Risk of kidney disease following a pregnancy complicated by diabetes: a longitudinal, population-based data-linkage study among Aboriginal women in the Northern Territory, Australia.

AIMS/HYPOTHESIS: The aim of this work was to investigate the risk of developing chronic kidney disease (CKD) or end-stage kidney disease (ESKD) following a pregnancy complicated by gestational diabetes mellitus (GDM) or pre-existing diabetes among Aboriginal women in the Northern Territory (NT), Australia. METHODS: We undertook a longitudinal study of linked healthcare datasets. All Aboriginal women who gave birth between 2000 and 2016 were eligible for inclusion. Diabetes status in the index pregnancy was as recorded in the NT Perinatal Data Collection. Outcomes included any stage of CKD and ESKD as defined by ICD-10 coding in the NT Hospital Inpatient Activity dataset between 2000 and 2018. Risk was compared using Cox proportional hazards regression. RESULTS: Among 10,508 Aboriginal women, the mean age was 23.1 (SD 6.1) years; 731 (7.0%) had GDM and 239 (2.3%) had pre-existing diabetes in pregnancy. Median follow-up was 12.1 years. Compared with women with no diabetes during pregnancy, women with GDM had increased risk of CKD (9.2% vs 2.2%, adjusted HR 5.2 [95% CI 3.9, 7.1]) and ESKD (2.4% vs 0.4%, adjusted HR 10.8 [95% CI 5.6, 20.8]). Among women with pre-existing diabetes in pregnancy, 29.1% developed CKD (adjusted HR 10.9 [95% CI 7.7, 15.4]) and 9.9% developed ESKD (adjusted HR 28.0 [95% CI 13.4, 58.6]). CONCLUSIONS/INTERPRETATION: Aboriginal women in the NT with GDM or pre-existing diabetes during pregnancy are at high risk of developing CKD and ESKD. Pregnancy presents an important opportunity to identify kidney disease risk. Strategies to prevent kidney disease and address the social determinants of health are needed.

Association between maternal hyperglycemia in pregnancy and offspring anthropometry in early childhood: the pandora wave 1 study.

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.

Postpartum uptake of diabetes screening tests in women with gestational diabetes: The PANDORA study.

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.

Management of type 2 diabetes in young adults aged 18-30 years: ADS/ADEA/APEG consensus statement.

INTRODUCTION: Type 2 diabetes in young adults (nominally, 18-30 years of age) is a more aggressive condition than that seen in older age, with a greater risk of major morbidity and early mortality. This first Australian consensus statement on the management of type 2 diabetes in young adults considers areas where existing type 2 diabetes guidance, directed mainly towards older adults, may not be appropriate or relevant for the young adult population. Where applicable, recommendations are harmonised with current national guidance for type 2 diabetes in children and adolescents (aged < 18 years). The full statement is available at https://www.diabetessociety.com.au, https://www.adea.com.au and https://www.apeg.org.au. MAIN RECOMMENDATIONS: Advice is provided on important aspects of care including screening, diabetes type, psychological care, lifestyle, glycaemic targets, pharmacological agents, cardiovascular disease risk management, comorbidity assessment, contraception and pregnancy planning, and patient-centred education. Special considerations for Aboriginal and Torres Strait Islander Australians are highlighted separately. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: Management recommendations for young adults, which differ from those for adults, include: ▪screening for diabetes in young adults with overweight or obesity and additional risk factors, including in utero exposure to type 2 diabetes or gestational diabetes mellitus; ▪more stringent glucose targets (glycated haemoglobin ≤ 6.5% [≤ 48 mmol/mol]); ▪in the context of obesity or higher cardio-renal risk, glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors are preferred second line agents; ▪ß-cell decline is more rapid, so frequent review, early treatment intensification and avoidance of therapeutic inertia are indicated; ▪a blood pressure target of < 130/80 mmHg, as the adult target of ≤ 140/90 mmHg is too high; ▪absolute cardiovascular disease risk calculators are not likely to be accurate in this age group; early statin use should therefore be considered; and ▪a multidisciplinary model of care including an endocrinologist and a certified diabetes educator.

