preterm birth. We found a positive joint effect on preterm birth across increasing quantiles of couples’ total mixture concentrations. Conclusion: In this prospective cohort of subfertile couples, maternal BPA and DEHP, and paternal DEHP exposure before conception were positively associated with preterm birth. Both parental windows jointly contributed to the outcome. These results suggest that preterm birth may be a couple-based pregnancy outcome.

Background: Exposure to ionizing radiation has been associated with hypertension, but the relationship between residential radon exposure and hypertensive disorders of pregnancy (HDP) has not been examined. Methods: We used the Massachusetts Birth Registry of Vital Records from 2001 to 2015 including women with a singleton pregnancy without prior hypertension. The binary outcome (HDP) included gestational hypertension and pre-eclampsia cases and was assessed using birth certificate data. We obtained 141,665 basement radon measurements from Spruce Environmental Technologies, Inc. and modeled the monthly zip code basement radon level. We used a logistic regression model adjusted for sociodemographic covariates, maternal comorbidities, PM2.5, season, temperature, and relative humidity. We examined effect modification by maternal age, race, and maternal education as an indicator of socio-economic status. Results: Of 975,528 women, 3.7% (36,530) of them developed HDP. Zip code level radon ranged from 22 to 333 mBq/m3. An interquartile range (IQR) increase in zip code radon level throughout pregnancy was associated with a 15% increase in the odds of HDP (95% CI 13% to 18%). In women less than 20 years old, an IQR increase in zip code level radon was associated with 38% increase in the odds of HDP (95% CI 24% to 50%), while the effect was smaller in older women. There was no effect modification by maternal race or education. Conclusions: In this cohort, higher levels of residential radon are associated with increased odds of HDP. After stratifying by age, this effect was stronger in participants younger than 20 years old. Since the burden of hypertensive disorders of pregnancy is increasing and affects women’s future cardiovascular health, identification of modifiable risk factors is of great importance.

In the past two decades, the Argo Program has collected, processed, and distributed over two million vertical profiles of temperature and salinity from the upper two kilometers of the global ocean. A similar number of subsurface velocity observations near 1,000 dbar have also been collected. This paper recounts the history of the global Argo Program, from its aspiration arising out of the World Ocean Circulation Experiment, to the development and implementation of its instrumentation and telecommunication systems, and the various technical problems encountered. We describe the Argo data system and its quality control procedures, and the gradual changes in the vertical resolution and spatial coverage of Argo data from 1999 to 2019. The accuracies of the float data have been assessed by comparison with high-quality shipboard measurements, and are concluded to be 0.002°C for temperature, 2.4 dbar for pressure, and 0.01 PSS-78 for salinity, after delayed-mode adjustments. Finally, the challenges faced by the vision of an expanding Argo Program beyond 2020 are discussed.

Background: Phenol exposure during pregnancy has been associated with preterm birth, but the potential effect of preconception exposure in either parent is unknown. There is a growing body of evidence to suggest that the preconception period is a critical window of vulnerability for adverse pregnancy outcomes. Objective: We examined whether maternal and paternal preconception urinary concentrations of select phenols were associated with the risk of preterm birth among couples attending fertility care. Methods: The analysis included 417 female and 229 male participants of the Environment and Reproductive Health (EARTH) Study who gave birth to 418 singleton infants between 2005 and 2018 and for whom we had phenol biomarkers quantified in at least one urine sample collected before conception. Mothers and fathers provided an average of 4 and 3 urine samples during the preconception period, respectively. We calculated the geometric mean of bisphenol A (BPA), bisphenol S (BPS), benzophenone-3, triclosan, and the molar sum of parabens (ΣParabens) urinary concentrations to estimate each participant’s preconception exposure. Risk ratios (RRs) of preterm birth (live birth before 37 completed weeks’ gestation) were estimated using modified Poisson regression models adjusted for covariates. Results: The mean (SD) gestational age among singletons was 39.3 (1.7) weeks with 8% born preterm. A natural log-unit increase in maternal preconception BPA (RR 1.94; 95% CI: 1.20, 3.14) and BPS (RR 2.42; 95% CI: 1.01, 5.77) concentration was associated with an increased risk of preterm birth. These associations remained after further adjustment for maternal prenatal and paternal preconception biomarker concentrations. Paternal preconception ΣParabens concentrations showed a possible elevated risk of preterm birth (RR 1.36; 95% CI: 0.94, 1.96). No consistent pattern of association was observed for benzophenone-3 or triclosan biomarkers in either parent. Discussion: Maternal preconception urinary BPA and BPS concentrations, as well as paternal preconception urinary parabens concentrations were prospectively associated with a higher risk of preterm birth. Subfertile couples’ exposure to select phenols during the preconception period may be an unrecognized risk factor for adverse pregnancy outcomes. Keywords: Bisphenol, Paraben, Triclosan, Benzophenone, Preconception, Preterm birth

