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

Evaluation of DLC, WC/C, and TiN Coatings on Martensitic Stainless Steel and Yttria-Stabilized Tetragonal Zirconia Polycrystal Substrates for Reusable Surgical Scalpels

DLC, WC/C, and TiN coated SF 100 martensitic stainless steel and Yttria-Stabilized Tetragonal Zirconia Polycrystal (Y-TZP) surgical scalpels were tested, characterized, and comparatively evaluated with regard to chemical leach, micromorphology, and mechanical properties in order to evaluate their suitability as reusable surgical scalpels. Vickers microhardness (HV), Scratch Hardness Number (), and sharpening by grinding and cutting capabilities of all the coated scalpels were deemed appropriate for reusable surgical scalpels. However, coated Y-TZP scalpels demonstrated higher Vickers microhardness than martensitic stainless steel scalpels coated with the same coatings, except DLC coating on Y-TZP substrate that presented less adhesion than the other coatings. Uncoated and coated martensitic stainless steel scalpels presented corrosion and chemical leach when soaked for a defined period of time in a simulant physiological saline solution, while uncoated and coated Y-TZP scalpels did not present these drawbacks. Therefore, DLC, WC/C, and TiN coated SF 100 martensitic stainless steel surgical scalpels are unsuitable as reusable surgical scalpels, limiting their application to disposable scalpels only, as the uncoated ones, despite their higher microhardness and expected longer cutting capability duration. Based on these experimental results, WC/C and TiN coated Y-TZP scalpels can be proposed as candidates for reusable surgical scalpel applications

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

Expanding the Clinical Spectrum of UBTF-Related Neurodevelopmental Disorder

Objectives: UBTF1 gene encodes for Upstream Binding Transcription Factor, an essential protein for RNA metabolism. A recurrent de novo variant (c.628G>A; p.Glu210Lys) has recently been associated with a childhood-onset neurodegenerative disorder characterized by motor and language regression, ataxia, dystonia, and acquired microcephaly. In this study, we report the clinical, metabolic, molecular genetics and neuroimaging findings and histologic, histochemical, and electron microscopy studies in muscle samples of 2 patients from unrelated families with a neurodevelopmental disorder. Methods: Data were retrospectively analyzed by medical charts revision. Results: Patient 1, a 16-year-old boy, presented a childhood-onset slowly progressive neurodegenerative disorder mainly affecting language skills, behavior, and motor coordination. Patient 2, a 22-year-old woman, presented with a severe and rapidly progressive disease with dystonic tetra paresis, acquired microcephaly, and severe cognitive deficit complicated by pseudobulbar syndrome characterized by involuntary and uncontrollable outbursts of laughing, dysphagia requiring tube feeding, and nocturnal hypoventilation treated with noninvasive ventilation. Both patients carried the recurrent previously described UBTF1 de novo variant and had signs of mitochondrial dysfunction at muscle biopsy. The metabolic profile of patient 2 also revealed a decrease in CSF biopterin. Discussion: These case reports add new insights to the UBTF1 disease spectrum instrumental to improving the diagnostic rate in neurodevelopmental disorders

Assessment of respiratory function and exercise tolerance at 4-6 months after COVID-19 infection in patients with pneumonia of different severity

The evaluation of COVID-19 systemic consequences is a wide research field in which respiratory function assessment has a pivotal role. However, the available data in the literature are still sparse and need further strengthening

Z-alpha1-antitrypsin polymers and small airways disease: a new paradigm in alfa-1 anti-trypsin deficiency-related COPD development?

The presence of Alpha1-Antitrypsin (AAT) polymers, known to promote a sustained pro-inflammatory activity, has been previously demonstrated in bronchial biopsies of subjects with Z-AAT deficiency (AATD) suggesting a possible role in the development of COPD through a small airway disease impairment. The study aimed to assess the presence of small airways dysfunction and the potential correlation with the presence of Z-AAT polymers obtained by Exhaled Breath Condensate (EBC) collection in PiZZ subjects, as compared with matched healthy PiMM subjects. We enrolled 19 asymptomatic, never smoker subjects: 9 PiZZ and 10 PiMM as controls, without obstructive ventilatory defect (i.e., normal FEV1/VC% ratio). All subjects underwent complete pulmonary function tests (PFT). EBC was collected in all subjects. ELISA test was applied to search for Z-AAT polymers. The PiZZ subjects showed normal lung volumes and DLCO values. However, in comparison with PiMM subjects, the single breath test N2 wash-out revealed significant differences regarding the phase III slope (1.45±0.35 N2/L vs. 0.96±0.40 N2/L) (p<0.02) in the PiZZ subjects, while the closing volume/vital capacity ratio (14.3±4.5 % vs. 11.3±6.3 %) was not significantly increased. The ELISA test detected the presence of Z-AAT polymers in 44% of PiZZ patients. Asymptomatic, never smoker PiZZ subjects with normal spirometry and lung diffusion capacity showed airways impairment when compared to PiMM subjects. Although Z-AAT polymers were found only in 44% of PiZZ subjects, these findings suggest the possibility that chronic bronchiolitis can develop as a result of the long-term pro-inflammatory activity of Z-AAT polymers in subjects with Z-related AATD