Development and validation of a risk score for hospitalization for heart failure in patients with Type 2 Diabetes Mellitus

<p>Abstract</p> <p>Background</p> <p>There are no risk scores available for predicting heart failure in Type 2 diabetes mellitus (T2DM). Based on the Hong Kong Diabetes Registry, this study aimed to develop and validate a risk score for predicting heart failure that needs hospitalisation in T2DM.</p> <p>Methods</p> <p>7067 Hong Kong Chinese diabetes patients without history of heart failure, and without history and clinical evidence of coronary heart disease at baseline were analyzed. The subjects have been followed up for a median period of 5.5 years. Data were randomly and evenly assigned to a training dataset and a test dataset. Sex-stratified Cox proportional hazard regression was used to obtain predictors of HF-related hospitalization in the training dataset. Calibration was assessed using Hosmer-Lemeshow test and discrimination was examined using the area under receiver's operating characteristic curve (aROC) in the test dataset.</p> <p>Results</p> <p>During the follow-up, 274 patients developed heart failure event/s that needed hospitalisation. Age, body mass index (BMI), spot urinary albumin to creatinine ratio (ACR), HbA_1c, blood haemoglobin (Hb) at baseline and coronary heart disease during follow-up were predictors of HF-related hospitalization in the training dataset. HF-related hospitalization risk score = 0.0709 × age (year) + 0.0627 × BMI (kg/m²) + 0.1363 × HbA_1c(%) + 0.9915 × Log₁₀(1+ACR) (mg/mmol) - 0.3606 × Blood Hb(g/dL) + 0.8161 × CHD during follow-up (1 if yes). The 5-year probability of heart failure = 1-S₀(5)^{EXP{0.9744 × (Risk Score - 2.3961)}}. Where S₀(5) = 0.9888 if male and 0.9809 if female. The predicted and observed 5-year probabilities of HF-related hospitalization were similar (p > 0.20) and the adjusted aROC was 0.920 for 5 years of follow-up.</p> <p>Conclusion</p> <p>The risk score had adequate performance. Further validations in other cohorts of patients with T2DM are needed before clinical use.</p

Fabrication Process Independent And Robust Aggregation Of Detonation Nanodiamonds In Aqueous Media

In the past detonation nanodiamonds (DNDs), sized 3–5 nm, have been praised for their colloidal stability in aqueous media, thereby attracting vast interest in a wide range of applications including nanomedicine. More recent studies have challenged the consensus that DNDs are monodispersed after their fabrication process, with their aggregate formation dynamics poorly understood. Here we reveal that DNDs in aqueous solution, regardless of their post-synthesis de-agglomeration and purification methods, exhibit hierarchical aggregation structures consisting of chain-like and cluster aggregate morphologies. With a novel characterization approach combining machine learning with direct cryo-transmission electron microscopy and with X-ray scattering and vibrational spectroscopy, we show that their aggregate morphologies of chain and cluster ratios and the corresponding size and fractal dimension distributions vary with the post-synthesis treatment methods. In particular DNDs with positive ζ-potential form to a hierarchical structure that assembles aggregates into large networks. DNDs purified with the gas phase annealing and oxidation tend to have more chain-like aggregates. Our findings provide important contribution in understanding the DND interparticle interactions to control the size, polydispersity and aggregation of DNDs for their desired applications

MOAP-1 Mediates Fas-Induced Apoptosis in Liver by Facilitating tBid Recruitment to Mitochondria

SummaryFas apoptotic signaling regulates diverse physiological processes. Acute activation of Fas signaling triggers massive apoptosis in liver. Upon Fas receptor stimulation, the BH3-only protein Bid is cleaved into the active form, tBid. Subsequent tBid recruitment to mitochondria, which is facilitated by its receptor MTCH2 at the outer mitochondrial membrane (OMM), is a critical step for commitment to apoptosis via the effector proteins Bax or Bak. MOAP-1 is a Bax-binding protein enriched at the OMM. Here, we show that MOAP-1-deficient mice are resistant to Fas-induced hepatocellular apoptosis and lethality. In the absence of MOAP-1, mitochondrial accumulation of tBid is markedly impaired. MOAP-1 binds to MTCH2, and this interaction appears necessary for MTCH2 to engage tBid. These findings reveal a role for MOAP-1 in Fas signaling in the liver by promoting MTCH2-mediated tBid recruitment to mitochondria

Impacts of chronic kidney disease and albuminuria on associations between coronary heart disease and its traditional risk factors in type 2 diabetic patients – the Hong Kong diabetes registry

