Long-Term Implications of Atrial Fibrillation in Patients With Degenerative Mitral Regurgitation

Background

Scientific guidelines consider atrial fibrillation (AF) complicating degenerative mitral regurgitation (DMR) a debated indication for surgery.

Ciliary melanin-concentrating hormone receptor 1 (MCHR1) is widely distributed in the murine CNS in a sex-independent manner

Melanin-concentrating hormone (MCH) is a ubiquitous vertebrate neuropeptide predominantly synthesized by neurons of the diencephalon that can act through two G protein-coupled receptors, called MCHR1 and MCHR2. The expression of Mchr1 has been investigated in both rats and mice, but its synthesis remains poorly described. After identifying an antibody that detects MCHR1 with high specificity, we employed immunohistochemistry to map the distribution of MCHR1 in the CNS of rats and mice. Multiple neurochemical markers were also employed to characterize some of the neuronal populations that synthesize MCHR1. Our results show that MCHR1 is abundantly found in a subcellular structure called the primary cilium, which has been associated, among other functions, with the detection of free neurochemical messengers present in the extracellular space. Ciliary MCHR1 was found in a wide range of areas, including the olfactory bulb, cortical mantle, striatum, hippocampal formation, amygdala, midline thalamic nuclei, periventricular hypothalamic nuclei, midbrain areas, and in the spinal cord. No differences were observed between male and female mice, and interspecies differences were found in the caudate-putamen nucleus and the subgranular zone. Ciliary MCHR1 was found in close association with several neurochemical markers, including tyrosine hydroxylase, calretinin, kisspeptin, estrogen receptor, oxytocin, vasopressin, and corticotropin-releasing factor. Given the role of neuronal primary cilia in sensing free neurochemical messengers in the extracellular fluid, the widespread distribution of ciliary MCHR1, and the diverse neurochemical populations who synthesize MCHR1, our data indicate that nonsynaptic communication plays a prominent role in the normal function of the MCH system.     

An unusual oral chronic graft-versus-host disease-like syndrome following a liver transplant

BACKGROUND: Giving the immunosuppressive drug tacrolimus (FK506) to liver transplant patients has helped to considerably reduce oral side effects such as gingival hyperplasia. Patients taking cyclosporin who suffer from gingival hyperplasia are often switched to tacrolimus. METHODS: We present here a pediatric liver transplantation case study. The patient has been followed for 5.5 years. She developed oral lesions that resulted in the immunosuppressive therapy being changed from tacrolimus to cyclosporin. In clinical terms, the atypical pathology consisted of hyperpigmented patches on the gingival margin, the internal surfaces of the cheeks, and the intraoral surfaces of the lips. When located on the lips, the hyperpigmented patches were associated with pruriginous and edematous lesions. RESULTS: Optical and electronic microscopic examinations of a gingival tissue sample revealed the presence of melanin incontinence and lichenoid lesions with degenerated keratinocytes and a mild infiltrate of lymphocytes. This points to a chronic graft-versus-host disease (cGvHD)-like syndrome linked to tacrolimus. This diagnosis was given further credence by improvement in the lesions following the switch to cyclosporin. CONCLUSION: To our knowledge, this is the first reported case of tacrolimus-associated chronic GvHD-like syndrome occurring in the oral mucosa.     

Effect of indomethacin on bone destruction during experimental periodontal disease in the hamster

A major event in periodontitis is the destruction of alveolar processes. It is demonstrated that indomethacin (IND), an inhibitor of prostaglandin synthesis, can inhibit bone resorption in vitro . The aim of this study was to test the effect of IND on bone destruction in hamster periodontal disease. Its action was compared to calcitonin (CT), an inhibitor of osteoclastic resorption. IND decreased the macroscopic bone loss by 28% and the number of osteoclasts per mm by 55% in diseased animals but not significantly. Conversely CT reduced significantly bone loss (p<0.05) and decreased the number of osteoclasts to the control level (p<0.01). The combination of the two drugs had the same effect than CT alone on the two parameters. These results show an effect of IND on bone destruction but an inhibitory action on prostaglandin synthesis can only be hypothesized. In this model of periodontitis CT appears more effective than IND.     

