Transcranial Magnetic Resonance Imaging-Guided Focused Ultrasound Treatment at 1.5 T: A Retrospective Study on Treatment- and Patient-Related Parameters Obtained From 52 Procedures

Objective: To present a retrospective analysis of patient- and sonication-related parameters of a group of patients treated with a transcranial magnetic resonance imaging (MRI)-guided focused ultrasound (tcMRgFUS) system integrated with a 1.5-T MRI unit. Methods: The data obtained from 59 patients, who underwent the tcMRgFUS procedure from January 2015 to April 2019, were retrospectively reviewed for this study. The following data, among others, were mainly collected: skull density ratio (SDR), skull area (SA), number of available transducer elements (Tx), and estimated focal power at target (FP). For each of the four different treatment stages, we calculated the number of sonication processes (S-n), user-defined sonication power (S-p), effective measured power (S-mp), sonication duration (S-d), user-defined energy (E), effective measured energy (E-m), maximum temperature (T-max), and MR thermometry plane orientation. Furthermore, the time delay between each sonication (S-t) and the total treatment time (T-t) were recorded. Results: Fifty-two patients (40 males and 12 females; age 64.51 +/- SD 11.90 years; range 26-86 years), who underwent unilateral Vim thalamotomy (left = 50, 96.15%; right = 2, 3.85%) for medication-refractory essential tremor (n = 39; 78%) or Parkinson tremor (n = 13; 22%) were considered. A total of 1,068 (95.10%) sonication processes were included in our final analysis (average S-n per treatment: 20.65 +/- 6.18; range 13-41). The energy released onto the planned target was found to decrease with the SDR for all temperature ranges. A positive correlation was observed between the slope of T-max vs. E-m plot and the SDR (R-2 = 0.765; p < 0.001). In addition, the T-max was positively correlated with SDR (R-2 = 0.398; p < 0.005). On the contrary, no significant correlation was found between SDR and SA or Tx. An analysis of the MR thermometry scanning plane indicated that, at our site, the axial and the coronal planes were used (on average) 10.4 (SD +/- 3.8) and 7.7 (SD +/- 3.0) times, respectively, whereas the sagittal plane was used only 2.5 (SD +/- 3.0) times per treatment. Conclusion: Our results confirm the factors that significantly influence the course of a tcMRgFUS procedure even when a 1.5-T MRI scanner is used for procedure guidance. The experience we gained in this study indicates that the SDR remains one of the most significant technical parameters to be considered in a tcMRgFUS procedure. The possibility of prospectively setting the sonication energy according to the presented curves of energy delivery as a function of SDR for each treatment stage could provide a further understanding and a greater awareness of this emerging technology

Weak formulation for singular diffusion equation with dynamic boundary condition

In this paper, we propose a weak formulation of the singular diffusion equation subject to the dynamic boundary condition. The weak formulation is based on a reformulation method by an evolution equation including the subdifferential of a governing convex energy. Under suitable assumptions, the principal results of this study are stated in forms of Main Theorems A and B, which are respectively to verify: the adequacy of the weak formulation; the common property between the weak solutions and those in regular problems of standard PDEs.Comment: 23 page

Clinical and biological heterogeneity in children with moderate asthma

To evaluate the relationship between inflammatory markers and severity of asthma in children, the amount of interleukin-8 (IL-8) and granulocyte/macrophage colony-stimulating factor (GM-CSF) released by peripheral blood mononuclear cells, exhaled nitric oxide (FE NO) levels, p65 nuclear factor-kappaB subunit, and phosphorylated IkBalpha expression by peripheral blood mononuclear cells were assessed in six control subjects, 12 steroid-naives subjects with intermittent asthma, and 17 children with moderate asthma. To investigate their predictive value, biomarker levels were correlated with the number of exacerbations during a 18-month follow-up period. We found that GM-CSF release was higher in moderate and intermittent asthmatics than in control subjects, whereas IL-8 release was higher in moderate than in intermittent asthmatics and control subjects. FE NO levels were similar among study groups. In moderate asthmatics, IL-8, GM-CSF, and FE NO significantly correlated with the exacerbation numbers. Moreover, p65 and phosphorylated IkBalpha levels were greater in moderate than in intermittent asthmatics and control subjects. According to GM-CSF, IL-8, and FE NO levels, two distinct subgroups of moderate asthmatics (low and high producers) were identified. High producers experienced more exacerbations than low producers. This study shows ongoing inflammation associated with biological and clinical heterogeneity in moderate asthmatics despite regular treatment and proposes that large prospective studies confirm the importance of biomarkers to assess inflammation and asthma control in children with asthma

Role of chronic exsposure to cigarette smoke on endoglin/CD105 expression in airway epithelium.

Dysregulation of airway epithelial cell function related to cigarette smoke exposure plays an important role in the pathophysiology of COPD and is associated to tissue damage and disease severity. CD105 is a component of the receptor complex of TGF-β, a pleiotropic cytokine involved in cellular proliferation, differentiation and migration. CD105 regulates the expression of different components of the extracellular matrix suggesting a role of CD105 in cellular transmigration and remodeling processes. The aim of the present study was to investigate the expression of endoglin/CD105 in airway epithelium of COPD patients and its involvement in tissue remodeling and progression of COPD. We evaluated the immunoreactivity for CD105 expression in bronchial biopsies isolated from COPD patients and healthy controls (HC). The analysis of metaplastic epithelium was performed in bronchial biopsies by Image Analysis software (Leica Quantimet system). Finally, we investigated the expression of CD105 protein receptor in human bronchial epithelial cells (16HBE cells) exposed to 5% Cigarette Smoke Extract (CSE) for 12 days by western blot. We found that the CD105 immunoreactivity was significantly higher in bronchial epithelium of COPD than HC. Morphometric analysis of bioptic samples of COPD showed an increase of the immunoreactivity for CD105 in the area of metaplastic than in not metaplastic epithelium. Long term exposure to CSE significantly up-regulated CD105 expression in 16HBE. Chronic inflammation due to cigarette smoke might play a critic role on the alteration of CD105 protein expression in COPD, promoting tissue remodeling, angiogenesis and dysregulation of physiological reparative mechanisms, leading to squamous metaplasia