Summary: Background: We aimed to evaluate and improve the accuracy of the ultrasound scan in estimating gestational age in late pregnancy (ie, after 24 weeks' gestation) in low-income and middle-income countries (LMICs), where access to ultrasound in the first half of pregnancy is rare and where intrauterine growth restriction is prevalent. Methods: This prospective, population-based, cohort study was done in three LMICs (Bangladesh, Pakistan, and Tanzania) participating in the WHO Alliance for Maternal and Newborn Health Improvement study. Women carrying a live singleton fetus dated by crown-rump length (CRL) measurements between 8+0–14+6 weeks of gestation, who were willing to return for two additional ultrasound scans, and who planned on delivering in the study area were enrolled in the study. Participants underwent ultrasonography at 24+0–29+6 weeks and at 30+0–36+6 weeks' gestation. Birthweights were measured within 72 h of birth, and the proportions of infants who had a small-for-gestational-age birthweight (ie, a birthweight

ObjectiveTo improve the accuracy of the prediction of gestational age (GA) before birth with the standardised measurement of symphysis-fundal height (SFH), estimation of uterine volume, and statistical modelling including maternal anthropometrics and other factors.DesignProspective pregnancy cohort study.SettingRural communities in Sylhet, Bangladesh.Participants1516 women with singleton pregnancies with early pregnancy ultrasound dating (37 weeks gestation. An estimated uterine volume (EUV) was calculated from these measures. Data on pregnancy characteristics and other maternal anthropometrics were also collected.Primary outcome measureGA at subsequent ANC visits, as defined by early ultrasound dating.Results1486 (98%) women had at least one subsequent ANC visit, 1102 (74%) women had two subsequent ANC visits, and 748 (50%) had three visits. Using the common clinical practice of approximating the GA (in weeks) with the SFH measurement (cm), SFH systematically underestimated GA in late pregnancy (mean difference −4.4 weeks, 95% limits of agreement −12.5 to 3.7). For the classification of GA

ObjectiveHIV-infected women on antiretroviral therapy have a higher risk of preterm birth than HIV-uninfected women in Botswana. To better understand the mechanism for preterm birth among HIV-infected women, we evaluated whether mid-trimester cervical length differed by HIV status as cervical shortening is associated with an increased risk for preterm birth.MethodsWe conducted a prospective cohort study among pregnant women receiving care at the Scottish Livingstone Hospital in Molepolole, Botswana. Consecutive women referred for routine obstetrical ultrasound were consented and enrolled if between 22w0d and 24w6d by ultrasound biometry. Blinded to maternal HIV status, an obstetrician measured transvaginal cervical length using standardized criteria. Cervical length, as well as the proportion of women with a short cervix (ResultsBetween April 2016 and April 2017, 853 women presenting for obstetric ultrasound were screened, 187 (22%) met eligibility criteria, and 179 (96%) were enrolled. Of those enrolled, 50 (28%) were HIV-infected (86% on antiretroviral therapy), 127 (71%) were HIV-uninfected, and 2 (1%) had unknown HIV status. There was no significant difference in mean cervical length between HIV-infected and HIV-uninfected women (32mm vs 31mm, p = 0.21), or in the proportion with a short cervix (10% vs 14%, p = 0.44). Acceptability data was available for 115 women who underwent a transvaginal ultrasound exam. Of these, 112 of 115 (97%) women deemed the transvaginal scan acceptable.ConclusionsThe increased risk of preterm birth observed among HIV-infected women receiving antiretroviral therapy in Botswana is unlikely associated with mid-trimester cervical shortening. Further research is needed to understand the underlying mechanism for preterm birth among HIV-infected women.

