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Indigenous Australians harbour rich and unique genomic diversity. However, Aboriginal and Torres Strait Islander ancestries are historically under-represented in genomics research and almost completely missing from reference datasets1-3. Addressing this representation gap is critical, both to advance our understanding of global human genomic diversity and as a prerequisite for ensuring equitable outcomes in genomic medicine. Here we apply population-scale whole-genome long-read sequencing4 to profile genomic structural variation across four remote Indigenous communities. We uncover an abundance of large insertion-deletion variants (20-49 bp; n = 136,797), structural variants (50 b-50 kb; n = 159,912) and regions of variable copy number (>50 kb; n = 156). The majority of variants are composed of tandem repeat or interspersed mobile element sequences (up to 90%) and have not been previously annotated (up to 62%). A large fraction of structural variants appear to be exclusive to Indigenous Australians (12% lower-bound estimate) and most of these are found in only a single community, underscoring the need for broad and deep sampling to achieve a comprehensive catalogue of genomic structural variation across the Australian continent. Finally, we explore short tandem repeats throughout the genome to characterize allelic diversity at 50 known disease loci5, uncover hundreds of novel repeat expansion sites within protein-coding genes, and identify unique patterns of diversity and constraint among short tandem repeat sequences. Our study sheds new light on the dimensions and dynamics of genomic structural variation within and beyond Australia.
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Aborigenas Australianos e Isleños del Estrecho de Torres , Genoma Humano , Variación Estructural del Genoma , Humanos , Alelos , Australia/etnología , Aborigenas Australianos e Isleños del Estrecho de Torres/genética , Conjuntos de Datos como Asunto , Variaciones en el Número de Copia de ADN/genética , Sitios Genéticos/genética , Genética Médica , Variación Estructural del Genoma/genética , Genómica , Mutación INDEL/genética , Secuencias Repetitivas Esparcidas/genética , Repeticiones de Microsatélite/genética , Genoma Humano/genéticaRESUMEN
White dwarfs, the extremely dense remnants left behind by most stars after their death, are characterized by a mass comparable to that of the Sun compressed into the size of an Earth-like planet. In the resulting strong gravity, heavy elements sink towards the centre and the upper layer of the atmosphere contains only the lightest element present, usually hydrogen or helium1,2. Several mechanisms compete with gravitational settling to change a white dwarf's surface composition as it cools3, and the fraction of white dwarfs with helium atmospheres is known to increase by a factor of about 2.5 below a temperature of about 30,000 kelvin4-8; therefore, some white dwarfs that appear to have hydrogen-dominated atmospheres above 30,000 kelvin are bound to transition to be helium-dominated as they cool below it. Here we report observations of ZTF J203349.8+322901.1, a transitioning white dwarf with two faces: one side of its atmosphere is dominated by hydrogen and the other one by helium. This peculiar nature is probably caused by the presence of a small magnetic field, which creates an inhomogeneity in temperature, pressure or mixing strength over the surface9-11. ZTF J203349.8+322901.1 might be the most extreme member of a class of magnetic, transitioning white dwarfs-together with GD 323 (ref. 12), a white dwarf that shows similar but much more subtle variations. This class of white dwarfs could help shed light on the physical mechanisms behind the spectral evolution of white dwarfs.
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Addressing Indigenous rights and interests in genetic resources has become increasingly challenging in an open science environment that promotes unrestricted access to genomic data. Although Indigenous experiences with genetic research have been shaped by a series of negative interactions, there is increasing recognition that equitable benefits can only be realized through greater participation of Indigenous communities. Issues of trust, accountability and equity underpin Indigenous critiques of genetic research and the sharing of genomic data. This Perspectives article highlights identified issues for Indigenous communities around the sharing of genomic data and suggests principles and actions that genomic researchers can adopt to recognize community rights and interests in data.
