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Research of solutions to problem in existing processes often deals with the tendency to follow mental schemes because of the psychological inertia. This study illustrates a knowledge-based systematic methodology of inventive problem solving for the effective development of new systems and solutions, a theory that consists of theoretical foundation, analytical and knowledge-based tools, applicable in conjunction with other creativity and engineering methodologies. The TRIZ (Theory of Inventive Problem Solution) applicability in process reliability can develop new and effective solutions thanks to the examination of contradiction, different prospective, and points of view. The systematic innovation process provides a platform to integrate heterogeneous resources and tools opening the problem-solving methodology to new and different interdisciplinary approaches. The deconstruction and identification of issues to analyze the problems in their context and in relation to other factors are adopted in many areas of industrial production as well as in the more general problem-solving matters. In particular, this study will show how TRIZ can be used in process optimization rather than research and development where this methodology is commonly adopted. This case represents a practical application of the TRIZ to increase quality and reliability in regard to a manufacturing process of an industry that designs and builds molds and equipment for the production of aluminum food containers. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

BACKGROUND: The need for more effective smoking-cessation interventions is firmly established. However, access to these services can be problematic in real life. E-mail messages may be a convenient alternative to deliver smoking-cessation interventions. The aim of this pilot study was to assess the effectiveness of incorporating tailored e-mail consultation messages in a smoking-cessation program for smokers willing to quit. METHODS: This pilot study examined the feasibility of integrating e-mail consultation messages in a smoking-cessation program for smokers willing to quit and with Internet access. At baseline, demographic data, smoking history and expired carbon monoxide (CO) levels were collected at a clinic visit. The subjects were provided with the specialist's e-mail address and instructed to prepare e-mail messages containing simple and clear information about their quitting progress. The counselor offered e-mail counseling throughout the smoking-cessation program. A 6-month follow-up visit was arranged, at which abstinence was reviewed. RESULTS: Of the 30 participants initially enrolled in the study, 21 (70%) attended the follow-up 6-month visit. E-mail counseling was more frequently offered (4-8 times) to the participants who completed the study, compared to those lost to follow-up (1-4 times). Comparisons with baseline exhaled CO values showed a significant within-group reduction at 6 months after smoking-cessation (P < .001) in the quitters, compared to smoking-cessation failures. Sustained smoking abstinence at 6 months was 37%. CONCLUSIONS: The integration of e-mail consultation counseling in a smoking-cessation intervention is feasible and effective. E-mail counseling as part of a smoking-cessation program warrants further evaluation. [ABSTRACT FROM AUTHOR]

This study adopts a special Fault Tree Analysis (FTA) method called Comparative FTA to compare the reliability of an electronic braking system with its mechanical counterpart. To this end two Top Events, ‘Ineffective parking braking’ and ‘Wheels jamming during emergency braking’, were analysed. One of the limitations of classic FTA is that the setting up of the tree diagram requires the long-term involvement—one to two months according to Fiat Auto—of specialists of the system being studied. For this reason, therefore, when dealing with relatively complex systems, classic FTA is only used when safety is involved. This paper introduces a simplified FTA model based on the same principle as the Parts Count Method, which limits its attention to the new branches, thereby avoiding the study of all the branches of the tree, in order to make FTA management easier and to encourage its use. The probability that a Top Event takes place is therefore evaluated by studying the different causes which diversify the solutions considered. This approach is a lean practice to minimize the resources and the time of the analysis. It has guaranteed very satisfactory results and, therefore, Fiat Auto has introduced the practice in their Corporate Instructions. Copyright © 2003 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The objective of the research described in this paper, which was carried out in collaboration with the Fiat Auto Direzione Tecnica, was the definition and development of a technical design standard for an electrical power steering (EPS) system, a system mounted on the steering column which assists the driver in maintaining directional control of the vehicle, and the subsequent integration of this standard with existing Fiat Auto Standards. This work required the development of correlation and risk matrices, well-established methodologies used by the Fiat Auto Technical Memory. [ABSTRACT FROM AUTHOR]

