174 results on '"Reynolds, RM"'
Search Results
2. Effects of maternal obesity on early and long-term outcomes for offspring
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Stirrat LI and Reynolds RM
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Pediatrics ,RJ1-570 - Abstract
Laura I Stirrat,1,2 Rebecca M Reynolds2,3 1Medical Research Council Centre for Reproductive Health, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK; 2Tommy's Centre for Maternal and Fetal Health, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK; 3Endocrinology Unit, University/British Heart Foundation Centre for Cardiovascular Science, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK Abstract: The prevalence of maternal obesity has increased significantly in recent years, and obesity is currently the most common comorbidity of pregnancy. Pregnancies of obese women are often defined as "high-risk" for the purposes of clinical care, with many well documented risks to the mother and developing baby. Maternal physiology and metabolism is dysregulated in the context of obesity, which may contribute to some of the adverse outcomes during pregnancy. Furthermore, maternal obesity has been hypothesized to cause harmful effects for the developing baby through "early life programming." This review will examine evidence from human studies for outcomes of offspring from obese women during pregnancy, during labor, during the neonatal period, and later in life. Keywords: pregnancy, short-term, physiology, metabolism, early life programming, neonatal complications, adverse intrauterine environment
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- 2014
3. Nutrition During Pregnancy, Lactation and Early Childhood and its Implications for Maternal and Long-Term Child Health
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Koletzko, B, Godfrey, KM, Poston, L, Szajewska, H, van Goudoever, JB, de Waard, M, Brands, B, Grivell, RM, Deussen, AR, Dodd, JM, Patro-Golab, B, Zalewski, BM, Alberdi, G, Buonocore, G, Campoy, C, Demmelmair, H, Desoye, G, Gomez, MD, Escribano, J, Geraghty, A, Gil, A, Hanson, M, Inskip, HM, Larque, E, Lassel, T, Luque, V, Mader, S, Manios, Y, Mearin, LM, Oddy, WH, Reynolds, RM, Rueda, R, Sherry, C, Socha, P, Taylor, P, Van der Beek, EM, Weber, M, Crespo-Escobar, P, Gutser, M, Kouwenhoven, SMP, Calvo-Lerma, J, Veldhorst, M, and EarlyNutr Project Systematic Revie
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0301 basic medicine ,Gerontology ,Infancy ,PROTEIN-INTAKE ,Maternal Health ,Breastfeeding ,Medicine (miscellaneous) ,Disease ,Overweight ,Recommendations ,Nutrition Policy ,0302 clinical medicine ,Pregnancy ,FORMULA-FED INFANTS ,AGE FOLLOW-UP ,Medicine ,Early childhood ,Micronutrients ,Infant Nutritional Physiological Phenomena ,Prenatal Nutritional Physiological Phenomena ,media_common ,2. Zero hunger ,Child health ,GESTATIONAL WEIGHT-GAIN ,Nutrition and Dietetics ,Preconception ,3. Good health ,Systematic review ,Breast Feeding ,Child, Preschool ,Female ,LIFE-STYLE ,medicine.symptom ,VITAMIN-D DEFICIENCY ,YOUNG-CHILDREN ,030209 endocrinology & metabolism ,Early nutrition ,Developmental programming ,03 medical and health sciences ,Metabolic programming ,media_common.cataloged_instance ,Humans ,Lactation ,Obesity ,European union ,Life Style ,030109 nutrition & dietetics ,business.industry ,Infant ,medicine.disease ,Lifestyle ,PERICONCEPTIONAL FOLIC-ACID ,BODY-MASS INDEX ,BREAST-FED INFANTS ,business ,Systematic Reviews as Topic - Abstract
Background: A considerable body of evidence accumulated especially during the last decade, demonstrating that early nutrition and lifestyle have long-term effects on later health and disease (“developmental or metabolic programming”). Methods: Researchers involved in the European Union funded international EarlyNutrition research project consolidated the scientific evidence base and existing recommendations to formulate consensus recommendations on nutrition and lifestyle before and during pregnancy, during infancy and early childhood that take long-term health impact into account. Systematic reviews were performed on published dietary guidelines, standards and recommendations, with special attention to long-term health consequences. In addition, systematic reviews of published systematic reviews on nutritional interventions or exposures in pregnancy and in infants and young children aged up to 3 years that describe effects on subsequent overweight, obesity and body composition were performed. Experts developed consensus recommendations incorporating the wide-ranging expertise from additional 33 stakeholders. Findings: Most current recommendations for pregnant women, particularly obese women, and for young children do not take long-term health consequences of early nutrition into account, although the available evidence for relevant consequences of lifestyle, diet and growth patterns in early life on later health and disease risk is strong. Interpretation: We present updated recommendations for optimized nutrition before and during pregnancy, during lactation, infancy and toddlerhood, with special reference to later health outcomes. These recommendations are developed for affluent populations, such as women and children in Europe, and should contribute to the primary prevention of obesity and associated non-communicable diseases.
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- 2019
4. An evaluation of the benefits and harms of antenatal corticosteroid treatment for women at risk of imminent preterm birth of prior to elective Caesarean-section: Study protocol for an individual participant data meta-analysis
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Wastnedge, E, Vogel, J, Been, Jasper, Bannerman-Gyamfi, C, Schuit, E, Roberts, D, Reynolds, RM, Stock, S, Pediatrics, and Public Health
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- 2020
5. Circulating plasma cortisol concentrations are not associated with coronary artery disease or peripheral vascular disease
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Reynolds, RM, Ilyas, B, Price, JF, Fowkes, FGR, Newby, DE, Webb, DJ, and Walker, BR
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- 2009
6. Reproductive dysfunction and associated pathology in women undergoing military training
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Gifford, RM, Reynolds, RM, Greeves, J, Anderson, RA, and Woods, D
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Evidence from civilian athletes raises the question of whether reproductive dysfunction may be seen in female soldiers as a result of military training. Such reproductive dysfunction consists of impaired ovulation with or without long term subfertility. We critically review pertinent evidence, which points towards reduced energy availability as the most likely explanation for exercise-induced reproductive dysfunction. Evidence also suggests reproductive dysfunction is mediated by activation of the hypothalamic-pituitary-adrenal axis and suppression of the hypothalamic-pituitary-gonadal axis, with elevated ghrelin and reduced leptin likely to play an important role. The observed reproductive dysfunction exists as part of a female athletic triad, together with osteopenia and disordered eating. If this phenomenon was shown to exist with UK military training this would be of significant concern. We hypothesise that the nature of military training and possibly field exercises may contribute to greater risk of reproductive dysfunction among female military trainees compared with exercising civilian controls. We discuss the features of military training and its participants, such as energy availability, age at recruitment, body phenotype, type of physical training, psychogenic stressors, altered sleep pattern and elemental exposure as contributors to reproductive dysfunction. We identify lines of future research to more fully characterise reproductive dysfunction in military women, and suggest possible interventions which, if indicated, could improve their future wellbeing.
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- 2017
7. Diabetic retinopathy and cognitive decline in older people with type 2 diabetes: the Edinburgh Type 2 Diabetes Study.
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Ding J, Strachan MW, Reynolds RM, Frier BM, Deary IJ, Fowkes FG, Lee AJ, McKnight J, Halpin P, Swa K, Price JF, Edinburgh Type 2 Diabetes Study Investigators, Ding, Jie, Strachan, Mark W J, Reynolds, Rebecca M, Frier, Brian M, Deary, Ian J, Fowkes, F Gerald R, Lee, Amanda J, and McKnight, Janet
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Objective: Cerebral microvascular disease associated with type 2 diabetes may exacerbate the effects of aging on cognitive function. A considerable homology exists between the retinal and cerebral microcirculations; a hypothesized association between diabetic retinopathy (DR) and cognitive decline was examined in older people with type 2 diabetes.Research Design and Methods: In the population-based Edinburgh Type 2 Diabetes Study, 1,046 men and women aged 60-75 years with type 2 diabetes underwent standard seven-field binocular digital retinal photography and a battery of seven cognitive function tests. A general cognitive ability score (g) was generated by principal components analysis. The Mill-Hill Vocabulary Scale was used to estimate premorbid cognitive ability. DR was graded using a modification of the Early Treatment of Diabetic Retinopathy Scale.Results: After age and sex adjustment, a significant relationship was observed with increasing severity of DR (none, mild, and moderate to severe) for most cognitive measures. Participants with moderate-to-severe retinopathy had the worst g and the worst performances on the individual tests. There was a significant interaction between sex and retinopathy for g. In male subjects, the associations of retinopathy with g (and with tests of verbal fluency, mental flexibility, and processing speed but not memory and nonverbal reasoning) persisted (P < 0.05) when further adjusted for vocabulary (to estimate lifetime cognitive decline), depression, sociodemographic characteristics, cardiovascular risk factors, and macrovascular disease.Conclusions: DR was independently associated with estimated lifetime cognitive decline in older men with type 2 diabetes, supporting the hypothesis that cerebral microvascular disease may contribute to their observed accelerated age-related cognitive decline. A sex interaction with stronger findings in men requires further confirmation. [ABSTRACT FROM AUTHOR]- Published
- 2010
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8. Morning cortisol levels and cognitive abilities in people with type 2 diabetes: the Edinburgh type 2 diabetes study.
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Reynolds RM, Strachan MW, Labad J, Lee AJ, Frier BM, Fowkes FG, Mitchell R, Seckl JR, Deary IJ, Walker BR, Price JF, Edinburgh Type 2 Diabetes Study Investigators, Reynolds, Rebecca M, Strachan, Mark W J, Labad, Javier, Lee, Amanda J, Frier, Brian M, Fowkes, F Gerald, Mitchell, Rory, and Seckl, Jonathan R
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Objective: People with type 2 diabetes are at increased risk of cognitive impairment but the mechanism is uncertain. Elevated glucocorticoid levels in rodents and humans are associated with cognitive impairment. We aimed to determine whether fasting cortisol levels are associated with cognitive ability and estimated lifetime cognitive change in an elderly population with type 2 diabetes.Research Design and Methods: This was a cross-sectional study of 1,066 men and women aged 60-75 years with type 2 diabetes, living in Lothian, Scotland (the Edinburgh Type 2 Diabetes Study). Cognitive abilities in memory, nonverbal reasoning, information processing speed, executive function, and mental flexibility were tested, and a general cognitive ability factor, g, was derived. Prior intelligence was estimated from vocabulary testing, and adjustment for scores on this test was used to estimate lifetime cognitive change. Relationships between fasting morning plasma cortisol levels and cognitive ability and estimated cognitive change were tested. Models were adjusted for potential confounding and/or mediating variables including metabolic and cardiovascular variables.Results: In age-adjusted analyses, higher fasting cortisol levels were not associated with current g or with performance in individual cognitive domains. However, higher fasting cortisol levels were associated with greater estimated cognitive decline in g and in tests of working memory and processing speed, independent of mood, education, metabolic variables, and cardiovascular disease (P < 0.05).Conclusions: High morning cortisol levels in elderly people with type 2 diabetes are associated with estimated age-related cognitive change. Strategies targeted at lowering cortisol action may be useful in ameliorating cognitive decline in individuals with type 2 diabetes. [ABSTRACT FROM AUTHOR]- Published
- 2010
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9. Association between raised inflammatory markers and cognitive decline in elderly people with type 2 diabetes: the Edinburgh Type 2 Diabetes Study.
