Insulin-regulated serine and lipid metabolism drive peripheral neuropathy.

Diabetes represents a spectrum of disease in which metabolic dysfunction damages multiple organ systems including liver, kidneys and peripheral nerves1,2. Although the onset and progression of these co-morbidities are linked with insulin resistance, hyperglycaemia and dyslipidaemia3-7, aberrant non-essential amino acid (NEAA) metabolism also contributes to the pathogenesis of diabetes8-10. Serine and glycine are closely related NEAAs whose levels are consistently reduced in patients with metabolic syndrome10-14, but the mechanistic drivers and downstream consequences of this metabotype remain unclear. Low systemic serine and glycine are also emerging as a hallmark of macular and peripheral nerve disorders, correlating with impaired visual acuity and peripheral neuropathy15,16. Here we demonstrate that aberrant serine homeostasis drives serine and glycine deficiencies in diabetic mice, which can be diagnosed with a serine tolerance test that quantifies serine uptake and disposal. Mimicking these metabolic alterations in young mice by dietary serine or glycine restriction together with high fat intake markedly accelerates the onset of small fibre neuropathy while reducing adiposity. Normalization of serine by dietary supplementation and mitigation of dyslipidaemia with myriocin both alleviate neuropathy in diabetic mice, linking serine-associated peripheral neuropathy to sphingolipid metabolism. These findings identify systemic serine deficiency and dyslipidaemia as novel risk factors for peripheral neuropathy that may be exploited therapeutically.

Glycocalyx engineering with heparan sulfate mimetics attenuates Wnt activity during adipogenesis to promote glucose uptake and metabolism.

Adipose tissue plays a crucial role in maintaining metabolic homeostasis by storing lipids and glucose from circulation as intracellular fat. As peripheral tissues like adipose tissue become insulin resistant, decompensation of blood glucose levels occurs causing type 2 diabetes (T2D). Currently, modulating the glycocalyx, a layer of cell-surface glycans, is an underexplored pharmacological treatment strategy to improve glucose homeostasis in T2D patients. Here, we show a novel role for cell-surface heparan sulfate (HS) in establishing glucose uptake capacity and metabolic utilization in differentiated adipocytes. Using a combination of chemical and genetic interventions, we identified that HS modulates this metabolic phenotype by attenuating levels of Wnt signaling during adipogenesis. By engineering, the glycocalyx of pre-adipocytes with exogenous synthetic HS mimetics, we were able to enhance glucose clearance capacity after differentiation through modulation of Wnt ligand availability. These findings establish the cellular glycocalyx as a possible new target for therapeutic intervention in T2D patients by enhancing glucose clearance capacity independent of insulin secretion.

CAR and CSTR Cardiac Computed Tomography (CT) Practice Guidelines: Part 2-Non-Coronary Imaging.

The cardiac computed tomography (CT) practice guidelines provide an updated review of the technological improvements since the publication of the first Canadian Association of Radiologists (CAR) cardiac CT practice guidelines in 2009. An overview of the current evidence supporting the use of cardiac CT in the most common clinical scenarios, standards of practice to optimize patient preparation and safety as well as image quality are described. Coronary CT angiography (CCTA) is the focus of Part I. In Part II, an overview of cardiac CT for non-coronary indications that include valvular and pericardial imaging, tumour and mass evaluation, pulmonary vein imaging, and imaging of congenital heart disease for diagnosis and treatment monitoring are discussed. The guidelines are intended to be relevant for community hospitals and large academic centres with established cardiac CT imaging programs.

CAR and CSTR Cardiac Computed Tomography (CT) Practice Guidelines: Part 1 Coronary CT Angiography (CCTA).

Imaging the heart is one of the most technically challenging applications of Computed Tomography (CT) due to the presence of cardiac motion limiting optimal visualization of small structures such as the coronary arteries. Electrocardiographic gating during CT data acquisition facilitates motion free imaging of the coronary arteries. Since publishing the first version of the Canadian Association of Radiologists (CAR) cardiac CT guidelines, many technological advances in CT hardware and software have emerged necessitating an update. The goal of these cardiac CT practice guidelines is to present an overview of the current evidence supporting the use of cardiac CT in various clinical scenarios and to outline standards of practice for patient safety and quality of care when establishing a cardiac CT program in Canada.

