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Since the first description of COVID-19 infection, among clinical manifestations of the disease, including fever, dyspnea, cough, and fatigue, it was observed a high incidence of thromboembolic events potentially evolving towards acute respiratory distress syndrome (ARDS) and COVID-19-associated-coagulopathy (CAC). The hypercoagulation state is based on an interaction between thrombosis and inflammation. The so-called CAC represents a key aspect in the genesis of organ damage from SARS-CoV-2. The prothrombotic status of COVID-19 can be explained by the increase in coagulation levels of D-dimer, lymphocytes, fibrinogen, interleukin 6 (IL-6), and prothrombin time. Several mechanisms have been hypothesized to explain this hypercoagulable process such as inflammatory cytokine storm, platelet activation, endothelial dysfunction, and stasis for a long time. The purpose of this narrative review is to provide an overview of the current knowledge on the pathogenic mechanisms of coagulopathy that may characterize COVID-19 infection and inform on new areas of research. New vascular therapeutic strategies are also reviewed.

The activation of the T cell mediated immune response relies on the fine interaction between the T cell receptor on the immune cell and the antigen-presenting major histocompatibility complex (MHC) molecules on the membrane surface of antigen-presenting cells. Both the distribution and quantity of MHC/peptide complexes and their adequate morphological presentation affect the activation of the immune cells. In several types of cancer the immune response is down-regulated due to the low expression of MHC-class I (MHC-I) molecules on the cell's surface, and in addition, the mechanical properties of the membrane seem to play a role. Herein, we investigate the distribution of MHC-I molecules and the related nanoscale mechanical environment on the cell surface of two cell lines derived from colon adenocarcinoma and a healthy epithelial colon reference cell line. Atomic force microscopy (AFM) force spectroscopy analysis using an antibody-tagged pyramidal probe specific for MHC-I molecules and a formula that relates the elasticity of the cell to the energy of adhesion revealed the different population distributions of MHC-I molecules in healthy cells compared to cancer cells. We found that MHC-I molecules are significantly less expressed in cancer cells. Moreover, the local elastic modulus is significantly reduced in cancer cells. We speculate that these results might be related to the proven ability of cancer cells to evade the immune system, not only by reducing MHC-I cell surface expression but also by modifying the local mechanical properties affecting the overall morphology of MHC-I synapse presentation to immune cells.

COVID-19 has been associated with an increased risk of thrombotic events; however, the reported incidence of deep vein thrombosis varies depending, at least in part, on the severity of the disease. Aim of this prospective, multicenter, observational study was to investigate the incidence of lower limb deep vein thrombosis as assessed by compression ultrasound in consecutive patients admitted to three pulmonary medicine wards designated to care for patients with COVID-19 related pneumonia, with or without respiratory failure but not requiring admission to an intensive care unit. Consecutive patients admitted between March 27 and May 6, 2020 were enrolled. Patients were excluded if they were less than 18-year-old or if compression ultrasound could not be performed for any reason. Patients were assessed at admission (t0) and after 7 days (t1). Major and non-major clinically relevant bleedings were recorded. Sixty-eight patients were enrolled. Two were excluded due to anatomical abnormalities that prevented compression ultrasound; sixty patients were retested at (t1). All patients were started on antithrombotic prophylaxis, unless therapeutic anticoagulation was required. Deep vein thrombosis as assessed by compression ultrasound was observed in 2 patients (3%); one of them was later deemed to represent a previous episode. No new episodes were detected at t1. One major and 2 non-major clinically relevant bleedings were observed. In the setting of patients with COVID-related pneumonia not requiring admission to an intensive care unit, the incidence of deep vein thrombosis is low and our data support not screening asymptomatic patients., Highlights • COVID-19 is characterized by increased risk of thrombotic events. • Compression ultrasound is an easy and reliable method to detect deep vein thrombosis. • The incidence of deep vein thrombosis in our COVID-19 patients not in ICU is very low. • Screening for deep vein thrombosis in these patients is not warranted.

Bronchial asthma is a chronic inflammatory condition with increasing prevalence worldwide that may present as heterogeneous phenotypes defined by the T2-mediated pattern of airway inflammation T2-high and T2-low asthma. Severe refractory asthma includes a subset of asthmatic patients who fail to control their disease despite maximal therapy and represent a group of patients needing marked resource utilization and hence may be eligible to add-on biological therapies. Among the new biologics, we focused our attention on two monoclonal antibodies: dupilumab, exerting a dual blockade of cytokine (interleukin (IL)-4 and IL-13) signaling; and tezepelumab, acting at a higher level preventing the binding of thymic stromal lymphopoietin (TSLP) to its receptor, thus blocking TSLP, IL-25, and IL-33 signaling, hence modulating airway T2 immune responses. With their different mechanisms of action, these two biologics represent important options to provide an enhanced personalized treatment regimen. Several clinical trials have been conducted testing the efficacy and safety of dupilumab in severe refractory asthmatic patients showing improvements in lung function, asthma control, and reducing exacerbations. Similar results were reported with tezepelumab that, differently from dupilumab, acts irrespectively on eosinophilic or non-eosinophilic phenotype. In this review, we provide an overview of the most important highlights regarding dupilumab and tezepelumab characteristics and mechanism of action with a critical review of the principal results of clinical (Phase II and III) studies concluded and those still in progress.