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Marioni RE, Strachan MW, Reynolds RM, Lowe GD, Mitchell RJ, Fowkes FG, Frier BM, Lee AJ, Butcher I, Rumley A, Murray GD, Deary IJ, Price JF, Marioni, Riccardo E, Strachan, Mark W J, Reynolds, Rebecca M, Lowe, Gordon D O, Mitchell, Rory J, Fowkes, F Gerry R, and Frier, Brian M
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Objective: To determine whether circulating levels of the inflammatory markers C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha are associated with cognitive ability and estimated lifetime cognitive decline in an elderly population with type 2 diabetes.Research Design and Methods: A cross-sectional study of 1,066 men and women aged 60-75 years with type 2 diabetes and living in Lothian, Scotland (the Edinburgh Type 2 Diabetes Study), was performed. Seven cognitive tests were used to measure abilities in memory, nonverbal reasoning, information processing speed, executive function, and mental flexibility. The results were used to derive a general intelligence factor (g). A vocabulary-based test was administered as an estimate of peak prior cognitive ability. Results on the cognitive tests were assessed for statistical association with inflammatory markers measured in a venous blood sample at the time of cognitive testing.Results: Higher IL-6 and TNF-alpha levels were associated with poorer age- and sex-adjusted scores on the majority of the individual cognitive tests. They were also associated with g using standardized regression coefficients -0.074 to -0.173 (P < 0.05). After adjusting for vocabulary, education level, cardiovascular dysfunction, duration of diabetes, and glycemic control, IL-6 remained associated with three of the cognitive tests and with g.Conclusions: In this representative population of people with type 2 diabetes, elevated circulating levels of inflammatory markers were associated with poorer cognitive ability. IL-6 levels were also associated with estimated lifetime cognitive decline. [ABSTRACT FROM AUTHOR]- Published
- 2010
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10. Approaches to screening for hyperglycaemia in pregnant women during and after the COVID‐19 pandemic
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David Simmons, David R. McCance, Jenny Myers, Robert S. Lindsay, Eleanor M. Scott, Helen R. Murphy, Rebecca M. Reynolds, Jennifer M. Yamamoto, Catherine E. Aiken, Claire L Meek, Meek, CL [0000-0002-4176-8329], Aiken, CE [0000-0002-6510-5626], Reynolds, RM [0000-0001-6226-8270], Simmons, D [0000-0003-0560-0761], Yamamoto, JM [0000-0002-3556-0820], Murphy, HR [0000-0001-6876-8727], and Apollo - University of Cambridge Repository
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Blood Glucose ,Endocrinology, Diabetes and Metabolism ,Hyperglycemia/diagnosis ,Comorbidity ,Fasting/blood ,Glycated Hemoglobin A/analysis ,0302 clinical medicine ,Endocrinology ,Pregnancy ,Risk Factors ,Mass Screening ,030212 general & internal medicine ,Research Articles ,COVID-19/epidemiology ,Glucose tolerance test ,medicine.diagnostic_test ,United Kingdom/epidemiology ,Obstetrics ,Pregnancy Outcome ,Gestational age ,Fasting ,Gestational diabetes ,Gestation ,Female ,Research Article ,Adult ,medicine.medical_specialty ,Gestational Age ,030209 endocrinology & metabolism ,Sensitivity and Specificity ,Pregnancy Outcome/epidemiology ,03 medical and health sciences ,Mass Screening/methods ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,Risk factor ,Pandemics ,Mass screening ,Retrospective Studies ,Glycated Hemoglobin ,SARS-CoV-2 ,business.industry ,COVID-19 ,Blood Glucose/analysis ,Glucose Tolerance Test ,medicine.disease ,United Kingdom ,Diabetes, Gestational/diagnosis ,Coronavirus ,Diabetes, Gestational ,Hyperglycemia ,business - Abstract
Aim: To evaluate the diagnostic and prognostic performance of alternative diagnostic strategies to oral glucose tolerance tests, including random plasma glucose, fasting plasma glucose and HbA 1c, during the COVID-19 pandemic. Methods: Retrospective service data (Cambridge, UK; 17 736 consecutive singleton pregnancies, 2004–2008; 826 consecutive gestational diabetes pregnancies, 2014–2019) and 361 women with ≥1 gestational diabetes risk factor (OPHELIA prospective observational study, UK) were included. Pregnancy outcomes included gestational diabetes (National Institute of Health and Clinical Excellence or International Association of Diabetes and Pregnancy Study Groups criteria), diabetes in pregnancy (WHO criteria), Caesarean section, large-for-gestational age infant, neonatal hypoglycaemia and neonatal intensive care unit admission. Receiver-operating characteristic curves and unadjusted logistic regression were used to compare random plasma glucose, fasting plasma glucose and HbA 1c performance. Results: Gestational diabetes diagnosis was significantly associated with random plasma glucose at 12 weeks [area under the receiver-operating characteristic curve for both criteria 0.81 (95% CI 0.79–0.83)], fasting plasma glucose [National Institute of Health and Clinical Excellence: area under the receiver-operating characteristic curve 0.75 (95% CI 0.65–0.85); International Association of Diabetes and Pregnancy Study Groups: area under the receiver-operating characteristic curve 0.92 (95% CI 0.85–0.98)] and HbA 1c at 28 weeks' gestation [National Institute of Health and Clinical Excellence: 0.83 (95% CI 0.75–0.90); International Association of Diabetes and Pregnancy Study Groups: 0.84 (95% CI 0.77–0.91)]. Each measure predicts some, but not all, pregnancy outcomes studied. At 12 weeks, ~5% of women would be identified using random plasma glucose ≥8.5 mmol/l (sensitivity 42%; specificity 96%) and at 28 weeks using HbA 1c ≥39 mmol/mol (sensitivity 26%; specificity 96%) or fasting plasma glucose ≥5.2–5.4 mmol/l (sensitivity 18–41%; specificity 97–98%). Conclusions: Random plasma glucose at 12 weeks, and fasting plasma glucose or HbA 1c at 28 weeks identify women with hyperglycaemia at risk of suboptimal pregnancy outcomes. These opportunistic laboratory tests perform adequately for risk stratification when oral glucose tolerance testing is not available.
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- 2020
11. Feline dystrophin-deficient muscular dystrophy misdiagnosed as Toxoplasma myositis.
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Reynolds RM, Marks SL, Guo LT, Shelton GD, and Graham KJ
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Case Summary: A 6-month-old male entire domestic shorthair cat presented for presumptive Toxoplasma myopathy that was non-responsive to antiprotozoal therapy. Clinical features included marked macroglossia, dysphagia, regurgitation, truncal muscle hypertrophy, pelvic limb gait abnormalities and megaoesophagus. Relevant diagnostics included serial creatine kinase activity, cardiac troponin I, fluoroscopic swallow study and routine muscle histopathology. Ultimately, post-mortem histopathology with immunostaining demonstrated markedly decreased or absent staining for the rod and carboxy terminus of dystrophin, confirming a dystrophin-deficient muscular dystrophy (MD). The misdiagnosis of toxoplasmosis was based on an increased IgG titre and muscle histopathology submitted to a local laboratory. Treatment for megaoesophagus included vertical feeding of wet food only, sildenafil and omeprazole. Dysphagia and regurgitation improved moderately. Presumptive hyperaesthesia and muscle pain were managed with anti-inflammatory doses of prednisolone. The patient was ultimately euthanased as a result of progressive MD signs and uraemia at 2 years of age., Relevance and Novel Information: This case report highlights the collective clinical features of MD, as they could be considered pathognomonic for this rare condition and must be differentiated from other myopathies via specific immunostaining of muscle biopsies. This is crucial to obtain a correct and early diagnosis, allowing instigation of potentially valuable treatments. Megaoesophagus is an inconsistent feature in feline MD in addition to the more commonly observed oropharyngeal dysphagia. Management with a canned diet, sildenafil, omeprazole and upright feeding was beneficial with moderate improvement in the frequency of regurgitation. Prednisolone was thought to minimise the presumptive myalgia., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)
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- 2024
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12. Real-world diagnostic potential of bacterial biomarkers of canine periodontitis.
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Wallis CV, Soltero-Rivera M, Harvey C, Reynolds RM, Carvell-Miller LJ, Colyer A, McKee TS, Mills T, Bergman PJ, Watson P, and Holcombe LJ
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Introduction: The objective of this study was to investigate the diagnostic potential of bacterial biomarkers by comparing the performance of molecular detection assays with clinical assessments of dog's oral health performed by veterinarians., Methods: Supragingival and subgingival plaque samples were collected from 127 client-owned dogs, pre-booked for procedures under general anesthesia, visiting veterinary practices in the United States. DNA was extracted and bacterial biomarkers quantified using quantitative polymerase chain reaction. Gingivitis and periodontitis were recorded by a trained clinician using the Weighted Gingivitis Periodontitis Score which involved assessing the buccal surfaces of 18 teeth while under general anesthesia. Intraoral dental radiographs of the left and right mandibular first molar teeth were also obtained. These data were then used to establish the diagnostic performance of the molecular assay to detect periodontitis., Results: An initial conscious, visual oral examination performed by the veterinarian identified 67.7% of dogs as having periodontitis, but examination under general anesthesia indicated a higher proportion (86.6%). Analysis of supragingival plaque samples collected by veterinarians from conscious and unconscious dogs demonstrated the assay had an accuracy of 77.7 to 80.9%, a sensitivity of 77.6 to 81.0%, and a specificity of 80.0%., Discussion: Use of this molecular screening tool in conscious dogs has the potential to improve early periodontal disease detection and support veterinary decision making, ultimately improving the oral health of dogs and consequently their quality of life., Competing Interests: CW, LC-M, RR, PB, TSM, TM, LH, PW, and AC are employees of Mars Petcare, a manufacturer of commercial petfood and provider of veterinary services. Mars Petcare has filed a number of patents relating to the compositional analysis of the canine oral microbiome as a diagnostic for canine periodontal disease. CH and MS-R received payment from Mars Petcare for consultation relating to this research. CH is employed by the company Colin Harvey LLC., (Copyright This work is authored by Wallis, Soltero-Rivera, Harvey, Reynolds, Carvell-Miller, Colyer, McKee, Millis, Bergman, Watson and Holcombe. © 2024 Mars Petcare UK and its affiliates for Wallis, Reynolds, Carvell-Miller, Colyer, Watson and Holcombe and © 2024 VCA Clinical Studies for McKee, Mills and Bergman.)
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- 2024
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13. The pharmacokinetics and pharmacodynamics of fentanyl administered via transdermal patch in horses.
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Reed RA, Berghaus LJ, Reynolds RM, Holmes BT, Krikorian AM, Sakai DM, Ishikawa Y, and Knych HK
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Introduction: Understanding the pharmacokinetics and pharmacodynamics of fentanyl in horses is crucial for optimizing pain management strategies in veterinary medicine., Methods: Six adult horses were enrolled in a randomized crossover design. Treatments included: placebo, two 100 mcg/h patches (LDF), four 100 mcg/h patches (MDF), and six 100 mcg/h patches (HDF). Patches were in place for 72 h. Blood was obtained for fentanyl plasma concentration determination, thermal threshold, mechanical threshold, heart rate, respiratory rate, and rectal temperature were obtained prior patch placement and at multiple time points following patch placement for the following 96 h. Fentanyl plasma concentration was determined using LC-MS/MS. Data were analyzed using a generalized mixed effects model., Results: Mean (range) maximum plasma concentration (Cmax), time to Cmax, and area under the curve extrapolated to infinity were 1.39 (0.82-1.82), 2.64 (1.21-4.42), 4.11 (2.78-7.12) ng/ml, 12.7 (8.0-16.0), 12.7 (8.0-16.0), 12 (8.0-16.0) h, 42.37 (27.59-55.56), 77.24 (45.62-115.06), 120.34 (100.66-150.55) h ng/ml for LDF, MDF, and HDF, respectively. There was no significant effect of treatment or time on thermal threshold, mechanical threshold, respiratory rate, or temperature ( p > 0.063). There was no significant effect of treatment on heart rate ( p = 0.364). There was a significant effect of time ( p = 0.003) on heart rate with overall heart rates being less than baseline at 64 h., Conclusions: Fentanyl administered via transdermal patch is well absorbed and well tolerated but does not result in an anti-nociceptive effect as measured by thermal and mechanical threshold at the doses studied., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Reed, Berghaus, Reynolds, Holmes, Krikorian, Sakai, Ishikawa and Knych.)
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- 2024
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14. Child educational progress in Born in Bradford pregnancies affected by gestational diabetes and also exposed to maternal common mental disorders.
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Wilson CA, Santorelli G, Howard LM, Ismail K, Reynolds RM, and Simonoff E
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- Pregnancy, Female, Humans, Child, Educational Status, Family, Diabetes, Gestational epidemiology, Diabetes, Gestational diagnosis, Mental Disorders epidemiology
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Gestational diabetes and the maternal mental disorders of anxiety and depression have been implicated in adverse offspring neuro-behavioural outcomes but these exposures have only been studied in isolation. 1051 children whose mothers were diagnosed with gestational diabetes in UK's Born in Bradford cohort had linkage to maternal primary care records, providing diagnostic and treatment codes for depression and anxiety. Education record linkage provided results of the Early Years Foundation Stage Profile from the first year of school, aged five. Risk of not attaining a 'Good level of development' was analysed using multivariable Poisson regression within a generalised estimating equation framework. Multiple imputation was implemented for missing data. There was limited evidence of increased risk of failure to attain a 'good level of development' in those additionally exposed to maternal mental disorders (adjusted RR 1.21; 95% CI 0.94, 1.55). However, there was more evidence in children of Pakistani maternal ethnicity (adjusted RR 1.36; 95% CI 1.04, 1.77) than White British; this may have been driven by English not being the primary language spoken in the home. Therefore there may be groups with GDM in whom it is particularly important to optimise both maternal physical and mental health to improve child outcomes., (© 2023. Springer Nature Limited.)
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- 2023
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15. Precision gestational diabetes treatment: a systematic review and meta-analyses.
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Benham JL, Gingras V, McLennan NM, Most J, Yamamoto JM, Aiken CE, Ozanne SE, and Reynolds RM
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Background: Gestational Diabetes Mellitus (GDM) affects approximately 1 in 7 pregnancies globally. It is associated with short- and long-term risks for both mother and baby. Therefore, optimizing treatment to effectively treat the condition has wide-ranging beneficial effects. However, despite the known heterogeneity in GDM, treatment guidelines and approaches are generally standardized. We hypothesized that a precision medicine approach could be a tool for risk-stratification of women to streamline successful GDM management. With the relatively short timeframe available to treat GDM, commencing effective therapy earlier, with more rapid normalization of hyperglycaemia, could have benefits for both mother and fetus., Methods: We conducted two systematic reviews, to identify precision markers that may predict effective lifestyle and pharmacological interventions., Results: There was a paucity of studies examining precision lifestyle-based interventions for GDM highlighting the pressing need for further research in this area. We found a number of precision markers identified from routine clinical measures that may enable earlier identification of those requiring escalation of pharmacological therapy (to metformin, sulphonylureas or insulin). This included previous history of GDM, Body Mass Index and blood glucose concentrations at diagnosis., Conclusions: Clinical measurements at diagnosis could potentially be used as precision markers in the treatment of GDM. Whether there are other sensitive markers that could be identified using more complex individual-level data, such as omics, and if these can feasibly be implemented in clinical practice remains unknown. These will be important to consider in future studies., (© 2023. Springer Nature Limited.)
