Alpha1-antitrypsin deficiency and cardiovascular disease: questions and issues of a debated relation

Alpha1-antitrypsin (AAT) is one of the major inhibitors involved in protease/antiprotease homeostasis, and it is mainly produced by hepatocytes and pulmonary epithelial cells. Its deficiency, called alpha1-antitrypsin deficit (AATD), leads to severe hepatic and respiratory issues. Also, AAT is released into the bloodstream providing systemic anti-inflammatory effects. Apart from acting as an acute-phase anti-inflammatory protein, it can be a biomarker for monitoring disease evolution. A reduced or defective production leads to a loss of anti-inflammatory function, protease-antiprotease imbalance and cellular engorgement due to polymers deposition, with system-wide repercussions. This review aims to evaluate AATD condition in the major vessels of the head and neck, thoracic and abdominal districts. Also, a dedicated focus on autoimmune vascular diseases will be provided. A critical revision of the main literature findings starting from the 1980s until now has been performed. Studies conducted over the years have provided several contradictory pieces of evidence. Most authors acknowledge the protective and anti-inflammatory AAT role on the vascular endothelium. However, correlations between AATD and major arteries, cerebral and cardiovascular conditions, and autoimmune diseases remain unclear. Most studies recognize the role of AATD in vascular diseases but only as a cofactor inducing cellular and tissue structure impairments. However, this condition alone is not enough to determine new disease onset. Due to the opposing results reported over the years, there is still a considerable lack of knowledge on the role covered by AATD in vascular diseases. A renewed interest in this research field should be encouraged to grant new solid evidence and validate the putative role of AATD screening and replacement therapy as useful diagnostic and treatment tools

Tidal airway closure in asthma and COPD

Functional closure of small airways can occur during tidal breathing above functional residual capacity (FRC) both in asthma and COPD patients, especially during exacerbations. Such event has several noxious consequences on gas exchange, airway hyperresponsiveness and mechanical stress and strain within lung tissue and airway wall, mostly due to increase in ventilation heterogeneity. The availability of simple functional tests based on sequential measurements of lung volumes (i.e.: FRC), by plethysmography and dilutional techniques may reveal and monitor easily tidal airway closure that can be and should be treated with the aim of abolishing or at least reducing this dangerous condition

Fantastic animals as an experimental model to teach animal adaptation

Background: Science curricula and teachers should emphasize evolution in a mannercommensurate with its importance as a unifying concept in science. The concept of adaptationrepresents a first step to understand the results of natural selection. We settled an experimentalproject of alternative didactic to improve knowledge of organism adaptation. Students wereinvolved and stimulated in learning processes by creative activities. To set adaptation in a historicframe, fossil records as evidence of past life and evolution were considered.Results: The experimental project is schematized in nine phases: review of previous knowledge;lesson on fossils; lesson on fantastic animals; planning an imaginary world; creation of an imaginaryanimal; revision of the imaginary animals; adaptations of real animals; adaptations of fossil animals;and public exposition. A rubric to evaluate the student's performances is reported. The projectinvolved professors and students of the University of Modena and Reggio Emilia and of the "G.Marconi" Secondary School of First Degree (Modena, Italy).Conclusion: The educational objectives of the project are in line with the National Indications ofthe Italian Ministry of Public Instruction: knowledge of the characteristics of living beings, themeanings of the term "adaptation", the meaning of fossils, the definition of ecosystem, and theparticularity of the different biomes. At the end of the project, students will be able to graspparticular adaptations of real organisms and to deduce information about the environment in whichthe organism evolved. This project allows students to review previous knowledge and to form theirpersonalities

Gaussian graphical modeling for spectrometric data analysis

Motivated by the analysis of spectrometric data, we introduce a Gaussian graphical model for learning the dependence structure among frequency bands of the infrared absorbance spectrum. The spectra are modeled as continuous functional data through a B-spline basis expansion and a Gaussian graphical model is assumed as a prior specification for the smoothing coefficients to induce sparsity in their precision matrix. Bayesian inference is carried out to simultaneously smooth the curves and to estimate the conditional independence structure between portions of the functional domain. The proposed model is applied to the analysis of infrared absorbance spectra of strawberry purees