Transcatheter versus surgical closure of atrial septal defects: a systematic review and meta-analysis of clinical outcomes.

BACKGROUND: Atrial septal defects are a common form of CHD and dependent on the size and nature of atrial septal defects, closure may be warranted. The paper aims to compare outcomes of transcatheter versus surgical repair of atrial septal defects. METHODS: A comprehensive electronic literature search was conducted. Primary studies were included if they compared both closure techniques. Primary outcomes included procedural success, mortality, and reintervention rate. Secondary outcomes included residual defect and mean hospital stay. RESULTS: A total of 33 studies were included in meta-analysis. Mean total hospital stay was significantly shorter in the transcatheter cohort across both the adult (95% confidence interval, mean difference -4.05 (-4.78, -3.32) p < 0.00001) and paediatric populations (95% confidence interval, mean difference -4.78 (-5.97, -3.60) p < 0.00001). There were significantly fewer complications in the transcatheter group across both the adult (odds ratio 0.45, 95% confidence interval, [0.28, 0.72], p < 0.00001) and paediatric cohorts (odds ratio 0.26, 95% confidence interval, [0.14, 0.49], p < 0.00001). No significant difference in overall mortality was found between transcatheter versus surgical closure across the two groups, adult (odds ratio 0.76, 95% confidence interval, [0.40, 1.45], p = 0.41), paediatrics (odds ratio 0.62, 95% confidence interval, [0.21, 1.83], p = 0.39). CONCLUSION: Both transcatheter and surgical approaches are safe and effective techniques for atrial septal defect closure. Our study has demonstrated the benefits of transcatheter closure in terms of lower complication rates and mean hospital stay. However, surgery still has a place for more complex closure and, as we have demonstrated, shows no difference in mortality.

Cardiac Surgery in Patients With Blood Disorders.

Blood disorders that can contribute to abnormal bleeding can have a detrimental effect during cardiac surgery. Patients who are known to have such pathologies should be investigated thoroughly and cautious measures would need to be taken when cardiac surgery is needed in this cohort. The majority of current literature for cardiac surgery in patients with von Willebrand Disease and haemophilia are case reports. Nevertheless, evidence shows that optimising factor levels pre, intra and postoperatively offers outcomes similar to that of patients without these disorders. Preoperative screening followed by appropriate iron therapy reduces mortality for patients with anaemia. In this group, haemoglobin levels can be improved postoperatively through iron supplementation. The management strategy of cardiac surgery for people with blood disorders requires a multidisciplinary approach that is highly individualised for each patient. It is essential to adequately adjust preoperative, perioperative and postoperative care to the patient's blood disorder in order to achieve outcomes similar to that of patients without blood disorders.

TOAC spin-labeled peptides tailored for DNP-NMR studies in lipid membrane environments.

The benefit of combining in-cell solid-state dynamic nuclear polarization (DNP) NMR and cryogenic temperatures is providing sufficient signal/noise and preservation of bacterial integrity via cryoprotection to enable in situ biophysical studies of antimicrobial peptides. The radical source required for DNP was delivered into cells by adding a nitroxide-tagged peptide based on the antimicrobial peptide maculatin 1.1 (Mac1). In this study, the structure, localization, and signal enhancement properties of a single (T-MacW) and double (T-T-MacW) TOAC (2,2,6,6-tetramethylpiperidine-N-oxyl-4-amino-4-carboxylic acid) spin-labeled Mac1 analogs were determined within micelles or lipid vesicles. The solution NMR and circular dichroism results showed that the spin-labeled peptides adopted helical structures in contact with micelles. The peptides behaved as an isolated radical source in the presence of multilamellar vesicles, and the electron paramagnetic resonance (EPR) electron-electron distance for the doubly spin-labeled peptide was ∼1 nm. The strongest paramagnetic relaxation enhancement (PRE) was observed for the lipid NMR signals near the glycerol-carbonyl backbone and was stronger for the doubly spin-labeled peptide. Molecular dynamics simulation of the T-T-MacW radical source in phospholipid bilayers supported the EPR and PRE observations while providing further structural insights. Overall, the T-T-MacW peptide achieved better 13C and 15N signal NMR enhancements and 1H spin-lattice T1 relaxation than T-MacW.