Background Work‐related lower airway symptoms (WR‐LAS), rhinitis (WRR), and asthma (WRA) are very common among bakers, due to airborne exposure to wheat flour and multigrain. Limited data is available regarding fractional exhaled nitric oxide (FeNO) in bakers in relation to respiratory burden and occupational sensitization in a real‐life situation. Objective To analyze FeNO levels in relation to WRR, WR‐LAS, and WRA with regard to allergic sensitization to occupational allergen in bakers. Methods Cross‐sectional, observational study of 174 bakers employed in traditional small bakeries in the Verona District. Subjects did FeNO measurements, spirometry, methacholine challenge, and skin prick test to common inhalant aeroallergens and bakeries occupational allergens. Results FeNO levels were higher in subjects sensitized to occupational allergens compared with bakers not sensitized to occupational allergens (22.8 ppb (18.9, 27.6) vs. 12.0 ppb (9.9, 14.5), p

Surface current patterns in single patch antennas are imaged by means of photoexpansion nanospectroscopy performed with an atomic force microscopy probe and a broadly tunable quantum cascade laser system. The local ohmic losses lead to temperature increase of a thin polymer layer positioned in the cavity, which then expands.

A thin layer of a mid-IR transparent polymer is inserted inside a metallic optical nano-resonator, where a photonic mode and an intersubband transition are strongly coupled together. Acting as a non-perturbative transducer, and without modifying the optical response, the polymer allows the detection of absorbed optical power in the form of thermal expansion due to heat dissipation. This innovative approach permits to identify - even at the single nano-resonator level - the typical anti crossing characteristic of the polaritonic system, and to perform direct imaging of the electromagnetic fields buried within the inside of an otherwise inaccessible optical nanocavity.

Sleep-related breathing disorders (SBDs) are characterized by abnormal respiration during sleep. Obstructive sleep apnea (OSA), a common SBD increasingly recognized by physicians, is characterized by recurrent episodes of partial or complete closure of the upper airway resulting in disturbed breathing during sleep. OSA syndrome (OSAS) is associated with decreased patients' quality of life (QoL) and the presence of significant comorbidities, such as daytime sleepiness. Similarly to what seen for OSAS, the prevalence of asthma has been steadily rising in recent years. Interestingly, severe asthma (SA) patients are also affected by poor sleep quality—often attributed to nocturnal worsening of their asthma—and increased daytime sleepiness and snoring compared to the general population. The fact that such symptoms are also found in OSAS, and that these two conditions share common risk factors, such as obesity, rhinitis, and gastroesophageal reflux, has led many to postulate an association between these two conditions. Specifically, it has been proposed a bidirectional correlation between SA and OSAS, with a mutual negative effect in term of disease severity. According to this model, OSAS not only acts as an independent risk factor of asthma exacerbations, but its co-existence can also worsen asthma symptoms, and the same is true for asthma with respect to OSAS. In this comprehensive review, we summarize past and present studies on the interrelationship between OSAS and SA, from endo-phenotype to clinical aspects, highlighting possible implications for clinical practice and future research directions.

The strong light-matter coupling is an exotic phenomenon of interest not only for basic physics, but also because it has potential for improving optoelectronic devices. When dealing with conduction band electrons in semiconductor quantum wells (QWs), intersubband (ISB) transitions can couple to the optical resonances of plasmonic antennas. In the case of strong light-matter coupling, a characteristic anticrossing of the "light" and "matter" excitations is observed. It stems from the appearance of new eigenmodes, called cavity polaritons.

We resolve the dispersion of multiple vibro-polariton modes issued from the coupling of several vibrational bands of the methylene group with a resonant modes of a mid-infrared micro-cavity. The experimental results are in excellent agreement with numerical simulations.

Cough variant asthma (CVA), a common asthma phenotype characterized by nonproductive cough and bronchial hyperreactivity (BHR), is usually detected by bronchial provocation tests (BPTs) which are time-consuming, expensive, and unsafe. The primary study objective was to provide proof of concept for the use of fractional exhaled nitric oxide (FENO), eosinophil count percentage in induced sputum (sEOS%), forced expiratory flow between 25 and 75% of forced vital capacity (FEF25–75%) % predicted value, and FEF25–75% z-scores as surrogate markers predicting BHR in young adults with suspected CVA; the secondary objective was to compare the diagnostic performance of the various techniques. Three hundred and ten subjects (median age 24 years) were included in a cross-sectional study. Subjects were characterized as BHR positive (POS) (n = 147) or BHR negative (NEG) (n = 163) according to methacholine BPT. Classification accuracies were expressed as areas under the receiver operator characteristic curves (AUC). Compared with BHR NEG, FEF25–75% % predicted value and FEF25–75% z-scores were lower in the BHR POS group (p < 0.001), whereas FENO (p < 0.001) and sEOS% were higher (p < 0.001). AUC values for detecting BHR were as follows: FENO, 0.98 (SD = 0.02); sEOS%, 0.98 (SD = 0.02); FEF25–75% % pred, 0.93 (SD = 0.05); FEF25–75% z scores, 0.92 (SD = 0.05). Optimal cutoff values (OCV) for BHR prediction were as follows: FENO, 32.7 ppb (sensitivity = 0.93, specificity = 0.96), sEOS%, 3.80% (sensitivity = 0.94, specificity = 0.94), FEF25–75% % predicted value, 80.0% (sensitivity = 0.90, specificity = 0.87), and FEF25–75% z-score, −0.87 (sensitivity = 0.89, specificity = 0.87). Non-invasive/semi-invasive airway inflammatory or small airway functional measures might be used as surrogate markers predicting BHR in young adults with suspected CVA.

