Attenuation of induced bronchoconstriction in healthy subjects: effects of breathing depth.

The effects of breathing depth in attenuating induced bronchoconstriction were studied in 12 healthy subjects. On four separate, randomized occasions, the depth of a series of five breaths taken soon (approximately 1 min) after methacholine (MCh) inhalation was varied from spontaneous tidal volume to lung volumes terminating at approximately 80, approximately 90, and 100% of total lung capacity (TLC). Partial forced expiratory flow at 40% of control forced vital capacity (V(part)) and residual volume (RV) were measured at control and again at 2, 7, and 11 min after MCh. The decrease in V(part) and the increase in RV were significantly less when the depth of the five-breath series was progressively increased (P < 0.001), with a linear relationship. The attenuating effects of deep breaths of any amplitude were significantly greater on RV than V(part) (P < 0.01) and lasted as long as 11 min, despite a slight decrease with time when the end-inspiratory lung volume was 100% of TLC. In conclusion, in healthy subjects exposed to MCh, a series of breaths of different depth up to TLC caused a progressive and sustained attenuation of bronchoconstriction. The effects of the depth of the five-breath series were more evident on the RV than on V(part), likely due to the different mechanisms that regulate airway closure and expiratory flow limitation

Airway responsiveness to methacholine: effects of deep inhalations and airway inflammation.

Abstract We determined the dose-response curves to inhaled methacholine (MCh) in 16 asthmatic and 8 healthy subjects with prohibition of deep inhalations (DIs) and with 5 DIs taken after each MCh dose. Flow was measured on partial expiratory flow-volume curves at an absolute lung volume (plethysmographically determined) equal to 25% of control forced vital capacity (FVC). Airway inflammation was assessed in asthmatic subjects by analysis of induced sputum. Even when DIs were prohibited, the dose of MCh causing a 50% decrease in forced partial flow at 25% of control FVC (PD(50)MCh) was lower in asthmatic than in healthy subjects (P < 0.0001). In healthy but not in asthmatic subjects, repeated DIs significantly decreased the maximum response to MCh [from 90 +/- 4 to 62 +/- 8 (SD) % of control, P < 0.001], increased PD(50)MCh (P < 0.005), without affecting the dose causing 50% of maximal response. In asthmatic subjects, neither PD(50)MCh when DIs were prohibited nor changes in PD(50)MCh induced by DIs were significantly correlated with inflammatory cell numbers or percentages in sputum. We conclude that 1) even when DIs are prohibited, the responsiveness to MCh is greater in asthmatic than in healthy subjects; 2) repeated DIs reduce airway responsiveness in healthy but not in asthmatic subjects; and 3) neither airway hyperresponsiveness nor the inability of DIs to relax constricted airways in asthmatic subjects is related to the presence of inflammatory cells in the airways

PLANT EXTRACTS AS GREEN POTENTIAL STRATEGIES TO CONTROL THE BIODETERIORATION OF CULTURAL HERITAGE

The biodeterioration of historic-artistic manufacts is related to several biological systems, including fungi and bacteria, whose metabolic activities and vegetative development have a direct consequence on the conservation of cultural assets. Generally, different chemical compounds are utilized as biocides in order to control biodeteriogens growth, but recently the attention has been focused on potential risks of their use towards human health (operators, visitors) and the environment. In order to develop alternative methods, various natural products have been tested, particularly to control the colonization by fungi and bacteria. In this study, antimicrobial activity of three different plant products, Tea tree essential oil, Calamintha nepeta and Allium sativum L. extracts, has been evaluated against Bacillus subtilis, Micrococcus luteus, Penicillium chrysogenum and Aspergillus spp. (previously isolated from colonized artworks) through three different in vitro antimicrobial assays (micro-dilution in microtiter plates, well plates diffusion and agar disc diffusion method). The bioassays show a different microbial susceptibility to plant extracts, establishing for each bacteria and fungi the Minimum Inhibitory Concentration (MIC) and defining the diameter of the growth inhibition area. This result supports the data reported in literature and shows an important potential suggestion for the possible use in the control of biodeterioration of cultural heritage, safe both for human health and environment