Phosphorylation of Troponin I finely controls the positioning of Troponin for the optimal regulation of cardiac muscle contraction.

Troponin is the Ca2+ molecular switch that regulates striated muscle contraction. In the heart, troponin Ca2+ sensitivity is also modulated by the PKA-dependent phosphorylation of a unique 31-residue N-terminal extension region of the Troponin I subunit (NH2-TnI). However, the detailed mechanism for the propagation of the phosphorylation signal through Tn, which results in the enhancement of the myocardial relaxation rate, is difficult to examine within whole Tn. Several models exist for how phosphorylation modulates the troponin response in cardiac cells but these are mostly built from peptide-NMR studies and molecular dynamics simulations. Here we used a paramagnetic spin labeling approach to position and track the movement of the NH2-TnI region within whole Tn. Through paramagnetic relaxation enhancement (PRE)-NMR experiments, we show that the NH2-TnI region interacts with a broad surface area on the N-domain of the Troponin C subunit. This region includes the Ca2+ regulatory Site II and the TnI switch-binding site. Phosphorylation of the NH2-TnI both weakens and shifts this region to an adjacent site on TnC. Interspin EPR distances between NH2-TnI and TnC further reveal a phosphorylation induced re-orientation of the TnC N-domain under saturating Ca2+ conditions. We propose an allosteric model where phosphorylation triggered cooperative changes in both the interaction of the NH2-TnI region with TnC, and the re-orientation of the TnC interdomain orientation, together promote the release of the TnI switch-peptide. Enhancement of the myocardial relaxation rate then occurs. Knowledge of this unique role of phosphorylation in whole Tn is important for understanding pathological processes affecting the heart.

Feasibility of once weekly exenatide-LAR and enhanced diabetes care in Indigenous Australians with type 2 diabetes (Long-acting-Once-Weekly-Exenatide laR-SUGAR, 'Lower SUGAR' study).

BACKGROUND: Diabetes is 3-4 times more prevalent in Indigenous Australians with blood glucose levels often above target range. Once weekly formulations of exenatide(exenatide-LAR) have demonstrated significantly greater improvements in glycaemic management with no increased risk of hypoglycaemia and with reductions in bodyweight but have not been studied in Indigenous Australians. AIMS: To assess the feasibility and metabolic effects of once weekly supervised injection of exenatide-LAR in addition to standard care in Indigenous Australians with type 2 diabetes. METHODS: Two communities in Central Australia with longstanding specialist clinical outreach services were allocated by random coin toss to receive once-weekly exenatide-LAR injection with weekly nurse review and adjustment of medication for 20 weeks (community with exenatide-LAR) or to weekly nurse review in addition to standard care over 20 weeks (community without exenatide-LAR). The primary outcome was the feasibility of an intensive diabetes management model of care with and without weekly supervised exenatide-LAR. Secondary outcomes included change in HbA1c. RESULTS: Thirteen participants from the community with exenatide-LAR and nine participants from the community without exenatide-LAR were analysed. Eighty-five percent of individuals in the community with exenatide-LAR and 67% in the community without exenatide-LAR attended more than half of clinic visits. Median difference in the change in HbA1c from baseline to final visit, adjusted for baseline HbA1c, between the community with exenatide-LAR and the community without exenatide-LAR was -3.1%, 95% CI (-5.80%, -0.38%; P = 0.03). CONCLUSIONS: Weekly exenatide-LAR combined with weekly nurse review demonstrated greater improvements in HbA1c, highlighting its potential for use in remote communities.