CETARS/CAR Practice Guideline on Imaging the Pregnant Trauma Patient.

Imaging of pregnant patients who sustained trauma often causes fear and confusion among patients, their families, and health care professionals regarding the potential for detrimental effects from radiation exposure to the fetus. Unnecessary delays or potentially harmful avoidance of the justified imaging studies may result from this understandable anxiety. This guideline was developed by the Canadian Emergency, Trauma and Acute Care Radiology Society (CETARS) and the Canadian Association of Radiologists (CAR) Working Group on Imaging the Pregnant Trauma Patient, informed by a literature review as well as multidisciplinary expert panel opinions and discussions. The working group included academic subspecialty radiologists, a trauma team leader, an emergency physician, and an obstetriciangynaecologist/maternal fetal medicine specialist, who were brought together to provide updated, evidence-based recommendations for the imaging of pregnant trauma patients, including patient safety aspects (eg, radiation and contrast concerns) and counselling, initial imaging in maternal trauma, specific considerations for the use of fluoroscopy, angiography, and magnetic resonance imaging. The guideline strives to achieve clarity and prevent added anxiety in an already stressful situation of injury to a pregnant patient, who should not be imaged differently.

Directive clinique no 443b : Opioïdes aux différentes étapes de la vie des femmes : Grossesse et allaitement.

OBJECTIF: Présenter aux professionnels de la santé les données probantes concernant l'utilisation des opioïdes et la santé des femmes. Les domaines d'intérêt sont la grossesse et les soins post-partum. POPULATION CIBLE: Toutes les femmes qui utilisent des opioïdes. RéSULTATS: Un dialogue ouvert et éclairé sur l'utilisation des opioïdes améliorera les soins aux patientes. BéNéFICES, RISQUES ET COûTS: L'exploration de l'utilisation d'opioïdes par une approche tenant compte des traumatismes antérieurs donne au professionnel de la santé et à la patiente l'occasion de bâtir une alliance solide, collaborative et thérapeutique. Cette alliance permet aux femmes de faire des choix éclairés. Elle favorise le diagnostic et le traitement possible du trouble lié à l'utilisation d'opioïdes. L'utilisation ne doit pas être stigmatisée, puisque la stigmatisation affaiblit le partenariat (le partenariat entre patiente et professionnel de la santé). Les professionnels de la santé ceus-ci doivent comprendre l'effet potentiel des opioïdes sur la santé les femmes enceintes et les aider à prendre des décisions éclairées sur leur santé. DONNéES PROBANTES: Une recherche a été conçue puis effectuée dans les bases de données PubMed et Cochrane Library pour la période d'août 2018 à mars 2023 des termes MeSH et mots clés suivants (et variantes) : opioids, opioid agonist therapy, illicit drugs, fertility, pregnancy, fetal development, neonatal abstinence syndrome et breastfeeding. MéTHODES DE VALIDATION: Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant le cadre méthodologique GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). Voir l'annexe A en ligne (tableau A1 pour les définitions et tableau A2 pour l'interprétation des recommandations fortes et conditionnelles [faibles]). PROFESSIONNELS CONCERNéS: Tous les professionnels de la santé qui prodiguent des soins aux femmes et aux nouveaux-nés. RéSUMé POUR TWITTER: La consommation d'opioïdes pendant la grossesse coïncide souvent avec des problèmes de santé mentale et est associée à des conséquences néfastes pour la mère, le fœtus et le nouveau-né ; le traitement des troubles liés à la consommation d'opioïdes par agonistes peut être sûr pendant la grossesse lorsque les risques sont plus nombreux que les avantages. DÉCLARATIONS SOMMAIRES: RECOMMANDATIONS.

Guideline No. 443a: Opioid Use Throughout Women's Lifespan: Fertility, Contraception, Chronic Pain, and Menopause.