IntroductionHypertensive disorders of pregnancy (HDP) are a leading cause of global perinatal (fetal and neonatal) and maternal morbidity and mortality. We sought to describe HDP and determine the magnitude and risk factors for adverse perinatal and maternal outcomes among women with HDP in southwestern Uganda.MethodsWe prospectively enrolled pregnant women admitted for delivery and diagnosed with HDP at a tertiary referral hospital in southwestern Uganda from January 2019 to November 2019, excluding women with pre-existing hypertension. The participants were observed and adverse perinatal and maternal outcomes were documented. We used multivariable logistic regression models to determine independent risk factors associated with adverse perinatal and maternal outcomes.ResultsA total of 103 pregnant women with a new-onset HDP were enrolled. Almost all women, 93.2% (n = 96) had either pre-eclampsia with severe features or eclampsia. The majority, 58% (n = 60) of the participants had an adverse perinatal outcome (36.9% admitted to the neonatal intensive care unit (ICU), 20.3% stillbirths, and 1.1% neonatal deaths). Fewer participants, 19.4% (n = 20) had an adverse maternal outcome HELLP syndrome (7.8%), ICU admission (3%), and postpartum hemorrhage (3%). In adjusted analyses, gestational age of < 34 weeks at delivery and birth weight ConclusionAmong women with HDP at our institution, majority had preeclampsia with severe symptoms or eclampsia and an unacceptably high rate of adverse perinatal and maternal outcomes; over a fifth of the mothers experiencing stillbirth. This calls for improved antenatal surveillance of women with HDP and in particular improved neonatal and maternal critical care expertise at delivering facilities. Earlier detection and referral, as well as improvement in initial management at lower level health units and on arrival at the referral site is imperative.

Abstract Background There is a paucity of recent prospective data on the incidence of postpartum infections and associated risk factors in sub-Saharan Africa. Retrospective studies estimate that puerperal sepsis causes approximately 10% of maternal deaths in Africa. Methods We enrolled 4231 women presenting to a Ugandan regional referral hospital for delivery or postpartum care into a prospective cohort and measured vital signs postpartum. Women developing fever (> 38.0 °C) or hypothermia (

Abstract Background Limited qualitative research has been performed in India to investigate views and behaviours of pregnant women regarding malaria despite the threat of malaria-related adverse maternal and neonatal outcomes. To address this gap, a comprehensive study on malaria prevention and treatment attitudes, knowledge and behaviour among pregnant women in India was conducted. Methods Pregnant women and healthcare workers (HCWs), encompassing clinic-based providers, traditional birth attendants, and auxiliary nurse-midwives were enrolled for in-depth interviews (IDIs) at 7 hospital sites and nearby communities in Jharkhand and Chhattisgarh States. Questions addressed health concerns and attitudes, knowledge and practices regarding malaria prevention and treatment; probing covered modern and traditional approaches. Data were analyzed using a thematic approach. Results A total of 83 pregnant women and 119 HCWs participated in 202 IDIs, 90 in Jharkhand and 112 in Chhattisgarh. A majority of Jharkhand respondents, but only one-fourth in Chhattisgarh, named malaria among top health issues for pregnant women. Just over half of pregnant women were willing to try new prevention methods (especially insecticide-treated bed nets), although cost-related barriers to such methods were stressed. Most respondents voiced concerns about malaria treatment during pregnancy, mainly citing potential harm to the baby. Most knew that mosquitoes transmitted malaria, but a substantial minority, including among HCWs, described incorrect transmission modes. Most knew a proven prevention method (usually bed nets or coils); a few knew other methods. A minority of pregnant women, but most HCWs, knew about malaria treatment, although some HCWs described unproven treatments. Most respondents described use of modern prevention methods in their communities, typically bed nets, although probing revealed irregular use. Half (especially in Jharkhand and particularly HCWs) described use of traditional prevention approaches such as burning leaves and rubbing oils on the body; traditional remedies for malaria treatment were common, and varied by site and population. Conclusions Understanding of malaria varied as a concern for pregnant women, continued use of unproven malaria prevention and treatment strategies was evident in this population in India. These results highlight the need to educate both pregnant women and HCWs about effective malaria methods to protect pregnant women and their babies from malaria.