HYDAMTIQ, a selective PARP-1 inhibitor, improves bleomycin-induced lung fibrosis by dampening the TGF-β/SMAD signalling pathway

Idiopathic pulmonary fibrosis is a severe disease characterized by excessive myofibroblast proliferation, extracellular matrix and fibrils deposition, remodelling of lung parenchyma and pulmonary insufficiency. Drugs able to reduce disease progression are available, but therapeutic results are unsatisfactory; new and safe treatments are urgently needed. Poly(ADP‐ribose) polymerases‐1 (PARP‐1) is an abundant nuclear enzyme involved in key biological processes: DNA repair, gene expression control, and cell survival or death. In liver and heart, PARP‐1 activity facilitates oxidative damage, collagen deposition and fibrosis development. In this study, we investigated the effects of HYDAMTIQ, a potent PARP‐1 inhibitor, in a murine model of lung fibrosis. We evaluated the role of PARP on transforming growth factor‐β (TGF‐β) expression and TGF‐β/SMAD signalling pathway in lungs. Mice were intratracheally injected with bleomycin and then treated with either vehicle or different doses of HYDAMTIQ for 21 days. Airway resistance to inflation and lung static compliance, markers of lung stiffness, were assayed. Histochemical and biochemical parameters to evaluate TGF‐β/SMAD signalling pathway with alpha‐smooth muscle actin (αSMA) deposition and the levels of a number of inflammatory markers (tumour necrosis factor‐α, interleukin‐1β, iNOS and COX‐2) were performed. Bleomycin administration increased lung stiffness. It also increased lung PARP activity, TGF‐β levels, pSMAD3 expression, αSMA deposition and content of inflammatory markers. HYDAMTIQ attenuated all the above‐mentioned physiological, biochemical and histopathological markers. Our findings support the proposal that PARP inhibitors could have a therapeutic potential in reducing the progression of signs and symptoms of the disease by decreasing TGF‐β expression and the TGF‐β/SMAD transduction pathway

House Dust Mite Allergy and the Der p1 Conundrum: A Literature Review and Case Series

The house dustmite (HDM) is globally ubiquitous in human habitats. Thirty-two allergens for Dermatophagoides farinae and 21 for Dermatophagoides pteronyssinus have been detected so far. The present minireview summarizes information about the role of Der p 1 as a key coordinator of the HDM-induced allergic response and reports on a series of Italian patients who are allergic to HDMs. We studied the specific IgE profiles in a population of patients with allergic asthma and rhinitis screened for specific immunotherapy (SIT) for HDMallergies, with the aim of obtaining insights into the pathogenic role of Der p1. Patients co-sensitized to other airborne allergens showed a higher prevalence of asthma (9/12 (75%) vs. 2/7 (29%); p < 0.05) than did HDMmono-sensitized patients. The latter group showed higher Der p1 concentrations than that of the co-sensitized group (p = 0.0360), and a direct correlation between Der p1 and Der p2 (r = 0.93; p = 0.0003) was observed. In conclusion, our study offers insights into the role of Der p1 in a population of patients with allergic rhinitis and asthma who were candidates for SIT. Interestingly, Der p1 positivity was associated with bronchial asthma and co-sensitization

Safety evaluations of a synthetic antimicrobial peptide administered intravenously in rats and dogs

The antimicrobial peptide SET-M33 is under study for the development of a new antibiotic against major Gram-negative pathogens. Here we report the toxicological evaluation of SET-M33 administered intravenously to rats and dogs. Dose range finding experiments determined the doses to use in toxicokinetic evaluation, clinical biochemistry analysis, necroscopy and in neurological and respiratory measurements. Clinical laboratory investigations in dogs and rats showed a dose-related increase in creatinine and urea levels, indicating that the kidneys are the target organ. This was also confirmed by necroscopy studies of animal tissues, where signs of degeneration and regeneration were found in kidney when SET-M33 was administered at the highest doses in the two animal species. Neurological toxicity measurements by the Irwin method and respiratory function evaluation in rats did not reveal any toxic effect even at the highest dose. Finally, repeated administration of SET-M33 by short infusion in dogs revealed a no-observed-adverse-effect-level of 0.5&nbsp;mg/kg/day