OBJECTIVE: To provide health care providers with the best evidence on opioid use and women's health. Areas of focus include general patterns of opioid use and safety of use; care of women who use opioids; stigma, screening, brief intervention, and referral to treatment; hormonal regulation; reproductive health, including contraception and fertility; sexual function; perimenopausal and menopausal symptoms; and chronic pelvic pain syndromes. TARGET POPULATION: The target population includes all women currently using or contemplating using opioids. OUTCOMES: Open, evidence-informed dialogue about opioid use will lead to improvements in patient care and overall health. BENEFITS, HARMS, AND COSTS: Exploring opioid use through a trauma-informed approach offers the health care provider and patient with an opportunity to build a strong, collaborative, and therapeutic alliance. This alliance empowers women to make informed choices about their own care. It also allows for the diagnosis and possible treatment of opioid use disorders. Use should not be stigmatized, as stigma leads to poor "partnered care" (i.e., the partnership between the patient and care provider). Therefore, health care providers and patients must understand the potential role of opioids in women's health (both positive and negative) to ensure informed decision-making. EVIDENCE: A literature search was designed and carried out in PubMed and the Cochrane Library databases from August 2018 until March 2023 using following MeSH terms and keywords (and variants): opioids, illicit drugs, fertility, pregnancy, breastfeeding, and aging. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations). INTENDED AUDIENCE: All health care providers who care for women. TWEETABLE ABSTRACT: Opioid use can affect female reproductive function; health care providers and patients must understand the potential role of opioids in women's health to ensure informed decision-making. SUMMARY STATEMENTS: RECOMMENDATIONS.

Guideline No. 443b: Opioid Use Throughout Women's Lifespan: Opioid Use in Pregnancy and Breastfeeding.

OBJECTIVE: To provide health care providers the best evidence on opioid use and women's health. Areas of focus include pregnancy and postpartum care. TARGET POPULATION: The target population includes all women currently using or contemplating using opioids. OUTCOMES: Open, evidence-informed dialogue about opioid use will improve patient care. BENEFITS, HARMS, AND COSTS: Exploring opioid use through a trauma-informed approach provides the health care provider and patient with an opportunity to build a strong, collaborative, and therapeutic alliance. This alliance empowers women to make informed choices about their own care. It also allows for the diagnosis and possible treatment of opioid use disorders. Opioid use should not be stigmatized, as stigma leads to poor "partnered care" (i.e., the partnership between the patient and care provider). Health care providers need to understand the effect opioids can have on pregnant women and support them to make knowledgeable decisions about their health. EVIDENCE: A literature search was designed and carried out in PubMed and the Cochrane Library databases from August 2018 until March 2023 using following MeSH terms and keywords (and variants): opioids, opioid agonist therapy, illicit drugs, fertility, pregnancy, fetal development, neonatal abstinence syndrome, and breastfeeding. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional [weak] recommendations). INTENDED AUDIENCE: All health care providers who care for pregnant and/or post-partum women and their newborns. TWEETABLE ABSTRACT: Opioid use during pregnancy often co-occurs with mental health issues and is associated with adverse maternal, fetal, and neonatal outcomes; treatment of opioid use disorder with agonist therapy for pregnant women can be safe during pregnancy where the risks outnumber the benefits. SUMMARY STATEMENTS: RECOMMENDATIONS.

Regulation of substrate utilization by the mitochondrial pyruvate carrier.

Pyruvate lies at a central biochemical node connecting carbohydrate, amino acid, and fatty acid metabolism, and the regulation of pyruvate flux into mitochondria represents a critical step in intermediary metabolism impacting numerous diseases. To characterize changes in mitochondrial substrate utilization in the context of compromised mitochondrial pyruvate transport, we applied (13)C metabolic flux analysis (MFA) to cells after transcriptional or pharmacological inhibition of the mitochondrial pyruvate carrier (MPC). Despite profound suppression of both glucose and pyruvate oxidation, cell growth, oxygen consumption, and tricarboxylic acid (TCA) metabolism were surprisingly maintained. Oxidative TCA flux was achieved through enhanced reliance on glutaminolysis through malic enzyme and pyruvate dehydrogenase (PDH) as well as fatty acid and branched-chain amino acid oxidation. Thus, in contrast to inhibition of complex I or PDH, suppression of pyruvate transport induces a form of metabolic flexibility associated with the use of lipids and amino acids as catabolic and anabolic fuels.