This paper introduces a special ‘quality’ parameter on automotive perspective, i.e. the quality index in order to measure the customer satisfaction with car manoeuvrability. In particular, it describes how the characteristic setting curves of a car shock-absorber can be optimized using subjective customer assessment of three categories of perception: handling, steering quality and ride-comfort. These, called manoeuvrability indices, were used to represent the assessment of customer satisfaction with car manoeuvrability. The characteristic curves for each shock-absorber setting were defined using parameters which uniquely determined their shape. Subsequent analysis was carried out using simulated experimental design which adopts a numeric model of vehicle simulation thereby enabling experimental costs to be reduced. This analysis made it possible to ascertain which setting parameter values provided the best compromise among the three categories of required performance. A codified method of optimization was then developed. This method, which includes the three categories of perception, will be extended to all new projects. Copyright © 2001 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Body Mass Index (BMI) is an informative factor on body fatness which has been associated to higher levels of Perinatal Depression (PD) and complications during pregnancy. We aimed to explore the impact of pre-pregnancy and postnatal BMI on the risk of Perinatal Depression and pregnancy outcomes among women recruited at their third trimester of pregnancy., Methods: We report on findings from a large multi-centre study conducted in the South of Italy and involving 1611 women accessing three urban gynaecological departments from July to November 2020. Pregnant women were assessed at their third trimester of pregnancy (T0) and after the childbirth (T1) ;The Edinburgh Postnatal Depression Scale (EPDS) has been employed for the screening of PD over time (T0 and T1) as well as other standardized measures for neuroticism, resilience, and quality of life at baseline. BMI (T0 and T1) and other socio-demographic and clinical characteristics have been collected., Results: Over-weight and obesity (higher levels of BMI) were associated with higher risk of PD (higher scores of EPDS), higher neuroticism and poorer subjective psychological well-being among enrolled women. Also, obesity and over-weight were associated with lower education, higher number of physical comorbidities, medical treatments and complications during pregnancy., Conclusions: Over-weight and obesity may impact on mental health and pregnancy outcome of women enrolled. Psycho-educational interventions aimed to improve the management of physical and emotional issues may reduce the risk of PD and complications during pregnancy.

Background: The prognosis for heart failure (HF) patients remains poor, with a high mortality rate, and a marked reduction in quality of life (QOL) and functional status. This study aims to explore the ongoing needs of HF management and the epidemiology of patients followed by Italian HF clinics, with a specific focus on cardiac contractility modulation (CCM)., Research Design and Methods: Data from patients admitted to 14 HF outpatients clinics over 4 weeks were collected and compared to the results of a survey open to physicians involved in HF management operating in Italian centers., Results: One hundred and five physicians took part in the survey. Despite 94% of patients receive a regular follow-up every 3-6 months, available therapies are considered insufficient in 30% of cases. Physicians reported a lack of treatment options for 23% of symptomatic patients with reduced ejection fraction (EF) and for 66% of those without reduced EF. Approximately 3% of HF population (two patients per month per HF clinic) meets the criteria for immediate CCM treatment, which is considered a useful option by 15% of survey respondents., Conclusions: Despite this relatively small percentage, considering total HF population, CCM could potentially benefit numerous HF patients, particularly the elderly, by reducing hospitalizations, improving functional capacity and QOL.

This paper investigates the effects on the material microstructure of varying the Inter-Layer Cooling Time (ILCT) during the printing process in laser powder bed fusion (L-PBF) multi-laser machines. Despite these machines allowing higher productivity rates compared to single laser machines, they are affected by lower ILCT values, which could be critical for material printability and microstructure. The ILCT values depend both on the process parameter sets and design choices for the parts and play an important role in the Design for Additive Manufacturing approach in L-PBF process. In order to identify the critical range of ILCT for this working condition, an experimental campaign is presented on the nickel-based superalloy Inconel 718, which is widely used for the printing of turbomachinery components. The effect of ILCT on the microstructure of the material is evaluated in terms of porosity and melt pool analysis on printed cylinder specimens, considering ILCT decreasing and increasing in the range of 22 to 2 s. The experimental campaign shows that an ILCT of less than 6 s introduces criticality in the material microstructure. In particular, at an ILCT value of 2 s, widespread keyhole porosity (close to 1‱) and critical and deeper melt pool (about 200 microns depth) are measured. This variation in melt pool shape indicates a change in the powder melting regime and, consequently, modifications of the printability window promoting the expansion of the keyhole region. In addition, specimens with geometry obstructing the heat flow have been studied using the critical ILCT value (2 s) to evaluate the effect of the surface-to-volume ratio. The results show an enhancement of the porosity value (about 3‱), while this effect is limited for the depth of the melt pool.