Surgical complications after pancreatic transplantation: A computed tomography imaging pictorial review

pancreatic transplantation should start with the evaluation of the arterial Y-graft, the venous anastomosis and the duodenojejunostomy. With regard to complications, CT allows for the identification of vascular complications, such as thrombosis or stenosis of blood vessels supplying the graft, the detection of pancreatic fluid collections, including pseudocysts, abscesses, or leaks, the assessment of bowel complications (anastomotic leaks, ileus or obstruction), and the identification of bleeding. The aim of this pictorial review is to illustrate CT findings of surgical-related complications after pancreatic transplantation. The knowledge of surgical techniques is of key importance to understand postoperative anatomic changes and imaging evaluation. Therefore, we first provide a short summary of the main techniques of pancreatic transplantation. Then, we provide a practical imaging approach to pancreatic transplantation and its complications providing tips and tricks for the prompt imaging diagnosis on CT.Pancreatic transplantation is considered by the American Diabetes Association and the European Association for the Study of Diabetes an acceptable surgical procedure in patients with type 1 diabetes also undergoing kidney transplantation in pre-final or end-stage renal disease if no contraindications are present. Pancreatic transplantation, however, is a complex surgical procedure and may lead to a range of postoperative complications that can significantly impact graft function and patient outcomes. Postoperative computed tomography (CT) is often adopted to evaluate perfusion of the transplanted pancreas, identify complications and as a guide for interventional radiology procedures. CT assessment afte

Mechanical correlates of dyspnea in bronchial asthma.

We hypothesized that dyspnea and its descriptors, that is, chest tightness, inspiratory effort, unrewarded inspiration, and expiratory difficulty in asthma reflect different mechanisms of airflow obstruction and their perception varies with the severity of bronchoconstriction. Eighty-three asthmatics were studied before and after inhalation of methacholine doses decreasing the 1-sec forced expiratory volume by ~15% (mild bronchoconstriction) and ~25% (moderate bronchoconstriction). Symptoms were examined as a function of changes in lung mechanics. Dyspnea increased with the severity of obstruction, mostly because of inspiratory effort and chest tightness. At mild bronchoconstriction, multivariate analysis showed that dyspnea was related to the increase in inspiratory resistance at 5 Hz (R 5) (r (2) = 0.10, P = 0.004), chest tightness to the decrease in maximal flow at 40% of control forced vital capacity, and the increase in R 5 at full lung inflation (r (2) = 0.15, P = 0.006), inspiratory effort to the temporal variability in R 5-19 (r (2) = 0.13, P = 0.003), and unrewarded inspiration to the recovery of R 5 after deep breath (r (2) = 0.07, P = 0.01). At moderate bronchoconstriction, multivariate analysis showed that dyspnea and inspiratory effort were related to the increase in temporal variability in inspiratory reactance at 5 Hz (X 5) (r (2) = 0.12, P = 0.04 and r (2) = 0.18, P &lt; 0.001, respectively), and unrewarded inspiration to the decrease in X 5 at maximum lung inflation (r (2) = 0.07, P = 0.04). We conclude that symptom perception is partly explained by indexes of airway narrowing and loss of bronchodilatation with deep breath at low levels of bronchoconstriction, but by markers of ventilation heterogeneity and lung volume recruitment when bronchoconstriction becomes more severe

Toll-like receptor 4 expression in the epithelium of inflammatory periapical lesions. An immunohistochemical study

Toll-like receptors (TLR) are essential for the innate immune response against invading pathogens and have been described in immunocompetent cells of areas affected by periapical disease. Besides initiating the inflammatory response, they also directly regulate epithelial cell proliferation and survival in a variety of settings. This study evaluates the in situ expression of TLR4 in periapical granulomas (PG) and radicular cysts, focusing on the epithelial compartment. Twenty-one periapical cysts (PC) and 10 PG were analyzed; 7 dentigerous non-inflamed follicular cyst (DC) served as control. TLR4 expression was assessed by immunohistochemistry. TLR4 immunoreaction products were detected in the epithelium of all specimens, with a higher percentage of immunostained cells in PG. Although TLR4 overexpression was detected in both PG and PC, there were differences that seemed to be related to the nature of the lesion, since in PG all epithelial cells of strands, islands and trabeculae were strongly immunoreactive for TLR4, whereas in PC only some areas of the basal and suprabasal epithelial layers were immunostained. This staining pattern is consistent with the action of TLR4: in PG it could promote formation of epithelial cell rests of Malassez and in epithelial strands and islands the enhancement of cell survival, proliferation and migration, whereas in PC TLR4 could protect the lining epithelium from extensive apoptosis. These findings go some way towards answering the intriguing question of why many epithelial strands or islands in PG and the lining epithelium of apical cysts regress after non-surgical endodontic therapy, and suggest that TLR4 plays a key role in the pathobiology of the inflammatory process related to periapical disease