Tracing compartmentalized NADPH metabolism in the cytosol and mitochondria of mammalian cells.

Eukaryotic cells compartmentalize biochemical processes in different organelles, often relying on metabolic cycles to shuttle reducing equivalents across intracellular membranes. NADPH serves as the electron carrier for the maintenance of redox homeostasis and reductive biosynthesis, with separate cytosolic and mitochondrial pools providing reducing power in each respective location. This cellular organization is critical for numerous functions but complicates analysis of metabolic pathways using available methods. Here we develop an approach to resolve NADP(H)-dependent pathways present within both the cytosol and the mitochondria. By tracing hydrogen in compartmentalized reactions that use NADPH as a cofactor, including the production of 2-hydroxyglutarate by mutant isocitrate dehydrogenase enzymes, we can observe metabolic pathway activity in these distinct cellular compartments. Using this system we determine the direction of serine/glycine interconversion within the mitochondria and cytosol, highlighting the ability of this approach to resolve compartmentalized reactions in intact cells.

Guideline No. 425a: Cannabis Use Throughout Women's Lifespans - Part 1: Fertility, Contraception, Menopause, and Pelvic Pain.

OBJECTIVE: To provide health care providers with the best evidence on cannabis use with respect to women's health. Areas of focus include general patterns of cannabis use as well as safety of use; care for women who use cannabis; stigma; screening, brief intervention, and referral to treatment; impact on hormonal regulation; reproductive health, including contraception and fertility; sexual function; effects on perimenopausal and menopausal symptoms; and use in chronic pelvic pain syndromes. TARGET POPULATION: The target population includes all women currently using or contemplating using cannabis. OUTCOMES: Open, evidence-informed dialogue about cannabis use, which will lead to improvement in patient care. BENEFITS, HARMS, AND COSTS: Exploring cannabis use through a trauma-informed approach provides the health care provider and patient with an opportunity to build a strong, collaborative, therapeutic alliance. This alliance empowers women to make informed choices about their own care. It also allows for the diagnosis and possible treatment of cannabis use disorders. Use should not be stigmatized, as stigma leads to poor "partnered care" (i.e., the partnership between the patient and care provider). Multiple side effects of cannabis use may be mistaken for other disorders. Currently, use of cannabis to treat women's health issues is not covered by public funding; as a result, individual users must pay the direct cost. The indirect costs of cannabis use are unknown. Thus, health care providers and patients must understand the role of cannabis in women's health issues, so that women can make knowledgeable decisions. EVIDENCE: PubMed, EMBASE, and grey literature were searched to identify studies of "cannabis use and effect on infertility, contraception, perimenopause and menopausal symptoms, and pelvic pain" published between January 1, 2018 and February 18, 2021. All clinical trials, observational studies, reviews (including systematic reviews and meta-analyses), guidelines, and conference consensus statements were included. Publications were screened for relevance. The search terms were developed using the Medical Subject Headings (MeSH) terms and keywords (and variants), including cannabis, cannabinoids, marijuana, dexanabinol, dronabinol, tetrahydrocannabinol; the specific terms to capture women's health were estrogen, estradiol, medroxyprogesterone acetate, vaginal contraception, oral contraceptives, fertilization, amenorrhea, oligomenorrhea, pelvic pain, dysmenorrhea, endometriosis, interstitial cystitis, vulvodynia, and menopause. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations). INTENDED AUDIENCE: All heath care providers who care for women. SUMMARY STATEMENTS: RECOMMENDATIONS.

Directive clinique no 425a : Le cannabis aux différentes périodes de la vie des femmes - Partie 1 : Fertilité, contraception, ménopause et douleur pelvienne.