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- 2023
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16. Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine.
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Tobias DK, Merino J, Ahmad A, Aiken C, Benham JL, Bodhini D, Clark AL, Colclough K, Corcoy R, Cromer SJ, Duan D, Felton JL, Francis EC, Gillard P, Gingras V, Gaillard R, Haider E, Hughes A, Ikle JM, Jacobsen LM, Kahkoska AR, Kettunen JLT, Kreienkamp RJ, Lim LL, Männistö JME, Massey R, Mclennan NM, Miller RG, Morieri ML, Most J, Naylor RN, Ozkan B, Patel KA, Pilla SJ, Prystupa K, Raghavan S, Rooney MR, Schön M, Semnani-Azad Z, Sevilla-Gonzalez M, Svalastoga P, Takele WW, Tam CH, Thuesen ACB, Tosur M, Wallace AS, Wang CC, Wong JJ, Yamamoto JM, Young K, Amouyal C, Andersen MK, Bonham MP, Chen M, Cheng F, Chikowore T, Chivers SC, Clemmensen C, Dabelea D, Dawed AY, Deutsch AJ, Dickens LT, DiMeglio LA, Dudenhöffer-Pfeifer M, Evans-Molina C, Fernández-Balsells MM, Fitipaldi H, Fitzpatrick SL, Gitelman SE, Goodarzi MO, Grieger JA, Guasch-Ferré M, Habibi N, Hansen T, Huang C, Harris-Kawano A, Ismail HM, Hoag B, Johnson RK, Jones AG, Koivula RW, Leong A, Leung GKW, Libman IM, Liu K, Long SA, Lowe WL Jr, Morton RW, Motala AA, Onengut-Gumuscu S, Pankow JS, Pathirana M, Pazmino S, Perez D, Petrie JR, Powe CE, Quinteros A, Jain R, Ray D, Ried-Larsen M, Saeed Z, Santhakumar V, Kanbour S, Sarkar S, Monaco GSF, Scholtens DM, Selvin E, Sheu WH, Speake C, Stanislawski MA, Steenackers N, Steck AK, Stefan N, Støy J, Taylor R, Tye SC, Ukke GG, Urazbayeva M, Van der Schueren B, Vatier C, Wentworth JM, Hannah W, White SL, Yu G, Zhang Y, Zhou SJ, Beltrand J, Polak M, Aukrust I, de Franco E, Flanagan SE, Maloney KA, McGovern A, Molnes J, Nakabuye M, Njølstad PR, Pomares-Millan H, Provenzano M, Saint-Martin C, Zhang C, Zhu Y, Auh S, de Souza R, Fawcett AJ, Gruber C, Mekonnen EG, Mixter E, Sherifali D, Eckel RH, Nolan JJ, Philipson LH, Brown RJ, Billings LK, Boyle K, Costacou T, Dennis JM, Florez JC, Gloyn AL, Gomez MF, Gottlieb PA, Greeley SAW, Griffin K, Hattersley AT, Hirsch IB, Hivert MF, Hood KK, Josefson JL, Kwak SH, Laffel LM, Lim SS, Loos RJF, Ma RCW, Mathieu C, Mathioudakis N, Meigs JB, Misra S, Mohan V, Murphy R, Oram R, Owen KR, Ozanne SE, Pearson ER, Perng W, Pollin TI, Pop-Busui R, Pratley RE, Redman LM, Redondo MJ, Reynolds RM, Semple RK, Sherr JL, Sims EK, Sweeting A, Tuomi T, Udler MS, Vesco KK, Vilsbøll T, Wagner R, Rich SS, and Franks PW
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- Humans, Consensus, Evidence-Based Medicine, Precision Medicine, Diabetes Mellitus diagnosis, Diabetes Mellitus genetics, Diabetes Mellitus therapy
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Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
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- 2023
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17. Post-anesthetic CPS and EQUUS-FAP scores in surgical and non-surgical equine patients: an observational study.
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Reed RA, Krikorian AM, Reynolds RM, Holmes BT, Branning MM, Lemons MB, Barletta M, Quandt JE, Burns CC, Dantino SC, and Sakai DM
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Background: Equine pain scoring may be affected by the residual effect of anesthetic drugs., Objectives: To compare pain scores in the hours immediately following anesthetic recovery to baseline pre-anesthetic scores in equine patients undergoing surgical and non-surgical procedures., Study Design: Clinical observational study., Methods: Fifty adult horses undergoing anesthesia for surgical or non-surgical procedures were enrolled. Horses underwent pain scoring using the Composite Pain Score (CPS) and Equine Utrecht University Scale for Facial Assessment of Pain (EQUUS-FAP) prior to anesthesia (T0) and following anesthetic recovery to standing, every hour for 5 h (T1-T5). Data were analyzed using a generalized linear mixed effects model. A post-hoc Dunnett's test for multiple comparisons was performed for variables where an effect was detected., Results: Mean (95% confidence interval) CPS scores for T0-T5 were 1.6 (1.2-2.0), 6.8 (6.0-7.6), 5.1 (4.3-5.9), 4.3 (3.4-5.2), 3.7 (2.8-4.6), and 2.8 (2.0-3.6) and EQUUS-FAP scores were 0.6 (0.3-0.9), 3.0 (2.5-3.5), 1.9 (1.6-2.2), 1.1 (0.8-1.4), 0.6 (0.4-0.8), and 0.7 (0.4-1.0), respectively. For the CPS, scores greater than 5, and for the EQUUS-FAP scores greater than 3, are consistent with minor pain. There was no effect of type of procedure (surgical vs non-surgical) on CPS or EQUUS-FAP scores. There was an effect of time with CPS scores significantly greater than baseline at T1-T5 and EQUUS-FAP scores significantly greater than baseline at T1 and T2., Main Limitations: Discomfort caused by hoisting was not quantified and it was difficult to ascertain if this affected the results., Conclusions: Post-anesthetic pain scores may be influenced by the residual effect of anesthetic agents for as long as 5 h and 2 h for the CPS and EQUUS-FAP, respectively., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Reed, Krikorian, Reynolds, Holmes, Branning, Lemons, Barletta, Quandt, Burns, Dantino and Sakai.)
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- 2023
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18. The role of brain structure in the association between pubertal timing and depression risk in an early adolescent sample (the ABCD Study®): A registered report.
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MacSweeney N, Allardyce J, Edmondson-Stait A, Shen X, Casey H, Chan SWY, Cullen B, Reynolds RM, Frangou S, Kwong ASF, Lawrie SM, Romaniuk L, and Whalley HC
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- Humans, Male, Adolescent, Female, Brain, Depression, Puberty
- Abstract
Background: Earlier pubertal timing is associated with higher rates of depressive disorders in adolescence. Neuroimaging studies report brain structural associations with both pubertal timing and depression. However, whether brain structure mediates the relationship between pubertal timing and depression remains unclear., Methods: The current registered report examined associations between pubertal timing (indexed via perceived pubertal development), brain structure (cortical and subcortical metrics, and white matter microstructure) and depressive symptoms in a large sample (N = ∼5000) of adolescents (aged 9-13 years) from the Adolescent Brain Cognitive Development (ABCD) Study. We used three waves of follow-up data when the youth were aged 10-11 years, 11-12 years, and 12-13 years, respectively. We used generalised linear-mixed models (H1) and structural equation modelling (H2 & H3) to test our hypotheses., Hypotheses: We hypothesised that earlier pubertal timing at Year 1 would be associated with increased depressive symptoms at Year 3 (H1), and that this relationship would be mediated by global (H2a-b) and regional (H3a-g) brain structural measures at Year 2. Global measures included reduced cortical volume, thickness, surface area and sulcal depth. Regional measures included reduced cortical thickness and volume in temporal and fronto-parietal areas, increased cortical volume in the ventral diencephalon, increased sulcal depth in the pars orbitalis, and reduced fractional anisotropy in the cortico-striatal tract and corpus callosum. These regions of interest were informed by our pilot analyses using baseline ABCD data when the youth were aged 9-10 years., Results: Earlier pubertal timing was associated with increased depressive symptoms two years later. The magnitude of effect was stronger in female youth and the association remained significant when controlling for parental depression, family income, and BMI in females but not in male youth. Our hypothesised brain structural measures did not however mediate the association between earlier pubertal timing and later depressive symptoms., Conclusion: The present results demonstrate that youth, particularly females, who begin puberty ahead of their peers are at an increased risk for adolescent-onset depression. Future work should explore additional biological and socio-environmental factors that may affect this association so that we can identify targets for intervention to help these at-risk youth., (Copyright © 2023. Published by Elsevier Ltd.)
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- 2023
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19. "I Crave a Blunt, I Don't Crave a Cigarillo": A Focus Group Study on Perceptions of Nicotine and Addiction among US Adults Who Currently Smoke Little Cigars or Cigarillos.
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Hackworth EE, Ntansah CA, Henderson KC, Pei D, Reynolds RM, Duong HT, Yang B, Ashley DL, Thrasher JF, and Popova L
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- Adult, Female, Humans, Male, Focus Groups, Nicotine, Cannabis, Craving, Tobacco Products, Smoking
- Abstract
While the US Food and Drug Administration (FDA)'s proposal to reduce the nicotine content in cigarettes is gaining traction, it is still undetermined whether the policy will also include other combustible tobacco products, such as little cigars and cigarillos (LCCs), and how such a policy should be communicated given the patterns of use and perceptions around LCCs. This study examined perceptions of nicotine and addiction related to LCC use and involved data collection from eight semi-structured virtual focus groups conducted in Summer 2021 in the US. Participants were adults who reported past-30-day use of LCCs, consisting of African American males ( n = 9), African American females ( n = 9), white males ( n = 14), and white females ( n = 11). Participants discussed their perceptions of nicotine and addiction in general and in relation to LCC use. Inductive thematic analysis of transcripts was conducted. Differences across race and sex groups were examined. Participants did not consider nicotine to be a characterizing feature of LCCs; rather, they generally associated nicotine with cigarettes. Participants' views of nicotine and addiction related to LCCs were discussed along four dimensions: context of use, frequency of use, the presence of cravings, and whether a product is modified (e.g., by adding marijuana). Social and infrequent use, a lack of cravings, and the use of LCCs for marijuana were considered indicative of a lack of addiction and reasons not to be concerned about nicotine in LCCs. Because perceptions of nicotine and addiction related to LCCs differ from those of cigarettes, communications about a reduced nicotine policy that includes LCCs should consider these differences to ensure the policy is understood by people who currently use LCCs and to prevent people who use cigarettes from switching to LCCs.
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- 2023
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20. Consortium for the Study of Pregnancy Treatments (Co-OPT): An international birth cohort to study the effects of antenatal corticosteroids.
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Frier EM, Lin C, Reynolds RM, Allegaert K, Been JV, Fraser A, Gissler M, Einarsdóttir K, Florian L, Jacobsson B, Vogel JP, Zoega H, Bhattacharya S, Krispin E, Henning Pedersen L, Roberts D, Kuhle S, Fahey J, Mol BW, Burgner D, Schuit E, Sheikh A, Wood R, Gyamfi-Bannerman C, Miller JE, Duhig K, Lahti-Pulkkinen M, Hadar E, Wright J, Murray SR, and Stock SJ
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- Infant, Newborn, Pregnancy, Infant, Child, Humans, Female, Child, Preschool, Child Health, Family, Adrenal Cortex Hormones therapeutic use, Birth Cohort, Premature Birth epidemiology
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Background: Antenatal corticosteroids (ACS) are widely prescribed to improve outcomes following preterm birth. Significant knowledge gaps surround their safety, long-term effects, optimal timing and dosage. Almost half of women given ACS give birth outside the "therapeutic window" and have not delivered over 7 days later. Overtreatment with ACS is a concern, as evidence accumulates of risks of unnecessary ACS exposure., Methods: The Consortium for the Study of Pregnancy Treatments (Co-OPT) was established to address research questions surrounding safety of medications in pregnancy. We created an international birth cohort containing information on ACS exposure and pregnancy and neonatal outcomes by combining data from four national/provincial birth registers and one hospital database, and follow-up through linked population-level data from death registers and electronic health records., Results and Discussion: The Co-OPT ACS cohort contains 2.28 million pregnancies and babies, born in Finland, Iceland, Israel, Canada and Scotland, between 1990 and 2019. Births from 22 to 45 weeks' gestation were included; 92.9% were at term (≥ 37 completed weeks). 3.6% of babies were exposed to ACS (67.0% and 77.9% of singleton and multiple births before 34 weeks, respectively). Rates of ACS exposure increased across the study period. Of all ACS-exposed babies, 26.8% were born at term. Longitudinal childhood data were available for 1.64 million live births. Follow-up includes diagnoses of a range of physical and mental disorders from the Finnish Hospital Register, diagnoses of mental, behavioural, and neurodevelopmental disorders from the Icelandic Patient Registers, and preschool reviews from the Scottish Child Health Surveillance Programme. The Co-OPT ACS cohort is the largest international birth cohort to date with data on ACS exposure and maternal, perinatal and childhood outcomes. Its large scale will enable assessment of important rare outcomes such as perinatal mortality, and comprehensive evaluation of the short- and long-term safety and efficacy of ACS., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Frier et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2023
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21. The Most Dangerous Game: A Review of Head and Neck Injuries in American Football and Rugby.
