Idiopathic pulmonary fibrosis (IPF) is the most common and lethal of the idiopathic interstitial pneumonias with an estimated 5-year survival of approximately 20%. In the last two decades our ...understanding of disease pathogenesis has substantially evolved and novel compounds have been developed consequent to the increasing knowledge of the mechanisms underlying disease pathobiology. The disease appears to be driven - following chronic injury - by abnormal/dysfunctional alveolar epithelial cells that promote fibroblast recruitment and proliferation, resulting in scarring of the lung and irreversible loss of function. With very few exceptions, clinical trials evaluating novel potential therapies have provided disappointing results. More recently, pirfenidone and nintedanib, two compounds with pleiotropic mechanisms of action, have proven effective in slowing functional decline and disease progression in IPF patients with mild to moderate functional impairment, highlighting the importance of timely diagnosis and administration of treatment in early stages of disease. However, due to the complexity and uncertainties intrinsic to IPF, it is essential that each therapeutic strategy be tailored to the individual patient, after evaluation of potential benefits and risks. This article provides an overview of the most recent clinical trials in IPF and discusses how their results are going to change the clinical and clinical research landscape in IPF. A number of agents with high potential are currently being tested and many more are ready for clinical trials. Their completion is critical for achieving the ultimate goal of curing patients with IPF.
Sarcoidosis is a heterogeneous inflammatory disorder of unknown origin that may affect virtually any organ, although intrathoracic engagement is almost universal. Sarcoidosis may present rather ...dramatically as an acute disease, which usually resolves either spontaneously or with treatment, while other patients have an insidious onset and a chronic/progressive disease course. The different clinical phenotypes have led to the suggestion that sarcoidosis may consist of several separate entities. Yet, the characteristic immune response eventually leading to granuloma formation indicates that a number of features are common to all subgroups of the disease. Through a classical candidate gene approach, several genes of importance for sarcoidosis have been identified, and in some cases such gene variants associate with distinct clinical phenotypes. More recently, another approach to the search for sarcoidosis-associated genes has been applied, that is, through genome-wide association studies (GWAS). GWAS have led to the identification of a number of new genetic associations, although several of them need to be validated. Conversely, some of the previously identified human leucocyte antigen (HLA) associations with sarcoidosis have already been replicated in different cohorts and found to be quite strong, particularly in specific patient subgroups. In highly specialised centres such HLA associations already represent a useful aid in clinic practice for improving patient management. For the future, there is an urgent need for a better understanding, in particular, of gene-gene as well as gene-environmental interactions, both likely to be of importance for developing sarcoidosis.
•1-Hz inhibitory rTMS was conducted over secondary somatosensory cortex (S2) or vertex.•rTMS over S2 decreased ratings of touch intensity for fast but not slow brushing.•rTMS over S2 did not alter ...touch pleasantness or tactile discrimination.•rTMS over S2 using the H8 deep TMS coil reduced somatosensory BOLD response in S2 but did not affect the insula.•Study results suggest that S2 is causally involved in the perception of touch intensity but not in touch pleasantness.
Research suggests that the discriminative and affective aspects of touch are processed differently in the brain. Primary somatosensory cortex is strongly implicated in touch discrimination, whereas insular and prefronal regions have been associated with pleasantness aspects of touch. However, the role of secondary somatosensory cortex (S2) is less clear. In the current study we used inhibitory repetitive transcranial magnetic stimulation (rTMS) to temporarily deactivate S2 and probe its role in touch perception. Nineteen healthy adults received two sessions of 1-Hz rTMS on separate days, one targeting right S2 and the other targeting the vertex (control). Before and after rTMS, subjects rated the intensity and pleasantness of slow and fast gentle brushing of the hand and performed a 2-point tactile discrimination task, followed by fMRI during additional brushing. rTMS to S2 (but not vertex) decreased intensity ratings of fast brushing, without altering touch pleasantness or spatial discrimination. MRI showed a reduced response to brushing in S2 (but not in S1 or insula) after S2 rTMS. Together, our results show that reducing touch-evoked activity in S2 decreases perceived touch intensity, suggesting a causal role of S2 in touch intensity perception.
Hypersensitivity pneumonitis (HP), also known as extrinsic allergic alveolitis, is a complex pulmonary syndrome mediated by the immune system and caused by inhalation of a wide variety of antigens to ...which the individual has been previously sensitized. The pathobiology of the disease is not fully understood, but in addition to the triggers that initiate the disease, host/genetic factors are likely to be important, as only a minority of exposed individuals develop HP. Due to the lack of a diagnostic gold standard, the diagnosis of HP is not straightforward and relies on the integration of a number of factors, including history of exposure, precipitating antibodies to the offending antigen, clinical features, bronchoalveolar lavage, and radiological and pathologic features. However, in the appropriate setting, a high index of suspicion is critically important and may obviate the need for more invasive tests. Clinical presentation and natural history vary widely. Acute forms generally resolve without sequelae, while chronic forms, which are caused by persistent low-grade exposures, are associated with poor prognosis. Corticosteroids may be useful in acute episodes for symptomatic relief or in chronic and progressive disease, but their long-term efficacy has never been validated in prospective clinical trials. Ideally, patients with HP should be referred to centers with expertise, as the overlap with other forms of interstitial lung disease may be substantial. Making the correct diagnosis has critical therapeutic and prognostic implications.