Arundoss Gangadharan,1 Paul McCoy,2 Aye Phyo,1 Michael P McGuigan,3 Poonam Dharmaraj,1 Renuka Ramakrishnan,1 Paul S McNamara,2,4 Joanne Blair1 1Department of Endocrinology, 2Department of Respiratory Medicine, Alder Hey Children’s Hospital, Liverpool, 3Department of Paediatrics, Countess of Chester Hospital NHS Foundation Trust, 4Institute in the Park, University of Liverpool, Alder Hey Children’s Hospital, Liverpool, UK Objective: To describe recovery of adrenal insufficiency in asthmatic children treated with inhaled corticosteroids (ICS) and cortisol replacement therapy.Design: Retrospective, observational study.Patients: A total of 113 patients, 74 male; age 10.4 (3.3–16.5) years; beclomethasone-­equivalent ICS dose, 800 µg, (100–1,000), tested by low dose short Synacthen (tetracosactide) test (LDSST), were studied. Test results were classified by basal and peak cortisol concentration: “normal” (basal >100 nmol/L, peak >500 nmol/L), “suboptimal” (basal >100 nmol/L, peak 350–499 nmol/L), “abnormal” (basal 15% [2× the inter-assay coefficient of variation]), change in BMI and height standard deviation score (SDS).Results: Baseline test results were abnormal in 17 patients (15%) and all of them had repeat tests. In 13 patients (76%), test results improved (normal in six, suboptimal in seven) and four (24%) remained abnormal. Baseline tests results were suboptimal in 54 patients (48%), of whom 50 (93%) were retested. Repeat tests were normal in 36 patients (72%), remained suboptimal in 11 (22%), and were abnormal in three (6%). Baseline tests results were normal in 42 patients, of whom six patients (14%) were retested. Results remained normal in three (50%), were suboptimal in two (33%), and abnormal in one (17%). Basal and peak cortisol levels increased by >15% in 33/73 (45%) and 42/73 (57%) patients, respectively, and decreased by >15% in 14/73 (19%) and 7/73 (10%), respectively. There was no significant change in height or BMI SDS.Conclusion: Recovery of adrenal function is common and occurs during continued ICS and cortisol replacement therapy. Keywords: HPA axis recovery, adrenal suppression, childhood asthma, inhaled steroids (ICS), LDSST

This single-center retrospective study of invasive fungal disease (IFD) enrolled 251 adult patients undergoing induction chemotherapy for newly diagnosed acute myeloid leukemia (AML) from 2014–2019. Patients had primary AML (n = 148, 59%); antecedent myelodysplastic syndrome (n = 76, 30%), or secondary AML (n = 27, 11%). Seventy-five patients (30%) received an allogeneic hematopoietic cell transplant within the first year after induction chemotherapy. Proven/probable IFD occurred in 17 patients (7%). Twelve of the 17 (71%) were mold infections, including aspergillosis (n = 6), fusariosis (n = 3), and mucomycosis (n = 3). Eight breakthrough IFD (B-IFD), seven of which were due to molds, occurred in patients taking antifungal prophylaxis. Patients with proven/probable IFD had a significantly greater number of cumulative neutropenic days than those without an IFD, HR = 1.038 (95% CI 1.018–1.059), p = 0.0001. By cause-specific proportional hazards regression, the risk for IFD increased by 3.8% for each day of neutropenia per 100 days of follow up. Relapsed/refractory AML significantly increased the risk for IFD, HR = 7.562 (2.585–22.123), p = 0.0002, and Kaplan-Meier analysis showed significantly higher mortality at 1 year in patients who developed a proven/probable IFD, p = 0.02. IFD remains an important problem among patients with AML despite the use of antifungal prophylaxis, and development of IFD is associated with increased mortality in these patients.

Abstract Background Repeated exposure to household air pollution may intermittently raise blood pressure (BP) and affect cardiovascular outcomes. We investigated whether hourly carbon monoxide (CO) exposures were associated with acute increases in ambulatory blood pressure (ABP); and secondarily, if switching to an improved cookstove was associated with BP changes. We also evaluated the feasibility of using 24-h ambulatory blood pressure monitoring (ABPM) in a cohort of pregnant women in Ghana. Methods Participants were 44 women enrolled in the Ghana Randomized Air Pollution and Health Study (GRAPHS). For 27 of the women, BP was measured using 24-h ABPM; home blood pressure monitoring (HBPM) was used to measure BP in the remaining 17 women. Personal CO exposure monitoring was conducted alongside the BP monitoring. Results ABPM revealed that peak CO exposure (defined as ≥4.1 ppm) in the 2 hours prior to BP measurement was associated with elevations in hourly systolic BP (4.3 mmHg [95% CI: 1.1, 7.4]) and diastolic BP (4.5 mmHg [95% CI: 1.9, 7.2]), as compared to BP following lower CO exposures. Women receiving improved cookstoves had lower post-intervention SBP (within-subject change in SBP of −2.1 mmHg [95% CI: -6.6, 2.4] as compared to control), though this result did not reach statistical significance. 98.1% of expected 24-h ABPM sessions were successfully completed, with 92.5% of them valid according to internationally defined criteria. Conclusions We demonstrate an association between acute exposure to carbon monoxide and transient increases in BP in a West African setting. ABPM shows promise as an outcome measure for assessing cardiovascular health benefits of cookstove interventions. Trial registration The GRAPHS trial was registered with clinicaltrials.gov on 13 April 2011 with the identifier NCT01335490 .