<p>Abstract</p> <p>Background</p> <p>Glycated haemoglobin (HbA_1c), blood pressure and body mass index (BMI) are risk factors for albuminuria, the latter in turn can lead to hyperlipidaemia. We used novel statistical analyses to examine how albuminuria and chronic kidney disease (CKD) may influence the effects of other risk factors on coronary heart disease (CHD).</p> <p>Methods</p> <p>A prospective cohort of 7067 Chinese type 2 diabetic patients without history of CHD enrolled since 1995 were censored on July 30^th, 2005. Cox proportional hazard regression with restricted cubic spline was used to auto-select predictors. Hazard ratio plots were used to examine the risk of CHD. Based on these plots, non-linear risk factors were categorised and the categorised variables were refitted into various Cox models in a stepwise manner to confirm the findings.</p> <p>Results</p> <p>Age, male gender, duration of diabetes, spot urinary albumin: creatinine ratio, estimated glomerular filtration rate, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and current smoking status were risk factors of CHD. Linear association between TC and CHD was observed only in patients with albuminuria. Although in general, increased HDL-C was associated with decreased risk of CHD, full-range HDL-C was associated with CHD in an A-shaped manner with a zenith at 1.1 mmol/L. Albuminuria and CKD were the main contributors for the paradoxically positive association between HDL-C and CHD for HDL-C values less than 1.1 mmol/L.</p> <p>Conclusion</p> <p>In type 2 diabetes, albuminuria plays a linking role between conventional risk factors and CHD. The onset of CKD changes risk associations between lipids and CHD.</p

A 50-Year-Old Woman with Recurrent Generalised Seizures

Ronald Ma and colleagues discuss the differential diagnosis, investigation, and management of this patient

OGLE-2016-BLG-1227L: A Wide-separation Planet from a Very Short-timescale Microlensing Event

We present the analysis of the microlensing event OGLE-2016-BLG-1227. The light curve of this short-duration event appears to be a single-lens event affected by severe finite-source effects. Analysis of the light curve based on single-lens single-source (1L1S) modeling yields very small values of the event timescale, t_E ∼ 3.5 days, and the angular Einstein radius, θ_E ∼ 0.009 mas, making the lens a candidate of a free-floating planet. Close inspection reveals that the 1L1S solution leaves small residuals with amplitude ΔI ≲ 0.03 mag. We find that the residuals are explained by the existence of an additional widely-separated heavier lens component, indicating that the lens is a wide-separation planetary system rather than a free-floating planet. From Bayesian analysis, it is estimated that the planet has a mass of _p = 0.79^(+1.30)_(−0.39) M_J and it is orbiting a low-mass host star with a mass of M_(host) = 0.10+0.17−0.05 M_⊙ located with a projected separation of a_ = 3.4^(+2.1)_(−1.0) au. The planetary system is located in the Galactic bulge with a line-of-sight separation from the source star of D_(LS) = 1.21^(+0.96)_(−0.63) kpc. The event shows that there are a range of deviations in the signatures of host stars for apparently isolated planetary lensing events and that it is possible to identify a host even when a deviation is subtle

Nutrient Cycling in Tropical and Temperate Coastal Waters: Is Latitude Making a Difference?

Tropical coastal waters are highly dynamic and amongst the most biogeochemically active zones in the ocean. This review compares nitrogen (N) and phosphorus (P) cycles in temperate and tropical coastal waters. We review the literature to identify major similarities and differences between these two regions, specifically with regards to the impact of environmental factors (temperature, sunlight), riverine inputs, groundwater, lateral fluxes, atmospheric deposition, nitrogen fixation, organic nutrient cycling, primary production, respiration, sedimentary burial, denitrification and anammox. Overall, there are some similarities but also key differences in nutrient cycling, with differences relating mainly to temperature, sunlight, and precipitation amounts and patterns. We conclude that due to the differences in biogeochemical processes, we cannot directly apply cause and effect relationships and models from temperate systems in tropical coastal waters. Our review also highlights the considerable gaps in knowledge of the biogeochemical processes of tropical coastal waters compared with temperate systems. Given the ecological and societal importance of tropical coastal waters, we hope that highlighting the differences and similarities to temperate systems as well as the existing gaps, will inspire further studies on their biogeochemical processes. Such knowledge will be essential to better understand and forecast impacts on tropical coastal nutrient cycling at local, regional, and global scales

A 21-Year-Old Pregnant Woman with Hypertension and Proteinuria

Ronald Ma and colleagues describe the differential diagnosis, investigation, and management of a 21-year-old pregnant woman presenting with hypertension and proteinuria at 20 weeks of gestation