OBJECTIF: Fournir aux fournisseurs de soins de santé les meilleures données probantes sur l'utilisation de cannabis et la santé des femmes. Les domaines d'intérêt sont : les profils généraux d'utilisation du cannabis ainsi que la sécurité de la consommation; les soins aux femmes qui utilisent le cannabis; la stigmatisation; le dépistage, l'intervention brève et l'orientation vers le traitement; les effets sur la régulation hormonale; la santé reproductive, y compris la contraception et la fertilité; la fonction sexuelle; les effets sur les symptômes périménopausiques et postménopausiques; et l'utilisation dans le traitement des syndromes de douleur pelvienne chronique. POPULATION CIBLE: La population cible comprend toutes les femmes qui consomment ou utilisent du cannabis ou qui envisagent de le faire. RéSULTATS: Un dialogue ouvert et fondé sur des données probantes relativement à l'utilisation et la consommation de cannabis, dialogue qui mènera à l'amélioration des soins aux patientes. BéNéFICES, RISQUES ET COûTS: L'exploration de l'utilisation et de la consommation de cannabis par une approche basée sur la connaissance des traumatismes donne l'occasion au fournisseur de soins et à la patiente de créer une solide alliance thérapeutique collaborative. Cette alliance permet aux femmes de faire des choix éclairés sur leurs propres soins. Elle facilite également le diagnostic et le traitement possible des troubles de l'usage du cannabis. Il ne faut pas stigmatiser la consommation, car la stigmatisation nuit à l'alliance thérapeutique (c'est-à-dire le partenariat entre la patiente et le fournisseur de soins). Plusieurs effets indésirables de la consommation de cannabis peuvent être confondus avec d'autres problèmes de santé. À l'heure actuelle, l'utilisation du cannabis pour traiter les problèmes de santé féminine n'est pas financée par le secteur public; par conséquent, les utilisatrices doivent assumer les coûts directs. Les coûts indirects de l'utilisation de cannabis sont inconnus. Ainsi, les fournisseurs de soins et les patientes doivent comprendre le rôle du cannabis dans les problèmes de santé féminine de sorte que les femmes puissent prendre des décisions éclairées. DONNéES PROBANTES: Des recherches ont été effectuées dans PubMed, Embase et la littérature grise pour recenser des études publiées entre le 1er janvier 2018 et le 18 février 2021 concernant l'utilisation du cannabis et ses effets sur l'infertilité, la contraception, les symptômes périménopausiques et postménopausiques et la douleur pelvienne. Toutes les publications des types suivants ont été incluses : essais cliniques, études observationnelles, revues (y compris les revues systématiques et les méta-analyses), directives cliniques et déclarations de conférences de consensus. Un survol des publications a été effectué pour en confirmer la pertinence. Les termes de recherche ont été définis à l'aide des termes MeSH (Medical Subject Headings) et mots clés (et variantes) suivants : cannabis, cannabinoids, marijuana, dexanabinol, dronabinol et tetrahydrocannabinol. À ces termes ont été combinés les termes suivants afin de cerner la santé des femmes : estrogen, estradiol, medroxyprogesterone acetate, vaginal contraception, oral contraceptives, fertilization, amenorrhea, oligomenorrhea, pelvic pain, dysmenorrhea, endometriosis, interstitial cystitis, vulvodynia et menopause. MéTHODES DE VALIDATION: Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant l'approche d'évaluation, de développement et d'évaluation (GRADE). Voir l'annexe A en ligne (tableau A1 pour les définitions et tableau A2 pour l'interprétation des recommandations fortes et faibles). PROFESSIONNELS CONCERNéS: Tous les fournisseurs de soins de santé qui prodiguent des soins aux femmes. DÉCLARATIONS SOMMAIRES: RECOMMANDATIONS.

Guideline No. 425b: Cannabis Use Throughout Women's Lifespans - Part 2: Pregnancy, the Postnatal Period, and Breastfeeding.