Cardiac output monitoring in paediatric cardiac surgery: a review.

The aim of this review is to present the current options for cardiac output (CO) monitoring in children undergoing cardiac surgery. Current technologies for monitoring identified were a range of invasive, minimally invasive, and non-invasive technologies. These include pulmonary artery catheter, transoesophageal echocardiography, pulse contour analysis, electrical cardiography, and thoracic bioreactance. A literature search was conducted using evidence databases which identified two current guidelines; the NHS Greater Glasgow and Clyde guideline and Royal College of Anaesthetics Guideline. These were appraised using the AGREE II tool and the evidence identified was used to create an overview summary of each technological option for CO monitoring. There is limited evidence regarding the accuracy of modalities available for CO monitoring in paediatric patients during cardiac surgery. Each technology has advantages and disadvantages; however, none could be championed as the most beneficial. Furthermore, a gold standard for CO monitoring has not yet been identified for paediatric populations, nor is it apparent whether one modality is preferable based on the available evidence. Additional evidence using a standardised method for comparing CO measurements should be conducted in order to determine the best option for CO monitoring in paediatrics. Furthermore, cost-effectiveness assessment of each modality should be conducted. Only then will it be possible for clear, evidence-based guidance to be written.

Outcomes of cardiac surgery in Jehovah's Witness patients: A review.

OBJECTIVE: To review current literature evidence on outcomes of cardiac surgery in Jehovah's Witness patients. METHODS: A comprehensive electronic literature search was done from 2010 to 20th August 2020 identifying articles that discussed optimisation/outcomes of cardiac surgery in Jehovah's Witness either as a solo cohort or as comparative to non-Jehovah's Witnesses. No limit was placed on place of publication and the evidence has been summarised in a narrative manner within the manuscript. RESULTS: The outcomes of cardiac surgery in Jehovah's Witness patients has been described, and also compared, to non-Witness patients within a number of case reports, case series and comparative cohort studies. Many of these studies note no significant differences between outcomes of the two groups for a number of variables, including mortality. Pre-, intra and post-operative optimisation of the patients by a multidisciplinary team is important to achieve good outcomes. CONCLUSION: The use of a bloodless protocol for Jehovah's Witnesses does not appear to significantly impact upon clinical outcomes when compared to non-Witness patients, and it has even been suggested that a bloodless approach could provide advantages to all patients undergoing cardiac surgery. Larger cohorts and research across multiple centres into the long term outcomes of these patients is required.

Oral health of aboriginal people with kidney disease living in Central Australia.

BACKGROUND: Associations between kidney disease and periodontal disease are not well documented among Aboriginal people of Australia. The purpose of this investigation was to report and compare demographic, oral health, anthropometric and systemic health status of Aboriginal Australians with kidney disease and to compare against relevant Aboriginal Australians and Australian population estimates. This provides much needed evidence to inform dental health service provision policies for Aboriginal Australians with kidney disease. METHODS: Sample frequencies and means were assessed in adults represented in six datasets including: (1) 102 Aboriginal Australians with kidney disease residing in Central Australia who participated in a detailed oral health assessment; (2) 312 Aboriginal participants of the Northern Territory's PerioCardio study; (3) weighted estimates from 4775 participants from Australia's National Survey of Adult Oral Health (NSAOH); (4) Australian 2016 Census (all Australians); (5) National Health Survey 2017-2018 (all Australians) and; (6) Australian Health Survey: Biomedical Results for Chronic Diseases, 2011-2012 (all Australians). Oral health status was described by periodontal disease and experience of dental caries (tooth decay). Statistically significant differences were determined via non-overlapping 95% confidence intervals. RESULTS: Aboriginal Australians with kidney disease were significantly older, less likely to have a tertiary qualification or be employed compared with both PerioCardio study counterparts and NSAOH participants. Severe periodontitis was found in 54.3% of Aboriginal Australians with kidney disease, almost 20 times the 2.8% reported in NSAOH. A higher proportion of Aboriginal Australians with kidney disease had teeth with untreated caries and fewer dental restorations when compared to NSAOH participants. The extent of periodontal attachment loss and periodontal pocketing among Aboriginal Australians with kidney disease (51.0%, 21.4% respectively) was several magnitudes greater than PerioCardio study (22.0%, 12.3% respectively) and NSAOH (5.4%, 1.3% respectively) estimates. CONCLUSIONS: Aboriginal Australians with kidney disease exhibited more indicators of poorer oral health than both the general Australian population and a general Aboriginal population from Australia's Northern Territory. It is imperative that management of oral health among Aboriginal Australians with kidney disease be included as part of their ongoing medical care.