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Privacidad Genética/ética , Genómica/ética , Pueblos Indígenas/genética , Difusión de la Información/ética , Acceso a la Información , Investigación Genética/ética , Genoma Humano/genética , Derechos Humanos , HumanosRESUMEN
Ribosomes are essential cellular machinery for protein synthesis. It is hypothesised that ribosome content supports muscle growth and that individuals with more ribosomes have greater increases in muscle size following resistance training (RT). Aerobic conditioning (AC) also elicits distinct physiological adaptations; however, no measures of ribosome content following AC have been conducted. We used ribosome-related gene expression as a proxy measure for ribosome content and hypothesised that AC and RT would increase ribosome-related gene expression. Fourteen young men and women performed 6 weeks of single-legged AC followed by 10 weeks of double-legged RT. Muscle biopsies were taken following AC and following RT in the aerobically conditioned (AC+RT) and unconditioned (RT) legs. No differences in regulatory genes (Ubf, Cyclin D1, Tif-1a and Polr-1b) involved in ribosomal biogenesis or ribosomal RNA (45S, 5.8S, 18S and 28S rRNAs) expression were observed following AC and RT, except for c-Myc (RT > AC+RT) and 5S rRNA (RT < AC+RT at pre-RT) with 18S external transcribed spacer and 5.8S internal transcribed spacer expression decreasing from pre-RT to post-RT in the RT leg only. When divided for change in leg-lean soft tissue mass (ΔLLSTM) following RT, legs with the greatest ΔLLSTM had lower expression in 11/13 measured ribosome-related genes before RT and decreased expression in 9/13 genes following RT. These results indicate that AC and RT did not increase ribosome-related gene expression. Contrary to previous research, the greatest increase in muscle mass was associated with lower changes in ribosome-related gene expression over the course of the 10-week training programme. This may point to the importance of translational efficiency rather than translational capacity (i.e. ribosome content) in mediating long-term exercise-induced adaptations in skeletal muscle.
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Músculo Esquelético , Entrenamiento de Fuerza , Ribosomas , Femenino , Humanos , Masculino , Regulación de la Expresión Génica , Hipertrofia/genética , Hipertrofia/metabolismo , Músculo Esquelético/metabolismo , Biosíntesis de Proteínas/genética , Ribosomas/genética , Adulto JovenRESUMEN
Conformational ensemble generation and the search for the global minimum conformation are important problems in computational chemistry. In this work, a variant on the conformer-rotamer ensemble sampling tool (CREST) iterative metadynamics (iMTD) algorithm designed for determining structural ensembles and energetics of noncovalent clusters of flexible molecules is presented. We term this new algorithm a low-energy diversity-enhanced variant on CREST, or LEDE-CREST. As with CREST, the energies are evaluated using the semiempirical GFN2-xTB extended tight binding approach. The utility of the algorithm is highlighted by generating ensembles for a variety of noncovalent clusters of flexible or rigid monomers using both CREST and LEDE-CREST.
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There is inherent tension between methodologies developed to address basic research questions in model species and those intended for preclinical to clinical translation: basic investigations require flexibility of experimental design as hypotheses are rapidly tested and revised, whereas preclinical models emphasize standardized protocols and specific outcome measures. This dichotomy is particularly relevant in alcohol research, which spans a diverse range of basic sciences in addition to intensive efforts towards understanding the pathophysiology of alcohol use disorder (AUD). To advance these goals there is a great need for approaches that facilitate synergy across basic and translational areas of nonhuman alcohol research. In male and female mice, we establish a modular alcohol reinforcement paradigm: Structured Tracking of Alcohol Reinforcement (STAR). STAR provides a robust platform for quantitative assessment of AUD-relevant behavioral domains within a flexible framework that allows direct crosstalk between translational and mechanistically oriented studies. To achieve cross-study integration, despite disparate task parameters, a straightforward multivariate phenotyping analysis is used to classify subjects based on propensity for heightened alcohol consumption and insensitivity to punishment. Combining STAR with extant preclinical alcohol models, we delineate longitudinal phenotype dynamics and reveal putative neuro-biomarkers of heightened alcohol use vulnerability via neurochemical profiling of cortical and brainstem tissues. Together, STAR allows quantification of time-resolved biobehavioral processes essential for basic research questions simultaneous with longitudinal phenotyping of clinically relevant outcomes, thereby providing a framework to facilitate cohesion and translation in alcohol research.