Exploiting the coupling of laser beams to atomic force microscopy probes, both scattering and absorption of mid-infrared radiation (wavelengths of 5 to $11\ \mu \mathrm{m}$ ) have been measured in the near field region of single patch-antennas, strongly coupled to the intersubband transition of an InGaAs/AlInAs quantum well.

Tobacco smoking impairs mucociliary clearance (MCC) efficiency as shown by prolonged saccharin test transit time (STTT). Avoiding exposure to tobacco smoke from combustible cigarettes may restore MCC function and former smokers have been shown to exhibit similar STTT as never smokers. The impact of switching from smoking to combustion-free tobacco products such as e-cigarettes (ECs) and heated tobacco products (HTPs) on STTT is not known. We report STTT of exclusive EC and HTP users. Test results were compared to those obtained in current, former, and never smokers.STTT were obtained from 39 current, 40 former, 40 never smokers and from 20 EC and 20 HTP users. Comparison of STTT values showed significant difference among the five study groups (p< 0.00001) with current smokers having a median (IQR) STTT of 13.15 min, which was significantly longer compared to that of all other study groups. In particular, compared to former (7.26 min) and never smokers (7.24 min), exclusive EC users and exclusive HTP users had similar STTT at 7.00 and 8.00 min respectively.Ex-smokers who have switched to exclusive regular use of combustion-free nicotine delivery systems (i.e. ECs and HTPs) exhibit similar saccharin transit time as never and former smokers. This suggests that combustion-free nicotine delivery technologies are unlikely to have detrimental effects on MCC function.

Data on characteristics of patients with pulmonary NTM in Italy are lacking. The Italian Registry on pulmonary NTM (IRENE) has been set up in April 2017 as a multicenter, prospective, observational, cohort study enrolling consecutive adults with active NTM pulmonary infection or NTM pulmonary disease (NTM-PD) from 48 centers across Italy. Data are collected at baseline with yearly follow-up visits. 500 patients have been enrolled in the registry so far. Median (IQR) age is 67 (55-75) years, 66% are females, median (IQR) BMI is 20 (18-22), and 45% are current/former smokers. 90% have pre-existing lung diseases, including bronchiectasis (66%), COPD (21%), cystic fibrosis (10%) and asthma (8%), 36% have GERD, and 25% at least one risk factor for immunosuppression. 355 (71%) patients met the 2007 ATS/IDSA criteria for NTM-PD. Among them, the most common NTM are M. avium complex (72%) -including M. intracellulare (28%) and M. avium (27%)-, M. abscessus complex (MABc) (13%) -including M. a.abscessus (10%)-, M. xenopi (4%) and M. kansasii (3%). 77% of the patients have cough, 55% sputum production, 51% fatigue, 47% shortness of breath, 37% weight loss, 27% intermittent fever, 26% haemoptysis, and 22% night sweats. In terms of radiology, 21% of the patients have cavitating nodules, 13% large cavities and 58% consolidations. Median (IQR) FEV1%pred. is 77% (59-94). A total of 77% of patients with NTM-PD underwent treatment, including azithromycin/clarithromycin, ethambutol, rifampicin/rifabutin. IRENE has the important role to inform the clinical and scientific communities on the current management of adults with pulmonary NTM in Italy and acts as a national network to increase disease awareness.

Un unexpected infection by a novel coronavirus (SAR CoV-2) started by the end of December in Wuhan, China, spreading all over other countries, and Italy was one of the most affected ones. WHO declared the pandemic on 11th March, 2020. Despite the numerous unknown aspects of this infection, the healthcare system had to face a multidimensional emergency. Albania, a small country with a geographical, historical and cultural relationship with Italy was one of the first countries giving support and starting a profitable collaboration focusing on the mission to provide the necessary help for the health care workers. In order to help the Italian healthcare system to face up to the situation two medical teams firstly (in March) and a group of 60 health care workers later in April were sent to Italy (Brescia Hospital) to support clinical activities in departments with COVID-19 patients. This important contribution showed the great solidarity and helped to strengthen the partnership between the two countries.

The mechanism promoting exacerbated immune responses in allergy and autoimmunity as well as those blunting the immune control of cancer cells are of primary interest in medicine. Diacylglycerol kinases (DGKs) are key modulators of signal transduction, which blunt diacylglycerol (DAG) signals and produce phosphatidic acid (PA). By modulating lipid second messengers, DGK modulate the activity of downstream signaling proteins, vesicle trafficking and membrane shape. The biological role of the DGK α and ζ isoforms in immune cells differentiation and effector function was subjected to in deep investigations. DGK α and ζ resulted in negatively regulating synergistic way basal and receptor induced DAG signals in T cells as well as leukocytes. In this way, they contributed to keep under control the immune response but also downmodulate immune response against tumors. Alteration in DGKα activity is also implicated in the pathogenesis of genetic perturbations of the immune function such as the X-linked lymphoproliferative disease 1 and localized juvenile periodontitis. These findings suggested a participation of DGK to the pathogenetic mechanisms underlying several immune-mediated diseases and prompted several researches aiming to target DGK with pharmacologic and molecular strategies. Those findings are discussed inhere together with experimental applications in tumors as well as in other immune-mediated diseases such as asthma.