Introduction: Perinatal depression (PD) is a cluster of clinical depressive symptoms occurring globally during pregnancy or after childbirth, with a prevalence of 11.9%. Risk factors for PD among pregnant women may include personality traits of neuroticism, low personal resilience, higher anxiety, avoidance in close relationships, as well as dysfunctional coping strategies., Methods: We report on descriptive findings of a screening/prevention program aimed to detect depressive symptoms and associated risk factors in a large sample of women ( N = 1,664) accessing the gynecological departments of the Regione Puglia (South of Italy) from July to November 2020. Pregnant women were assessed in their third trimester of pregnancy (T0), after childbirth (T1), and those at risk for PD within 1 year from delivery (T2-T4); The Edinburgh Postnatal Depression Scale (EPDS) has been employed for the screening of PD over time as well as other standardized measures for neuroticism, resilience, coping strategies, and quality of life., Results: Of 1,664, n = 1,541 were tested at T1, and 131 scored ≥ 12 at EPDS (14.6 ± 2.95), showing a higher risk for PD. They were followed over time at 1, 6, and 12 months after childbirth (T2-T4), and 15 of them scored ≥ 12 (EPDS) at T4. Women with a higher risk of PD also reported higher levels of neuroticism, lower levels of personal resilience, more anxiety and avoidance in close relationships, higher employment of dysfunctional coping strategies (e.g., denial, self-blame, etc.), and lower quality of life (0.0008 < all p < 0.0001)., Conclusion: This study confirmed the benefit of screening programs for the early detection of PD among pregnant women. We may suggest a set of risk factors to be considered in the clinical assessment of PD risk as well as the promotion of similar programs to improve depressive outcomes and pathways to care for PD on the basis of a more accurate assessment and referral., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bellomo, Severo, Petito, Nappi, Iuso, Altamura, Marconcini, Giannaccari, Maruotti, Palma, Vicino, Perrone, Tufariello, Sannicandro, Milano, Arcidiacono, Di Salvatore, Caroli, Di Pinto and Ventriglio.)

In October 2019, the Italian Drug Agency (AIFA) restricted reimbursement criteria for vitamin D (VD) use outside the osteoporosis setting (Note 96). However, whether this restriction could also have involved patients at risk for or with osteoporotic fractures has not yet been investigated. We retrospectively analyzed databases from five Italian Local Health Units. Patients aged ≥50 years with either at least one prescription for osteoporosis treatment or with fragility fractures and evidence of osteoporosis from 2011 to 2020 were included. The proportion of subjects with an interruption in VD treatment before and after the introduction of the new reimbursement criteria and predictors of this interruption were analyzed. A total of 94,505 patients (aged 69.4 years) were included. Following the introduction of Note 96, a 2-fold (OR 1.98, 95% CI: 1.92-2.04) increased risk of VD discontinuation was observed. These findings were independent of seasonal variation, osteoporosis treatment patterns, as well as other confounding variables. However, a higher rate of interruption was observed in patients without vertebral/femur fracture (37.8%) vs. those with fracture (32.9%). Rheumatoid arthritis, dyslipidemia and previous fracture were associated with a lower risk of VD interruption, while stroke increased the risk of VD interruption. Our results highlight that a possible misinterpretation of newly introduced criteria for reimbursement restrictions in VD outside of osteoporosis have resulted in an inadequate level of VD supplementation in patients with osteoporosis. This undertreatment could reduce the effect of osteoporosis therapies leading to increased risk of negative outcome.