Associations of gestational diabetes and type 2 diabetes during pregnancy with breastfeeding at hospital discharge and up to 6 months: the PANDORA study.

AIMS/HYPOTHESIS: Women with gestational diabetes mellitus (GDM) and obesity experience lower rates of breastfeeding. Little is known about breastfeeding among mothers with type 2 diabetes. Australian Indigenous women have a high prevalence of type 2 diabetes in pregnancy. We aimed to evaluate the association of hyperglycaemia, including type 2 diabetes, with breastfeeding outcomes. METHODS: Indigenous (n = 495) and non-Indigenous (n = 555) participants of the Pregnancy And Neonatal Diabetes Outcomes in Remote Australia (PANDORA) cohort included women without hyperglycaemia in pregnancy (n = 222), with GDM (n = 684) and with type 2 diabetes (n = 144). The associations of hyperglycaemia in pregnancy and breastfeeding at hospital discharge, 6 weeks and 6 months post-partum were evaluated with logistic regression, after adjustment for maternal obesity, ethnicity, maternal and neonatal characteristics. RESULTS: Indigenous women were more likely to predominantly breastfeed at 6 weeks across all levels of hyperglycaemia. Compared with women with no hyperglycaemia in pregnancy, women with type 2 diabetes had lower odds for exclusive breastfeeding at discharge (adjusted OR for exclusive breastfeeding 0.4 [95% CI 0.2, 0.8] p = 0.006). At 6 weeks and 6 months, the relationship between type 2 diabetes and predominant breastfeeding was not statistically significant (6 weeks 0.7 [0.3, 1.6] p = 0.40, 6 months 0.8 [0.4, 1.6] p = 0.60). Women with gestational diabetes were as likely to achieve predominant breastfeeding at 6 weeks and 6 months as women without hyperglycaemia in pregnancy. CONCLUSIONS/INTERPRETATION: Indigenous women had high rates of breastfeeding. Women with type 2 diabetes had difficulty establishing exclusive breastfeeding at hospital discharge. Further research is needed to assess the impact on long-term breastfeeding outcomes. Graphical abstract.

Cord blood metabolic markers are strong mediators of the effect of maternal adiposity on fetal growth in pregnancies across the glucose tolerance spectrum: the PANDORA study.