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Richardson J, Stanbouly D, Moynihan H, Reynolds RM, Recker MJ, and Markiewicz MR
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Study Design: The investigators designed and implemented a 20-year cross-sectional study using the National Electronic Injury Surveillance System database., Objective: The purpose of this study is to estimate and compare hospital admission (danger) rates between rugby and football of those who presented to the emergency department with head and neck injuries after playing these sports., Methods: The primary predictor variable was sport played. The primary outcome variable was danger, measured by hospital admission rates., Results: Over the past 20 years, there has been a trend of decreasing incidence of injuries presenting to the emergency department in both sports. There was no difference in the rate of hospital admission when comparing football and rugby (OR, 1.2; P = .1). Male gender was associated with an increased risk of admission. Other variables associated with hospital admission included white racial group, injury taking place in the fall, being either young (15-24 years old) or senior (65 years of age and over), and being injured at school or at a sport/recreational facility., Conclusions: There is no difference in danger as measured by admission rates between American football and rugby. There exists, however, several variables that are associated with admission when sustaining injury to the head and neck, when playing these two sports., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)
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- 2023
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22. Implementation of a novel ultrasound training programme for midwives in Malawi: A mixed methods evaluation using the RE-AIM framework.
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Viner AC, Malata MP, Mtende M, Membe-Gadama G, Masamba M, Makwakwa E, Bamuya C, Lissauer D, Stock SJ, Norman JE, Reynolds RM, Magowan B, Freyne B, Gadama L, Cunningham-Burley S, Nyondo-Mipando L, and Chipeta E
- Abstract
Introduction: Despite recommendation that all women receive an ultrasound in pregnancy prior to 24 weeks', this remains unavailable to many women in low-income countries where trained practitioners are scarce. Although many programmes have demonstrated efficacy, few have achieved longterm sustainability, with a lack of information about how best to implement such programmes. This mixed-methods study aimed to evaluate the implementation of a novel education package to teach ultrasound-naive midwives in Malawi basic obstetric ultrasound, assessing its impact in the context of the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework., Methods: The study ran across six sites in Malawi between October 2020 and June 2021, encompassing three phases; pre-implementation, implementation and post-implementation. Twenty nine midwives underwent a bespoke education package with matched pre and post course surveys assessed their knowledge, attitudes and confidence and "hands on" assessments evaluating practical skills. Training evaluation forms and in-depth interviews explored their satisfaction with the package, with repeat assessment and remote image review evaluating maintenance of skills., Results: 28/29 midwives completed the training, with significant increases in knowledge, confidence and practical skills. Adherence to the education package varied, however many changes to the proposed methodology were adaptive and appeared to facilitate the efficacy of the programme. Unfortunately, despite reporting approval regarding the training itself, satisfaction regarding supervision and follow up was mixed, reflecting the difficulties encountered with providing ongoing in-person and remote support., Conclusion: This programme was successful in improving trainees' knowledge, confidence and skill in performing basic obstetric ultrasound, largely on account of an adaptive approach to implementation. The maintenance of ongoing support was challenging, reflected by trainee dissatisfaction. By evaluating the success of this education package based on its implementation and not just its efficacy, we have generated new insights into the barriers to sustainable upscale, specifically those surrounding maintenance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Viner, Malata, Mtende, Membe-Gadama, Masamba, Makwakwa, Bamuya, Lissauer, Stock, Norman, Reynolds, Magowan, Freyne, Gadama, Cunningham-Burley, Nyondo-Mipando and Chipeta.)
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- 2023
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23. Associations between parental type 2 diabetes risk and offspring birthweight and placental weight: a survival analysis using the Walker cohort.
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Sánchez-Soriano C, Pearson ER, and Reynolds RM
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- Male, Humans, Female, Pregnancy, Birth Weight genetics, Genome-Wide Association Study, Placenta, Parents, Survival Analysis, Diabetes Mellitus, Type 2 genetics
- Abstract
Aims/hypothesis: Low birthweight (BW) is associated with the development of type 2 diabetes. Genome-wide analyses have identified a strong genetic component to this association, with many BW-associated loci also involved in glucose metabolism. We hypothesised that offspring BW and placental weight (PW) are correlated with parental type 2 diabetes risk, reflecting the inheritance of diabetes risk alleles that also influence fetal growth., Methods: The Walker cohort, a collection of birth records from Dundee, Scotland, from the 1950s and the 1960s was used to test this hypothesis by linking BW and PW measurements to parental health outcomes. Using data from SCI-Diabetes and the national death registry, we obtained health records for over 20,000 Walker parents. We performed Fine-Gray survival analyses of parental type 2 diabetes risk with competing risk of death, and Cox regression analyses of risk of death, independently in the maternal and paternal datasets, modelled by offspring BW and PW., Results: We found significant associations between increased paternal type 2 diabetes risk and reduced offspring BW (subdistribution hazard ratio [SHR] 0.92 [95% CI 0.87, 0.98]) and PW (SHR 0.87 [95% CI 0.81, 0.94]). The association of maternal type 2 diabetes risk with offspring BW or PW was not significant. Lower offspring BW was also associated with increased risk of death in both mothers (HR 0.91 [95% CI 0.89, 0.94]) and fathers (HR 0.95 [95% CI 0.92, 0.98]), and higher offspring PW was associated with increased maternal mortality risk (HR 1.08 [95% CI 1.04, 1.13]) when adjusted for BW., Conclusions/interpretation: We identified associations between offspring BW and reduced paternal type 2 diabetes risk, most likely resulting from the independent effects of common type 2 diabetes susceptibility alleles on fetal growth, as described by the fetal insulin hypothesis. Moreover, we identified novel associations between offspring PW and reduced paternal type 2 diabetes risk, a relationship that might also be caused by the inheritance of diabetes predisposition variants. We found differing associations between offspring BW and PW and parental risk of death. These results provide novel epidemiological support for the use of offspring BW and PW as predictors for future risk of type 2 diabetes and death in mothers and fathers., (© 2022. The Author(s).)
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- 2022
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24. Variability in energy expenditure is much greater in males than females.
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Halsey LG, Careau V, Pontzer H, Ainslie PN, Andersen LF, Anderson LJ, Arab L, Baddou I, Bedu-Addo K, Blaak EE, Blanc S, Bonomi AG, Bouten CVC, Bovet P, Buchowski MS, Butte NF, Camps SGJA, Close GL, Cooper JA, Das SK, Cooper R, Dugas LR, Ekelund U, Entringer S, Forrester T, Fudge BW, Goris AH, Gurven M, Hambly C, Hamdouchi AE, Hoos MB, Hu S, Joonas N, Joosen AM, Katzmarzyk P, Kempen KP, Kimura M, Kraus WE, Kushner RF, Lambert EV, Leonard WR, Lessan N, Martin CK, Medin AC, Meijer EP, Morehen JC, Morton JP, Neuhouser ML, Nicklas TA, Ojiambo RM, Pietiläinen KH, Pitsiladis YP, Plange-Rhule J, Plasqui G, Prentice RL, Rabinovich RA, Racette SB, Raichlen DA, Ravussin E, Reynolds RM, Roberts SB, Schuit AJ, Sjödin AM, Stice E, Urlacher SS, Valenti G, Van Etten LM, Van Mil EA, Wilson G, Wood BM, Yanovski J, Yoshida T, Zhang X, Murphy-Alford AJ, Loechl CU, Luke AH, Rood J, Sagayama H, Schoeller DA, Westerterp KR, Wong WW, Yamada Y, and Speakman JR
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- Adult, Aged, Aging metabolism, Animals, Female, Humans, Male, Mammals, Reproduction physiology, Sex Characteristics, Body Composition, Energy Metabolism physiology
- Abstract
In mammals, trait variation is often reported to be greater among males than females. However, to date, mainly only morphological traits have been studied. Energy expenditure represents the metabolic costs of multiple physical, physiological, and behavioral traits. Energy expenditure could exhibit particularly high greater male variation through a cumulative effect if those traits mostly exhibit greater male variation, or a lack of greater male variation if many of them do not. Sex differences in energy expenditure variation have been little explored. We analyzed a large database on energy expenditure in adult humans (1494 males and 3108 females) to investigate whether humans have evolved sex differences in the degree of interindividual variation in energy expenditure. We found that, even when statistically comparing males and females of the same age, height, and body composition, there is much more variation in total, activity, and basal energy expenditure among males. However, with aging, variation in total energy expenditure decreases, and because this happens more rapidly in males, the magnitude of greater male variation, though still large, is attenuated in older age groups. Considerably greater male variation in both total and activity energy expenditure could be explained by greater male variation in levels of daily activity. The considerably greater male variation in basal energy expenditure is remarkable and may be explained, at least in part, by greater male variation in the size of energy-demanding organs. If energy expenditure is a trait that is of indirect interest to females when choosing a sexual partner, this would suggest that energy expenditure is under sexual selection. However, we present a novel energetics model demonstrating that it is also possible that females have been under stabilizing selection pressure for an intermediate basal energy expenditure to maximize energy available for reproduction., Competing Interests: Conflicts of interest The authors have no conflicts of interest to declare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2022
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25. Disparities among smokers during the COVID-19 pandemic: Examination of COVID-19-related worries by sociodemographic factors in a U.S. Nationally representative survey.
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Fairman RT, Weaver SR, Nyman AL, Popova L, Massey Z, Reynolds RM, and Spears CA
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Low-socioeconomic status (SES) and certain racial/ethnic minority groups disproportionately experience tobacco-related disease and death. Underserved populations of smokers may be at disproportionate risk for elevated stress and worry related to basic needs and healthcare during the pandemic, which could impede smoking cessation and exacerbate health disparities. This study examined whether experiences with stress and worry among smokers during the COVID-19 pandemic differed by sociodemographic factors, and whether these factors predicted serious psychological distress (SPD). Data came from an October-November 2020 U.S. national representative survey of 1,223 current cigarette smokers. Analyses examined associations between sociodemographic factors with COVID-19-related worries and past-month SPD. Worry in most domains (e.g., food, housing, finances, healthcare) was more prevalent among participants with less than high school education, income less than $30,000, and those who were unemployed. Women and participants aged 30-44, with income less than $30,000, with less than high school education, not working/disabled, or on Medicaid were more likely to experience SPD. Examined separately, each COVID-19 worry predicted higher likelihood of SPD. In adjusted models, COVID-19 worries about finances (aOR = 2.3) and isolation/loneliness (aOR = 3.0) uniquely predicted SPD. Among U.S. adult smokers during the COVID-19 pandemic, those with lower SES indicated disproportionately high worry about access to basic needs and were more likely to experience SPD. Policies and interventions that address basic needs and mental health among marginalized populations of tobacco users are needed., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)
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- 2022
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26. Impaired wound healing following cranial vault reconstruction in a patient with an atypical phenotype of Marfan syndrome: A case report.
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Recker MJ, Kronenwetter N, Reynolds RM, Sadler LS, and Markiewicz MR
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Background: Marfan syndrome (MFS) is an autosomal dominant disorder of the connective tissues caused by mutations in the FBN1 gene which can result in widespread systemic involvement. Loeys-Dietz syndrome (LDS) is a related autosomal dominant disorder of connective tissue with widespread systemic involvement which has phenotypic overlap with MFS. LDS is caused by heterozygous pathogenic variants in six different genes, the most common of which involve transforming growth factor beta-receptor 1 or 2. While LDS is commonly associated with craniofacial manifestations, MFS is not typically characterized by craniosynostosis., Case Description: We present a 7-month-old female patient with MFS and metopic craniosynostosis with an unusual clinical presentation who underwent cranial vault reconstruction with fronto-orbital advancement and anterior cranial vault remodeling. Her course was complicated by impaired wound healing after surgery, requiring return to the operating room., Conclusion: Phenotypic overlap between genetic disorders can confound clinical diagnosis as illustrated in this case. Genetic testing can be highly valuable in the diagnosis of clinically variable disorders. Patients with MFS who undergo cranial surgery may be at increased risk for wound healing complications., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Surgical Neurology International.)
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- 2022
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27. Pregnancy and the SARS-CoV-2 pandemic.
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Reynolds RM, Stock SJ, Denison FC, Maybin JA, and Critchley HOD
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- Female, Humans, Pandemics, Pregnancy, SARS-CoV-2, COVID-19, Pregnancy Complications, Infectious epidemiology
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- 2022
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28. Human total, basal and activity energy expenditures are independent of ambient environmental temperature.