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Alcoholismo , Etanol , Masculino , Femenino , Ratones , Animales , Consumo de Bebidas Alcohólicas , Refuerzo en Psicología , Proyectos de InvestigaciónRESUMEN
We have made the compound 2O-BaPtO3 by high-pressure, high-temperature synthesis, determined its structure, and tested its catalytic activity. Compounds of the same stoichiometry have been reported and tentatively identified as hexagonal perovskites, and although no structural model was ever established, 2O-BaPtO3 is clearly different and, to the best of our knowledge, unique. It features continuous chains of face-sharing PtO6 octahedra, like the well-known 2H hexagonal perovskite type, but with a staggered offset between the chains that breaks hexagonal symmetry and disrupts the close-packed array of A = Ba and X = O that is a defining characteristic of ABX3 perovskites. We investigated this structure and its stability vs the conventional 2H form using X-ray and neutron diffraction, X-ray absorption spectroscopy, and ab initio calculations. Catalytic testing of 2O-BaPtO3 showed that it is active for hydrogen evolution.
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OBJECTIVE: To determine the psychometric properties of an Aboriginal and Torres Strait Islander-developed depressive symptom screening scale. DESIGN: Prospective diagnostic accuracy study. SETTING: Ten primary health care services or residential alcohol and other drug rehabilitation services in Australia that predominantly serve Aboriginal and Torres Strait Islander peoples. PARTICIPANTS: 500 adults (18 years or older) who identified as Aboriginal and/or Torres Strait Islander and were able to communicate sufficiently to respond to questionnaire and interview questions. Recruitment occurred between 25 March 2015 and 2 November 2016. MAIN OUTCOME MEASURE: Criterion validity of seven Aboriginal and Torres Strait Islander-developed items, using the adapted Patient Health Questionnaire 9 (aPHQ-9) and depression module of the Mini International Neuropsychiatric Interview (MINI) 6.0.0 as the criterion standards. RESULTS: The seven-item scale had good internal consistency (α = 0.83) and correlated highly with the aPHQ-9 (ρ = 0.76). All items were significantly associated with diagnosis of a current major depressive episode. Discriminant function and decision tree analysis identified three items forming a summed scale that classified 85% of participants correctly. These three items showed equivalent sensitivity and specificity to the aPHQ-9 when compared with the MINI-identified diagnosis of a current major depressive episode. CONCLUSION: Three items developed by and for Aboriginal and Torres Strait Islander people may provide effective, efficient and culturally appropriate screening for depression in Aboriginal and Torres Strait Islander health care contexts.