Fractures and vascular calcifications (VCs) are common in patients with chronic kidney disease (CKD). They are related to abnormalities in vitamin D metabolism, calcium, phosphorus, parathyroid hormone, and fibroblast growth factor 23 (FGF23)/Klotho that occur with CKD. Impaired vitamin D metabolism and abnormal levels of calcium, phosphate, parathyroid hormone (PTH), and FGF23/Klotho drive bone and vascular changes in CKD. It is unclear if oral calcitriol safely mitigates fracture risk without increasing the burden of calcifications. Therefore, we investigated whether treatment with calcitriol affected the prevalence of fractures and VC progression in hemodialysis (HD) patients. This report is a secondary analysis of the Vitamin K Italian (VIKI) study, a cross-sectional study involving 387 HD patients. We assessed vitamin 25(OH)D, alkaline phosphatase, PTH, calcium, phosphate, osteocalcin or bone Gla protein, matrix Gla protein, and vitamin K levels. Vertebral fractures (VFs) and VCs were determined by spine radiograph. A reduction of >20% of vertebral body height was considered a VF. VCs were quantified by the length of calcific lesions along the arteries. The patients treated with oral calcitriol were 177 of 387 patients (45.7%). The prevalence of VF was lower in patients receiving oral calcitriol than in those untreated (48.6% versus 61.0%, p = 0.015), whereas the presence of aortic and iliac calcifications was similar (aortic: 81.9% versus 79.5%, respectively, p = 0.552; iliac: 52.0% and 59.5%, respectively, p = 0.167). In multivariable logistic regression analysis, oral calcitriol was associated with a 40.2% reduced odds of fracture (OR 0.598; 95% confidence interval [CI], 0.363-0.985; p = 0.043). In conclusion, we found a significant association between oral calcitriol and lower VF in HD patients without an increase in the burden of VC. Further prospective and interventional studies are needed to confirm these findings. © 2021 American Society for Bone and Mineral Research (ASBMR)., (© 2021 American Society for Bone and Mineral Research (ASBMR).)

Background: It is believed that HPV infection can result in the death of placental trophoblasts and cause miscarriages or preterm birth. In clinical cases of placental villi positive for HPV DNA reported by other authors, contamination is suspected in the act of crossing the cervical canal. We analyzed placental samples of women who resorted to elective abortion obtained by hysterosuction of ovular material, bypassing any contact with the cervical canal and vagina., Methods: We studied the chorionic villi of the placenta of 64 women who resorted to voluntary termination of pregnancy, in the first trimester. To avoid contamination of the villi by the cervical canal, we analyzed placental samples obtained by hysterosuction of ovular material, bypassing any contact with the cervical canal and vagina. All samples of chorionic villi were manually selected from the aborted material and subjected to research for HPV DNA., Results: HPV DNA was detected in 10 out of 60 women (16.6%). The HPV DNA identified in the placenta belonged to genotypes 6, 16, 35, 53, and 90., Conclusion: The study shows that papillomavirus DNA can infect the placenta and that placenta HPV infection can occur as early as the first trimester of pregnancy.

Background: Transplantation (Tx) is an effective therapeutic option in patients with end-stage organ failure and osteoporosis and related fractures are a recognized complication in these patients. Aim of this study was to evaluate the efficacy of neridronate in patients with reduced bone mass after Tx of the heart, liver or lung., Methods: In this multicenter randomized double-blind controlled trial (RCT), 22 patients were treated with neridronate (25 mg i.m./month) and 17 received placebo. All patients received daily oral calcium (500 mg) and vitamin D (400 IU). Dual-energy X-ray absorptiometry (DXA) was evaluated at 0, 6 and 12 months and markers of bone turnover at 0, 3, 6, 9 and 12 months., Results: Thirty-nine patients (11 heart Tx, 21 liver Tx, 7 lung Tx), aged 49.3±9.1 years, with a T-score <-2.0 SD at lumbar spine or femoral level were included. In neridronate-treated patients, a significant increase in lumbar bone mineral density (BMD) was observed after 12 months vs. placebo control (0.92±0.13 g/cm 2 vs. 0.84±0.08 g/cm 2 ; P=0.005). Femur and hip BMD remained unchanged between groups. Total alkaline phosphatase, bone alkaline phosphatase and beta-cross-laps significantly decreased over the 12 months in neridronate-treated patients vs. placebo, respectively (107.4±74 U/L vs. 157.6±107.1 U/L, P=0.002; 5.7±3.3 µg/L vs. 11.7±4.3 µg/L, P<0.001 and 0.25±0.13 ng/mL vs. 0.73±0.57 ng/mL, P<0.001). No difference was observed between neridronate and placebo groups regarding safety profile., Conclusions: This is the first RCT that demonstrates the efficacy of neridronate in increasing bone density and reducing bone turnover in organ Tx recipients with significant skeletal morbidity.

