Clinical significance of left atrial geometry in dilated cardiomyopathy patients: A cardiovascular magnetic resonance study

BackgroundClinical significance of left atrial (LA) function and geometry in patients with dilated cardiomyopathy (DCM) remains uncertain.HypothesisLA geometric parameters assessed by cardiac magnetic resonance (CMR) predict the prognosis in patients with DCM.MethodsThe present study included patients with DCM and sinus rhythm who underwent CMR between December 2007 and April 2018. LA volume was measured using CMR. LA sphericity index was computed as the ratio of the measured maximum LA volume by the volume of a sphere with maximum LA length diameter.ResultsWe included 255 patients in this study. During the mean follow‐up of 3.92 years, hospitalization for HF occurred in 37 patients. The LA sphericity index was significantly higher in patients with hospitalization for HF than in those without (0.78 ± 0.35 vs. 0.58 ± 0.18, p < .001). Multivariable Cox regression analysis identified a higher LA sphericity index as an independent predictor of hospitalization for HF. Patients were categorized based on the median of LA sphericity index. The Kaplan–Meier curve showed that patients with a high LA sphericity index (≥0.57) had a significantly higher risk of hospitalization for HF than those with a low LA sphericity index (<0.57).ConclusionLA sphericity index was an independent predictor of hospitalization for HF. Assessment of LA geometric parameters might be useful for risk stratification in patients with DCM.     

Rationale and design of a randomized trial to assess the effects of beta-blocker in diastolic heart failure; Japanese Diastolic Heart Failure Study (J-DHF)

BACKGROUND: Heart failure consists of two phenotypes: systolic heart failure and diastolic heart failure (DHF). A growing body of evidence demonstrated benefits of beta-blocker, angiotensin-converting enzyme inhibitor, and angiotensin II receptor blocker in systolic heart failure; however, evidence leading to therapeutic strategy of DHF is lacking. METHODS AND RESULTS: The Japanese Diastolic Heart Failure Study (J-DHF) is a multicenter, prospective, randomized trial designed to assess effects of beta-blocker in patients with DHF. A total of 800 patients (400 patients in each group) will be enrolled. The primary outcome is a composite of cardiovascular death and unplanned admission to hospital for congestive heart failure. Other outcomes include all-cause mortality, worsening of the symptoms of heart failure, or a need for modification of the treatment for heart failure. Serial assessment of echocardiographic and neurohumoral parameters and cost analysis of the treatment regimen will be conducted. The follow-up period is a minimum of 2 years. CONCLUSION: This study will provide important evidences for the treatment of DHF.     

A Case of Cardiac Amyloidosis Presenting with Mid- to Late Diastolic Retrograde Flow from the Left Atrium to the Pulmonary Vein: Transesophageal Pulsed Doppler Echocardiographic Observations

A patient of cardiac amyloidosis was found to have mid-to late diastolic retrograde flow from the left atrium (LA) to the pulmonary vein. Congo-red staining was positive for amyloid in the rectal tissue. M-mode and two-dimensional echocardiograms revealed symmetric hypertrophy and typical speckled pattern of the left ventricle (LV). The LV pressure curve showed a dip and plateau configuration during diastole, and end-diastolic pressure was 28 mmHg. In addition, the LV pressure was high at mid-diastole, surpassing the pulmonary capillary wedge pressure from mid-to late diastole. The transmitral flow velocity revealed "restrictive" pattern, and the pulmonary venous flow velocity showed retrograde flow from the LA to the pulmonary vein during mid-diastole and atrial systole. It is suggested that recording of the pulmonary venous flow velocity by transesophageal pulsed Doppler echocardiography is useful for understanding the mechanism of the development of pulmonary congestion or edema.     

Group 2 innate lymphoid cells support hematopoietic recovery under stress conditions

The cell-cycle status of hematopoietic stem and progenitor cells (HSPCs) becomes activated following chemotherapy-induced stress, promoting bone marrow (BM) regeneration; however, the underlying molecular mechanism remains elusive. Here we show that BM-resident group 2 innate lymphoid cells (ILC2s) support the recovery of HSPCs from 5-fluorouracil (5-FU)–induced stress by secreting granulocyte-macrophage colony-stimulating factor (GM-CSF). Mechanistically, IL-33 released from chemo-sensitive B cell progenitors activates MyD88-mediated secretion of GM-CSF in ILC2, suggesting the existence of a B cell–ILC2 axis for maintaining hematopoietic homeostasis. GM-CSF knockout mice treated with 5-FU showed severe loss of myeloid lineage cells, causing lethality, which was rescued by transferring BM ILC2s from wild-type mice. Further, the adoptive transfer of ILC2s to 5-FU–treated mice accelerates hematopoietic recovery, while the reduction of ILC2s results in the opposite effect. Thus, ILC2s may function by “sensing” the damaged BM spaces and subsequently support hematopoietic recovery under stress conditions.     

Optical control of cell differentiation on synthetic collagen-like scaffolds

Abstract

We have developed biocompatible scaffolds that enable cell fate control with visible light. The scaffolds are based on synthetic collagen-like polypeptide, poly(prolyl-hydroxyprolyl-glycyl) {poly(Pro-Hyp-Gly)} which has been used for cosmetics and other healthcare applications. Bioactive peptides were conjugated to the scaffolds via photoactivation reaction utilizing 488?nm visible light. In addition, the use of a photocleavable crosslinker enables dissociation of chemical moieties by 405?nm laser irradiation. The synthesis scheme enables optical control to attach and detach functional peptides in pre-patterned shapes. Using bone forming peptide (BFP), we demonstrate that calcium deposition by rat bone stromal cells can be directed on the scaffold. Using other signaling molecules and three-dimensional scaffolds, controlled differentiation of stem cells can be achieved by spatio-temporally specific irradiation of confocal microscope laser.     