Background. Pulmonary hypertension (PH) is a progressive fatal disease thus, noninvasive prognostic tools are needed to follow these patients. The aim of our study was to evaluate fractional exhaled nitric oxide (FeNO) and exhaled breath temperature (EBT) values in patients with PH from different causes and to correlate them with respiratory functional data. Methods. Twenty-four PH patients underwent spirometry, carbon monoxide diffusion (DLCO) test, transthoracic echocardiography, right-heart catheterization, and FeNO and EBT measurements. Results. We studied 3 groups according to the type of PH: 10 patients with pulmonary arterial hypertension (PAH) (group A), 11 patients with PH due to chronic obstructive pulmonary disease (COPD) (group B), and 3 patients with PH associated with left heart disease (group C). Mean FeNO values tend to be higher in group B (15.0 ± 9.3ppb) compared with other groups (respectively, 9.9 ± 5.7 and 8.5 ± 5.2 ppb in groups A and C; p = 0.271) but no statistical significance has been reached. Mean values of alveolar NO concentration (CANO) were higher in groups A and B compared to group C (respectively, 16.9 ± 12.6; 13.9 ± 6.8; and 6.7 ± 2.0 ppb) (p = 0.045). EBT mean values were significantly lower in group C when compared with other groups (group C: 29.0 +- 1.3°C, groups A and B: 30.9 ± 1.3 and 31.2 ± 1.2°C, respectively: p = 0.041). EBT levels were inversely correlated to mean pulmonary artery pressure (PAPm) levels (Spearman coefficient -0.481; p = 0.017). Conclusions. eNO, CANO, and EBT have been evaluated in three groups of PH patients. Interestingly EBT reduction was correlated with PAPm increase, whereas FeNO was higher in COPD patients and CANO in PAH and COPD groups. Further studies are needed to clarify EBT, FeNO, and CANO roles as biomarkers in the monitoring of patients with PH.

We present a mid-IR ($\lambda \approx$ 8.3 $\mu$m) quantum well infrared photodetector (QWIP) fabricated on a mid-IR transparent substrate, allowing photodetection with illumination from either the front surface or through the substrate. The device is based on a 400 nm-thick GaAs/AlGaAs semiconductor QWIP heterostructure enclosed in a metal-insulator-metal (MIM) cavity and hosted on a mid-IR transparent ZnSe substrate. Metallic stripes are symmetrically patterned by e-beam lithography on both sides of the active region. The detector spectral coverage spans from $\lambda \approx 7.15$ $\mu$m to $\lambda \approx 8.7$ $\mu$m by changing the stripe width L - from L = 1.0 $\mu$m to L = 1.3 $\mu$m - thus frequency-tuning the optical cavity mode. Both micro-FTIR passive optical characterizations and photocurrent measurements of the two-port system are carried out. They reveal a similar spectral response for the two detector ports, with an experimentally measured T$_{BLIP}$ of $\approx$ 200K., Comment: Copyright 2021 Mario Malerba, Mathieu Jeannin, Stefano Pirotta, Lianhe Li, Alexander Giles Davies, Edmund Linfield, Adel Bousseksou, Jean-Michel Manceau and Raffaele Colombelli. This article is distributed under a Creative Commons Attribution (CC BY) License. The following article has been submitted to APL Photonics. After it is published, it will be found at https://aip.scitation.org/journal/app

Obstructive sleep apnea (OSA) and insomnia are the two most common sleep disorders among the general population, and they may often coexist in patients with sleep-disordered breathing (SDB). The higher prevalence of insomnia symptoms in patients with OSA (40–60%) compared to that observed in the general population has thus led researchers to identify a new disorder named comorbid insomnia and OSA (COMISA), whose true burden has been so far largely underestimated. The combined treatment of COMISA patients with positive-airway pressure ventilation (PAP) with cognitive behavioral therapy for insomnia (CBTi) has shown a better patient outcome compared to that obtained with a single treatment. Furthermore, recent evidence has shown that an innovative patient-centered approach taking into consideration patient characteristics, treatment preferences and accessibility to treatment is recommended to optimize clinical management of COMISA patients. However, in this complex mosaic, many other sleep disorders may overlap with COMISA, so there is an urgent need for further research to fully understand the impact of these therapies on outcomes for OSA patients with comorbidity. In light of this need, this review focuses on the major sleep disorders comorbid with OSA and the recent advances in the management of these insomniac patients.

Introduction Patients with chronic obstructive pulmonary disease (COPD) have an increased risk of cardiovascular disease. The endothelial dysfunction likely plays a central role in increasing cardiovascular risk. Objectives This cross-sectional, study investigated the prevalence and extent of endothelial dysfunction in patients with stable COPD. Methods Peripheral arterial tonometry (PAT) was measured by post-ischemic reactive hyperemia index (RHI) in 16 COPD patients, 16 healthy controls and 16 subjects with treated systemic arterial hypertension (AH) and analysed with covariates condition (dyslipidemia, and medications). Results The prevalence of endothelial dysfunction was significantly higher in COPD group than in the other groups. Mean RHI was significantly lower in COPD patients compared with the other groups. At linear regression FEV1 and RHI were directly correlated (Spearman index = 0.553; P = .026). COPD patients in groups C and D according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages showed lower RHI compared with patients classified as A and B (P

Heat dissipation in a plasmonic nanostructure is generally assumed to be ruled only by its own optical response even though also the temperature should be considered for determining the actual energy-to-heat conversion. Indeed, temperature influences the optical response of the nanostructure by affecting its absorption efficiency. Here, we show both theoretically and experimentally how, by properly nanopatterning a metallic surface, it is possible to increase or decrease the light-to-heat conversion rate depending on the temperature of the system. In particular, by borrowing the concept of matching condition from the classical antenna theory, we first analytically demonstrate how the temperature sets a maximum value for the absorption efficiency and how this quantity can be tuned, thus leading to a temperature-controlled optical heat dissipation. In fact, we show how the nonlinear dependence of the absorption on the electron-phonon damping can be maximized at a specific temperature, depending on the system geometry. In this regard, experimental results supported by numerical calculations are presented, showing how geometrically different nanostructures can lead to opposite dependence of the heat dissipation on the temperature, hence suggesting the fascinating possibility of employing plasmonic nanostructures to tailor the light-to-heat conversion rate of the system.

