Impact of Right Ventricular Pressure Overload on Myocardial Stiffness Assessed by Natural Wave Imaging.

BACKGROUND: Right ventricular (RV) hemodynamic performance determines the prognosis of patients with RV pressure overload. Using ultrafast ultrasound, natural wave velocity (NWV) induced by cardiac valve closure was proposed as a new surrogate to quantify myocardial stiffness. OBJECTIVES: This study aimed to assess RV NWV in rodent models and children with RV pressure overload vs control subjects and to correlate NWV with RV hemodynamic parameters. METHODS: Six-week-old rats were randomized to pulmonary artery banding (n = 6), Sugen hypoxia-induced pulmonary arterial hypertension (n = 7), or sham (n = 6) groups. They underwent natural wave imaging, echocardiography, and hemodynamic assessment at baseline and 6 weeks postoperatively. The authors analyzed NWV after tricuspid and after pulmonary valve closure (TVC and PVC, respectively). Conductance catheters were used to generate pressure-volume loops. In parallel, the authors prospectively recruited 14 children (7 RV pressure overload; 7 age-matched control subjects) and compared RV NWV with echocardiographic and invasive hemodynamic parameters. RESULTS: NWV significantly increased in RV pressure overload rat models (4.99 ± 0.27 m/s after TVC and 5.03 ± 0.32 m/s after PVC in pulmonary artery banding at 6 weeks; 4.89 ± 0.26 m/s after TVC and 4.84 ± 0.30 m/s after PVC in Sugen hypoxia at 6 weeks) compared with control subjects (2.83 ± 0.15 m/s after TVC and 2.72 ± 0.34 m/s after PVC). NWV after TVC correlated with both systolic and diastolic parameters including RV dP/dtmax (r = 0.75; P < 0.005) and RV Ees (r = 0.81; P < 0.005). NWV after PVC correlated with both diastolic and systolic parameters and notably with RV end-diastolic pressure (r = 0.65; P < 0.01). In children, NWV after both right valves closure in RV pressure overload were higher than in healthy volunteers (P < 0.01). NWV after PVC correlated with RV E/E' (r = 0.81; P = 0.008) and with RV chamber stiffness (r = 0.97; P = 0.03). CONCLUSIONS: Both RV early-systolic and early-diastolic myocardial stiffness show significant increase in response to pressure overload. Based on physiology and our observations, early-systolic myocardial stiffness may reflect contractility, whereas early-diastolic myocardial stiffness might be indicative of diastolic function.

Impact of Ventricular Geometric Characteristics on Myocardial Stiffness Assessment Using Shear-Wave Velocity in Healthy Children and Young Adults.

BACKGROUND: Diastolic myocardial stiffness (MS) can serve as a key diagnostic parameter for congenital or acquired heart diseases. Using shear modulus and shear-wave velocity (SWV), shear-wave elastography (SWE) is an emerging ultrasound-based technique that can allow noninvasive assessment of MS. However, MS extrinsic parameters such as left ventricular geometric characteristics could affect shear-wave propagation. The aims of this study were to determine a range of normal values of MS using SWE in age groups of healthy children and young adults and to explore the impact of left ventricular geometric characteristics on SWE. METHODS: Sixty healthy volunteers were recruited in the study and divided into 2 groups: neonates (0-1 months old, n = 15) and >1 month old (1 month to 45 years of age, n = 45). SWE was performed using the Verasonics Vantage systems with a phased-array ultrasound probe. The anteroseptal basal segment was assessed in two views. SWE was electrocardiographically triggered during the end-diastolic phase. Conventional echocardiography was performed to assess ventricular function and anatomy. Results are presented as stiffness values along with mean velocity measurements and SDs. Simple and multivariate linear regression analyses were performed. RESULTS: For neonates, mean MS was 1.87 ± 0.79 kPa (range, 0.59-2.91 kPa; mean SWV, 1.37 ± 0.57 m/sec), with high variability and no correlation with age (P = .239). For this age group, no statistically significant correlation was found between MS and any demographic or echocardiographic parameters (P > .05). For the >1 month old group, a mean MS value of 1.67 ± 0.53 kPa was observed (range, 0.6-3 kPa; mean SWV, 1.29 ± 0.49 m/sec) for healthy volunteers. When paired for age, no sex-related difference was observed (P = .55). In univariate linear regression analysis, age (r = 0.83, P < .01), diastolic interventricular septal thickness (r = 0.72, P < .01), and left ventricular end-diastolic diameter (r = 0.67, P < .01) were the parameters with the highest correlation coefficients with MS. In a multiple linear regression analysis incorporating these three parameters as cofounding factors, age was the only statistically significant parameters (r = 0.81, P = .02). CONCLUSION: Diastolic MS increases linearly in children and young adults. Diastolic MS correlates more robustly with age than with myocardial and left ventricular geometric characteristics. However, the geometry affects SWV, implying the need to determine well-established boundaries in future studies for the clinical application of SWE.