Temporal Contribution of Myeloid-Lineage TLR4 to the Transition to Chronic Pain: A Focus on Sex Differences

Complex regional pain syndrome (CRPS) is a chronic pain disorder with a clear acute-to-chronic transition. Preclinical studies demonstrate that toll-like receptor 4 (TLR4), expressed by myeloid-lineage cells, astrocytes, and neurons, mediates a sex-dependent transition to chronic pain; however, evidence is lacking on which exact TLR4-expressing cells are responsible. We used complementary pharmacologic and transgenic approaches in mice to more specifically manipulate myeloid-lineage TLR4 and outline its contribution to the transition from acute-to-chronic CRPS based on three key variables: location (peripheral vs central), timing (prevention vs treatment), and sex (male vs female). We demonstrate that systemic TLR4 antagonism is more effective at improving chronic allodynia trajectory when administered at the time of injury (early) in the tibial fracture model of CRPS in both sexes. In order to clarify the contribution of myeloid-lineage cells peripherally (macrophages) or centrally (microglia), we rigorously characterize a novel spatiotemporal transgenic mouse line, Cx3CR1-Cre^ERT2-eYFP;TLR4^fl/fl (TLR4 cKO) to specifically knock out TLR4 only in microglia and no other myeloid-lineage cells. Using this transgenic mouse, we find that early TLR4 cKO results in profound improvement in chronic, but not acute, allodynia in males, with a significant but less robust effect in females. In contrast, late TLR4 cKO results in partial improvement in allodynia in both sexes, suggesting that downstream cellular or molecular TLR4-independent events may have already been triggered. Overall, we find that the contribution of TLR4 is time- and microglia-dependent in both sexes; however, females also rely on peripheral myeloid-lineage (or other TLR4 expressing) cells to trigger chronic pain.SIGNIFICANCE STATEMENT The contribution of myeloid cell TLR4 to sex-specific pain progression remains controversial. We used complementary pharmacologic and transgenic approaches to specifically manipulate TLR4 based on three key variables: location (peripheral vs central), timing (prevention vs treatment), and sex (male vs female). We discovered that microglial TLR4 contributes to early pain progression in males, and to a lesser extent in females. We further found that maintenance of chronic pain likely occurs through myeloid TLR4-independent mechanisms in both sexes. Together, we define a more nuanced contribution of this receptor to the acute-to-chronic pain transition in a mouse model of complex regional pain syndrome.     

Theoretical study on aromatic and open-shell characteristics of carbon nanobelts composed of indeno[1,2-b]fluorene units: dependence on the number of units and charge states

In this study, we theoretically investigate the aromatic and open-shell characteristics of carbon nanobelts (CNBs) composed of five- and six-membered rings. We have designed nanobelts composed of indeno[1,2-b]fluorene ([1,2-b]IF) units, which are referred to as [N]IF-CNB (N: the number of five-membered rings). The number of π-electrons, n_π, in neutral [N]IF-CNB is 7N, and thus depending on N and charge states, n_π can be 4n + 2 and 4n. Quantum chemical calculations on neutral [6]IF-CNB and [8]IF-CNB and dicationic [8]IF-CNB²⁺ have revealed that they are expected to exhibit unique aromatic and open-shell characteristics depending on n_π, there are several analogies of the electronic structures in [N]IF-CNB to those in [N]annulene. Delocalized and intermediate open-shell electronic structures of [N]IF-CNB are also useful to drastically change the third-order nonlinear optical properties. These results suggest that theoretically designed [N]IF-CNB can be attractive and challenging targets of organic synthesis for realizing novel open-shell functional conjugated macrocycles.

Dependence of aromatic and open-shell characteristics on the number of units and charged states was theoretically investigated for carbon nanobelts composed of indeno[1,2-b]fluorene units by using quantum chemical calculations.     

Repeated General Anesthesia in a Patient With Noonan Syndrome

Noonan syndrome (NS) is an autosomal dominant disorder characterized by facial anomalies, short stature, chest deformity, congenital heart diseases, and other comorbidities. The challenges faced during anesthetic management of patients with NS could be due to congenital heart diseases, hemostatic disorders, and airway anomalies. Here we describe dental treatment under general anesthesia performed for a 28-year-old man with NS. He had characteristic features of NS along with mild pulmonary valve stenosis. Dental treatment under general anesthesia was performed successfully on 13 occasions with nasotracheal intubation under curve-tipped suction catheter guidance or insertion of a reinforced laryngeal mask airway. This case suggests that for patients with NS, who might present several challenges, dental anesthesiologists should consider the extent of the patient''s disorders to enable them to perform dental treatment safely under general anesthesia.Key Words: Repeated general anesthesia, Noonan syndromeNoonan syndrome (NS) is an autosomal dominant disorder and was first reported by Noonan and Ehmke.¹ The primary features of this multisystem disorder include hypertelorism, low-set ears, down-slanting eyes, a webbed neck, congenital heart diseases, short stature, chest deformity, and intellectual impairment.^2,3 NS affects males and females equally and has an estimated incidence of 1 in 1000 to 1 in 2500 live births.^2,4The challenges faced during anesthetic management of patients with NS could be due to congenital heart diseases, hemostatic disorders, and airway anomalies.^5–8 The present report describes repeated administration of general anesthesia performed by adopting nasotracheal intubation or reinforced laryngeal mask airway insertion for a patient with NS at the time of dental treatment in our hospital.