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Zhang X, Yamada Y, Sagayama H, Ainslie PN, Blaak EE, Buchowski MS, Close GL, Cooper JA, Das SK, Dugas LR, Gurven M, El Hamdouchi A, Hu S, Joonas N, Katzmarzyk P, Kraus WE, Kushner RF, Leonard WR, Martin CK, Meijer EP, Neuhouser ML, Ojiambo RM, Pitsiladis YP, Plasqui G, Prentice RL, Racette SB, Ravussin E, Redman LM, Reynolds RM, Roberts SB, Sardinha LB, Silva AM, Stice E, Urlacher SS, Van Mil EA, Wood BM, Murphy-Alford AJ, Loechl C, Luke AH, Rood J, Schoeller DA, Westerterp KR, Wong WW, Pontzer H, and Speakman JR
- Abstract
Lower ambient temperature (T
a ) requires greater energy expenditure to sustain body temperature. However, effects of Ta on human energetics may be buffered by environmental modification and behavioral compensation. We used the IAEA DLW database for adults in the USA (n = 3213) to determine the effect of Ta (-10 to +30°C) on TEE, basal (BEE) and activity energy expenditure (AEE) and physical activity level (PAL). There were no significant relationships (p > 0.05) between maximum, minimum and average Ta and TEE, BEE, AEE and PAL. After adjustment for fat-free mass, fat mass and age, statistically significant (p < 0.01) relationships between TEE, BEE and Ta emerged in females but the effect sizes were not biologically meaningful. Temperatures inside buildings are regulated at 18-25°C independent of latitude. Hence, adults in the US modify their environments to keep TEE constant across a wide range of external ambient temperatures., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Authors.)- Published
- 2022
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29. Suitability of Dried Blood Spots for Accelerating Veterinary Biobank Collections and Identifying Metabolomics Biomarkers With Minimal Resources.
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Allaway D, Alexander JE, Carvell-Miller LJ, Reynolds RM, Winder CL, Weber RJM, Lloyd GR, Southam AD, and Dunn WB
- Abstract
Biomarker discovery using biobank samples collected from veterinary clinics would deliver insights into the diverse population of pets and accelerate diagnostic development. The acquisition, preparation, processing, and storage of biofluid samples in sufficient volumes and at a quality suitable for later analysis with most suitable discovery methods remain challenging. Metabolomics analysis is a valuable approach to detect health/disease phenotypes. Pre-processing changes during preparation of plasma/serum samples may induce variability that may be overcome using dried blood spots (DBSs). We report a proof of principle study by metabolite fingerprinting applying UHPLC-MS of plasma and DBSs acquired from healthy adult dogs and cats (age range 1-9 years), representing each of 4 dog breeds (Labrador retriever, Beagle, Petit Basset Griffon Vendeen, and Norfolk terrier) and the British domestic shorthair cat (n = 10 per group). Blood samples (20 and 40 μL) for DBSs were loaded onto filter paper, air-dried at room temperature (3 h), and sealed and stored (4°C for ~72 h) prior to storage at -80°C. Plasma from the same blood draw (250 μL) was prepared and stored at -80°C within 1 h of sampling. Metabolite fingerprinting of the DBSs and plasma produced similar numbers of metabolite features that had similar abilities to discriminate between biological classes and correctly assign blinded samples. These provide evidence that DBSs, sampled in a manner amenable to application in in-clinic/in-field processing, are a suitable sample for biomarker discovery using UHPLC-MS metabolomics. Further, given appropriate owner consent, the volumes tested (20-40 μL) make the acquisition of remnant blood from blood samples drawn for other reasons available for biobanking and other research activities. Together, this makes possible large-scale biobanking of veterinary samples, gaining sufficient material sooner and enabling quicker identification of biomarkers of interest., Competing Interests: DA, JA, LC-M, and RR are employed by Mars Petcare. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Allaway, Alexander, Carvell-Miller, Reynolds, Winder, Weber, Lloyd, Southam and Dunn.)
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- 2022
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30. Impact of Metformin Treatment on Human Placental Energy Production and Oxidative Stress.
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Tarry-Adkins JL, Robinson IG, Reynolds RM, Aye ILMH, Charnock-Jones DS, Jenkins B, Koulmann A, Ozanne SE, and Aiken CE
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Metformin is increasingly prescribed in pregnancy, with beneficial maternal effects. However, it is not known how metformin-treatment impacts metabolism and energy production in the developing feto-placental unit. We assessed the human placental response to metformin using both in vivo and in vitro treated samples. trophoblasts were derived from placentas collected from non-laboured Caesarean deliveries at term, then treated in vitro with metformin (0.01 mM, 0.1 mM or vehicle). Metformin-concentrations were measured using liquid-chromatography mass-spectrometry. Oxygen consumption in cultured-trophoblasts was measured using a Seahorse-XF Mito Stress Test. Markers of oxidative-stress were assayed using qRT-PCR. Metformin-transporter mRNA and protein-levels were determined by quantitative RT-PCR and Western-blotting respectively. Metformin concentrations were also measured in sample trios (maternal plasma/fetal plasma/placental tissue) from pregnancies exposed to metformin on clinical-grounds. Maternal and fetal metformin concentrations in vivo were highly correlated over a range of concentrations (R
2 = 0.76, p < 0.001; average fetal:maternal ratio 1.5; range 0.8-2.1). Basal respiration in trophoblasts was reduced by metformin treatment (0.01 mM metformin; p < 0.05, 0.1 mM metformin; p < 0.001). Mitochondrial-dependent ATP production and proton leak were reduced after treatment with metformin ( p < 0.001). Oxidative stress markers were significantly reduced in primary-trophoblast-cultures following treatment with metformin. There is a close linear relationship between placental, fetal, and maternal metformin concentrations. Primary-trophoblast cultures exposed to clinically-relevant metformin concentrations have reduced mitochondrial-respiration, mitochondrial-dependent ATP-production, and reduced markers of oxidative-stress. Given the crucial role of placental energy-production in supporting fetal growth and well-being during pregnancy, the implications of these findings are concerning for intrauterine fetal growth and longer-term metabolic programming in metformin-exposed pregnancies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tarry-Adkins, Robinson, Reynolds, Aye, Charnock-Jones, Jenkins, Koulmann, Ozanne and Aiken.)- Published
- 2022
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31. Training in Ultrasound to Determine Gestational Age (TUDA): Evaluation of a Novel Education Package to Teach Ultrasound-Naive Midwives Basic Obstetric Ultrasound in Malawi.
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Viner AC, Membe-Gadama G, Whyte S, Kayambo D, Masamba M, Makwakwa E, Lissauer D, Stock SJ, Norman JE, Reynolds RM, Magowan B, Freyne B, and Gadama L
- Abstract
Introduction: Although ultrasound to determine gestational age is fundamental to the optimum management of pregnancy and is recommended for all women by the World Health Organisation, it remains unavailable to many women in low-income countries where trained practitioners are scarce. This study aimed to evaluate a novel, context-specific education package to teach midwives basic obstetric ultrasound, including the determination of gestational age by measurement of fetal femur length., Methods: The study was conducted across six sites in Malawi in January 2021. Following a virtual "training of the trainers", local teams delivered a 10-day programme encompassing both didactic and "hands on" components. Matched pre and post course tests assessed participants' knowledge of key concepts, with Objective Structured Clinical Examinations used to evaluate practical skills. To achieve a pass, trainees were required to establish the gestational age to within ±7 days of an experienced practitioner and achieve an overall score of >65% on five consecutive occasions. A matched pre and post course survey explored participants' attitudes and confidence in performing ultrasound examinations., Results: Of the 29 midwives who participated, 28 finished the programme and met the criteria specified to pass. 22 midwives completed the matched knowledge tests, with the mean (SD) score increasing from 10.2 (3.3) to 18 (2.5) after training ( P <0.0001). Mean difference 7.9, 95% CI 6.5-9.2. Midwives passed 87% of the Observed Structured Clinical Examinations, establishing the gestational age to within ±7 days of an experienced practitioner in 89% of assessments. Beliefs regarding the importance of antenatal ultrasound increased post course ( p = 0.02), as did confidence in performing ultrasound examinations ( p <0.0001)., Conclusion: This study demonstrates not only that ultrasound-naive practitioners can be taught to perform basic obstetric ultrasound dating scans, confidently and competently, after 10 days of training, but also that local teams can be orientated to successfully deliver the programme virtually. Previous ultrasound training initiatives, while often more comprehensive in their syllabus, have been of considerably longer duration and this is likely to be a barrier to upscaling opportunities. We propose that this focused training increases the potential for widescale and sustainable implementation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Viner, Membe-Gadama, Whyte, Kayambo, Masamba, Makwakwa, Lissauer, Stock, Norman, Reynolds, Magowan, Freyne and Gadama.)
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- 2022
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32. AiDAPT: automated insulin delivery amongst pregnant women with type 1 diabetes: a multicentre randomized controlled trial - study protocol.
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Lee TTM, Collett C, Man MS, Hammond M, Shepstone L, Hartnell S, Gurnell E, Byrne C, Scott EM, Lindsay RS, Morris D, Brackenridge A, Dover AR, Reynolds RM, Hunt KF, McCance DR, Barnard-Kelly K, Rankin D, Lawton J, Bocchino LE, Sibayan J, Kollman C, Wilinska ME, Hovorka R, and Murphy HR
- Subjects
- Blood Glucose analysis, Blood Glucose Self-Monitoring, Female, Humans, Hypoglycemic Agents therapeutic use, Infant, Newborn, Insulin therapeutic use, Insulin Infusion Systems, Multicenter Studies as Topic, Pregnancy, Pregnant Women, Randomized Controlled Trials as Topic, Diabetes Mellitus, Type 1 drug therapy
- Abstract
Background: Pregnant women with type 1 diabetes strive for tight glucose targets (3.5-7.8 mmol/L) to minimise the risks of obstetric and neonatal complications. Despite using diabetes technologies including continuous glucose monitoring (CGM), insulin pumps and contemporary insulin analogues, most women struggle to achieve and maintain the recommended pregnancy glucose targets. This study aims to evaluate whether the use of automated closed-loop insulin delivery improves antenatal glucose levels in pregnant women with type 1 diabetes., Methods/design: A multicentre, open label, randomized, controlled trial of pregnant women with type 1 diabetes and a HbA1c of ≥48 mmol/mol (6.5%) at pregnancy confirmation and ≤ 86 mmol/mol (10%) at randomization. Participants who provide written informed consent before 13 weeks 6 days gestation will be entered into a run-in phase to collect 96 h (24 h overnight) of CGM glucose values. Eligible participants will be randomized on a 1:1 basis to CGM (Dexcom G6) with usual insulin delivery (control) or closed-loop (intervention). The closed-loop system includes a model predictive control algorithm (CamAPS FX application), hosted on an android smartphone that communicates wirelessly with the insulin pump (Dana Diabecare RS) and CGM transmitter. Research visits and device training will be provided virtually or face-to-face in conjunction with 4-weekly antenatal clinic visits where possible. Randomization will stratify for clinic site. One hundred twenty-four participants will be recruited. This takes into account 10% attrition and 10% who experience miscarriage or pregnancy loss. Analyses will be performed according to intention to treat. The primary analysis will evaluate the change in the time spent in the target glucose range (3.5-7.8 mmol/l) between the intervention and control group from 16 weeks gestation until delivery. Secondary outcomes include overnight time in target, time above target (> 7.8 mmol/l), standard CGM metrics, HbA1c and psychosocial functioning and health economic measures. Safety outcomes include the number and severity of ketoacidosis, severe hypoglycaemia and adverse device events., Discussion: This will be the largest randomized controlled trial to evaluate the impact of closed-loop insulin delivery during type 1 diabetes pregnancy., Trial Registration: ISRCTN 56898625 Registration Date: 10 April, 2018., (© 2022. The Author(s).)
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- 2022
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33. Training in Ultrasound to Determine Gestational Age in Low- and Middle- Income Countries: A Systematic Review.
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Viner AC, Okolo ID, Norman JE, Stock SJ, and Reynolds RM
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Introduction: Establishing an accurate gestational age is essential for the optimum management of pregnancy, delivery and neonatal care, with improved estimates of gestational age considered a public health priority by the World Health Organization (WHO). Although ultrasound is considered the most precise method to achieve this, it is unavailable to many women in low- and middle- income countries (LMICs), where the lack of trained practitioners is considered a major barrier. This systematic review explores what initiatives have previously been undertaken to train staff to date pregnancies using ultrasound, which were successful and what barriers and facilitators influenced training., Methods: The systematic review was conducted according to PRISMA guidelines and the protocol registered (PROSPERO CRD42019154619). Searches were last performed in July 2021. Studies were screened independently by two assessors, with data extracted by one and verified by the other. Both reviewers graded the methodological quality using the Mixed Methods Assessment Tool. Results were collated within prespecified domains, generating a narrative synthesis., Results: 25/1,262 studies were eligible for inclusion, all of which were programme evaluations. Eighteen were undertaken in Africa, three in South-East Asia, one in South America, and three across multiple sites, including those in Africa, Asia, and South America. Five programs specified criteria to pass, and within these 96% of trainees did so. Trainee follow up was undertaken in 18 studies. Ten met recommendations for training outlined by the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) but only 1 met the current standards set by the WHO., Discussion: This systematic review is the first to evaluate this topic and has uncovered major inconsistencies in the delivery and reporting of basic obstetric ultrasound training in LMICs, with the majority of programs not meeting minimum recommendations. By identifying these issues, we have highlighted key areas for improvement and made recommendations for reporting according to the RE-AIM framework. With an increasing focus on the importance of improving estimates of gestational age in LMICs, we believe these findings will be of significance to those seeking to develop and expand the provision of sustainable obstetric ultrasound in LMICs., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019154619, PROSPERO CRD42019154619., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Viner, Okolo, Norman, Stock and Reynolds.)