Pulmonary rehabilitation improves functional outcomes and quality of life in post-SARS-CoV-2 mild-to-moderate infection patients: a pilot study

: SARS-CoV-2 infection impairs functional outcomes and quality of life, even in its mild-to-moderate form. It is therefore appropriate to draw attention to the role played by respiratory rehabilitation and physiotherapists in the pulmonary rehabilitation process that post-SARS-CoV-2 patients must undergo. We enrolled 80 patients in a prospective case-control study; 40 cases (mild-to-moderate post-SARS-CoV-2 infection patients) and 38 control subjects (i.e. patients affected by other respiratory diseases) completed a full pulmonary rehabilitation cycle. 6 Minute Walking Distance, Borg CR10 Scale, modified Medical Research Council (mMRC) Dyspnoea scale, EuroQoL EQ-5D-3L questionnaire, Barthel scale, arterial blood gas test and peripheral oxygen saturation (SpO2) were compared for all patients before and after rehabilitation. All patients experienced significant improvements in all parameters analyzed, except for arterial blood gas test. Results were similar for both groups, in particular both groups experienced improvements in mMRC scale, EuroQoL questionnaire, Barthel scale and 6-minute walking distance. Pulmonary rehabilitation appears to improve exercise tolerance, dyspnea and quality of life in patients recovering from mild-to-moderate SARS-CoV-2 infection. Further studies are needed on larger sample size population to validate these results

The Outcome of Technical Intraoperative Complications Occurring in Standard Aortic Endovascular Repair

Background Technical intraoperative complications (TICs) may occur during standard endovascular repair (EVAR) with possible effects on the outcome. This study evaluates the early and midterm effects of TICs on EVARs. Methods All EVARs (from 2012 to 2016) were analyzed to identify all TICs: (1) endoluminal defects (stenosis, dissection, rupture, compression of native arteries, or endograft); (2) type I-III endoleaks; (3) unplanned artery coverage; and (4) surgical access complications. Follow-up was performed by Doppler ultrasound/ontrast enhanced ultrasound/computed tomography scan at yearly intervals. The outcome was compared with that of uneventful cases (UCs) through Fisher's exact test and Kaplan-Maier curve. Results TICs occurred in 68 (18%) of 377 patients undergoing EVAR. Thirty-two endoluminal defects were relined endovascularly; 24 type I-III endoleaks were treated with cuff deployment/forced ballooning (23) and surgical conversion (1); 3 of 8 unplanned artery coverages were revascularized (2 renal and 1 hypogastric); 5 hypogastric coverages had an unsuccessful correction; and 4 access artery injuries were repaired. Although fluoroscopy time and contrast usage were significantly higher in the TIC group than those in the UC group (309 cases), 30-day outcome was similar for death (1.4% TIC vs 0% UC, P = 0.18), reintervention (0% TIC vs 0.3% UC, P = 1), type I-III endoleak (0% TIC vs 0.9% UC, P = 1), steno-occlusions (0% TIC vs 0.3% UC, P = 1), buttock claudication, and renal failure (0% in both groups). At 24 months, TIC and UC groups had similar survival (91.7 ± 8% vs 96.2 ± 2.1%, P = 0.5), freedom from reintervention (81.4 ± 9.9% vs 96 ± 2.2%, P = 0.49), overall complication rate (13.4 ± 7.6% vs 11.4 ± 3.5%, P = 0.49), type I-III endoleak (11.2 ± 7.5% vs 7 ± 2.9%, P = 0.8), buttock claudication (0% vs 2 ± 2% P = 0.6), and hemodialysis (0% in both). Midterm iliac leg occlusion was significantly higher in the TIC group (26.9 ± 12.3% vs 3 ± 2.1%, P = 0.01). Conclusion TICs may affect several aspects during EVAR, leading to the necessity of adjunctive maneuvers, which have no impact on early outcome but may cause an increased rate of midterm iliac leg occlusion