Correction: Cognitive Impairment in Type 2 Diabetes Mellitus.

[This corrects the article DOI: 10.7759/cureus.22193.].

Cognitive Impairment in Type 2 Diabetes Mellitus.

Objective To determine the incidence of cognitive impairment established on the mini-mental state assessment in type 2 diabetic patients presenting at Holy Family Hospital, Rawalpindi. Materials and methods This cross-sectional descriptive study was carried out from June 2019 to December 2019. Individuals with a diagnosis of type 2 diabetes mellitus were included, and detailed history, physical examination, and biochemical variables were noted. They were assessed through Mini-Mental State Examination (MMSE) (Urdu translation) to look for the primary outcome variable, i.e., cognitive impairment. All patients with type 2 diabetes mellitus diagnosed at least one year back, irrespective of gender, were included in this investigation. Patients with a previous history of head injury, epilepsy, stroke, those on an antidepressant or antipsychotic medications, those with deranged renal function tests, and those already diagnosed with dementia were excluded from the study. Results Three hundred thirty-two patients meeting the inclusion criteria were included in the study. The mean ± standard deviation age of the study population was 65.32 ± 11.33 years, with maximum age being 80 years and the minimum being 50 years. Two hundred patients (60.24%) were below 65 years of age, and 132 patients (39.76%) were 65 years of age or above. Two hundred sixteen (65.06%) were males, and 116 (34.96%) were females. The mean duration of diabetes mellitus (DM) was 10.17 ± 4.81. The mean MMSE score was 22.69 ± 5.26. Out of 332 patients, 81 (24.4%) patients had cognitive impairment. Patients who were 65 or older had a significantly higher proportion of cognitive impairment, compared to those below 65 years of age (p-value = 0.0214). There was no significant difference in the proportion of cognitively impaired patients between males and females (p-value = 0.2497). Similarly, there was no significant difference between those who were diagnosed with type 2 diabetes for 10 years or more and those who were diagnosed less than 10 years ago (p-value = 0.3791). Conclusion Cognitive impairment is common in individuals having type 2 diabetes mellitus. It is also associated with the increasing age of diabetic patients. However, cognitive impairment in type 2 diabetes mellitus is not associated with gender. In addition, there is no significant difference in cognitive impairment between the patients who were diagnosed with diabetes more than 10 years ago and those who had it diagnosed less than 10 years ago.

A guide for assessment of myocardial stiffness in health and disease.

Myocardial stiffness is an intrinsic property of the myocardium that influences both diastolic and systolic cardiac function. Myocardial stiffness represents the resistance of this tissue to being deformed and depends on intracellular components of the cardiomyocyte, particularly the cytoskeleton, and on extracellular components, such as collagen fibers. Myocardial disease is associated with changes in myocardial stiffness, and its assessment is a key diagnostic marker of acute or chronic pathological myocardial disease with the potential to guide therapeutic decision-making. In this Review, we appraise the different techniques that can be used to estimate myocardial stiffness, evaluate their advantages and disadvantages, and discuss potential clinical applications.