OBJECTIVE: To provide health care providers with the best evidence on cannabis use and women's health. Areas of focus include screening, dependence, and withdrawal; communication and documentation; pregnancy (including maternal and fetal outcomes); maternal pain control; postpartum care (including second-hand smoking and parenting); and breastfeeding. TARGET POPULATION: The target population includes women who are planning a pregnancy, pregnant, or breastfeeding. BENEFITS, HARMS, AND COSTS: Discussing cannabis use with women who are planning a pregnancy, pregnant, or breastfeeding allows them to make informed choices about their cannabis use. Based on the limited evidence, cannabis use in pregnancy or while breastfeeding should be avoided, or reduced as much as possible if abstaining is not feasible, given the absence of safety and long-term follow up data on cannabis-exposed pregnancies and infants. EVIDENCE: PubMed and Cochrane Library databases were searched for articles relevant to cannabis use during pregnancy and breastfeeding published between January 1, 2018, and February 5, 2021. The search terms were developed using the MeSH terms and keywords and their variants, including cannabis, cannabinoids, cannabidiol, CBD, THC, marijuana, edible, pregnancy, pregnant, prenatal, perinatal, postnatal, breastfeed, breastfed, lactation, nursing, fetus, fetal, neonatal, newborn, and child. In terms of publication type, all clinical trials, observational studies, reviews (including systematic reviews and meta-analyses), guidelines, and conference consensus statements were included. The main inclusion criteria were pregnant and breastfeeding women as the target population, and exposure to cannabis as the intervention of interest. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations). INTENDED AUDIENCE: All health care providers who care for women of reproductive age. SUMMARY STATEMENTS: RECOMMENDATIONS.

Directive clinique no 425b : Le cannabis aux différentes périodes de la vie des femmes - Partie 2 : Grossesse, période postnatale et allaitement.

OBJECTIF: Fournir aux fournisseurs de soins les meilleures données probantes sur l'utilisation de cannabis et la santé des femmes. Les domaines d'intérêt sont le dépistage, la dépendance et le sevrage; la communication et la tenue de dossier; la grossesse (y compris les issues fœtales et maternelles); la gestion de la douleur maternelle; les soins postnataux (y compris la fumée secondaire et la parentalité); et l'allaitement. POPULATION CIBLE: Femmes enceintes, allaitantes ou qui planifient une grossesse. BéNéFICES, RISQUES ET COûTS: Discuter de l'utilisation de cannabis avec les femmes enceintes, allaitantes ou qui planifient une grossesse les aide à faire des choix éclairés. D'après des données probantes limitées, il faut éviter l'utilisation de cannabis pendant la grossesse ou l'allaitement, ou réduire la consommation au maximum si l'abstention n'est pas un objectif atteignable, étant donné l'absence de données sur l'innocuité et le suivi à long terme des grossesses et nourrissons exposés au cannabis. DONNéES PROBANTES: Les auteurs ont interrogé les bases de données PubMed et Cochrane Library pour extraire des articles sur l'utilisation de cannabis pendant la grossesse et l'allaitement publiés entre le 1er janvier 2018 et le 5 février 2021. Les termes de recherche ont été déterminés à partir de termes de recherche MeSH, de mots clés et de leurs variantes : cannabis, cannabinoids, cannabidiol, CBD, THC, marijuana, edible, pregnancy, pregnant, prenatal, perinatal, postnatal, breastfeed, breastfed, lactation, nursing, fetus, fetal, neonatal, newborn et child. Les auteurs ont inclus toutes les publications des types suivants : essais cliniques, études observationnelles, revues (y compris les revues systématiques et les méta-analyses), directives cliniques et déclarations de conférences de consensus. Les principaux critères d'inclusion étaient les femmes enceintes et allaitantes, comme population cible, et l'exposition au cannabis, comme intervention d'intérêt. MéTHODES DE VALIDATION: Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant le cadre méthodologique d'évaluation, de développement et d'évaluation (GRADE). Voir l'annexe A en ligne (tableau A1 pour les définitions et tableau A2 pour l'interprétation des recommandations fortes et faibles). PROFESSIONNELS CONCERNéS: Tous les fournisseurs de soins de santé qui prodiguent des soins aux femmes en âge de procréer. DÉCLARATIONS SOMMAIRES: RECOMMANDATIONS.

Vaping During Pregnancy: What Are the Potential Health Outcomes and Perceptions Pregnant Women Have?

