3D imaging of CRP and ultrasonic tomography to detect decay in a living adult holm oak (Quercus ilex L.) in Sardinia (Italy)

A field-integrated methodology using 3D ultrasonic tomography supported by close range photogrammetry (CRP) has been developed and evaluated as a tool to detect the presence and patterns of decay forms in a living adult holm oak (Quercus ilex L.) in an urban green area of the city of Cagliari, Sardinia, Italy. Close range photogrammetry was used to compute a high resolution 3D model of the studied tree, texturized with natural colors. Moreover, following the implemented workflow process it was possible to evaluate the deformation pattern of the studied tree over time. In a second step of our integrated approach, and in order to diagnose the state of health of the inner part of the studied tree in a non-invasive way, laboratory and in situ non-invasive ultrasonic techniques were applied. The results of the close range photogrammetry analysis supported the optimal design of the 3D ultrasonic tomography of the living adult holm oak. Ultrasonic tomography is one of the most powerful non-destructive testing techniques for the full-volume inspection of a structure. It produced physical information on the inner structure of the stem of the investigated tree. The results of the study show that the integrated application of close range photogrammetry and 3D ultrasonic tomography is a powerful tool for a highly accurate and objective evaluation of the external and internal decay of trees and for monitoring their conservation states. With the fully integrated approach, the diagnostic process aimed to prevent instability and the failure of trees can be greatly improved

Targeting SIRT1 Rescues Age- and Obesity-Induced Microvascular Dysfunction in Ex Vivo Human Vessels

ackground: Experimental evidence suggests a key role of SIRT1 (silent information regulator 1) in age- and metabolic-related vascular dysfunction. Whether these effects hold true in the human microvasculature is unknown. We aimed to investigate the SIRT1 role in very early stages of age- and obesity-related microvascular dysfunction in humans. Methods: Ninety-five subjects undergoing elective laparoscopic surgery were recruited and stratified based on their body mass index status (above or below 30 kg/m2) and age (above or below 40 years) in 4 groups: Young Nonobese, Young Obese, Old Nonobese, and Old Obese. We measured small resistance arteries' endothelial function by pressurized micromyography before and after incubation with a SIRT1 agonist (SRT1720) and a mitochondria reactive oxygen species (mtROS) scavenger (MitoTEMPO). We assessed vascular levels of mtROS and nitric oxide availability by confocal microscopy and vascular gene expression of SIRT1 and mitochondrial proteins by qPCR. Chromatin immunoprecipitation assay was employed to investigate SIRT1-dependent epigenetic regulation of mitochondrial proteins. Results: Compared with Young Nonobese, obese and older patients showed lower vascular expression of SIRT1 and antioxidant proteins (FOXO3 [forkhead box protein O3] and SOD2) and higher expression of pro-oxidant and aging mitochondria proteins p66Shc and Arginase II. Old Obese, Young Obese and Old Nonobese groups endothelial dysfunction was rescued by SRT1720. The restoration was comparable to the one obtained with mitoTEMPO. These effects were explained by SIRT1-dependent chromatin changes leading to reduced p66Shc expression and upregulation of proteins involved in mitochondria respiratory chain. Conclusions: SIRT1 is a novel central modulator of the earliest microvascular damage induced by age and obesity. Through a complex epigenetic control mainly involving p66Shc and Arginase II, it influences mtROS levels, NO availability, and the expression of proteins of the mitochondria respiratory chain. Therapeutic modulation of SIRT1 restores obesity- and age-related endothelial dysfunction. Early targeting of SIRT1 might represent a crucial strategy to prevent age- and obesity-related microvascular dysfunction. Keywords: aging; endothelial cells; microcirculation; mitochondria; obesity; sirtuin

Use of three-dimensional ultrasonic tomography to detect decay in a living adult holm oak (Quercus ilex l.) in Sardinia (Italy)