Multifunctional nanoparticles as theranostic agents for therapy and imaging of breast cancer.

Over the last decade, there has been significant developments in nanotechnology, in particular for combined imaging and therapeutic applications (theranostics). The core or shell of nanoemulsions (NEs) can be loaded with various therapeutic agents, including drugs with low solubility for effective treatment, or various imaging agents for specific imaging modalities (e.g., MRI, fluorescence). In this work, perfluorohexane (PFH) NEs were synthesized for theranostic applications and were coupled to silica coated gold nanoparticles (scAuNPs) to increase the generation of PFH bubbles upon laser induced vaporization (i.e., optical droplet vaporization). The localized heat generated from the absorption properties of these nanoparticles (used to provide photoacoustic signals) can also be used to treat cancer without significantly damaging nearby healthy tissues. The theranostic potential of these PFH-NEs for contrast imaging of tumors and as a drug-delivery vehicle for therapeutic purposes were demonstrated for both in vitro and in vivo systems using a combination of photoacoustic, ultrasound and fluorescence imaging modalities. The ability of PFH-NEs to couple with scAuNPs, attach to the membranes of cancer cells and internalize within cancer cells, are encouraging for targeted chemotherapeutic applications for directly inducing cancer cell death via vaporization in clinical settings.

Ligand modulation of the conformational dynamics of the A2A adenosine receptor revealed by single-molecule fluorescence.

G protein-coupled receptors (GPCRs) are the largest class of transmembrane proteins, making them an important target for therapeutics. Activation of these receptors is modulated by orthosteric ligands, which stabilize one or several states within a complex conformational ensemble. The intra- and inter-state dynamics, however, is not well documented. Here, we used single-molecule fluorescence to measure ligand-modulated conformational dynamics of the adenosine A2A receptor (A2AR) on nanosecond to millisecond timescales. Experiments were performed on detergent-purified A2R in either the ligand-free (apo) state, or when bound to an inverse, partial or full agonist ligand. Single-molecule Förster resonance energy transfer (smFRET) was performed on detergent-solubilized A2AR to resolve active and inactive states via the separation between transmembrane (TM) helices 4 and 6. The ligand-dependent changes of the smFRET distributions are consistent with conformational selection and with inter-state exchange lifetimes ≥ 3 ms. Local conformational dynamics around residue 2296.31 on TM6 was measured using fluorescence correlation spectroscopy (FCS), which captures dynamic quenching due to photoinduced electron transfer (PET) between a covalently-attached dye and proximal aromatic residues. Global analysis of PET-FCS data revealed fast (150-350 ns), intermediate (50-60 µs) and slow (200-300 µs) conformational dynamics in A2AR, with lifetimes and amplitudes modulated by ligands and a G-protein mimetic (mini-Gs). Most notably, the agonist binding and the coupling to mini-Gs accelerates and increases the relative contribution of the sub-microsecond phase. Molecular dynamics simulations identified three tyrosine residues (Y112, Y2887.53, and Y2907.55) as being responsible for the dynamic quenching observed by PET-FCS and revealed associated helical motions around residue 2296.31 on TM6. This study provides a quantitative description of conformational dynamics in A2AR and supports the idea that ligands bias not only GPCR conformations but also the dynamics within and between distinct conformational states of the receptor.

Peripartum Cardiomyopathy During Puerperium Co-existing with Pre-eclampsia and Complicated by Acute Renal Failure: A Case Report.

We report a case of peripartum cardiomyopathy (PPCM), which presented with antenatal pre-eclampsia complicated by acute kidney injury (AKI). A 25-year-old patient in her 27th week of gestation presented with high blood pressure. She was later diagnosed with PPCM, which was complicated by AKI. Our case report indicated PPCM presentation during the prepartum period, which is a rare entity. On her fifth day of admission, our patient had spontaneous expulsion of her neonate, who was found to be dead on antenatal ultrasound.