Background and Aim: Lung ultrasound (LUS) is a convenient imaging modality in the setting of coronavirus disease-19 (COVID-19) because it is easily available, can be performed bedside and repeated over time. We herein examined LUS patterns in relation to disease severity and disease stage among patients with COVID-19 pneumonia., Methods: We performed a retrospective case series analysis of patients with confirmed SARS-CoV-2 infection who were admitted to the hospital because of pneumonia. We recorded history, clinical parameters and medications. LUS was performed and scored in a standardized fashion by experienced operators, with evaluation of up to 12 lung fields, reporting especially on B-lines and consolidations., Results: We included 96 patients, 58.3% men, with a mean age of 65.9 years. Patients with a high-risk quick COVID-19 severity index (qCSI) were older and had worse outcomes, especially for the need for high-flow oxygen. B-lines and consolidations were located mainly in the lower posterior lung fields. LUS patterns for B-lines and consolidations were significantly worse in all lung fields among patients with high versus low qCSI. B-lines and consolidations were worse in the intermediate disease stage, from day 7 to 13 after onset of symptoms. While consolidations correlated more with inflammatory biomarkers, B-lines correlated more with end-organ damage, including extrapulmonary involvement., Conclusions: LUS patterns provide a comprehensive evaluation of patients with COVID-19 pneumonia that correlated with severity and dynamically reflect disease stage. LUS patterns may reflect different pathophysiological processes related to inflammation or tissue damage; consolidations may represent a more specific sign of localized disease, whereas B-lines seem to be also dependent upon generalized illness due to SARS-CoV-2 infection.

Little information is available on the beneficial effects of cholecalciferol treatment in comorbid patients hospitalized for COVID-19. The aim of this study was to retrospectively examine the clinical outcome of patients receiving in-hospital high-dose bolus cholecalciferol. Patients with a positive diagnosis of SARS-CoV-2 and overt COVID-19, hospitalized from 15 March to 20 April 2020, were considered. Based on clinical characteristics, they were supplemented (or not) with 400,000 IU bolus oral cholecalciferol (200,000 IU administered in two consecutive days) and the composite outcome (transfer to intensive care unit; ICU and/or death) was recorded. Ninety-one patients (aged 74 ± 13 years) with COVID-19 were included in this retrospective study. Fifty (54.9%) patients presented with two or more comorbid diseases. Based on the decision of the referring physician, 36 (39.6%) patients were treated with vitamin D. Receiver operating characteristic curve analysis revealed a significant predictive power of the four variables: (a) low (<50 nmol/L) 25(OH) vitamin D levels, (b) current cigarette smoking, (c) elevated D-dimer levels (d) and the presence of comorbid diseases, to explain the decision to administer vitamin D (area under the curve = 0.77, 95% CI: 0.67-0.87, p < 0.0001). Over the follow-up period (14 ± 10 days), 27 (29.7%) patients were transferred to the ICU and 22 (24.2%) died (16 prior to ICU and six in ICU). Overall, 43 (47.3%) patients experienced the combined endpoint of transfer to ICU and/or death. Logistic regression analyses revealed that the comorbidity burden significantly modified the effect of vitamin D treatment on the study outcome, both in crude ( p = 0.033) and propensity score-adjusted analyses ( p = 0.039), so the positive effect of high-dose cholecalciferol on the combined endpoint was significantly amplified with increasing comorbidity burden. This hypothesis-generating study warrants the formal evaluation (i.e., clinical trial) of the potential benefit that cholecalciferol can offer in these comorbid COVID-19 patients.

Aims: We investigated whether pre-existing diabetes, newly-diagnosed diabetes, and admission hyperglycemia were associated with COVID-19 severity independently from confounders., Methods: We retrospectively analyzed data on patients with COVID-19 hospitalized between February and April 2020 in an outbreak hospital in North-East Italy. Pre-existing diabetes was defined by self-reported history, electronic medical records, or ongoing medications. Newly-diagnosed diabetes was defined by HbA1c and fasting glucose. The primary outcome was a composite of ICU admission or death., Results: 413 subjects were included, 107 of whom (25.6%) had diabetes, including 21 newly-diagnosed. Patients with diabetes were older and had greater comorbidity burden. The primary outcome occurred in 37.4% of patients with diabetes compared to 20.3% in those without (RR 1.85; 95%C.I. 1.33-2.57; p < 0.001). The association was stronger for newly-diagnosed compared to pre-existing diabetes (RR 3.06 vs 1.55; p = 0.004). Higher glucose level at admission was associated with COVID-19 severity, with a stronger association among patients without as compared to those with pre-existing diabetes (interaction p < 0.001). Admission glucose was correlated with most clinical severity indexes and its association with adverse outcome was mostly mediated by a worse respiratory function., Conclusion: Newly-diagnosed diabetes and admission hyperglycemia are powerful predictors of COVID-19 severity due to rapid respiratory deterioration., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Nowadays, computer experiments are used increasingly more to solve complex engineering and technological issues. Computer experiments are analysed through suitable metamodels acting as statistical interpolators of the simulated input-output data: Kriging is the most appropriate and widely used one. We optimise the braking performance of freight trains through computer experiments and Kriging modelling by focussing on the payload distribution along the train, so as to reduce the effects of in-train forces among wagons during a train emergency braking. One contribution of this manuscript is that to improve the freight train efficiency in terms of braking performance, we consider that the train is composed of several train sections with each one characterised by its own overall payload. A suitable Latin hypercube design is planned for the computer experiment that achieves excellent space-filling properties with a relatively low number of experimental runs. Kriging models with anisotropic covariance function are subsequently applied to assess which is the best payload distribution capable of reducting the in-train forces according to the specific train-set arrangement considered. The results are very satisfactory and confirm that our approach represents a valid method to be successfully applied by interested Railway Undertakings., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2020 Informa UK Limited, trading as Taylor & Francis Group.)