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INTRODUCTION: The 2023 Australian guideline for assessing and managing cardiovascular disease risk provides updated evidence-based recommendations for the clinical assessment and management of cardiovascular disease (CVD) risk for primary prevention. It includes the new Australian CVD risk calculator (Aus CVD Risk Calculator), based on an equation developed from a large New Zealand cohort study, customised and recalibrated for the Australian population. The new guideline replaces the 2012 guideline that recommended CVD risk assessment using the Framingham risk equation. MAIN RECOMMENDATIONS: The new guideline recommends CVD risk assessment in people without known CVD: all people aged 45-79 years, people with diabetes from 35 years, and First Nations people from 30 years. The new Aus CVD Risk Calculator should be used to estimate and categorise CVD risk into low (< 5% risk over five years), intermediate (5% to < 10% risk over five years) or high risk (≥ 10% over five years). The following reclassification factors may be applied to recategorise calculated risk to improve accuracy of risk prediction, particularly in individuals close to a risk threshold: Indigenous status/ethnicity, estimated glomerular filtration rate, urine albumin to creatinine ratio measurements, severe mental illness, coronary artery calcium score and family history of premature CVD. A variety of communication formats is available to communicate CVD risk to help enable shared decision making. Healthy lifestyle modification, including smoking cessation, nutrition, physical activity and limiting alcohol, is encouraged for all individuals. Blood pressure-lowering and lipid-modifying pharmacotherapies should be prescribed for high risk and considered for intermediate risk individuals, unless contraindicated or clinically inappropriate. Reassessment of CVD risk should be considered within five years for individuals at low risk and within two years for those with intermediate risk. Reassessment of CVD risk is not recommended for individuals at high risk. CHANGES IN ASSESSMENT AND MANAGEMENT AS A RESULT OF THE GUIDELINE: The updated guideline recommends assessment over a broader age range and uses the Aus CVD Risk Calculator, which replaces the previous Framingham-based equation. It incorporates new variables: social disadvantage, diabetes-specific risk markers, diagnosis of atrial fibrillation and use of blood pressure-lowering and lipid-modifying therapies. Reclassification factors are also a new addition. Updated risk categories and thresholds are based on the new Aus CVD Risk Calculator. The proportion of the population in the high risk category (≥ 10% over five years) is likely to be broadly comparable to more than 15% risk from the Framingham-based equation. The full guideline and Aus CVD Risk Calculator can be accessed at www.cvdcheck.org.au.
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Enfermedades Cardiovasculares , Humanos , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/terapia , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Australia , Medición de Riesgo/métodos , Persona de Mediana Edad , Anciano , Femenino , Masculino , Factores de Riesgo de Enfermedad Cardiaca , Guías de Práctica Clínica como Asunto , Prevención Primaria , AdultoRESUMEN
Presented in this work is a thorough determination of the transition states between the different isomers of cyclic tetra-atomic silicon carbide, germanium carbide, and germanium silicide clusters. Through use of density functional theory (B3LYP-D3BJ, M06-2X, ωB97X-D4, and B2GP-PLYP) in conjunction with the aug-cc-pVTZ basis set, transition state structures and their barrier heights are determined for the interconversions between the various isomers for the family of tetra-atomic SiC, GeC, and GeSi compounds. SiC dust grains are known to be prevalent in interstellar dust, and among this group, so far only diamond-shaped (d-)SiC3 has been detected in the interstellar medium (ISM). Determining which other structures might be detectable not only depends on their intrinsic spectroscopic features, but whether or not they are likely to exist as isomers in interstellar environments. By examining the energy barrier heights for transitions between isomers, we determined that many of these structures are unlikely to exhibit interconversion in the ISM, outside of hotter circumstellar environments. Although Boltzmann population ratios at approximate circumstellar temperatures suggest the presence of higher energy minima, it is likely that once interconversion happens, as molecules travel away from a star and cool, they will get kinetically trapped in the potential energy well they inhabit, making how the ratios freeze out dependent on the time and pathways the molecules take to cool down. As such, many of these higher energy minima may still be good candidates for detection including (rhomboidal) r-SiC3, r-GeC3, r-GeSi3, (trapezoidal) t-Si2C2, r-Ge2C2, and d-Si3C.
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In this work, we present a density functional theory benchmark on antioxidant-related properties for a series of six polyphenols that are well-known antioxidants: caffeic acid, cyanidin, ellagic acid, gallic acid, myricetin, and phloretin. Computations on the 24 O-H bond dissociation enthalpies (BDEs) and 6 ionization potentials (IPs) were performed using twenty-three exchange-correlation functionals combined with four different basis sets in the gas-phase, water, and methanol; calibration against the Domain-based Local Pair Natural Orbital CCSD(T) (DLPNO-CCSD(T)) approach was employed. Mean absolute deviation (MAD) as well as linear fitting results suggested the LC-PBE approach as the most suitable for O-H BDEs in the gas-phase. The LC-PBE, M06-2X, and M05-2X results presented the smallest MADs for O-H BDEs when compared to the reference, in water. The LC-PBE results had the smallest MADs for IPs in the gas-phase while M05-2X, M06-2X, LC-PBE, and LC-ωPBE exhibited the best results for MAD in water. We expect the outcomes from the present work will serve as general guidance for researchers working in the field.