We developed a technique that enables replacement of a metallic waveguide cladding with a low-index (n≈1.4) material - CaF

Combining individual drugs in a single inhaler is the most convenient way to deliver triple therapy. A long-acting muscarinic receptor antagonist (LAMA) added to an inhaled corticosteroid (ICS)/long-acting β2-adrenoceptor agonist (LABA) fixed-dose combination (FDC) can improve efficacy of pharmacological treatment of patients with chronic obstructive pulmonary disease (COPD). New inhaled ICS/LABA/LAMA FDCs, including fluticasone furoate/vilanterol/umeclidinium, budesonide/formoterol/glycopyrronium and beclometasone/formoterol/glycopyrronium, are in Phase III of clinical development for COPD. Triple inhaled therapy might be particularly useful in patients with severe to very severe COPD, above all in those with peripheral blood or sputum eosinophilia, asthma-COPD overlap syndrome (ACOS) or frequent exacerbators. Future prospective studies should assess efficacy and safety of triple ICS/LABA/LAMA therapy in selected COPD phenotypes.

Background Electronic cigarette (EC) use is an emerging behaviour that has been shown to help smokers to reduce cigarette consumption. The aim of this study was to illustrate long-term changes in exhaled breath measurements and respiratory symptoms in smokers invited to quit or reduce their cigarette consumption by switching to ECs. Materials and methods Prospective evaluation of cigarette consumption, fractional nitric oxide concentration in exhaled breath (FeNO), exhaled carbon monoxide (eCO) and symptom scores was performed in a 1-year randomized, controlled trial of ‘healthy’ smokers receiving 2·4% nicotine, 1·8% nicotine or no nicotine ECs. FeNO and eCO data are presented on the basis of participants’ pooled continuous smoking phenotype classification (failures, reducers and quitters). Results A significant effect of quitting classification was found on FeNo and eCO at all time points (P < 0·0001). Among quitters, FeNO (medians and interquartile range) rose from 5·5 (4·5–6·9) ppb to 17·7 (13·3–18·9) ppb by week 52. Baseline eCO (medians and interquartile range) decreased from 17 (12–20) ppm to 3 (1–4) ppm by week 52. No significant changes in FeNO and eCO levels were observed in failures and reducers. Improvements in FeNO and eCO levels were correlated with attenuations in symptom scores. Conclusions Smokers invited to switch to electronic cigarettes who completely abstained from smoking showed steady progressive improvements in their exhaled breath measurements and symptom scores. FeNo and eCO normalization is highly supportive of improved respiratory health outcomes and adds to the notion that quitting from tobacco smoking can reverse harm in the lung.

COVID-19, a novel severe acute respiratory syndrome (SARS) emerging in China’s Hubei province in late 2019, due to a new coronavirus (SARS-CoV-2), is causing a global pandemic involving many areas of the world, which so far counts more than 43 million cases and more than 1,155,000 deaths worldwide [...]

Besides advanced age and the presence of multiple comorbidities as major contributors to increased risk of severe disease and fatal outcome from Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19), there is now emerging evidence that overweight and obesity predispose to severe symptoms and negative prognosis. Remarkably, the severity of COVID-19 appears to rise with increasing body mass index (BMI). The association between COVID-19 outcomes and overweight/obesity has biological and physiological plausibility. Potential pathophysiological mechanisms that may explain this strong association include the chronic pro-inflammatory state, the excessive oxidative stress response, and the impaired immunity that is commonly reported in these individuals. The role of cytokines, mammalian target of rapamycin (mTOR), and altered natural killer cell polarization in the dangerous liaison between COVID-19 and obesity are discussed here. These pathways can favor and accelerate the deleterious downstream cellular effects of SARS-CoV-2. Moreover, obesity is well known to be associated with reduced lung function and poor response to mechanical ventilation, thus placing these individuals at high risk of severe illness and mortality from COVID-19. Furthermore, obesity may lead to other complications, such as renal failure, cardiovascular dysfunction, hypertension, and vascular damage, which in turn can further accelerate negative clinical outcomes from COVID-19. Obese individuals should be shielded against any potential viral exposure to SARS-CoV-2 with consequential considerations for compulsory protection devices and social distancing. Health care providers should be aware that obesity predisposes to severe symptoms and negative prognosis in COVID-19 patients.

Chronic obstructive pulmonary disease (COPD) is a common disabling disease characterized by progressive airflow obstruction. Great efforts were spent in the development of drugs able to improve symptoms, quality of life, reduce exacerbations, hospitalizations and the frequency of death of patients with COPD. The cornerstones of treatment are bronchodilator drugs of two different classes: beta agonists and muscarinic antagonists. Currently the Global initiative for COPD suggests the use of long acting beta agonists (LABAs) and long acting muscarinic antagonists (LAMAs) in combination for the majority of COPD patients, thus great interest is associated with the developing of LAMA/LABA fixed combination in the maintenance treatment of stable COPD. Many LAMA/LABA fixed dose combinations have been licensed in different countries and the clinical use of these drugs stimulated the performance of many clinical trials. The purpose of this review is a complete criticism of pharmacological and clinical aspects related to the use of LAMA/LABA single inhalers for the maintenance treatment of stable COPD, with particular mention to the most debated topics and future prospects in the field.