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- 2022
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34. Development of type 2 diabetes in women with comorbid gestational diabetes and common mental disorders in the Born in Bradford cohort.
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Wilson CA, Santorelli G, Reynolds RM, Simonoff E, Howard LM, and Ismail K
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- Comorbidity, Female, Humans, Pregnancy, Prospective Studies, Diabetes Mellitus, Type 2 epidemiology, Diabetes, Gestational epidemiology, Mental Disorders epidemiology
- Abstract
Objectives: To compare, in a population of women with gestational diabetes mellitus (GDM), the time to diagnosis of Type 2 diabetes in those with and without common mental disorder (CMD) (depression and/or anxiety) during pregnancy., Design and Setting: prospective study of the Born in Bradford cohort in Bradford, UK., Participants: 909 women diagnosed with GDM between 2007 and 2010, with linkage to their primary care records until 2017. The exposed population were women with an indicator of CMD during pregnancy in primary care records. The unexposed were those without an indicator., Outcome Measures: Time to diagnosis of type 2 diabetes as indicated by a diagnosis in primary care records., Analysis: time to event analysis using Cox regression was employed. Multiple imputation by chained equations was implemented to handle missing data. Models were adjusted for maternal age, ethnicity, education, preconception CMD and tobacco smoking during pregnancy., Results: 165 women (18%) were diagnosed with type 2 diabetes over a follow-up period of around 10 years. There was no evidence of an effect of antenatal CMD on the development of type 2 diabetes following GDM (adjusted HR 0.95; 95% CI 0.57 to 1.57)., Conclusions: Women with CMD were not at an increased risk of type 2 diabetes following GDM. This is reassuring for women with these co-morbidities but requires replication in other study populations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)
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- 2022
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35. High prevalence of obstructive sleep apnea in pregnant women with class III obesity: a prospective cohort study.
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Johns EC, Hill EA, Williams S, Sabil A, Riha RL, Denison FC, and Reynolds RM
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- Cohort Studies, Female, Humans, Obesity complications, Obesity epidemiology, Pregnancy, Prevalence, Prospective Studies, Pregnant Women, Sleep Apnea, Obstructive complications, Sleep Apnea, Obstructive epidemiology
- Abstract
Study Objectives: To determine the prevalence of obstructive sleep apnea (OSA) in a cohort of women with class III obesity, and a comparator lean group, in the second and third trimesters of pregnancy. Secondary objectives were to compare characteristics of women with obesity with and without OSA and to assess factors that were predictive of OSA., Methods: We performed a prospective cohort study involving 33 women with class III obesity (mean body mass index 43.5 ± 3.9 kg/m
2 ) and 39 lean women (body mass index 22.0 ± 1.7 kg/m2 ) with singleton pregnancies. Participants completed 2 level 3 sleep studies between 12-22 weeks and 32-38 weeks gestation. OSA was defined as a respiratory event index ≥ 5 events/h (≥ 3% desaturation criteria). Levels of interleukin-6, glucose, and C-peptide were quantified in maternal blood. Logistic regression analysis was performed to determine predictors of OSA., Results: OSA was identified in 12 (37.5%) and 14 (50.0%) women with obesity and in 1 (2.6%) and 3 (9.1%) lean women in the second and third trimesters, respectively. Women with obesity with OSA were older than those with no OSA but otherwise had similar characteristics. In unadjusted analysis of women with obesity, increased age, body mass index, homeostatic model assessment of insulin resistance, and history of nonsmoking were associated with increased odds of OSA. In multivariable analysis, only increased age remained significantly associated with OSA., Conclusions: OSA is highly prevalent in pregnant women with class III obesity. Further research is required to establish effective management strategies for the growing number of women in this high-risk group., Citation: Johns EC, Hill EA, Williams S, et al. High prevalence of obstructive sleep apnea in pregnant women with class III obesity: a prospective cohort study. J Clin Sleep Med . 2022;18(2):423-432., (© 2022 American Academy of Sleep Medicine.)- Published
- 2022
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36. Trust in COVID-19 information sources and perceived risk among smokers: A nationally representative survey.
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Reynolds RM, Weaver SR, Nyman AL, and Eriksen MP
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- Adult, Aged, Aged, 80 and over, Attitude to Health, COVID-19 prevention & control, Cigarette Smoking adverse effects, Disease Susceptibility psychology, Educational Status, Female, Health Knowledge, Attitudes, Practice, Humans, Information Dissemination methods, Male, Middle Aged, Public Health trends, Risk Factors, SARS-CoV-2 pathogenicity, Surveys and Questionnaires, Trust psychology, United States, COVID-19 psychology, Patient Acceptance of Health Care psychology, Smokers psychology
- Abstract
Background: Public health officials have classified smoking as a risk factor for COVID-19 disease severity. Smokers generally have less trust in health experts than do nonsmokers, leading to reduced risk perceptions. This study addresses smokers' trust in information sources about COVID-19 and how trust is associated with perceived COVID-19 susceptibility and severity among smokers., Methods and Findings: A nationally representative sample of 1,223 current smokers were surveyed between October and November 2020, indicating their level of trust in COVID-19 information sources, and their perceptions of risk from COVID-19. Multiple differences in trustworthiness emerged; smokers trusted their personal doctor for information about COVID-19 more than other information sources, while news media were generally distrusted. In addition, the FDA was trusted less than the NIH and CDC. Several "trust gaps" were observed, indicating disparities in levels of trust associated with gender, ethnicity, education, and political orientation, which had the strongest association with trust of all factors. Political orientation was also a significant predictor of COVID-19 risk perceptions, but there was no independent effect of political orientation when accounting for trust, which was predictive of all risk perception outcomes., Conclusions: Trusted sources, such as personal doctors, may most effectively convey COVID-19 information across political orientations and sociodemographic groups. News media may be ineffective at informing smokers due to their low credibility. The results suggest that trust may explain the apparent effect of political orientation on COVID-19 risk perceptions. Implications for researchers, communication professionals, and policy makers are discussed., Competing Interests: The authors have declared that no competing interests exist.
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- 2022
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37. Total energy expenditure is repeatable in adults but not associated with short-term changes in body composition.
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Rimbach R, Yamada Y, Sagayama H, Ainslie PN, Anderson LF, Anderson LJ, Arab L, Baddou I, Bedu-Addo K, Blaak EE, Blanc S, Bonomi AG, Bouten CVC, Bovet P, Buchowski MS, Butte NF, Camps SGJA, Close GL, Cooper JA, Das SK, Dugas LR, Ekelund U, Entringer S, Forrester T, Fudge BW, Goris AH, Gurven M, Hambly C, El Hamdouchi A, Hoos MB, Hu S, Joonas N, Joosen AM, Katzmarzyk P, Kempen KP, Kimura M, Kraus WE, Kushner RF, Lambert EV, Leonard WR, Lessan N, Martin CK, Medin AC, Meijer EP, Morehen JC, Morton JP, Neuhouser ML, Nicklas TA, Ojiambo RM, Pietiläinen KH, Pitsiladis YP, Plange-Rhule J, Plasqui G, Prentice RL, Rabinovich RA, Racette SB, Raichlen DA, Ravussin E, Reynolds RM, Roberts SB, Schuit AJ, Sjödin AM, Stice E, Urlacher SS, Valenti G, Van Etten LM, Van Mil EA, Wells JCK, Wilson G, Wood BM, Yanovski J, Yoshida T, Zhang X, Murphy-Alford AJ, Loechl CU, Luke AH, Rood J, Schoeller DA, Westerterp KR, Wong WW, Speakman JR, and Pontzer H
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- Adult, Bayes Theorem, Child, Databases, Factual, Female, Humans, Isotope Labeling, Longitudinal Studies, Male, Middle Aged, Weight Gain physiology, Adipose Tissue metabolism, Body Composition physiology, Energy Metabolism physiology, Water metabolism
- Abstract
Low total energy expenditure (TEE, MJ/d) has been a hypothesized risk factor for weight gain, but repeatability of TEE, a critical variable in longitudinal studies of energy balance, is understudied. We examine repeated doubly labeled water (DLW) measurements of TEE in 348 adults and 47 children from the IAEA DLW Database (mean ± SD time interval: 1.9 ± 2.9 y) to assess repeatability of TEE, and to examine if TEE adjusted for age, sex, fat-free mass, and fat mass is associated with changes in weight or body composition. Here, we report that repeatability of TEE is high for adults, but not children. Bivariate Bayesian mixed models show no among or within-individual correlation between body composition (fat mass or percentage) and unadjusted TEE in adults. For adults aged 20-60 y (N = 267; time interval: 7.4 ± 12.2 weeks), increases in adjusted TEE are associated with weight gain but not with changes in body composition; results are similar for subjects with intervals >4 weeks (N = 53; 29.1 ± 12.8 weeks). This suggests low TEE is not a risk factor for, and high TEE is not protective against, weight or body fat gain over the time intervals tested., (© 2022. The Author(s).)
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- 2022
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38. Interventions to reduce preterm birth and stillbirth, and improve outcomes for babies born preterm in low- and middle-income countries: A systematic review.
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Wastnedge E, Waters D, Murray SR, McGowan B, Chipeta E, Nyondo-Mipando AL, Gadama L, Gadama G, Masamba M, Malata M, Taulo F, Dube Q, Kawaza K, Khomani PM, Whyte S, Crampin M, Freyne B, Norman JE, and Reynolds RM
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- Developing Countries, Female, Humans, Infant, Infant, Newborn, Infant, Premature, Pregnancy, Resuscitation, Premature Birth epidemiology, Premature Birth prevention & control, Stillbirth epidemiology
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Background: Reducing preterm birth and stillbirth and improving outcomes for babies born too soon is essential to reduce under-5 mortality globally. In the context of a rapidly evolving evidence base and problems with extrapolating efficacy data from high- to low-income settings, an assessment of the evidence for maternal and newborn interventions specific to low- and middle-income countries (LMICs) is required., Methods: A systematic review of the literature was done. We included all studies performed in LMICs since the Every Newborn Action Plan, between 2013 - 2018, which reported on interventions where the outcome assessed was reduction in preterm birth or stillbirth incidence and/or a reduction in preterm infant neonatal mortality. Evidence was categorised according to maternal or neonatal intervention groups and a narrative synthesis conducted., Results: 179 studies (147 primary evidence studies and 32 systematic reviews) were identified in 82 LMICs. 81 studies reported on maternal interventions and 98 reported on neonatal interventions. Interventions in pregnant mothers which resulted in significant reductions in preterm birth and stillbirth were (i) multiple micronutrient supplementation and (ii) enhanced quality of antenatal care. Routine antenatal ultrasound in LMICs increased identification of fetal antenatal conditions but did not reduce stillbirth or preterm birth due to the absence of services to manage these diagnoses. Interventions in pre-term neonates which improved their survival included (i) feeding support including probiotics and (ii) thermal regulation. Improved provision of neonatal resuscitation did not improve pre-term mortality rates, highlighting the importance of post-resuscitation care. Community mobilisation, for example through community education packages, was found to be an effective way of delivering interventions., Conclusions: Evidence supports the implementation of several low-cost interventions with the potential to deliver reductions in preterm birth and stillbirth and improve outcomes for preterm babies in LMICs. These, however, must be complemented by overall health systems strengthening to be effective. Quality improvement methodology and learning health systems approaches can provide important means of understanding and tackling implementation challenges within local contexts. Further pragmatic efficacy trials of interventions in LMICs are essential, particularly for interventions not previously tested in these contexts., Competing Interests: Competing interests: The authors completed the ICMJE Unified Competing Interest form (available upon request from the corresponding author), and declare no conflicts of interest., (Copyright © 2021 by the Journal of Global Health. All rights reserved.)
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- 2021
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39. Spinal cord detethering without laminectomy or laminotomy.
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Housley SB, Patel D, Nyabuto E, and Reynolds RM
- Abstract
Background: Tethered cord syndrome occurs when there is abnormal tension on the distal spinal cord, which limits its elevation as patients grow. This results in stretching of the neural elements and microvasculature, resulting in both direct and ischemic injury.[7] Animal studies suggest that impairment of oxidative metabolic pathways may contribute to neuronal injury.[7] Associated conditions include myelomeningocele, lipomyelomeningocele, intraspinal lipomas, diastematomyelia, thickened/fatty filum terminale, and trauma.[2] Tethering may be asymptomatic or result in a variety of symptoms including lower extremity weakness/sensory deficits, bowel/bladder dysfunction, scoliosis, pes cavus, and back/leg pain.[6] Early surgical intervention has been shown to improve outcomes and may be performed prophylactically or to prevent symptom progression.[1,3] More specifically, retrospective studies demonstrate that surgical intervention in patients under the age of 2 years is associated with improved outcomes.[5] In some cases, detethering may result in clinical improvement.[3]., Case Description: We present a case of a 6-month-old male with a low-lying conus medullaris, lumbar syrinx, mildly abnormal urodynamic studies, and asymmetric utilization of his lower extremities observed during the evaluation of a Y-shaped gluteal cleft. He underwent elective spinal cord detethering via the safe and effective, minimally invasive technique described in the video.The patient's parents gave informed consent for treatment and video recording. Institutional review board approval was deemed unnecessary., Conclusion: Given the variety of surgical techniques used for cord detethering, this video may assist other surgeons in developing techniques that require little to no compromise of the developing bony spinal column while achieving sufficient release of the spinal cord.[4]., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Surgical Neurology International.)