Lean Management and Six Sigma are nowadays applied not only to the manufacturing industry but also to service industry and public administration. The manifold variables affecting the Health Care system minimize the effect of a narrow Lean intervention. Therefore, this paper aims to discuss a comprehensive, system-based approach to achieve a factual holistic optimization of patient flows. This paper debates the efficacy of Lean principles applied to the optimization of patient flows and related activities, structures, and resources, developing a theoretical framework based on the principles of the Axiomatic Design. The demand for patient-oriented and efficient health services leads to use these methodologies to improve hospital processes. In the framework, patients with similar characteristics are clustered in families to achieve homogeneous flows through the value stream. An optimization checklist is outlined as the result of the mapping between Functional Requirements and Design Parameters, with the right sequence of the steps to optimize the patient flow according to the principles of Axiomatic Design. The Axiomatic Design-based top-down implementation of Health Care evidence, according to Lean principles, results in a holistic optimization of hospital patient flows, by reducing the complexity of the system.

Background: Regular treatment with inhaled corticosteroids (ICS) is known to reduce airway hyperresponsiveness (AHR) to adenosine 5'-monophosphate (AMP) in asthma even after a single dose of fluticasone propionate (FP)., Aim: To determine whether this rapid protective effect of a single dose of FP is also present in COPD., Methods: 23 mild asthmatic and 24 COPD subjects with documented AHR to both AMP and methacholine took part in a randomized, double-blind, placebo-controlled, crossover study to measure AHR to inhaled AMP and methacholine 2 h after either 1000 μg FP or matched placebo., Results: In subjects with asthma, 1000 μg FP in a single dose significantly attenuated the constrictor response to AMP, geometric mean (range) PC20AMP values increasing from a 19.2 (1.3-116.3) to 81.5 (9.6-1600.0) (p < 0.001; post-placebo vs post-FP) mg/ml. Change in the airways response to inhaled AMP after FP was well within test variability in patients with COPD, with PC20AMP values 59.6 (11.3-183.9) and 76.3 (21.0-445.3) (p = 0.022; post-placebo vs post-FP) mg/ml. Additionally, FP failed to significantly attenuate the bronchial response to methacholine in both asthma and COPD subjects. A change in doubling dilution, between placebo and following a single dose of FP, in AMP had a better sensitivity and specificity of 95.8% and 65.2%, compared to methacholine of 79.2% and 43.5% respectively in delineating between COPD and asthma., Conclusion: A single dose of 1000 μg FP rapidly improves AHR to AMP in asthmatics but not in COPD subjects. This may provide a convenient way by which provocation challenge with inhaled AMP may help in discriminating asthma from COPD., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Smoking-cessation drugs are inadequate at addressing the behavioural component of tobacco dependence. Nicotine-free inhalators are plastic devices that may provide a coping mechanism for conditioned smoking by replacing some of the rituals associated with smoking gestures. This study assessed the effect of using a nicotine-free inhalator to improve success in a cessation programme. At baseline, 120 smokers attending a smoking-cessation programme were assessed for their sociodemographic factors, smoking history, depression, physical and behavioural dependence, and motivation. Participants were randomly assigned to two groups, nicotine-free inhalator group (PAIPO; Echos Srl, Milan, Italy) versus reference group. For the whole sample, no significant difference was found in quit rates at 24 weeks between the PAIPO group and the reference group. However, the quit rate in the PAIPO group (66.7%) was more than three-fold higher than the reference group (19.2%) for those individuals with high Glover-Nilsson Smoking Behavioural Questionnaire (GN-SBQ) scores at baseline. The results of the logistic model analysis indicate that a high GN-SBQ score is a strong independent predictor for successful quitting at 24 weeks (OR 8.88; 95% CI 2.08-37.94) in the PAIPO group. Nicotine-free inhalators may be beneficial when used in the context of smoking-cessation interventions, particularly for those smokers for whom handling and manipulation of their cigarettes plays an important part in the ritual of smoking.