The prevalence of electronic nicotine delivery systems, such as vaping, is a growing public health concern, and there is limited information on the use of these devices during pregnancy. The objective of this rapid review was to summarize the available literature on human studies of the potential maternal or fetal health effects of vaping or women's perceptions of vaping during pregnancy. A systematic search was completed in the following databases: Medline, EMBASE, Scopus, Web of Science, and CINAHL. A search strategy was developed combining the terms pregnancy and vaping. Findings were divided into two groups and summarized as: 1) Health outcomes following vaping during pregnancy; and 2) Perceptions pregnant women have related to vaping during pregnancy. A total of 760 articles were retrieved and, after applying the inclusion/exclusion criteria and screening, 19 studies were included. Five included studies provided evidence on potential health outcomes and 14 were focused on perceptions. There is emerging evidence that vaping during pregnancy may increase the risk of small for gestational age newborns. Pregnant women generally report that they used vaping products during pregnancy for smoking cessation and perceived that this was a healthier alternative to traditional cigarettes. Overall, there was consensus that there is a lack of information on maternal and fetal health outcomes following vaping during pregnancy. Based on the findings of this rapid review, there is an urgent need for high-quality studies in pregnant women to evaluate the potential in utero and long-term effects of exposure to prenatal vaping.

Methamphetamine Use in Pregnancy: A Call for Action.

Substance use during pregnancy continues to be an area of concern in Canada. Rates of substance use appear to be increasing among women of childbearing age, and use during pregnancy may effect maternal and fetal outcomes. Little is known of the prevalence of methamphetamine use during pregnancy and its impact, but maternity care providers are encountering patients who use methamphetamines in their practices. These health care providers are asking for evidence-based recommendations for management and treatment. There is an immediate and urgent need to address this gap in order to improve the health of pregnant women and their babies.

Perspectives of Canadian Health Care Providers on Fetal Alcohol Spectrum Disorder: Has Anything Changed in 15 years? A Brief Report.

Initiatives have been implemented to provide training to health care providers (HCPs) on the adverse health outcomes associated with alcohol use during pregnancy, including the risk of fetal alcohol spectrum disorder (FASD). The purpose of this exploratory study was to compare two cross-sectional data sets of HCP perspectives over 15 years. In 2002 and 2017, two samples of HCPs received a survey on FASD. The findings from these surveys may inform the development of ongoing educational initiatives to help HCPs with screening for alcohol use during pregnancy and early diagnosis and prevention of FASD.

Enzyme promiscuity drives branched-chain fatty acid synthesis in adipose tissues.

Fatty acid synthase (FASN) predominantly generates straight-chain fatty acids using acetyl-CoA as the initiating substrate. However, monomethyl branched-chain fatty acids (mmBCFAs) are also present in mammals but are thought to be primarily diet derived. Here we demonstrate that mmBCFAs are de novo synthesized via mitochondrial BCAA catabolism, exported to the cytosol by adipose-specific expression of carnitine acetyltransferase (CrAT), and elongated by FASN. Brown fat exhibits the highest BCAA catabolic and mmBCFA synthesis fluxes, whereas these lipids are largely absent from liver and brain. mmBCFA synthesis is also sustained in the absence of microbiota. We identify hypoxia as a potent suppressor of BCAA catabolism that decreases mmBCFA synthesis in obese adipose tissue, such that mmBCFAs are significantly decreased in obese animals. These results identify adipose tissue mmBCFA synthesis as a novel link between BCAA metabolism and lipogenesis, highlighting roles for CrAT and FASN promiscuity influencing acyl-chain diversity in the lipidome.

Guideline No. 405: Screening and Counselling for Alcohol Consumption During Pregnancy.