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- 2021
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40. Associations between COVID-19 risk perceptions and smoking and quitting behavior among U.S. adults.
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Nyman AL, Spears CA, Churchill V, Do VV, Henderson KC, Massey ZB, Reynolds RM, and Huang J
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Objectives: The COVID-19 pandemic may impact cigarette smokers' behaviors. Among smokers, perceptions about the risks of contracting COVID-19 and the severity of COVID-19 illness likely vary, and perceptions may be associated with individual smoking behavior. Our study measured smokers' perceptions of COVID-19 risks and their association with smoking and quitting outcomes., Methods: A sample of 1,223 U.S. adult cigarette smokers participated in an online survey in October-November 2020 to assess their COVID-19-related risk perceptions and changes in smoking, readiness to quit, and quit attempts during the COVID-19 pandemic., Results: More smokers believed smoking could increase the severity of COVID-19 (43.6%, 95% CI: 40.1, 47.3) than believed smoking makes them more susceptible to COVID-19 (20.0%, 95% CI: 17.2, 23.0.). While there were no associations between perceptions of COVID-19 susceptibility and smoking behaviors or intentions, perceptions of greater smoking-related COVID-19 severity were associated with both higher likelihood of smoking increases (aOR: 2.16, 95% CI: 1.19, 3.93) and greater readiness to quit smoking (aOR: 1.65, 95% CI: 1.18, 2.30). Greater perceptions of general COVID-19 severity were associated with higher likelihood of smoking reductions (aOR: 1.12, 95% CI: 1.02, 1.22), greater readiness to quit smoking (aOR: 1.14, 95% CI: 1.07, 1.22), and higher likelihood of making a quit attempt (aOR: 1.12, 95% CI: 1.04, 1.22)., Conclusions: Smokers' perceptions about COVID-19 severity are related to their smoking behavior and likelihood of making a quit attempt. Providing smokers with accurate information on the relationship between smoking and the severity of COVID-19 may alter smoking behaviors., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)
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- 2021
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41. Physical activity and fat-free mass during growth and in later life.
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Westerterp KR, Yamada Y, Sagayama H, Ainslie PN, Andersen LF, Anderson LJ, Arab L, Baddou I, Bedu-Addo K, Blaak EE, Blanc S, Bonomi AG, Bouten CVC, Bovet P, Buchowski MS, Butte NF, Camps SGJA, Close GL, Cooper JA, Das SK, Cooper R, Dugas LR, Ekelund U, Entringer S, Forrester T, Fudge BW, Goris AH, Gurven M, Hambly C, El Hamdouchi A, Hoos MB, Hu S, Joonas N, Joosen AM, Katzmarzyk P, Kempen KP, Kimura M, Kraus WE, Kushner RF, Lambert EV, Leonard WR, Lessan N, Martin CK, Medin AC, Meijer EP, Morehen JC, Morton JP, Neuhouser ML, Nicklas TA, Ojiambo RM, Pietiläinen KH, Pitsiladis YP, Plange-Rhule J, Plasqui G, Prentice RL, Rabinovich RA, Racette SB, Raichlen DA, Ravussin E, Reynolds RM, Roberts SB, Schuit AJ, Sjödin AM, Stice E, Urlacher SS, Valenti G, Van Etten LM, Van Mil EA, Wells JCK, Wilson G, Wood BM, Yanovski J, Yoshida T, Zhang X, Murphy-Alford AJ, Loechl CU, Luke AH, Pontzer H, Rood J, Schoeller DA, Wong WW, and Speakman JR
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Cross-Sectional Studies, Energy Metabolism, Female, Humans, Male, Middle Aged, Young Adult, Adipose Tissue metabolism, Body Composition, Exercise
- Abstract
Background: Physical activity may be a way to increase and maintain fat-free mass (FFM) in later life, similar to the prevention of fractures by increasing peak bone mass., Objectives: A study is presented of the association between FFM and physical activity in relation to age., Methods: In a cross-sectional study, FFM was analyzed in relation to physical activity in a large participant group as compiled in the International Atomic Energy Agency Doubly Labeled Water database. The database included 2000 participants, age 3-96 y, with measurements of total energy expenditure (TEE) and resting energy expenditure (REE) to allow calculation of physical activity level (PAL = TEE/REE), and calculation of FFM from isotope dilution., Results: PAL was a main determinant of body composition at all ages. Models with age, fat mass (FM), and PAL explained 76% and 85% of the variation in FFM in females and males < 18 y old, and 32% and 47% of the variation in FFM in females and males ≥ 18 y old, respectively. In participants < 18 y old, mean FM-adjusted FFM was 1.7 kg (95% CI: 0.1, 3.2 kg) and 3.4 kg (95% CI: 1.0, 5.6 kg) higher in a very active participant with PAL = 2.0 than in a sedentary participant with PAL = 1.5, for females and males, respectively. At age 18 y, height and FM-adjusted FFM was 3.6 kg (95% CI: 2.8, 4.4 kg) and 4.4 kg (95% CI: 3.2, 5.7 kg) higher, and at age 80 y 0.7 kg (95% CI: -0.2, 1.7 kg) and 1.0 kg (95% CI: -0.1, 2.1 kg) higher, in a participant with PAL = 2.0 than in a participant with PAL = 1.5, for females and males, respectively., Conclusions: If these associations are causal, they suggest physical activity is a major determinant of body composition as reflected in peak FFM, and that a physically active lifestyle can only partly protect against loss of FFM in aging adults., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)
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- 2021
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42. Energy compensation and adiposity in humans.
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Careau V, Halsey LG, Pontzer H, Ainslie PN, Andersen LF, Anderson LJ, Arab L, Baddou I, Bedu-Addo K, Blaak EE, Blanc S, Bonomi AG, Bouten CVC, Buchowski MS, Butte NF, Camps SGJA, Close GL, Cooper JA, Das SK, Cooper R, Dugas LR, Eaton SD, Ekelund U, Entringer S, Forrester T, Fudge BW, Goris AH, Gurven M, Hambly C, El Hamdouchi A, Hoos MB, Hu S, Joonas N, Joosen AM, Katzmarzyk P, Kempen KP, Kimura M, Kraus WE, Kushner RF, Lambert EV, Leonard WR, Lessan N, Martin CK, Medin AC, Meijer EP, Morehen JC, Morton JP, Neuhouser ML, Nicklas TA, Ojiambo RM, Pietiläinen KH, Pitsiladis YP, Plange-Rhule J, Plasqui G, Prentice RL, Rabinovich RA, Racette SB, Raichlen DA, Ravussin E, Reilly JJ, Reynolds RM, Roberts SB, Schuit AJ, Sjödin AM, Stice E, Urlacher SS, Valenti G, Van Etten LM, Van Mil EA, Wells JCK, Wilson G, Wood BM, Yanovski J, Yoshida T, Zhang X, Murphy-Alford AJ, Loechl CU, Luke AH, Rood J, Sagayama H, Schoeller DA, Wong WW, Yamada Y, and Speakman JR
- Subjects
- Energy Intake, Energy Metabolism physiology, Humans, Adiposity, Obesity metabolism
- Abstract
Understanding the impacts of activity on energy balance is crucial. Increasing levels of activity may bring diminishing returns in energy expenditure because of compensatory responses in non-activity energy expenditures.
1-3 This suggestion has profound implications for both the evolution of metabolism and human health. It implies that a long-term increase in activity does not directly translate into an increase in total energy expenditure (TEE) because other components of TEE may decrease in response-energy compensation. We used the largest dataset compiled on adult TEE and basal energy expenditure (BEE) (n = 1,754) of people living normal lives to find that energy compensation by a typical human averages 28% due to reduced BEE; this suggests that only 72% of the extra calories we burn from additional activity translates into extra calories burned that day. Moreover, the degree of energy compensation varied considerably between people of different body compositions. This association between compensation and adiposity could be due to among-individual differences in compensation: people who compensate more may be more likely to accumulate body fat. Alternatively, the process might occur within individuals: as we get fatter, our body might compensate more strongly for the calories burned during activity, making losing fat progressively more difficult. Determining the causality of the relationship between energy compensation and adiposity will be key to improving public health strategies regarding obesity., Competing Interests: Declaration of interests The authors have no conflicts of interest to declare., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2021
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43. Longitudinal Metabolic Profiling of Maternal Obesity, Gestational Diabetes, and Hypertensive Pregnancy Disorders.
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Kivelä J, Sormunen-Harju H, Girchenko PV, Huvinen E, Stach-Lempinen B, Kajantie E, Villa PM, Reynolds RM, Hämäläinen EK, Lahti-Pulkkinen M, Murtoniemi KK, Laivuori H, Eriksson JG, Räikkönen K, and Koivusalo SB
- Subjects
- Adult, Body Mass Index, Female, Gestational Age, Humans, Longitudinal Studies, Magnetic Resonance Spectroscopy, Metabolomics methods, Obesity complications, Pre-Eclampsia, Pregnancy, Pregnancy Complications blood, Diabetes, Gestational blood, Hypertension, Pregnancy-Induced blood, Metabolome physiology, Obesity, Maternal blood
- Abstract
Context: Comprehensive assessment of metabolism in maternal obesity and pregnancy disorders can provide information about the shared maternal-fetal milieu and give insight into both maternal long-term health and intergenerational transmission of disease burden., Objective: To assess levels, profiles, and change in the levels of metabolic measures during pregnancies complicated by obesity, gestational diabetes (GDM), or hypertensive disorders., Design, Setting and Participants: A secondary analysis of 2 study cohorts, PREDO and RADIEL, including 741 pregnant women., Main Outcome Measures: We assessed 225 metabolic measures by nuclear magnetic resonance in blood samples collected at median 13 [interquartile range (IQR) 12.4-13.7], 20 (IQR 19.3-23.0), and 28 (27.0-35.0) weeks of gestation., Results: Across all 3 time points women with obesity [body mass index (BMI) ≥ 30kg/m2] in comparison to normal weight (BMI 18.5-24.99 kg/m2) had significantly higher levels of most very-low-density lipoprotein-related measures, many fatty and most amino acids, and more adverse metabolic profiles. The change in the levels of most metabolic measures during pregnancy was smaller in obese than in normal weight women. GDM, preeclampsia, and chronic hypertension were associated with metabolic alterations similar to obesity. The associations of obesity held after adjustment for GDM and hypertensive disorders, but many of the associations with GDM and hypertensive disorders were rendered nonsignificant after adjustment for BMI and the other pregnancy disorders., Conclusions: This study shows that the pregnancy-related metabolic change is smaller in women with obesity, who display metabolic perturbations already in early pregnancy. Metabolic alterations of obesity and pregnancy disorders resembled each other suggesting a shared metabolic origin., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)
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- 2021
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44. Hair glucocorticoids are associated with childhood adversity, depressive symptoms and reduced global and lobar grey matter in Generation Scotland.
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Green C, Stolicyn A, Harris MA, Shen X, Romaniuk L, Barbu MC, Hawkins EL, Wardlaw JM, Steele JD, Waiter GD, Sandu AL, Campbell A, Porteous DJ, Seckl JR, Lawrie SM, Reynolds RM, Cavanagh J, McIntosh AM, and Whalley HC
- Subjects
- Depression, Glucocorticoids, Gray Matter, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Middle Aged, Pituitary-Adrenal System, Adverse Childhood Experiences, Depressive Disorder, Major
- Abstract
Hypothalamic-pituitary-adrenal (HPA) axis dysregulation has been commonly reported in major depressive disorder (MDD), but with considerable heterogeneity of results; potentially due to the predominant use of acute measures of an inherently variable/phasic system. Chronic longer-term measures of HPA-axis activity have yet to be systematically examined in MDD, particularly in relation to brain phenotypes, and in the context of early-life/contemporaneous stress. Here, we utilise a temporally stable measure of cumulative HPA-axis function (hair glucocorticoids) to investigate associations between cortisol, cortisone and total glucocorticoids with concurrent measures of (i) lifetime-MDD case/control status and current symptom severity, (ii) early/current-life stress and (iii) structural neuroimaging phenotypes, in N = 993 individuals from Generation Scotland (mean age = 59.1 yrs). Increased levels of hair cortisol were significantly associated with reduced global and lobar brain volumes with reductions in the frontal, temporal and cingulate regions (β
range = -0.057 to -0.104, all PFDR < 0.05). Increased levels of hair cortisone were significantly associated with MDD (lifetime-MDD status, current symptoms, and severity; βrange = 0.071 to 0.115, all PFDR = < 0.05), with early-life adversity (β = 0.083, P = 0.017), and with reduced global and regional brain volumes (global: β = -0.059, P = 0.043; nucleus accumbens: β = -0.075, PFDR = 0.044). Associations with total glucocorticoids followed a similar pattern to the cortisol findings. In this large community-based sample, elevated glucocorticoids were significantly associated with MDD, with early, but not later-life stress, and with reduced global and regional brain phenotypes. These findings provide important foundations for future mechanistic studies to formally explore causal relationships between early adversity, chronic rather than acute measures of glucocorticoids, and neurobiological associations relevant to the aetiology of MDD., (© 2021. The Author(s).)- Published
- 2021
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45. Parent priorities for research and communication concerning childhood outcomes following preterm birth.