Abstract Background Over 3 million stillbirths occur annually in sub Saharan Africa; most occur intrapartum and are largely preventable. The standard of care for fetal heart rate (FHR) assessment in most sub-Saharan African settings is a Pinard Stethoscope, limiting observation to one person, at one point in time. We aimed to test the functionality and acceptability of a wireless FHR monitor that could allow for expanded monitoring capacity in rural Southwestern Uganda. Methods In a mixed method prospective study, we enrolled 1) non-laboring healthy term pregnant women to wear the device for 30 min and 2) non-study clinicians to observe its use. The battery-powered prototype uses Doppler technology to measure fetal cardiotocographs (CTG), which are displayed via an android device and wirelessly transmit to cloud storage where they are accessible via a password protected website. Prototype functionality was assessed by the ability to obtain and transmit a 30-min CTG. Three obstetricians independently rated CTGs for readability and agreement between raters was calculated. All participants completed interviews on acceptability. Results Fifty pregnant women and 7 clinicians were enrolled. 46 (92.0%) CTGs were successfully recorded and stored. Mean scores for readability were 4.71, 4.71 and 4.83 (out of 5) with high agreement (intra class correlation 0.84; 95% CI 0.74 to 0.91). All pregnant women reported liking or really liking the device, as well as high levels of comfort, flexibility and usefulness of the prototype; all would recommend it to others. Clinicians described the prototype as portable, flexible, easy-to-use and a time saver. Adequate education for clinicians and women also seemed to improve correct usage and minimise concerns on safety of the device. Conclusions This prototype wireless FHR monitor functioned well in a low-resource setting and was found to be acceptable and useful to both pregnant women and clinicians. The device also seemed to have potential to improve the experience of the users compared with standard of care and expand monitoring capacity in settings where bulky, wired or traditional equipment are unreliable. Further research needs to investigate the potential impact and cost of such innovations to improve perinatal outcomes.

Abstract Background Specialized cardiology services have contributed to reduced mortality in acute coronary syndromes (ACS). We sought to evaluate the outcomes of ACS patients admitted to non-cardiology services in Southern Alberta. Methods Retrospective chart review performed on all troponin-positive patients in the Calgary Health Region identified those diagnosed with ACS by their attending team. Patients admitted to non-cardiology and cardiology services were compared, using linked data from the Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH) registry and the Strategic Clinical Network for Cardiovascular Health and Stroke. Results From January 1, 2007 to December 31, 2008, 2105 ACS patients were identified, with 1636 (77.7%) admitted to cardiology and 469 (22.3%) to non-cardiology services. Patients admitted to non-cardiology services were older, had more comorbidities, and rarely received cardiology consultation (5.1%). Cardiac catheterization was underutilized (5.1% vs 86.4% in cardiology patients (p

Climate change impacts on fisheries will undoubtedly have socio-economic impacts on coastal communities and the seafood market. However, it is a challenge to integrate climate change information in a form that can be used efficiently by adaptation planners, policy makers, and fishery managers. In this study, we frame a climate change impact assessment using a geographical perspective based on the management units of the dominant fishery, in this case, American lobster in Nova Scotia, Canada. The information considered here includes economic dependence on the fishery, population size, diversity of the fishery revenue, status of harbor infrastructure, total replacement cost of each harbor, increased relative sea level and flooding, and the vulnerability of offshore lobster to ocean warming and changes in zooplankton composition and anticipatory changes in fishery productivity across management borders. Using two ocean models to provide multi-decadal scale projections of bottom temperature, changes in offshore lobster distribution are projected to have a neutral, or positive impact on the region as a whole. However, when lobster vulnerability is combined with climate change related vulnerabilities of coastal fishing communities, it is evident that adaptation planning is needed for long-term sustainability. This impact assessment provides both a framework and information for further in-depth analyses by climate change adaptation planners and fishery managers.