Synergistic effects of fluticasone propionate and salmeterol on in vitro T-cell activation and apoptosis in asthma

In asthma T cells are characterized by an increased activation state and by reduced apoptosis

Interactions of Bacillus Mojavensis and Fusarium Verticillioides With a Benzoxazolinone (Boa) and Its Transformation Product, Apo

En:Journal of Chemical Ecology (2007, vol. 33, n. 10, p. 1885-1897)The benzoxazolinones, specifically benzoxazolin-2(3H)-one (BOA), are important transformation products of the benzoxazinones that can serve as allelochemicals providing resistance to maize from pathogenic bacteria, fungi, and insects. However, maize pathogens such as Fusarium verticillioides are capable of detoxifying the benzoxazolinones to 2-aminophenol (AP), which is converted to the less toxic N-(2-hydroxyphenyl) malonamic acid (HPMA) and 2-acetamidophenol (HPAA). As biocontrol strategies that utilize a species of endophytic bacterium, Bacillus mojavensis, are considered efficacious as a control of this Fusarium species, the in vitro transformation and effects of BOA on growth of this bacterium was examined relative to its interaction with strains of F. verticillioides. The results showed that a red pigment was produced and accumulated only on BOA-amended media when wild type and the progeny of genetic crosses of F. verticillioides are cultured in the presence of the bacterium. The pigment was identified as 2-amino-3H-phenoxazin-3-one (APO), which is a stable product. The results indicate that the bacterium interacts with the fungus preventing the usual transformation of AP to the nontoxic HPMA, resulting in the accumulation of higher amounts of APO than when the fungus is cultured alone. APO is highly toxic to F. verticillioides and other organisms. Thus, an enhanced biocontrol is suggested by this in vitro study. =580 $aEn:Journal of Chemical Ecolog

The role of transforming growth factor-\u3b21 in airway inflammation of childhood asthma

TGF-beta-targeting structural and inflammatory cells has been implicated in the mechanisms leading to the inflammatory and restructuring processes in asthma, suggesting an impact of TGF-beta1 signaling on the development and persistency of this disease. We investigated the potential early involvement of TGF-beta1 activity in the immunological and molecular mechanisms underlying progression of inflammation in childhood asthma. We evaluated the levels of TGF-beta1 in induced sputum supernatants (ISSs) and the expression of small mother cell against decapentaplegic (Smad) 2 and Smad7 proteins in induced sputum cells (ISCs) from children with intermittent asthma (IA), moderate asthma (MA) and control subjects (C). Furthermore, we investigated the regulatory role of TGF-beta1 activity on eosinophil and neutrophil adhesion to epithelial cells using adhesion assay, and on the granulocyte expression of adhesion molecule CD11b/CD18 Macrophage-1 antigen (MAC-1), by flow cytometry. We found that the levels of TGF-beta1 are increased in ISSs of IA and MA in comparison to C, concomitantly to the activation of intracellular signaling TGFbeta/Smads pathway in ISCs. In MA, TGF-beta1 levels correlated with the number of sputum eosinophils and neutrophils. Furthermore, we showed the ability of sputum TGF-beta1 to promote eosinophil and neutrophil adhesion to epithelial cells, and to increase the expression of MAC-1 on the granulocyte surface. This study shows the activation of TGFbeta/Smad signaling pathway in the airways of children with IA and, despite the regular ICS treatment, in children with MA, and provides evidence for the contribution of TGF-beta1 in the regulation of granulocyte activation and trafficking

IMMUNOLOGICAL ASPECTS OF CROHN'S DISEASE: A REGULATORY FUNCTION OF TIM-3/GALECTIN-9 IN LYTH1.

Crohn's disease (CD) is a type of inflammatory bowel disease (IBD) and its etiology is multifactorial and involves a combination of genetic environmental factors. The interaction of these factors causes an imbalance of the microbiota, leading to the activation of several immunological and inflammatory mechanism. From an immunological point of view, there seems to be an involvement of the TIM-3/GALECTIN-9 pathway and of the autoregulation of lyTh1. These studies show that in patients with CD the autoregulation of lyth1 is lost due to a reduced concentration of galectin-9 and a reduced TIM-3 expression in LyTh1. This could be one of the reason for the state of perpetual activation of lyTh1, resulting in the chronic inflammation process

Conventional MRI-Derived Biomarkers of Adult-Type Diffuse Glioma Molecular Subtypes: A Comprehensive Review

The introduction of molecular criteria into the classification of diffuse gliomas has added interesting practical implications to glioma management. This has created a new clinical need for correlating imaging characteristics with glioma genotypes, also known as radiogenomics or imaging genomics. Although many studies have primarily focused on the use of advanced magnetic resonance imaging (MRI) techniques for radiogenomics purposes, conventional MRI sequences remain the reference point in the study and characterization of brain tumors. A summary of the conventional imaging features of glioma molecular subtypes should be useful as a tool for daily diagnostic brain tumor management. Hence, this article aims to summarize the conventional MRI features of glioma molecular subtypes in light of the recent literature