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An extensive, high-level theoretical study on tetra-atomic germanium carbide/silicide clusters is presented. Accurate harmonic and anharmonic vibrational frequencies and rotational constants are calculated at the CCSD(T)-F12a(b)/cc-pVT(Q)Z-F12 levels of theory. With growing capabilities to discern more of the chemical composition of the interstellar medium (ISM), an accurate database of reference material is required. The presence of carbon is ubiquitous in the ISM, and silicon is known to be present in interstellar dust grains; however, germanium-containing molecules remain elusive. To begin understanding the presence and role of germanium in the ISM, we present this study of the vibrational and rotational spectroscopic properties of various germanium-containing molecules to aid in their potential identification in the ISM with modern observational tools such as the James Webb Space Telescope. Structures studied herein include rhomboidal (r-), diamond (d-), and trapezoidal (t-) tetra-atomic molecules of the form GexC4-x and GexSi4-x, where x = 0-4. The most promising structure for detection is r-Ge2C2 via the ν4 mode with a frequency of 802.7 cm-1 (12.5 µm) and an intensity of 307.2 km mol-1. Other molecules that are potentially detectable, i.e., through vibrational modes or rotational transitions, include r-Ge3C, r-GeSi3, d-GeC3, r-GeC3, and t-Ge2C2.
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BACKGROUND AND AIM: Quantifying stroke incidence and mortality is crucial for disease surveillance and health system planning. Administrative data offer a cost-effective alternative to "gold standard" population-based studies. However, the optimal methodology for establishing stroke deaths from administrative data remains unclear. We aimed to determine the optimal method for identifying stroke-related deaths in administrative datasets as the fatal component of stroke incidence, comparing counts derived using underlying and all causes of death (CoD). METHOD: Using whole-population multijurisdictional person-level linked data from hospital and death datasets from South Australia, the Northern Territory, and Western Australia, we identified first-ever stroke events between 2012 and 2015, using underlying CoD and all CoD to identify fatal stroke counts. We determined the 28-day case fatality for both counts and compared results with gold standard Australian population-based stroke incidence studies. RESULTS: The total number of incident stroke events was 16,150 using underlying CoD and 18,074 using all CoD. Case fatality was 24.7% and 32.7% using underlying and all CoD, respectively. Case fatality using underlying CoD was similar to that observed in four Australian "gold standard" population-based studies (20%-24%). CONCLUSIONS: Underlying CoD generates fatal incident stroke estimates more consistent with population-based studies than estimates based on stroke deaths identified from all-cause fields in death registers.
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Accidente Cerebrovascular , Humanos , Incidencia , Masculino , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/epidemiología , Femenino , Australia/epidemiología , Anciano , Causas de Muerte/tendencias , Persona de Mediana Edad , Anciano de 80 o más Años , Tasa de Supervivencia/tendencias , Bases de Datos FactualesRESUMEN
ISSUES ADDRESSED: Aboriginal and Torres Strait Islander (Aboriginal) people in South Australia are overburdened by cardiovascular disease, diabetes and cancer. The South Australian Aboriginal Chronic Disease Consortium (Consortium) was established in June 2017 as a collaborative partnership to lead the implementation of three state-wide chronic disease plans using a strategic approach to identifying key priority areas for action. METHODS: In 2017-2018, the Consortium Coordinating Centre facilitated a priority setting process, which involved extensive consultation, including a prioritisation survey and stakeholder workshops. The Consortium's Aboriginal Community Reference Group was instrumental in leading the identification of priorities for action. RESULTS: The Consortium RoadMap for Action identified seven across-plan priorities and six condition-specific priorities. It acknowledged that: strengthening social and emotional well-being is central to improving health outcomes; prevention and early detection, acute management and ongoing management are all components of the continuum of care; and improving access to services, strengthening the workforce, and monitoring and evaluation are required across the continuum of care. CONCLUSION: Widespread implementation failure in the past across the health system and health services implementation and research translation highlights the value of the Consortium approach and its commitment to implementing the state-wide chronic disease plans in a collaborative manner. The Consortium relies on and fosters cross-sectoral alignment, with all key players including all public, private and Aboriginal Community Controlled health services, to progress its priorities and aspirations to improve health outcomes for Aboriginal people using evidence-based strategies. SO WHAT?: Rigorous and transparent priority setting processes that bring together research, clinical practice, health services operations, policy and community perspectives can foster intersectoral collaboration and partnership and support the implementation of shared priorities.