Due to recent human activity many holm oak trees (Quercus ilex L.) are planted in the public and private gardens in Sardinia. At present many of these trees are afflicted by decay especially that caused by pathogenic fungi which produce tail disease and bark cancer. A field methodology using ultrasonic tomography supported by a digital photogrammetry survey has been developed and evaluated as a tool to detect the presence and patterns of internal decay in a living adult holm oak tree. Ultrasonic methods are commonly used to detect the elastic characteristics and thus the dynamic properties of different materials (e.g. stone, concrete, wood) although the interpretation of the data is very complex because elastic wave propagation strictly depends on the heterogeneity, the porosity and other material properties. Weak materials, the presence of fractures or decay zones, small cavities, and cracks within the materials are potential defects characterized by low ultrasonic velocity compared to the velocity in healthy materials. In this sense, ultrasonic velocity can be used effectively as one of the main diagnostic physical parameters to detect internal decay and define the healthy state of the investigated holm oak stem with diameter at breast height (DBH) of 32 cm. In this study, considering the nature and size of the investigated tree and the target of the study, an ultrasonic investigation by the three-dimensional ultrasonic tomography technique was carried out at 24kHz . The ultrasonic measurements were performed in situ using the portable ultrasonic non-destructive digital indicating tester (PUNDIT Lab plus) by Proceq (Schwerzenbach, Switzerland) and piezoelectric transducers. Silicone snug sheets were chosen as the coupling agent because they provided the best contact transducer material as deduced from many tests. The travel time of the longitudinal elastic waves was measured along a large number of measurement paths between stations located on the perimeter of the stem. Each station was alternatively used as a transmitter and a receiver. The sector of the stem was criss-crossed by a large number of discrete rays. Each ray between stations was divided into small segments, each corresponding to a pixel element. The travel time of the longitudinal ultrasonic signals along the source-receiver ray paths was recorded together with the relative position and orientation of each ray. The ultrasonic data volume was processed by specific software exploiting appropriate reconstruction algorithms to obtain a three-dimensional representation of the distribution of the longitudinal wave velocity inside the stem. Results show that ultrasonic tomography may be an effective tool for a high accuracy evaluation of the internal decay of the investigated tree and for monitoring its conservation state

Acute liver damage following intravenous glucocorticoid treatment for Graves’ ophthalmopathy

Purpose: Over the last years, there have been several reports on the occurrence of acute liver damage (ALD) in patients affected with Graves’ ophthalmopathy (GO) receiving intravenous glucocorticoids (ivGCs). This article is aimed at reviewing the literature on this specific topic and reporting two new cases of ALD occurring in GO patients while on ivGCs. Methods: The terms “glucocorticoid therapy” and “Graves’ Ophthalmopathy”/“Graves’ Orbitopathy”/”Thyroid eye disease” were used both separately and in conjunction with the terms “liver disease,” “liver damage,” “hepatotoxicity,” “liver failure,” to search MEDLINE for articles published since the first report of ALD in 2000 and up to 2015. Results: ALD [defined as an increase in alanine aminotransferase (ALT) >300 U/L] during or after completion of ivGCs has been so far reported in 17 fully documented cases. Overall, one-half of those patients were diagnosed as having autoimmune hepatitis (AIH) and in the vast majority of the remaining cases a diagnosis of methylprednisolone(MP)-induced hepatotoxicity was suspected. The clinical course of liver injury varied from asymptomatic hypertransaminasemia in the vast majority of patients to fatal hepatic failure in four patients receiving higher (>8 g) cumulative doses of MP. Conclusions: The overall risk of ALD is relatively low (~1 %), and seems higher using a single dose >0.5 g and a cumulative dose >8.5 g MP. Whenever ivGC treatment is required, serum liver enzymes, viral hepatitis markers, and autoantibodies related to AIH should be obtained prior to ivGC administration. Liver function should be monitored during ivGC and up to 6 months after the end of treatment. Prolonging observation after 6 months is likely unnecessary, since all cases of ALD so far reported always occurred well within this term

Surgical Treatment of Intrathyroid Metastases: Preliminary Results of a Multicentric Study

Background: Intrathyroid metastases (ITM) are rare and usually have a dismal prognosis. The aim of this study was to detect which neoplasms metastasize most often to the thyroid gland, their clinical features and treatment options. Materials and Methods: Retrospective analysis of clinical files of 17,122 patients submitted to surgery for thyroid disease between 1995 and 2005. Twenty-five patients (median age 61 years) were affected by ITM. Results: The site of the primary Minor was: kidney (15), lung (4), colon (3), breast (1), melanoma (l), and unknown in I patient. Ten patients (40%) complained of preoperative symptoms, in the others, thyroid involvement was incidentally discovered during the follow-up for the primary cancer. Twenty patients (80%) underwent total thyroidectomy, 3 received thyroid lobectomy and 2 palliative procedures. Morbidity was 16%, mortality was nil. The median follow-up was 24 months. Conclusion: ITM should always be suspected in any patient with a previous history of malignancy. Fine-needle agobiopsy (FNAB) with immunohistochemical stains may help in preoperative workup. A long delay between the primary tumor and the recurrence Warrants surgery and total thyroidectomy seems to be the treatment of choice because of the multifocality of metastasis to the thyroid gland