OBJECTIVE: To establish national standards of care for screening and counselling pregnant women and women of child-bearing age about alcohol consumption and possible alcohol use disorder based on current best evidence. INTENDED USERS: Health care providers who care for pregnant women and women of child-bearing age. TARGET POPULATION: Pregnant women and women of child-bearing age and their families. EVIDENCE: Medline, EMBASE, and CENTRAL databases were searched for "alcohol use and pregnancy." The results were filtered for a publication date between 2010 and September 2018. The search terms were developed using Medical Subject Headings terms and keywords, including pre-pregnancy, pregnant, breastfeeding, lactation, female, women, preconception care, prenatal care, fetal alcohol spectrum disorder, prenatal alcohol exposure, drinking behavior, alcohol abstinence, alcohol drinking, binge drinking, alcohol-related disorders, alcoholism, alcohol consumption, alcohol abuse, benzodiazepines, disulfiram, naltrexane, acamprosate, ondansetron, topiramate, cyanamide, calcium carbimide, alcohol deterrents, disease management, detoxification, Alcoholics Anonymous, alcohol counselling, harm reduction, pre-pregnancy care, prenatal care, incidence, prevalence, epidemiological monitoring, and brief intervention. Evidence was included from clinical trials, observational studies, reviews, systematic reviews and meta-analyses, guidelines, and conference consensus. VALIDATION METHODS: The content and recommendations in this guideline were drafted and agreed upon by the authors. The Board of Directors of the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology framework. BENEFITS, HARMS, COSTS: Implementation of the recommendations in these guidelines using validated screening tools and brief intervention approaches may increase obstetrical care provider recognition of alcohol consumption and problematic alcohol use among women of child-bearing age and those who are pregnant. It is anticipated that health care providers will become confident and competent in managing and supporting these women so they can achieve optimal health and pregnancy outcomes. SUMMARY STATEMENTS (GRADE RATINGS IN PARENTHESES): RECOMMENDATIONS (GRADE RATINGS IN PARENTHESES).

Directive clinique no 405 : Dépistage et conseils en matière de consommation d'alcool pendant la grossesse.

OBJECTIF: Établir des normes pancanadiennes fondées sur les meilleures données probantes actuelles sur le dépistage et les conseils en matière de consommation d'alcool et de troubles de consommation d'alcool chez les femmes enceintes ou en âge de procréer. PROFESSIONNELS CONCERNéS: Les fournisseurs de soins qui prodiguent des soins aux femmes enceintes et aux femmes en âge procréer. POPULATION CIBLE: Les femmes enceintes, les femmes en âge de procréer et leurs familles. DONNéES PROBANTES: Des recherches ont été effectuées dans les bases de données Medline, Embase et CENTRAL avec le thème « alcohol use and pregnancy ¼. Les résultats ont été filtrés de façon à obtenir des publications parues entre 2010 et septembre 2018. Les termes de recherche ont été mis au point à partir des termes du thésaurus de référence biomédicale MeSH et de mots clés, dont les suivants : pre-pregnancy, pregnant, breastfeeding, lactation, female, women, preconception care, prenatal care, fetal alcohol spectrum disorder, prenatal alcohol exposure, drinking behavior, alcohol abstinence, alcohol drinking, binge drinking, alcohol-related disorders, alcoholism, alcohol consumption, alcohol abuse, benzodiazepines, disulfiram, naltrexane, acamprosate, ondansetron, topiramate, cyanamide, calcium carbimide, alcohol deterrents, disease management, detoxification, Alcoholics Anonymous, alcohol counselling, harm reduction, pre-pregnancy care, prenatal care, incidence, prevalence, epidemiological monitoring et brief intervention. Les données probantes retenues proviennent d'essais cliniques, d'études observationnelles, de revues de la littérature, d'analyses systématiques et méta-analyses, de lignes directrices et de conférences de consensus. MéTHODES DE VALIDATION: Les auteurs ont rédigé et accepté le contenu et les recommandations de la présente directive. Le conseil d'administration de la Société des obstétriciens et gynécologues du Canada a approuvé la version définitive aux fins de publication. La qualité des données probantes a été évaluée au moyen des critères de l'approche GRADE (Grading of Recommendations Assessment, Development, and Evaluation) (consulter les tableaux A1 et A2 de l'annexe en ligne). BéNéFICES, RISQUES, COûTS: La mise en œuvre des recommandations de la présente directive à l'aide d'outils de dépistage validés et de stratégies d'intervention brève peut améliorer la capacité des fournisseurs de soins obstétricaux à reconnaître la consommation d'alcool et la consommation problématique d'alcool chez les femmes enceintes ou en âge de procréer. Il est attendu des fournisseurs de soins de santé qu'ils deviennent confiants et compétents en matière de prise en charge et de soutien de ces femmes afin qu'elles puissent avoir la meilleure santé possible et une issue de grossesse optimale. DÉCLARATIONS SOMMAIRES (CLASSEMENT GRADE ENTRE PARENTHèSES): RECOMMANDATIONS (CLASSEMENT GRADE ENTRE PARENTHèSES).