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Systematic evolution of ligands by exponential enrichment (SELEX) has been used to discover thousands of aptamers since its development in 1990. Aptamers are short single-stranded oligonucleotides capable of binding to targets with high specificity and selectivity through structural recognition. While aptamers offer advantages over other molecular recognition elements such as their ease of production, smaller size, extended shelf-life, and lower immunogenicity, they have yet to show significant success in real-world applications. By analyzing the importance of structured library designs, reviewing different SELEX methodologies, and the effects of chemical modifications, we provide a comprehensive overview on the production of aptamers for applications in drug delivery systems, therapeutics, diagnostics, and molecular imaging.
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Aptámeros de Nucleótidos , Aptámeros de Nucleótidos/química , Técnica SELEX de Producción de Aptámeros/métodos , Biblioteca de Genes , Ligandos , Sistemas de Liberación de MedicamentosRESUMEN
BACKGROUND: Most estimates of stroke incidence among Aboriginal and Torres Strait Islander (hereinafter Aboriginal) Australians are confined to single regions and include small sample sizes. We aimed to measure and compare stroke incidence in Aboriginal and non-Aboriginal residents across central and western Australia. METHODS: Whole-population multijurisdictional person-linked data from hospital and death datasets were used to identify stroke admissions and stroke-related deaths (2001-2015) in Western Australia, South Australia, and the Northern Territory. Fatal (including out-of-hospital deaths) and nonfatal incident (first-ever) strokes in patients aged 20-84 years were identified during the 4-year study period (2012-2015), using a 10-year lookback period to exclude people with prior stroke. Incidence rates per 100 000 population/year were estimated for Aboriginal and non-Aboriginal populations, age-standardized to the World Health Organization World Standard population. RESULTS: In a population of 3 223 711 people (3.7% Aboriginal), 11 740 incident (first-ever) strokes (20.6% regional/remote location of residence; 15.6% fatal) were identified from 2012 to 2015, 675 (5.7%) in Aboriginal people (73.6% regional/remote; 17.0% fatal). Median age of Aboriginal cases (54.5 years; 50.1% female) was 16 years younger than non-Aboriginal cases (70.3 years; 44.1% female; P<0.001), with significantly greater prevalence of comorbidities. Age-standardized stroke incidence in Aboriginal people (192/100 000 [95% CI, 177-208]) was 2.9-fold greater than in non-Aboriginal people (66/100 000 [95% CI, 65-68]) aged 20-84 years; fatal incidence was 4.2-fold greater (38/100 000 [95% CI, 31-46] versus 9/100 000 [95% CI, 9-10]). Disparities were particularly apparent at younger ages (20-54 years), where age-standardized stroke incidence was 4.3-fold greater in Aboriginal people (90/100 000 [95% CI, 81-100]) than non-Aboriginal people (21/100 000 [95% CI, 20-22]). CONCLUSIONS: Stroke occurred more commonly, and at younger ages, in Aboriginal than non-Aboriginal populations. Greater prevalence of baseline comorbidities was present in the younger Aboriginal population. Improved primary prevention is required. To optimize stroke prevention, interventions should include culturally appropriate community-based health promotion and integrated support for nonmetropolitan health services.
