Diabetic cardiomyopathy: Pathophysiology, theories and evidence to date

The prevalence of type 2 diabetes (T2D) has increased worldwide and doubled over the last two decades. It features among the top 10 causes of mortality and morbidity in the world. Cardiovascular disease is the leading cause of complications in diabetes and within this, heart failure has been shown to be the leading cause of emergency admissions in the United Kingdom. There are many hypotheses and well-evidenced mechanisms by which diabetic cardiomyopathy as an entity develops. This review aims to give an overview of these mechanisms, with particular emphasis on metabolic inflexibility. T2D is associated with inefficient substrate utilisation, an inability to increase glucose metabolism and dependence on fatty acid oxidation within the diabetic heart resulting in mitochondrial uncoupling, glucotoxicity, lipotoxicity and initially subclinical cardiac dysfunction and finally in overt heart failure. The review also gives a concise update on developments within clinical imaging, specifically cardiac magnetic resonance studies to characterise and phenotype early cardiac dysfunction in T2D. A better understanding of the pathophysiology involved provides a platform for targeted therapy in diabetes to prevent the development of early heart failure with preserved ejection fraction

Do bilinguals have different concepts? The case of shape and material in Japanese L2 users of English

An experiment investigated whether Japanese speakers’ categorisation of objects and substances as shape or material is influenced by acquiring English, based on Imai and Gentner (1997). Subjects were presented with an item such as a cork pyramid and asked to choose between two other items that matched it for shape (plastic pyramid) or for material (piece of cork). The hypotheses were that for simple objects the number of shape-based categorisations would increase according to experience of English and that the preference for shape and material-based categorisations of Japanese speakers of English would differ from mono¬lingual speakers of both languages. Subjects were 18 adult Japanese users of English who had lived in English-speaking countries between 6 months and 3 years (short-stay group), and 18 who had lived in English-speaking countries for 3 years or more (long-stay group). Both groups achieved above criterion on an English vocabulary test. Results were: both groups preferred material responses for simple objects and substances but not for complex objects, in line with Japanese mono¬linguals, but the long-stay group showed more shape preference than the short-stay group and also were less different from Americans. These effects of acquiring a second language on categorisation have implications for conceptual representation and methodology

A case report of refractory angina in a patient with diabetes and apical hypertrophic cardiomyopathy

Background: Using serial imaging over time, this case reviews the natural history of co-morbid Type two diabetes (T2D) and apical hypertrophic cardiomyopathy (HCM) and assesses the potential combined impact on myocardial structure and perfusion. Case summary: A 59-year-old patient with concomitant T2D and an apical phenotype of HCM was seen over a 11-year period with a significant burden of anginal chest pain. Chest pain was refractory to anti-anginal medical therapy and persisted at on-going follow-up. Multi-modality imaging demonstrated significant deterioration in coronary microvascular function and increased myocardial scar burden despite unobstructed epicardial coronary arteries. Discussion: Comorbidity with T2D and apical HCM resulted in a significant increase in myocardial fibrosis and deterioration in coronary microvascular function

Does stress perfusion imaging improve the diagnostic accuracy of late gadolinium enhanced cardiac magnetic resonance for establishing the etiology of heart failure?

Background Late gadolinium enhanced cardiovascular magnetic resonance (LGE-CMR) has excellent specificity, sensitivity and diagnostic accuracy for differentiating between ischemic cardiomyopathy (ICM) and non-ischemic dilated cardiomyopathy (NICM). CMR first-pass myocardial perfusion imaging (perfusion-CMR) may also play role in distinguishing heart failure of ischemic and non-ischemic origins, although the utility of additional of stress perfusion imaging in such patients is unclear. The aim of this retrospective study was to assess whether the addition of adenosine stress perfusion imaging to LGE-CMR is of incremental value for differentiating ICM and NICM in patients with severe left ventricular systolic dysfunction (LVSD) of uncertain etiology. Methods We retrospectively identified 100 consecutive adult patients (median age 69 years (IQR 59–73)) with severe LVSD (mean LV EF 26.6 ± 7.0%) referred for perfusion-CMR to establish the underlying etiology of heart failure. The cause of heart failure was first determined on examination of CMR cine and LGE images in isolation. Subsequent examination of complete adenosine stress perfusion-CMR studies (cine, LGE and perfusion images) was performed to identify whether this altered the initial diagnosis. Results On LGE-CMR, 38 patients were diagnosed with ICM, 46 with NICM and 16 with dual pathology. With perfusion-CMR, there were 39 ICM, 44 NICM and 17 dual pathology diagnoses. There was excellent agreement in diagnoses between LGE-CMR and perfusion-CMR (κ 0.968, p<0.001). The addition of adenosine stress perfusion images to LGE-CMR altered the diagnosis in only two of the 100 patients. Conclusion The addition of adenosine stress perfusion-CMR to cine and LGE-CMR provides minimal incremental diagnostic yield for determining the etiology of heart failure in patients with severe LVSD

Multiple Etiologies to Myocardial Injury in COVID-19

In patients with acute myocardial injury secondary to coronavirus disease-2019 (COVID-19), cardiovascular magnetic resonance imaging can identify the underlying pathology. We highlight a case of acute myocardial injury secondary to COVID-19, which demonstrated both epicardial vessel thrombosis and the recently described phenomenon of microvascular thrombosis. (Level of Difficulty: Advanced.