Objectives
To determine the association between Mediterranean-Style Dietary Pattern Score and physical performance.
Design
Data analysis of a longitudinal study of a representative, age stratified, ...population sample.
Setting
The TREVISO LONGEVA (TRELONG) Study, in Treviso, Italy.
Participants
In 2010, 123 men and 181 women, age 77 years and over (mean age 86.3 ± 6.8 years).
Measurements
Performing a logistic regression in a multivariate analysis, hand grip strength and Short Physical Performance Battery (SPPB) were tested in relation to Mediterranean-Style Dietary Pattern Score (MSDPS).
Results
The hand grip mean value was 10.9 kg (± 9.5) and the SPPB score was 6.3 (± 3.8). The MSDPS mean value in this study sample was 38.1/100 (± 8.1). A significant association (p=0.036) between a high adherence to the Mediterranean diet (fourth quartile) and higher performance lower limbs (SPPB>7) was found. No correlation was reported for the hand grip strength.
Conclusion
We found an association statistically significant between a high adherence to the Mediterranean diet and higher physical performance.
The Italian institute for nuclear physics (INFN) has financed the SIMP project (2019–2021) in order to strengthen its skills and technologies in the field of meV detectors with the ultimate aim of ...developing a single microwave photon detector. This goal will be pursued by improving the sensitivity and the dark-count rate of two types of photodetectors: current-biased Josephson junction (CBJJ) for the frequency range 10–50 GHz and transition-edge sensor (TES) for the frequency range 30–100 GHz. Preliminary results on materials and devices characterization are presented.
In this paper, we address the problem of moving object segmentation using background subtraction. Solving this problem is very important for many applications: visual surveillance of both in outdoor ...and indoor environments, traffic control, behavior detection during sport activities, and so on. All these applications require as a first step, the detection of moving objects in the observed scene before applying any further technique for object recognition and activity identification.
We propose a reliable foreground segmentation algorithm that combines temporal image analysis with a reference background image. We are especially careful of the core problem arising in the analysis of outdoor daylight scenes: continuous variations of lighting conditions that cause unexpected changes in intensities on the background reference image. In this paper, a new approach for background adaptation to changes in illumination is presented. All the pixels in the image, even those covered by foreground objects, are continuously updated in the background model. The experimental results demonstrate the effectiveness of the proposed algorithm when applied in different outdoor and indoor environments.
The clinical outcome of sarcoidosis is quite variable. Several scoring systems have been used to assess the level of disease and clinical outcome. The definition of clinical phenotypes has become an ...important goal as genetic studies have identified distinct genotypes associated with different clinical phenotypes. In addition, treatment strategies have been developed for patients with resolving versus non resolving disease. A task force was established by the World Association of Sarcoidosis and Other Granulomatous diseases (WASOG) to define clinical phenotypes of the disease based on the clinical outcome status (COS). The committee chose to examine patients five years after diagnosis to determine the COS. Several features of the disease were incorporated into the final nine categories of the disease. These included the current or past need for systemic therapy, the resolution of the disease, and current status of the condition. Sarcoidosis patients who were African American or older were likely to have a higher COS, indicating more chronic disease. The COS may be useful in future studies of sarcoidosis.
Pulmonary hypertension (PH) decreases resistance to fatigue and life expectancy. The aim of this study was to correlate some indirect Doppler indices of PH with tricuspid and pulmonary regurgitation ...criteria and to relate PH on different indices with the severity of clinical signs. Furthermore the pathogenetic mechanisms associated to PH development were discussed. Dogs with Doppler echocardiographic evidence of PH diagnosed by assessment of pulmonary and tricuspid regurgitant jet velocity were selected, their clinical records were reviewed and a clinical score was computed. Seventeen cases of PH were identified. The degree of PH was assessed based on systolic or diastolic pulmonary pressure and the indirect Doppler indices (AT/ET and Tei Index) were calculated; data were statistically evaluated. Indirect Doppler indices were calculated also in a control group of seven healthy dogs. The most common clinical signs were coughing, dyspnea and syncope; the most common condition associated to PH development was the left-sided valvular heart disease. A significant positive correlation was found between Tei Index and both the systolic pressure and the severity of PH while no correlations were found between PH on different indices and clinical score and/or severity of clinical signs. Results of this study suggest that Tei-index could be an useful support not only to reveal PH but also to give information on the severity of PH. The clinical picture in dogs with PH is apparently unpredictable and not strictly correlated with the severity of PH.
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