Large-scale neural recordings with high spatial and temporal accuracy are instrumental to understand how the brain works. To this end, it is of key importance to develop probes that can be conveniently scaled up to a high number of recording channels. Despite recent achievements in complementary metal-oxide semiconductor (CMOS) multi-electrode arrays probes, in current circuit architectures an increase in the number of simultaneously recording channels would significantly increase the total chip area. A promising approach for overcoming this scaling issue consists in the use of the modular Active Pixel Sensor (APS) concept, in which a small front-end circuit is located beneath each electrode. However, this approach imposes challenging constraints on the area of the in-pixel circuit, power consumption and noise. Here, we present an APS CMOS-probe technology for Simultaneous Neural recording that successfully addresses all these issues for whole-array read-outs at 25 kHz/channel from up to 1024 electrode-pixels. To assess the circuit performances, we realized in a 0.18 μm CMOS technology an implantable single-shaft probe with a regular array of 512 electrode-pixels with a pitch of 28 μm. Extensive bench tests showed an in-pixel gain of 45.4 ± 0.4 dB (low pass, F-3 dB = 4 kHz), an input referred noise of 7.5 ± 0.67 μVRMS (300 Hz to 7.5 kHz) and a power consumption

Electrophysiological signals in the brain are distributed over broad spatial and temporal scales. Monitoring these signals at multiple scales is fundamental in order to decipher how brain circuits operate and might dysfunction in disease. A possible strategy to enlarge the experimentally accessible spatial and temporal scales consists in combining the use of multiple probes with different resolutions and sensing areas. Here, we propose a neural recording system capable of simultaneous and synchronous acquisitions from a new generation of high-resolution CMOS probes (512 microelectrodes, 25 kHz/electrode whole-array sampling frequency) as well as from a custom-designed CMOS-based headstage. While CMOS probes can provide recordings from a large number of closely spaced electrodes on single-shaft devices, the CMOS-based headstage can be used to interface the wide range of available intra- or epi-cortical passive electrode array devices. The current platform was designed to simultaneously manage high-resolution recordings from up to four differently located CMOS probes and from a single 36-channels low-resolution passive electrode array device. The design, implementation, and performances for both ICs and for the FPGA-based interface are presented. Experiments on retina and neuronal culture preparations demonstrate the recording of neural spiking activity for both CMOS devices and the functionality of the system.

Substrate-integrated multielectrode arrays (MEAs) enable multisite, long-term, and label-free sensing and actuation of neuronal electrical signals in reduced cell culture models for network electrophysiology. Conventional, thin-film fabricated passive MEAs typically provide a few tens of electrode sites. New generations of active CMOS-based high-resolution arrays provide the capabilities of simultaneous recordings from thousands of neurons over fields of view of several square millimeters, yet allowing extracellular electrical imaging to be achieved down to the subcellular scale. In turn, such advancement in chip-based electrical readouts can significantly complement recently developed biotechnological and bimolecular techniques for neurobiology applications. Here, we describe (1) a simple method to fabricate passive MEAs and (2) protocols for preparing and growing primary rat hippocampal neuronal cultures and human iPS-derived neurons on MEAs. The aim is to provide reliable protocols for initiating the reader to this technology and for stimulating their further development and experimental use in neurobiology.

Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease characterized by progressive loss of lung function and poor prognosis. The so-called acute exacerbation of IPF (AE-IPF) may lead to severe hypoxemia requiring mechanical ventilation in the intensive care unit (ICU). AE-IPF shares several pathophysiological features with acute respiratory distress syndrome (ARDS), a very severe condition commonly treated in this setting. A review of the literature has been conducted to underline similarities and differences in the management of patients with AE-IPF and ARDS. During AE-IPF, diffuse alveolar damage and massive loss of aeration occurs, similar to what is observed in patients with ARDS. Differently from ARDS, no studies have yet concluded on the optimal ventilatory strategy and management in AE-IPF patients admitted to the ICU. Notwithstanding, a protective ventilation strategy with low tidal volume and low driving pressure could be recommended similarly to ARDS. The beneficial effect of high levels of positive end-expiratory pressure and prone positioning has still to be elucidated in AE-IPF patients, as well as the precise role of other types of respiratory assistance (e.g., extracorporeal membrane oxygenation) or innovative therapies (e.g., polymyxin-B direct hemoperfusion). The use of systemic drugs such as steroids or immunosuppressive agents in AE-IPF is controversial and potentially associated with an increased risk of serious adverse reactions. Common pathophysiological abnormalities and similar clinical needs suggest translating to AE-IPF the lessons learned from the management of ARDS patients. Studies focused on specific therapeutic strategies during AE-IPF are warranted.

Substrate-integrated multielectrode arrays (MEAs) enable multisite, long-term, and label-free sensing and actuation of neuronal electrical signals in reduced cell culture models for network electrophysiology. Conventional, thin-film fabricated passive MEAs typically provide a few tens of electrode sites. New generations of active CMOS-based high-resolution arrays provide the capabilities of simultaneous recordings from thousands of neurons over fields of view of several square millimeters, yet allowing extracellular electrical imaging to be achieved down to the subcellular scale. In turn, such advancement in chip-based electrical readouts can significantly complement recently developed biotechnological and bimolecular techniques for neurobiology applications. Here, we describe (1) a simple method to fabricate passive MEAs and (2) protocols for preparing and growing primary rat hippocampal neuronal cultures and human iPS-derived neurons on MEAs. The aim is to provide reliable protocols for initiating the reader to this technology and for stimulating their further development and experimental use in neurobiology.