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Ginnell L, Boardman JP, Reynolds RM, and Fletcher-Watson S
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Background: Children born preterm (before 37 weeks of gestation) are at risk for several adverse childhood outcomes. Parent priorities for research into these outcomes, and preferences for receiving information about these risks, have not previously been established. Here we report the results of an online survey designed to understand parent priorities for research and their preferences for receiving information about childhood outcomes. Methods: An online survey was circulated through social media and was completed by 148 parents of preterm children between the ages of 0 and 12 years from around the United Kingdom (UK). Survey questions were in the form of rating scale, multiple choice, ranking or open-ended free text questions. Descriptive analysis was applied to the quantitative data. Illustrative quotes were extracted from the qualitative free text data and a subset of these questions were analysed using framework analysis. Results: Parent priorities for research centre around identification of factors which can protect against or improve adverse cognitive or developmental outcomes. The majority of parents would prefer for communication to begin within the first year of the child's life. Parents reported a knowledge gap among health visitors, early years educators and schools. Conclusions: In order to align with parent preferences, research should prioritise identification of protective factors and the development of effective interventions to improve outcomes. Training for health visitors and educational professionals could improve the experiences of families and children., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Ginnell L et al.)
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- 2021
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46. A Life Course Approach to the Relationship Between Fetal Growth and Hypothalamic-Pituitary-Adrenal Axis Function.
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Martin WN, Wang CA, Lye SJ, Matthews SG, Reynolds RM, McLaughlin CE, Smith R, and Pennell CE
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- Adolescent, Birth Weight, Female, Humans, Hydrocortisone blood, Male, Stress, Psychological physiopathology, Young Adult, Fetal Development physiology, Hypothalamo-Hypophyseal System physiology, Pituitary-Adrenal System physiology
- Abstract
Context: Human and animal studies suggest that hypothalamic-pituitary-adrenal axis (HPA-A) function may be programmed in utero; however, these findings are inconsistent. Given the powerful metabolic actions of cortisol, it is important to clarify the influence of early life on adult HPA-A function., Objective: To determine the relationship between fetal growth and HPA-A stress response to a psychosocial stressor in young adults., Design: Multigenerational, prospective cohort study (the Raine Study) conducted between 1989 and 1991., Setting: King Edward Memorial Hospital, Perth, Western Australia, Australia., Participants: A total of 917 participants aged 18 years from Gen2 of the Raine Study., Main Outcome Measures: Measures of hypothalamic-pituitary-adrenal axis function before and after exposure to the Trier Social Stress Test., Results: In fully adjusted models, an inverse linear relationship was observed between birthweight and plasma measures of (1) baseline cortisol (β = -0.90%, 95% CI: -1.73 to -0.07; P = 0.03); (2) peak cortisol (β = -0.78%, 95% CI -1.51 to -0.06; P = 0.03); (3) area under the curve with respect to ground (β = -0.89%, 95% CI -1.60 to -0.18; P = 0.01); and (4) adrenal sensitivity (β = -1.02, 95% CI: -1.85 to -0.18; P = 0.02). Similar results were demonstrated for percent optimal birthweight. No consistent quadratic relationships were identified. No associations were found between measures of fetal adiposity and HPA-A function at age 18 years, or fetal growth and HPA-A response pattern. Removal of anticipatory responders from the models substantially attenuated the observed relationships., Conclusion: We observed an inverse linear relationship between fetal growth and HPA-A function at age 18 years. This differs from the inverse parabolic relationship (inverted U curve) reported in adults of advanced age. Altered adrenal sensitivity may underlie this relationship., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2021
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47. Reproductive and metabolic adaptation to multistressor training in women.
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Gifford RM, O'Leary TJ, Wardle SL, Double RL, Homer NZM, Howie AF, Greeves JP, Anderson RA, Woods DR, and Reynolds RM
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- Adult, Body Composition, Female, Gonadotropin-Releasing Hormone metabolism, Humans, Hypothalamo-Hypophyseal System metabolism, Progesterone metabolism, Prospective Studies, Young Adult, Adaptation, Physiological, Reproductive Physiological Phenomena, Stress, Psychological metabolism
- Abstract
Hypothalamic-pituitary-gonadal (HPG) axis suppression in exercising women can be caused by low energy availability (EA), but the impact of a real-world, multistressor training environment on reproductive and metabolic function is unknown. This study aimed to characterize reproductive and metabolic adaptation in women undertaking basic military training. A prospective cohort study in women undertaking 11-month initial military training ( n = 47) was carried out. Dynamic low-dose 1-h gonadotrophin-releasing hormone (GnRH) tests were completed after 0 and 7 mo of training. Urine progesterone was sampled weekly throughout. Body composition (dual X-ray absorptiometry), fasting insulin resistance (homeostatic modeling assessment 2, HOMA2), leptin, sex steroids, anti-Müllerian hormone (AMH), and inhibin B were measured after 0, 7, and 11 mo with an additional assessment of body composition at 3 mo. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) responses were suppressed after 7 mo (both P < 0.001). Among noncontraceptive users ( n = 20), 65% had regular (23-35 days) cycles preenrollment, falling to 24% by 7 mo of training. Of women in whom urine progesterone was measured ( n = 24), 87% of cycles showed no evidence of ovulation. There was little change in AMH, LH, and estradiol, although inhibin B and FSH increased ( P < 0.05). Fat mass fluctuated during training but at month 11 was unchanged from baseline. Fat-free mass did not change. Visceral adiposity, HOMA2, and leptin increased (all P < 0.001). HPG axis suppression with anovulation occurred in response to training without evidence of low EA. Increased insulin resistance may have contributed to the observed pituitary and ovarian dysfunction. Our findings are likely to represent an adaptive response of reproductive function to the multistressor nature of military training. NEW & NOTEWORTHY We characterized reproductive endocrine adaptation to prolonged arduous multistressor training in women. We identified marked suppression of hypothalamic-pituitary-gonadal (HPG) axis function during training but found no evidence of low energy availability despite high energy requirements. Our findings suggest a complex interplay of psychological and environmental stressors with suppression of the HPG axis via activation of the hypothalamic-pituitary adrenal (HPA) axis. The neuroendocrine impact of nonexercise stressors on the HPG axis during arduous training should be considered.
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- 2021
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48. Maternal body mass index in pregnancy and mental disorders in adult offspring: a record linkage study in Aberdeen, Scotland.
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Lahti-Pulkkinen M, Räikkönen K, Bhattacharya S, and Reynolds RM
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- Adult, Body Mass Index, Female, Humans, Longitudinal Studies, Neurodevelopmental Disorders etiology, Neurodevelopmental Disorders psychology, Obesity complications, Obesity physiopathology, Overweight complications, Overweight physiopathology, Pregnancy, Pregnancy Complications etiology, Pregnancy Complications psychology, Risk Factors, Scotland, Thinness complications, Adult Children psychology, Birth Weight physiology, Mental Disorders etiology, Mental Disorders psychology, Prenatal Exposure Delayed Effects etiology, Prenatal Exposure Delayed Effects psychology
- Abstract
Maternal obesity in pregnancy predicts offspring psychopathology risk in childhood but it remains unclear whether maternal obesity or underweight associate with adult offspring mental disorders. We examined longitudinally whether maternal body mass index (BMI) in pregnancy predicted mental disorders in her offspring and whether the associations differed by offspring birth year among 68,571 mother-child dyads of Aberdeen Maternity and Neonatal Databank, Scotland. The offspring were born 1950-1999. Maternal BMI was measured at a mean 15.7 gestational weeks and classified into underweight, normal weight, overweight, moderate obesity and severe obesity. Mental disorders were identified from nationwide registers carrying diagnoses of all hospitalizations and deaths in Scotland in 1996-2017. We found that maternal BMI in pregnancy was associated with offspring mental disorders in a time-dependent manner: In offspring born 1950-1974, maternal underweight predicted an increased hazard of mental disorders [Hazard Ratio (HR) = 1.74; 95% Confidence Interval (CI) = 1.01-3.00)]. In offspring born 1975-1999, maternal severe obesity predicted increased hazards of any mental (HR 1.60; 95% CI 1.08-2.38) substance use (HR 1.91; 95% CI 1.03-3.57) and schizophrenia spectrum (HR 2.80; 95% CI 1.40-5.63) disorders. Our findings of time-specific associations between maternal prenatal BMI and adult offspring mental disorders may carry important public health implications by underlining possible lifelong effects of maternal BMI on offspring psychopathology., (© 2021. The Author(s).)
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- 2021
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49. Cohort profile for the STratifying Resilience and Depression Longitudinally (STRADL) study: A depression-focused investigation of Generation Scotland, using detailed clinical, cognitive, and neuroimaging assessments.
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Habota T, Sandu AL, Waiter GD, McNeil CJ, Steele JD, Macfarlane JA, Whalley HC, Valentine R, Younie D, Crouch N, Hawkins EL, Hirose Y, Romaniuk L, Milburn K, Buchan G, Coupar T, Stirling M, Jagpal B, MacLennan B, Priba L, Harris MA, Hafferty JD, Adams MJ, Campbell AI, MacIntyre DJ, Pattie A, Murphy L, Reynolds RM, Elliot R, Penton-Voak IS, Munafò MR, Evans KL, Seckl JR, Wardlaw JM, Lawrie SM, Haley CS, Porteous DJ, Deary IJ, Murray AD, and McIntosh AM
- Abstract
STratifying Resilience and Depression Longitudinally (STRADL) is a population-based study built on the Generation Scotland: Scottish Family Health Study (GS:SFHS) resource. The aim of STRADL is to subtype major depressive disorder (MDD) on the basis of its aetiology, using detailed clinical, cognitive, and brain imaging assessments. The GS:SFHS provides an important opportunity to study complex gene-environment interactions, incorporating linkage to existing datasets and inclusion of early-life variables for two longitudinal birth cohorts. Specifically, data collection in STRADL included: socio-economic and lifestyle variables; physical measures; questionnaire data that assesses resilience, early-life adversity, personality, psychological health, and lifetime history of mood disorder; laboratory samples; cognitive tests; and brain magnetic resonance imaging. Some of the questionnaire and cognitive data were first assessed at the GS:SFHS baseline assessment between 2006-2011, thus providing longitudinal measures relevant to the study of depression, psychological resilience, and cognition. In addition, routinely collected historic NHS data and early-life variables are linked to STRADL data, further providing opportunities for longitudinal analysis. Recruitment has been completed and we consented and tested 1,188 participants., Competing Interests: Competing interests: ISP-V and MRM are co-directors of Jericoe Ltd, a company that designs software for the assessment and modification of emotion recognition., (Copyright: © 2021 Habota T et al.)
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- 2021
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50. Tibial Macrostructure and Microarchitecture Adaptations in Women During 44 Weeks of Arduous Military Training.
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O'Leary TJ, Wardle SL, Gifford RM, Double RL, Reynolds RM, Woods DR, and Greeves JP
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- Absorptiometry, Photon, Adult, Bone Density, Bone and Bones, Female, Humans, Radius, Young Adult, Military Personnel, Tibia diagnostic imaging
- Abstract
Bone adapts to unaccustomed, high-impact loading but loses mechanosensitivity quickly. Short periods of military training (≤12 weeks) increase the density and size of the tibia in women. The effect of longer periods of military training, where the incidence of stress fracture is high, on tibial macrostructure and microarchitecture in women is unknown. This observational study recruited 51 women (age 19 to 30 years) at the start of 44 weeks of British Army Officer training. Tibial volumetric bone mineral density (vBMD), geometry, and microarchitecture were measured by high-resolution peripheral quantitative computed tomography (HRpQCT). Scans of the right tibial metaphysis (4% site) and diaphysis (30% site) were performed at weeks 1, 14, 28, and 44. Measures of whole-body areal bone mineral density (aBMD) were obtained using dual-energy X-ray absorptiometry (DXA). Blood samples were taken at weeks 1, 28, and 44, and were analyzed for markers of bone formation and resorption. Trabecular vBMD increased from week 1 to 44 at the 4% site (3.0%, p < .001). Cortical vBMD decreased from week 1 to 14 at the 30% site (-0.3%, p < .001). Trabecular area decreased at the 4% site (-0.4%); trabecular bone volume fraction (3.5%), cortical area (4.8%), and cortical thickness (4.0%) increased at the 4% site; and, cortical perimeter increased at the 30% site (0.5%) from week 1 to 44 (p ≤ .005). Trabecular number (3.5%) and thickness (2.1%) increased, and trabecular separation decreased (-3.1%), at the 4% site from week 1 to 44 (p < .001). Training increased failure load at the 30% site from week 1 to 44 (2.5%, p < .001). Training had no effect on aBMD or markers of bone formation or resorption. Tibial macrostructure and microarchitecture continued to adapt across 44 weeks of military training in young women. Temporal decreases in cortical density support a role of intracortical remodeling in the pathogenesis of stress fracture. © 2021 Crown copyright. Journal of Bone and Mineral Research © 2021 American Society for Bone and Mineral Research (ASBMR). This article is published with the permission of the Controller of HMSO and the Queen's Printer for Scotland., (© 2021 Crown copyright. Journal of Bone and Mineral Research © 2021 American Society for Bone and Mineral Research (ASBMR). This article is published with the permission of the Controller of HMSO and the Queen's Printer for Scotland.)
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- 2021
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