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Accidente Cerebrovascular , Femenino , Humanos , Masculino , Persona de Mediana Edad , Australia/epidemiología , Aborigenas Australianos e Isleños del Estrecho de Torres/estadística & datos numéricos , Incidencia , Pueblos Indígenas/estadística & datos numéricos , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etnología , Almacenamiento y Recuperación de la Información , Adulto Joven , Adulto , Anciano , Anciano de 80 o más AñosRESUMEN
Expanded carrier screening (ECS) for recessive monogenic diseases requires prior knowledge of genomic variation, including DNA variants that cause disease. The composition of pathogenic variants differs greatly among human populations, but historically, research about monogenic diseases has focused mainly on people with European ancestry. By comparison, less is known about pathogenic DNA variants in people from other parts of the world. Consequently, inclusion of currently underrepresented Indigenous and other minority population groups in genomic research is essential to enable equitable outcomes in ECS and other areas of genomic medicine. Here, we discuss this issue in relation to the implementation of ECS in Australia, which is currently being evaluated as part of the national Government's Genomics Health Futures Mission. We argue that significant effort is required to build an evidence base and genomic reference data so that ECS can bring significant clinical benefit for many Aboriginal and/or Torres Strait Islander Australians. These efforts are essential steps to achieving the Australian Government's objectives and its commitment "to leveraging the benefits of genomics in the health system for all Australians." They require culturally safe, community-led research and community involvement embedded within national health and medical genomics programs to ensure that new knowledge is integrated into medicine and health services in ways that address the specific and articulated cultural and health needs of Indigenous people. Until this occurs, people who do not have European ancestry are at risk of being, in relative terms, further disadvantaged.
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Metagenómica/métodos , Grupos de Población/genética , Australia , Variación Genética/genética , HumanosRESUMEN
BACKGROUND: In-utero hyperglycemia exposure influences later cardiometabolic risk, although few studies include women with pre-existing type 2 diabetes (T2D) or assess maternal body mass index (BMI) as a potential confounder. OBJECTIVE: To explore the association of maternal T2D and gestational diabetes mellitus (GDM) with childhood anthropometry, and the influence of maternal BMI on these associations. METHODS: The PANDORA cohort comprises women (n = 1138) and children (n = 1163). Women with GDM and T2D were recruited from a hyperglycemia in pregnancy register, and women with normoglycemia from the community. Wave 1 follow-up included 423 children, aged 1.5-5 years (median follow-up age 2.5 years). Multivariable linear regression assessed associations between maternal antenatal variables, including BMI and glycemic status, with offspring anthropometry (weight, height, BMI, skinfold thicknesses, waist, arm and head circumferences). RESULTS: Greater maternal antenatal BMI was associated with increased anthropometric measures in offspring independent of maternal glycemic status. After adjustment, including for maternal BMI, children exposed to maternal GDM had lower mean weight (-0.54 kg, 95% CI: -0.99, -0.11), BMI (-0.55 kg/m2, 95% CI: -0.91, -0.20), head (-0.52 cm, 95% CI: -0.88, -0.16) and mid-upper arm (-0.32 cm, 95% CI: -0.63, -0.01) circumferences, and greater mean suprailiac skinfold (0.78 mm, 95% CI: 0.13, 1.43), compared to children exposed to normoglycemia. Adjustment for maternal BMI strengthened the negative association between GDM and child weight, BMI and circumferences. Children exposed to maternal T2D had smaller mean head circumference (-0.82 cm, 95% CI: -1.33, -0.31) than children exposed to normoglycemia. Maternal T2D was no longer associated with greater child mean skinfolds (p = 0.14) or waist circumference (p = 0.18) after adjustment for maternal BMI. CONCLUSIONS: Children exposed to GDM had greater suprailiac skinfold thickness than unexposed children, despite having lower mean weight, BMI and mid-upper arm circumference, and both GDM and T2D were associated with smaller mean head circumference. Future research should assess whether childhood anthropometric differences influence lifetime cardiometabolic and neurodevelopmental risk.