AIMS/HYPOTHESIS: We aimed to assess associations between cord blood metabolic markers and fetal overgrowth, and whether cord markers mediated the impact of maternal adiposity on neonatal anthropometric outcomes among children born to Indigenous and Non-Indigenous Australian women with normal glucose tolerance (NGT), gestational diabetes mellitus (GDM) and pregestational type 2 diabetes mellitus. METHODS: From the Pregnancy and Neonatal Outcomes in Remote Australia (PANDORA) study, an observational cohort of 1135 mother-baby pairs, venous cord blood was available for 645 singleton babies (49% Indigenous Australian) of women with NGT (n = 129), GDM (n = 419) and type 2 diabetes (n = 97). Cord glucose, triacylglycerol, HDL-cholesterol, C-reactive protein (CRP) and C-peptide were measured. Multivariable logistic and linear regression were used to assess the associations between cord blood metabolic markers and the outcomes of birthweight z score, sum of skinfold thickness (SSF), being large for gestational age (LGA) and percentage of body fat. Pathway analysis assessed whether cord markers mediated the associations between maternal and neonatal adiposity. RESULTS: Elevated cord C-peptide was significantly associated with increasing birthweight z score (ß 0.57 [95% CI 0.42, 0.71]), SSF (ß 0.83 [95% CI 0.41, 1.25]), percentage of body fat (ß 1.20 [95% CI 0.69, 1.71]) and risk for LGA [OR 3.14 [95% CI 2.11, 4.68]), after adjusting for age, ethnicity and diabetes type. Cord triacylglycerol was negatively associated with birthweight z score for Indigenous Australian women only. No associations between cord glucose, HDL-cholesterol and CRP >0.3 mg/l (2.9 nmol/l) with neonatal outcomes were observed. C-peptide mediated 18% (95% CI 13, 36) of the association of maternal BMI with LGA and 11% (95% CI 8, 17) of the association with per cent neonatal fat. CONCLUSIONS/INTERPRETATION: Cord blood C-peptide is an important mediator of the association between maternal and infant adiposity, across the spectrum of maternal glucose tolerance.

Characterization of optofluidic devices for the sorting of sub-micrometer particles.

In this work, we investigate methods of fabricating a device for the optical actuation of nanoparticles. To create the microfluidic channel, we pursued three fabrication methods: SU-8 to molded polydimethylsiloxane soft lithography, laser etching of glass, and deep reactive ion etching of fused silica. We measured the surface roughness of the etched sidewalls, and the laser power transmission through each device. We then measured the radiation pressure on 0.5-µm particles in the best-performing fabricated device (etched fused silica) and in a square glass capillary.

Outcomes in minimally invasive double valve surgery.

OBJECTIVE: To review current literature evidence on outcomes of minimally invasive double valve surgeries (MIS). METHODS: A comprehensive electronic literature search was done from inception to 20th June 2020 identifying articles that discussed outcomes of minimally invasive approach in double valve surgeries either as a solo cohort or as comparative to conventional sternotomies. No limit was placed on time and place of publication and the evidence has been summarized in narrative manner within the manuscript. RESULTS: Majority of current literature reported similar perioperative and clinical outcomes between MIS and conventional median sternotomy; except that MIS has better cosmetic effects and pain control. Nevertheless, minimal invasive techniques are associated with longer cardiopulmonary bypass and aortic cross-clamp times which may have impact on the reported outcomes and overall morbidity and mortality rates. CONCLUSION: Minimally invasive double valve surgery continues to develop, but scarcity in the literature suggests uptake is slow, possibly due to the learning curve associated with MIS. Many outcomes appear to be comparable to conventional sternotomy. There is need for larger, multi-center, and randomized trial to fully evaluate and establish the early, mid- and long-term morbidity and mortality rates associated with both techniques.

Characterization of the L29Q Hypertrophic Cardiomyopathy Mutation in Cardiac Troponin C by Paramagnetic Relaxation Enhancement Nuclear Magnetic Resonance.

The key events in regulating muscle contraction involve the troponin (Tn) heterotrimeric protein complex in which the binding to and release of Ca2+ from the highly conserved troponin C (TnC) subunit trigger a series of structural changes within Tn, and the other thin filament proteins, to result in contraction. In the heart, the control of contraction and relaxation events can be altered by many single-point mutations that may result in cardiomyopathy and sometimes sudden cardiac death. Here we have examined the structural effects of one hypertrophic cardiomyopathy mutation, L29Q, on Ca2+-induced structural transitions within whole TnC. This mutation is of particular interest as several physiological and structural studies have indicated that the response of TnC to Ca2+ binding is altered in the presence of the L29Q mutation, but the structural nature of these changes continues to be debated. In addition, little is known about the effect of this mutation in the Ca2+ free state. Here we have used paramagnetic relaxation enhancement nuclear magnetic resonance (PRE-NMR) to assess the structural effects arising from the L29Q mutation. PRE-NMR distances obtained from a nitroxide spin-label at Cys84 showed that the L29Q mutation perturbs the structure of the TnC N-domain in the presence and absence of Ca2+, with a more "open" TnC N-domain observed in the apo form. In addition, binding of Ca2+ to the TnC-L29Q construct triggers a change in the orientation between the two domains of TnC. Together, these structural perturbations, revealed by PRE-NMR, provide insight into the pathogenesis of this mutation.