Singular Coexistence-curve Diameters: Experiments and Simulations

Precise calculations of the coexistence-curve diameters of a hard-core square-we ll (HCSW) fluid and the restricted primitive model (RPM) electrolyte exhibit mar ked deviations from rectilinear behavior. The HCSW diameter displays a $|t|^{1- alpha}$ singularity that sets in sharply for $|t|\equiv |T-T_c|/T_c\lesssim 10^{-3}$; this compares favorably with extensive data for ${SF}_6$, also reflec ted in C$_2$H$_6$, N$_2$, etc. By contrast, the curvature of the RPM diameter va ries slowly over a wide range $|t|\lesssim 0.1$; this behavior mirrors observati ons for liquid alkali metals, specifically Rb and Cs. Amplitudes for the leading singular terms can be estimated numerically but their values cannot be taken li terally.Comment: 9 pages and 4 figure

A comparison of standard and high dose adenosine protocols in routine vasodilator stress cardiovascular magnetic resonance: dosage affects hyperaemic myocardial blood flow in patients with severe left ventricular systolic impairment

Background: Adenosine stress perfusion cardiovascular magnetic resonance (CMR) is commonly used in the assessment of patients with suspected ischaemia. Accepted protocols recommend administration of adenosine at a dose of 140 µg/kg/min increased up to 210 µg/kg/min if required. Conventionally, adequate stress has been assessed using change in heart rate, however, recent studies have suggested that these peripheral measurements may not reflect hyperaemia and can be blunted, in particular, in patients with heart failure. This study looked to compare stress myocardial blood flow (MBF) and haemodynamic response with different dosing regimens of adenosine during stress perfusion CMR in patients and healthy controls. Methods: 20 healthy adult subjects were recruited as controls to compare 3 adenosine perfusion protocols: standard dose (140 µg/kg/min for 4 min), high dose (210 µg/kg/min for 4 min) and long dose (140 µg/kg/min for 8 min). 60 patients with either known or suspected coronary artery disease (CAD) or with heart failure and different degrees of left ventricular (LV) dysfunction underwent adenosine stress with standard and high dose adenosine within the same scan. All studies were carried out on a 3 T CMR scanner. Quantitative global myocardial perfusion and haemodynamic response were compared between doses. Results: In healthy controls, no significant difference was seen in stress MBF between the 3 protocols. In patients with known or suspected CAD, and those with heart failure and mild systolic impairment (LV ejection fraction (LVEF) ≥ 40%) no significant difference was seen in stress MBF between standard and high dose adenosine. In those with LVEF < 40%, there was a significantly higher stress MBF following high dose adenosine compared to standard dose (1.33 ± 0.46 vs 1.10 ± 0.47 ml/g/min, p = 0.004). Non-responders to standard dose adenosine (defined by an increase in heart rate (HR) < 10 bpm) had a significantly higher stress HR following high dose (75 ± 12 vs 70 ± 14 bpm, p = 0.034), but showed no significant difference in stress MBF. Conclusions: Increasing adenosine dose from 140 to 210 µg/kg/min leads to increased stress MBF in patients with significantly impaired LV systolic function. Adenosine dose in clinical perfusion assessment may need to be increased in these patients

Existence of a critical point in the phase diagram of the ideal relativistic neutral Bose gas

We explore the phase transitions of the ideal relativistic neutral Bose gas confined in a cubic box, without assuming the thermodynamic limit nor continuous approximation. While the corresponding non-relativistic canonical partition function is essentially a one-variable function depending on a particular combination of temperature and volume, the relativistic canonical partition function is genuinely a two-variable function of them. Based on an exact expression of the canonical partition function, we performed numerical computations for up to hundred thousand particles. We report that if the number of particles is equal to or greater than a critical value, which amounts to 7616, the ideal relativistic neutral Bose gas features a spinodal curve with a critical point. This enables us to depict the phase diagram of the ideal Bose gas. The consequent phase transition is first-order below the critical pressure or second-order at the critical pressure. The exponents corresponding to the singularities are 1/2 and 2/3 respectively. We also verify the recently observed `Widom line' in the supercritical region.Comment: 1+25 pages, 6 B/W figures: Comment on the Widom line added. Minor improvement. Version to appear in `New Journal of Physics

Analysis of satellite-derived Arctic tropospheric BrO columns in conjunction with aircraft measurements during ARCTAS and ARCPAC

We derive tropospheric column BrO during the ARCTAS and ARCPAC field campaigns in spring 2008 using retrievals of total column BrO from the satellite UV nadir sensors OMI and GOME-2 using a radiative transfer model and stratospheric column BrO from a photochemical simulation. We conduct a comprehensive comparison of satellite-derived tropospheric BrO column to aircraft in-situ observations of BrO and related species. The aircraft profiles reveal that tropospheric BrO, when present during April 2008, was distributed over a broad range of altitudes rather than being confined to the planetary boundary layer (PBL). Perturbations to the total column resulting from tropospheric BrO are the same magnitude as perturbations due to longitudinal variations in the stratospheric component, so proper accounting of the stratospheric signal is essential for accurate determination of satellite-derived tropospheric BrO. We find reasonably good agreement between satellite-derived tropospheric BrO and columns found using aircraft in-situ BrO profiles, particularly when satellite radiances were obtained over bright surfaces (albedo \u3e0.7), for solar zenith angl