Endothelial activation/injury following exposure to cigarette smoke may explain incidence of atherosclerosis and cardiovascular disease in smokers. We investigated cigarette smoke extract (CSE) effects relative to activation, injury, and survival of human umbilical vein endothelial cells (HUVEC) and compared circulating levels of specific endothelial activation markers between smokers and healthy non-smokers before and after smoking cessation. Viability and toxicity of HUVEC were tested by MTT and LDH assay. Release (by endothelial cells) and circulating levels (in smokers) of von Willebrand Factor (vWF), thrombomodulin (TM), was evaluated by ELISA. Incubation with increasing concentrations of CSE reduced the percentage of viable cells, being 33.9%, 23.9% after CSE 4%, 6% respectively. Dose- and time-dependent release of LDH was observed after incubation with CSE. vWF, TM release were assayed after CSE 2% HUVEC stimulation. Significant 42%, 61%, 76% increase in vWF concentration was detected respectively at 30', 60', 120'. Reduction in circulating levels of vWF, from a median value of 144.0% to 123.7%, was observed in the quitters group after smoking cessation. Exposure to cigarette smoke is cytotoxic and induces activation/injury of endothelium in vitro and in vivo. These findings may provide pathogenetic basis by which smoking can predispose to development of atherothrombosis and cardiovascular disease.

Background: Inhaled corticosteroids (ICS) are the most effective anti-inflammatory agents available for the treatment of asthma but they produce only modest effects on airway inflammation and non-specific bronchial hyperresponsiveness (BHR). However, little is known about the possibility that treatment with ICS might cause additional protection on BHR to inhaled tachykinins such as neurokinin A (NKA)., Objective: Therefore, we compared the effects of beclomethasone dipropionate (BDP) on the degree of BHR to inhaled histamine and NKA in a double-blind, controlled, cross-over study of asthmatic patients., Methods: Patients attended the laboratory before and after each 6 weeks treatment period to undertake concentration-response studies with histamine and NKA. Bronchial responsiveness to both funs was expressed as the provocative concentration producing a 20% decrease in FEV(1) from baseline (PC(20))., Results: BDP therapy attenuated the constrictor response to both agonists to a similar degree, their geometric mean (range) PC(20) values increasing from 0.47 (0.21-1.41) mg/ml to 2.43 (0.51-4.50) mg/ml (P<0.01, post-salb vs. post-BDP treatment) and from 101.7 (27.3-356.1) microg/ml to 666.7 (151.5-1,000) microg/ml (P<0.01, post-salb vs. post-BDP treatment) for histamine and NKA, respectively., Conclusion: Airway responsiveness to histamine and NKA is reduced by BDP to the same extent. As a result of these findings, provocation with NKA is unlikely to provide additional useful information in the assessment of airway inflammation in asthma.

Interest in the role of adenosine in asthma has escalated considerably since the early observation of its powerful bronchoconstrictor effects in asthmatic but not normal airways. A growing body of evidence has emerged in support of a proinflammatory and immunomodulatory role for the purine nucleoside adenosine in the pathogenic mechanisms of chronic inflammatory disorders of the airways such as asthma. The fact that adenosine enhances mast cell allergen-dependent activation, that elevated levels of adenosine are present in chronically inflamed airways, and that adenosine given by inhalation cause dose-dependent bronchoconstriction in subjects with asthma emphasizes the importance of adenosine in the initiation, persistence and progression of these common inflammatory disorders of the airways. These distinctive features of adenosine have been recently exploited in the clinical and research setting to identify innovative diagnostic applications for asthma. In addition, because adenosine exerts its multiple biological activities by interacting with four adenosine receptor subtypes, selective activation or blockade of these receptors may lead to the development of novel therapies for asthma.