The prognostic role of Gender-Age-Physiology system in idiopathic pulmonary fibrosis patients treated with pirfenidone

Introduction: Gender, age, physiology (GAP) system have proven to be an easy tool for predicting disease stages and survival in idiopathic pulmonary fibrosis (IPF) patients. Objective: To validate mortality risk as determined by the GAP system in a real-life multicentre IPF population treated with pirfenidone. Methods: The study included patients who received pirfenidone for at least 6 months. The GAP calculator and the GAP index were determined. The primary outcome was all-cause mortality. The prognostic accuracy of the GAP system was evaluated with respect to calibration and discrimination. Results and Conclusion: Sixty-eight IPF patients were enrolled in the study. The median follow-up was 2.4 years (range 0.1-7.4 years). A total of 22 deaths as first event (32%) and of 10 lung transplantation (15%) were recorded. The cumulative incidence of mortality at 1, 2 and 3 years was 10.4%, 22.4% and 38.4%, respectively. The differences between the predicted and observed mortality were not significant for the GAP index while the observed mortality become comparable to that predicted by the GAP calculator only in the third year of follow-up. The C-index for the GAP index was 0.74 (95% CI 0.57-0.93) while the C-statistic value for the GAP calculator was 0.77 (95% CI 0.59-0.95)

The prognostic role of Gender-Age-Physiology system in idiopathic pulmonary fibrosis patients treated with pirfenidone

GAP system have proven to be an easy tool for predicting disease stages and survival in IPF patients

The prognostic role of Gender-Age-Physiology system in idiopathic pulmonary fibrosis patients treated with pirfenidone

GAP system have proven to be an easy tool for predicting disease stages and survival in IPF patients

Unique expansion of IL-21+ Tfh and Tph cells under control of ICOS identifies Sjögren's syndrome with ectopic germinal centres and MALT lymphoma.

OBJECTIVES To explore the relevance of T-follicular-helper (Tfh) and pathogenic peripheral-helper T-cells (Tph) in promoting ectopic lymphoid structures (ELS) and B-cell mucosa-associated lymphoid tissue (MALT) lymphomas (MALT-L) in Sjögren's syndrome (SS) patients. METHODS Salivary gland (SG) biopsies with matched peripheral blood were collected from four centres across the European Union. Transcriptomic (microarray and quantitative PCR) analysis, FACS T-cell immunophenotyping with intracellular cytokine detection, multicolor immune-fluorescence microscopy and hybridisation were performed to characterise lesional and circulating Tfh and Tph-cells. SG-organ cultures were used to investigate functionally the blockade of T-cell costimulatory pathways on key proinflammatory cytokine production. RESULTS Transcriptomic analysis in SG identified Tfh-signature, interleukin-21 (IL-21) and the inducible T-cell co-stimulator (ICOS) costimulatory pathway as the most upregulated genes in ELS+SS patients, with parotid MALT-L displaying a 400-folds increase in IL-21 mRNA. Peripheral CD4CXC-motif chemokine receptor 5 (CXCR5)programmed cell death protein 1 (PD1)ICOS Tfh-like cells were significantly expanded in ELS+SS patients, were the main producers of IL-21, and closely correlated with circulating IgG and reduced complement C4. In the SG, lesional CD4CD45ROICOSPD1 cells selectively infiltrated ELS+ tissues and were aberrantly expanded in parotid MALT-L. In ELS+SG and MALT-L parotids, conventional CXCR5CD4PD1ICOSFoxp3 Tfh-cells and a uniquely expanded population of CXCR5CD4PD1ICOSFoxp3 Tph-cells displayed frequent IL-21/interferon-γ double-production but poor IL-17 expression. Finally, ICOS blockade in SG-organ cultures significantly reduced the production of IL-21 and inflammatory cytokines IL-6, IL-8 and tumour necrosis factor-α (TNF-α). CONCLUSIONS Overall, these findings highlight Tfh and Tph-cells, IL-21 and the ICOS costimulatory pathway as key pathogenic players in SS immunopathology and exploitable therapeutic targets in SS