Plasmonic metamolecules have received much interest in the last years because they can produce a wide spectrum of different hybrid optical resonances. Most of the configurations presented so far, however, considered planar resonators lying on a dielectric substrate. This typically yields high damping and radiative losses, which severely limit the performance of the system. Here we show that these limits can be overcome by considering a 3D arrangement made from slanted nanorod dimers extruding from a silver baseplate. This configuration mimics an out-of-plane split ring resonator capable of a strong near-field interaction at the terminations and a strong diffractive coupling with nearby nanostructures. Compared to the corresponding planar counterparts, higher values of electric and magnetic fields are found (about a factor 10 and a factor 3, respectively). High-quality-factor resonances (Q ≈ 390) are produced in the mid-IR as a result of the efficient excitation of collective modes in dimer arrays.

Display Omitted An approach for the fabrication of hybrid nanostructures has been proposed.ZnO flowers have been grown selectively on the top of gold nanopillars.Raman analysis have shown that ZnO presents a wurtzite structure.Such systems could find application in photocatalysis or energy harvesting. We fabricated flower-like shaped ZnO nanorods on the apexes of hollow gold nanopillars by Focused Ion Beam lithography and hydrothermal growth. The hollow nanopillar geometry was defined on a photoresist by ion-beam induced inversion and subsequently metalized. Then the bottom section of the pillars was protected by a second resist coating, exposing only the nanopillar tips for hydrothermal growth of ZnO. The wurtzite crystalline structure of the ZnO nanorods that composes the flowers was confirmed by Raman spectroscopy. Such novel 3D hybrid metal semiconductor nanostructures are promising materials for catalysis and energy harvesting.

Chronic obstructive pulmonary disease (COPD) is characterized by poorly reversible airflow limitation, with an abnormal pulmonary and systemic inflammatory response to tobacco smoking. Systemic inflammation promotes atherosclerosis, to treat the complications of which beta-blockers are paramount. In the COPD setting, however, the use of beta-blockers has been limited by fears that they could adversely affect lung function. However, by controlling adrenergic drive and reducing the heart rate, beta-blockers could reduce the risk of arrhythmias and sudden death among COPD patients. Thus, beta-blocker use is strongly supported by evidence in COPD patients with history of myocardial infarction, but warrants consideration in other cardiovascular comorbidities. Studies specifically designed to ascertain the role of beta-blockers in patients with COPD with cardiovascular conditions are still needed, because the majority of the current evidence is based on retrospective observational studies.

Understanding the interplay among the spectrum of electrophysiological signals in the brain, distributed over broad spatial and temporal scales, is fundamental to decipher how brain circuits operate and might dysfunction in disease. Here, we present a multiscale recording system for simultaneous and synchronous acquisitions from a new generation of im-plantable CMOS active probes (single-shaft, 512 microelectrodes, 25 kHz/electrode full-array sampling) as well as from implantable conventional electrode array probes interfaced with a custom-designed CMOS-based headstage. The platform can manage highresolution recordings from up to 4 differently located probes, and one 36-channels low-resolution passive electrode array. As presented here, and prior to complete in-vivo validation, the design and recording performance of high- and low-density electrode array ICs were experimentally tested ex-vivo on retinal whole-mounts.

The electro-magnetic field generated within and around dissipative nano-structures upon light radiation is intimately associated to the formation of localized heat sources. In turn, this phenomenon determines localized temperature variations, effect which can be exploited for applications such as photocatalysis [1], nanochemistry [2] or sensor devices [3]. Here we show how the geometrical characteristics of plasmonic nano-structures can indeed be used to modulate the temperature response. The idea is that when metallic structures interact with an electromagnetic field they heat up due to Joule effect. The corresponding temperature variation modifies the optical response of the structure [4,5] and thus its heating process. The key finding is that, depending on the structures geometry, absorption efficiency can either increase or decrease with temperature. Since absorption relates to the thermal energy dissipation and thus to temperature increase, the mechanism leads to positive or negative loops. Consequently, not only an error would be made by neglecting the role of temperature, but it would be not even possible to know, a priori, if the error is towards higher or lower absorption values. Our model can be utilized to study opto-thermal phenomena when high temperature or high intensity sources are employed. [1] M. Honda et al., Appl. Phys. Lett. 104, 061108 (2014) [2] G. Baffou et al., Chem. Soc. Rev. 43, 3898 (2014) [3] S. Ozdemir et al., J. Lightwave Tech. 21, 805 (2003) [4] A. Alabastri et al., ACS Photonics 2, 115 (2015) [5] A. Alabastri et al., Materials 6, 4879 (2013)

The cancer stem cell (CSC) model is describing tumors as a hierarchical organized system and CSCs are suggested to be responsible for cancer recurrence after therapy. The identification of specific markers of CSCs is therefore of paramount importance. Here, we show that high levels of lipid droplets (LDs) are a distinctive mark of CSCs in colorectal (CR) cancer. This increased lipid content was clearly revealed by label-free Raman spectroscopy and it directly correlates with well-accepted CR-CSC markers as CD133 and Wnt pathway activity. By xenotransplantation experiments, we have finally demonstrated that CR-CSCs overexpressing LDs retain most tumorigenic potential. A relevant conceptual advance in this work is the demonstration that a cellular organelle, the LD, is a signature of CSCs, in addition to molecular markers. A further functional characterization of LDs could lead soon to design new target therapies against CR-CSCs. Stem Cells 2015;33:35–44

In this work we show the effect of high temperature on the plasmonic properties of metallic nanorods. Within this context, the dielectric function of metal has been modified to keep into account both the electron–electron and electron–phonon temperature dependent scattering mechanisms. In fact, the mentioned damping processes are very sensible to temperature variation. It is found that the damping modifications due to temperature change substantially modify both the near and far field optical response of metallic nanorods. Furthermore, the response alteration can be very different depending on the rod aspect ratio, suggesting the need of accurate investigations when metallic nanostructures are to be employed within high-temperature environments or under high intensity irradiation. In this regard, by taking into account different nanorods aspect ratio and incident powers, we provide detailed calculations showing the error committed in evaluating absorption, scattering efficiencies, and near-field enhanceme...