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Hiperglucemia , Estado Prediabético , Niño , Humanos , Preescolar , Femenino , Embarazo , Diabetes Gestacional/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/etiología , Antropometría , Índice de Masa Corporal , Hiperglucemia/epidemiologíaRESUMEN
Factors influencing inter-individual variability of responses to resistance training (RT) remain to be fully elucidated. We have proposed the importance of capillarization in skeletal muscle for the satellite cell (SC) response to RT-induced muscle hypertrophy, and hypothesized that aerobic conditioning (AC) would augment RT-induced adaptations. Fourteen healthy young (22 ± 2 years) men and women underwent AC via 6 weeks of unilateral cycling followed by 10 weeks of bilateral RT to investigate how AC alters SC content, activity, and muscle hypertrophy following RT. Muscle biopsies were taken at baseline (unilateral), post AC (bilateral), and post RT (bilateral) in the aerobically conditioned (AC + RT) and unconditioned (RT) legs. Immunofluorescence was used to determine muscle capillarization, fiber size, SC content, and activity. Type I and type II fiber cross-sectional area (CSA) increased following RT, and when legs were analyzed independently, AC + RT increased type I, type II, and mixed-fiber CSA, where the RT leg tended to increase type II (p = .05), but not type I or mixed-fiber CSA. SC content, activation, and differentiation increased with RT, where type I total and quiescent SC content was greater in AC + RT compared to the RT leg. Those with the greatest capillary-to-fiber perimeter exchange index before RT had the greatest change in CSA following RT and a significant relationship was observed between type II fiber capillarization and the change in type II-fiber CSA with RT (r = 0.35). This study demonstrates that AC prior to RT can augment RT-induced muscle adaptions and that these differences are associated with increases in capillarization.
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Entrenamiento de Fuerza , Células Satélite del Músculo Esquelético , Capilares/patología , Femenino , Humanos , Hipertrofia/patología , Masculino , Fibras Musculares Esqueléticas/patología , Músculo Esquelético/patologíaRESUMEN
AIMS: To determine rates and predictors of postpartum diabetes screening among Aboriginal and/or Torres Strait Islander and non-Indigenous women with gestational diabetes mellitus (GDM). METHODS: PANDORA is a prospective longitudinal cohort of women recruited in pregnancy. Postpartum diabetes screening rates at 12 weeks (75-g oral glucose tolerance test (OGTT)) and 6, 12 and 18 months (OGTT, glycated haemoglobin [HbA1C ] or fasting plasma glucose) were assessed for women with GDM (n = 712). Associations between antenatal factors and screening with any test (OGTT, HbA1C , fasting plasma glucose) by 6 months postpartum were examined using Cox proportional hazards regression. RESULTS: Postpartum screening rates with an OGTT by 12 weeks and 6 months postpartum were lower among Aboriginal and/or Torres Strait Islander women than non-Indigenous women (18% vs. 30% at 12 weeks, and 23% vs. 37% at 6 months, p < 0.001). Aboriginal and/or Torres Strait Islander women were more likely to have completed a 6-month HbA1C compared to non-Indigenous women (16% vs. 2%, p < 0.001). Screening by 6 months postpartum with any test was 41% for Aboriginal and/or Torres Strait Islander women and 45% for non-Indigenous women (p = 0.304). Characteristics associated with higher screening rates with any test by 6 months postpartum included, insulin use in pregnancy, first pregnancy, not smoking and lower BMI. CONCLUSIONS: Given very high rates of type 2 diabetes among Aboriginal and Torres Strait Islander women, early postpartum screening with the most feasible test should be prioritised to detect prediabetes and diabetes for intervention.