Acoustic excitations and elastic heterogeneities in disordered solids

In the recent years, much attention has been devoted to the inhomogeneous nature of the mechanical response at the nanoscale in disordered solids. Clearly, the elastic heterogeneities that have been characterized in this context are expected to strongly affect the nature of the sound waves which, in contrast to the case of perfect crystals, cannot be completely rationalized in terms of phonons. Building on previous work on a toy model showing an amorphization transition, we investigate the relationship between sound waves and elastic heterogeneities in a unified framework by continuously interpolating from the perfect crystal, through increasingly defective phases, to fully developed glasses. We provide strong evidence of a direct correlation between sound wave features and the extent of the heterogeneous mechanical response at the nanoscale.In crystals, molecules thermally oscillate around the periodic lattice sites and vibrational excitations are well understood in terms of quantized plane waves, the phonons (1). The vibrational density of states (vDOS) in the low-frequency regime is well described by the Debye model, where the vibrational modes are the acoustic phonons. In contrast, disordered solids, including structural glasses and disordered crystals, exhibit specific vibrational properties compared with the corresponding pure crystalline phases. It is not possible here to give a fair review of the extensive theoretical and experimental work generated by these issues; we therefore mention below a few facts that we consider the most relevant in the present context. The origin of the vDOS modes in excess over the Debye prediction around ω ∼1 THz, the so-called Boson peak (BP), is still debated (see, among many others, refs. 2 and 3). At the BP frequency, Ω^BP, localized modes have also been observed (4). Acoustic plane waves, which are exact normal modes in crystals, can still propagate in disordered solids. Indeed, at low frequencies, Ω, and long wavelengths, Λ, acoustic sound waves do not interact with disorder and can propagate conforming to the expected macroscopic limit. However, as Ω is increased beyond the Ioffe–Regel (IR) limit, Ω^IR, acoustic excitations interact with the disorder and are significantly scattered (5–7). Interestingly, this strong scattering regime occurs around the BP position, Ω^IR ∼ Ω^BP (8, 9). The exact origin of this phenomenon and its connection to the BP remain elusive.A possible rationalization of the above issues is based on the existence of elastic heterogeneities (10), which can originate from structural disorder, as in structural glasses (2), or disordered interparticle potentials, even in lattice structures such as disordered colloidal crystals (11). In the heterogeneous-elasticity theory of refs. 7 and 12 this amounts to consider spatial statistical fluctuations of the shear modulus. Within the framework of jamming approaches and using effective medium theories, elastic heterogeneities are related to the proximity of local elastic instabilities (13). Recent simulation work (14–16) has clearly demonstrated their existence in disordered solids. This is at variance with the case of simple crystals, which are characterized by a fully affine response and homogeneous moduli distributions (17). More specifically, in the large length scale limit, macroscopic moduli are observed. In contrast, as the length scale is reduced, moduli heterogeneities are detected, at a typical length scale ξ ≃ 10−15σ (15), where σ is the typical atomic diameter. Breakdown of both continuum mechanics (18) and Debye approximation (5, 6) has been demonstrated at the same mesoscopic length-scale ξ, where they are still valid for crystals. Remarkably, the wave frequency corresponding to the wavelength Λ ∼ ξ is very close to Ω^IR ∼ Ω^BP (19). Altogether these results indicate that a close connection must exist between elastic heterogeneities and acoustic excitations. In this paper we precisely address this point.In ref. 20 we considered a numerical model featuring an amorphization transition (21). We showed how to systematically deform the local moduli distributions, evaluated by coarse-graining the system in small domains of linear length scale w. We characterized the degree of elastic heterogeneity in terms of SD of those distributions and studied the effect on normal modes (eigenvalues of the Hessian matrix) and thermal conductivity. Building on that work, we are now in the position to investigate the relation between elastic heterogeneities and acoustic excitations, unifying in a single framework ordered and disordered solid states and considering quantities directly probed by experiments. By interpolating in a controlled way from perfect crystals, through increasingly defective phases, to fully developed amorphous structures, we (i) calculate the dynamical structure factors, extracting the relevant spectroscopic parameters; (ii) characterize the wave vector dependence of sound velocity and broadening of the acoustic excitations and clarify their nature in terms of the IR limit; and (iii) provide, for the first time to our knowledge, direct evidence of the correlation of the excitations lifetimes and Ω^IR with the magnitude of the elastic heterogeneities.     

Lung ultrasonography for assessment of oxygenation response to prone position ventilation in ARDS

Purpose

Prone position (PP) improves oxygenation and outcome of acute respiratory distress syndrome (ARDS) patients with a PaO₂/FiO₂ ratio <150 mmHg. Regional changes in lung aeration can be assessed by lung ultrasound (LUS). Our aim was to predict the magnitude of oxygenation response after PP using bedside LUS.

Methods

We conducted a prospective multicenter study that included adult patients with severe and moderate ARDS. LUS data were collected at four time points: 1 h before (baseline) and 1 h after turning the patient to PP, 1 h before and 1 h after turning the patient back to the supine position. Regional lung aeration changes and ultrasound reaeration scores were assessed at each time. Overdistension was not assessed.

Results

Fifty-one patients were included. Oxygenation response after PP was not correlated with a specific LUS pattern. The patients with focal and non-focal ARDS showed no difference in global reaeration score. With regard to the entire PP session, the patients with non-focal ARDS had an improved aeration gain in the anterior areas. Oxygenation response was not associated with aeration changes. No difference in PaCO₂ change was found according to oxygenation response or lung morphology.

Conclusions

In ARDS patients with a PaO₂/FiO₂ ratio ≤150 mmHg, bedside LUS cannot predict oxygenation response after the first PP session. At the bedside, LUS enables monitoring of aeration changes during PP.