Chronic obstructive pulmonary disease (COPD) is characterized by large phenotype variability, reflected by a highly variable response to pharmacological treatment. Nevertheless, current guidelines suggest that patients with COPD of similar severity should be treated in the same way. The phenotype-based pharmacotherapeutic approach proposes bronchodilators alone in the nonfrequent exacerbator phenotype and a combination of bronchodilators and inhaled corticosteroids in patients with asthma-COPD overlap syndrome (ACOS) and moderate-to-severe exacerbator phenotype. The clinical importance of phenotypes is changing the paradigm of COPD management from evidence-based to personalized medicine. However, the personalized pharmacological strategy of COPD has to be validated in future clinical studies.

Tailored hydrophobic and oleophobic surfaces are exploited for controlling the wetting behaviour and evaporation process of solution dropped on them. This enables molecules and nano-objects that are dissolved in water or organic solvents to be delivered and arranged in a well-defined 2D layout.

Chronic Obstructive Pulmonary Disease (COPD) is defined as a disease characterized by persistent, progressive airflow limitation. Recent studies have underlined that COPD is correlated to many systemic manifestations, probably due to an underlying pattern of systemic inflammation. In COPD fractional exhaled Nitric Oxide (FeNO) levels are related to smoking habits and disease severity, showing a positive relationship with respiratory functional parameters. Moreover FeNO is increased in patients with COPD exacerbation, compared with stable ones. In alpha-1 antitrypsin deficiency, a possible cause of COPD, FeNO levels may be monitored to early detect a disease progression. FeNO measurements may be useful in clinical setting to identify the level of airway inflammation,per seand in relation to comorbidities, such as pulmonary arterial hypertension and cardiovascular diseases, either in basal conditions or during treatment. Finally, some systemic inflammatory diseases, such as psoriasis, have been associated with higher FeNO levels and potentially with an increased risk of developing COPD. In these systemic inflammatory diseases, FeNO monitoring may be a useful biomarker for early diagnosis of COPD development.

Diacylglycerol kinases (DGKs) play a key role in phosphoinositide signaling by removing diacylglycerol and generating phosphatidic acid. Besides the well-documented role of DGKα and DGKζ as negative regulators of lymphocyte responses, a robust body of literature points to those enzymes, and specifically DGKα, as crucial regulators of leukocyte function. Upon neutrophil stimulation, DGKα activation is necessary for migration and a productive response. The role of DGKα in neutrophils is evidenced by its aberrant behavior in juvenile periodontitis patients, which express an inactive DGKα transcript. Together with in vitro experiments, this suggests that DGKs may represent potential therapeutic targets for disorders where inflammation, and neutrophils in particular, plays a major role. In this paper we focus on obstructive respiratory diseases, including asthma and chronic obstructive pulmonary disease (COPD), but also rare genetic diseases such as alpha-1-antitrypsin deficiency. Indeed, the biological role of DGKα is understudied outside the T lymphocyte field. The recent wave of research aiming to develop novel and specific inhibitors as well as KO mice will allow a better understanding of DGK’s role in neutrophilic inflammation. Better knowledge and pharmacologic tools may also allow DGK to move from the laboratory bench to clinical trials.

Asthma is a chronic airway inflammatory disease associated with airway hyperresponsiveness which affects subjects with genetic predisposition. An association has been reported between some polymorphisms in various cytokine genes and asthma. Most of them are single nucleotide polymorphisms (SNPs). These polymorphisms are detected in the protein coding sequence or in the promoter region thus influencing cytokine production. We investigated the involvement of SNP mapping in 5 cytokine genes in mild to severe asthmatics of Italian Caucasians. The frequency of alleles and genotypes, relatively to 10 allelic specificities of the cytokine genes, was defined in 57 asthmatics and in 124 control subjects by a Polymerase Chain Reaction-Sequence Specific Primer method. TNF-alpha -308A and TNF-alpha -238A allele frequencies were higher in asthmatics than in controls (p less than 0.001). Significant differences in the frequency of IL-4 -590T allele and of IL-4Ralpha +1902A allele were also detected in asthmatics in comparison with controls (pless than 0.001 and p=0.005, respectively). Similarly, IL-1alpha -889C allele was present in 84.1 percent of asthmatics and in 70.2 percent of controls (p=0.013). Furthermore, the IL-4Ralpha +1902A/A and IL-1alpha -889C/C homozygous conditions and the TNF-alpha -308G/A, TNF-alpha -238G/A, IL-4 -590T/C and IL-10 -1082G/A heterozygous conditions were significantly associated with asthma (p less than 0.05). ACA haplotype of IL-10 was observed only in asthmatic patients. This study reports, for the first time, the frequency of 10 different single nucleotide polymorphisms in 5 cytokine genes in the Italian Caucasians. Furthermore, we also indicate that in our population some single nucleotide polymorphisms are associated with mild to severe bronchial asthma.