Patients and doctors group meetings: an innovative way to explore severe asthma backstage

Severe asthma patients' life is heavily influenced by the disease, which has impact on personal and professional choic-es or general lifestyle. Despite the available tools to help physicians investigating the patient-reported outcomes there is a need for a more standardised and structured approach to include the evaluation of quality of life together with the emotions of patients into the routine clinical interaction. We hereby report the use of an active listening and insight approach to understand the emotions of patients with severe asthma through dedicated in-person meetings involving a group of patients with their doctors, caregivers and an external moderator. The initiative "Patients insight meeting" was organized within 17 specialist referral centres for severe asthma in Italy in 2019 and involved 149 patients. Insights related to 4 different items were collected and a task force composed by the external moderators produced a general report including the suggestions from the participating centres. This experience of group-meetings involving both patients and doctors together represents an innovative way to investigate real life experience and the emotions of asthmatic patients, highlighting unmet needs related to patient's experience of his/her disease that need to be included in severe asthmatics' management strategy

Does MtN5 play a double role in root responses to symbiontic and pathogenic microorganisms?

MtN5, a new Lipid Transfer Protein, has been identified in nodulated roots of Medicago truncatula andpreliminarily classified as early nodulin, which is expressed in response to rhizobial symbiosis. Wehave shown that the recombinant MtN5 exerts antifungal and antimicrobial activity in vitro againstFusarium semitectum and Rhizobium leguminosarum, respectively. In vivo, the fungal infection leadsto the expression of MtN5 in the whole root apparatus of M. truncatula plants, whereas the inoculationwith rhizobia induces an early and nodule-specific expression of the protein, that is also maintained inmature nodules. These two different expression patterns suggest a putative double role for MtN5, whichcould be involved both in a general response mechanism against fungi and in sensing or controlling theinfection of the symbiont. This last hypothesis is supported by the observation that M.truncatula rootstransformed with an hairpin construct aiming to silence endogenous MtN5, are impaired in noduleformation respect to control roots. Therefore, MtN5 is hereby proposed as a novel, multifunctionalprotein taking part in the symbiotic process

Effectiveness of benralizumab in severe eosinophilic asthma: Distinct sub-phenotypes of response identified by cluster analysis.

Background: Benralizumab is effective in severe eosinophilic asthma (SEA), but suboptimal responses are observed in some patients. Although several factors have been associated with benralizumab response, no cluster analysis has yet been undertaken to identify different responsiveness sub-phenotypes. Objective: To identify SEA sub-phenotypes with differential responsiveness to benralizumab. Methods: One hundred and five patients diagnosed with SEA who had completed 6&nbsp;months of benralizumab treatment were included in a hierarchical cluster analysis based on a set of clinical variables that can be easily collected in routine practice (age, age at disease onset, disease length, allergen sensitization status, blood eosinophil count, IgE levels, FEV1% predicted, nasal polyposis, bronchiectasis). Results: Four clusters were identified: Clusters 2 and 3 included patients with high levels of both IgE and eosinophils (type-2 biomarkers high), whereas Clusters 1 and 4 included patients with only one type-2 biomarker at a high level: IgE in Cluster 1 and eosinophils in Cluster 4. Clusters 2 and 3 (both type-2 biomarkers high) showed the highest response rate to benralizumab in terms of elimination of exacerbations (79% and 80% respectively) compared to Clusters 1 and 4 (52% and 60% respectively). When super-response (the absence of exacerbation without oral corticosteroid use) was assessed, Cluster 2, including patients with more preserved lung function than the other clusters, but comparable exacerbation rate, oral corticosteroid use and symptom severity, was the most responsive cluster (87.5% of patients). Conclusions: Our cluster analysis identified benralizumab differential response sub-phenotypes in SEA, with the potential of improving disease treatment and precision management