Contribution of cardiometabolic risk factors to estimated glomerular filtration rate decline in Indigenous Australians with and without albuminuria - the eGFR Follow-up Study.

AIM: We assessed associations between cardiometabolic risk factors and estimated glomerular filtration rate (eGFR) decline according to baseline albuminuria to identify potential treatment targets in Indigenous Australians. METHODS: The eGFR Follow-up Study is a longitudinal cohort of 520 Indigenous Australians. Linear regression was used to estimate associations between baseline cardiometabolic risk factors and annual Chronic Kidney Disease Epidemiology Collaboration eGFR change (mL/min per 1.73m2 /year), among those classified with baseline normoalbuminuria (urine albumin-to-creatinine ratio (uACR) <3 mg/mmol; n = 297), microalbuminuria (uACR 3-30 mg/mmol; n = 114) and macroalbuminuria (uACR ≥30 mg/mmol; n = 109). RESULTS: After a median of 3 years follow-up, progressive declines of the age- and sex-adjusted mean eGFR were observed across albuminuria categories (-2.0 [-2.6 to -1.4], -2.5 [-3.7 to -1.3] and -6.3 [-7.8 to -4.9] mL/min per 1.72m2 /year). Although a borderline association was observed between greater baseline haemoglobin A1c and eGFR decline in those with macroalbuminuria (P = 0.059), relationships were not significant in those with microalbuminuria (P = 0.187) or normoalbuminuria (P = 0.23). Greater baseline blood pressure, C-reactive protein, waist-to-hip ratio and lower high-density lipoprotein cholesterol showed non-significant trends with greater eGFR decline in the presence of albuminuria. CONCLUSION: Over a 3 year period, marked eGFR decline was observed with greater baseline albuminuria. Cardiometabolic risk factors were not strong predictors for eGFR decline in Indigenous Australians without albuminuria. Longer follow-up may elucidate the role of these predictors and other mechanisms in chronic kidney disease progression in this population.

The concerted movement of the switch region of Troponin I in cardiac muscle thin filaments as tracked by conventional and pulsed (DEER) EPR.

The absence of a crystal structure of the calcium free state of the cardiac isoform of the troponin complex has hindered our understanding of how the simple binding of Ca2+ triggers conformational changes in troponin which are then propagated to enable muscle contraction. Here we have used continuous wave (CW) and Double Electron-Electron Resonance (DEER) pulsed EPR spectroscopy to measure distances between TnI and TnC to track the movement of the functionally important regulatory 'switch' region of cardiac Tn. Spin labels were placed on the switch region of Troponin I and distances measured to Troponin C. Under conditions of high Ca2+, the interspin distances for one set (TnI151/TnC84) were 'short' (9-10Å) with narrow distance distribution widths (3-8Å) indicating the close interaction of the switch region with the N-lobe of TnC. Additional spin populations representative of longer interspin distances were detected by DEER. These longer distance populations, which were ∼16-19Å longer than the short distance populations, possessed notably broader distance distribution widths (14-29Å). Upon Ca2+ removal, the interspin population shifted toward the longer distances, indicating the release of the switch region from TnC and an overall increase in disorder for this region. Together, our results suggest that under conditions of low Ca2+, the close proximity of the TnI switch region to TnC in the cardiac isoform is necessary for promoting the interaction between the regulatory switch helix with the N-lobe of cardiac Troponin C, which, unlike the skeletal isoform, is largely in a closed conformation.