Conformational response to ligand binding of TMPRSS2, a protease involved in SARS-CoV-2 infection: Insights through computational modeling.

Thanks to the considerable research which has been undertaken in the last few years to improve our understanding of the biology and mechanism of action of SARS-CoV-2, we know how the virus uses its surface spike protein to infect host cells. The transmembrane prosthesis, serine 2 (TMPRSS2) protein, located on the surface of human cells, recognizes the cleavage site in the spike protein, leading to the release of the fusion peptide and entry of the virus into the host cells. Because of its role, TMPRSS2 has been proposed as a drug target to prevent infection by the virus. In this study, we aim to increase our understanding of TMPRSS2 using long scale microsecond atomistic molecular dynamics simulations, focusing on the conformational changes over time. The comparison between simulations conducted on the protein in the native (apo) and inhibited form (holo), has shown that in the holo form the inhibitor stabilizes the catalytic site and induces rearrangements in the extracellular domain of the protein. In turn, it leads to the formation of a new cavity in the vicinity of the ligand binding pocket that is stable in the microsecond time scale. Given the low specificity of known protease inhibitors, these findings suggest a new potential drug target site that can be used to improve TMPRSS2 specific recognition by newly designed inhibitors.

Quantitative ultrasound fatty liver evaluation in a pediatric population: comparison with magnetic resonance imaging of liver proton density fat fraction.

BACKGROUND: Biopsy remains the gold standard for the diagnosis of hepatic steatosis, the leading cause of pediatric chronic liver disease; however, its costs call for less invasive methods. OBJECTIVE: This study examined the diagnostic accuracy and reliability of quantitative ultrasound (QUS) for the assessment of liver fat content in a pediatric population, using magnetic resonance imaging proton density fat fraction (MRI-PDFF) as the reference standard. MATERIALS AND METHODS: We enrolled 36 patients. MRI-PDFF involved a 3-dimensional T2*-weighted with Dixon pulse multiple-echo sequence using iterative decomposition of water and fat with echo asymmetry and least squares estimation (IDEAL IQ). QUS imaging relied on the ultrasound system "RS85 A" (Samsung Medison, Seoul, South Korea) and the following software: Hepato-Renal Index with automated region of interest recommendation (EzHRI), Tissue Attenuation Imaging (TAI), and Tissue Scatter Distribution Imaging (TSI). For each QUS index, receiver operating characteristic (ROC) curve analysis against MRI-PDFF was used to identify the associated cut-off value and the area under the ROC curve (AUROC). Concordance between two radiologists was assessed by intraclass correlation coefficients (ICCs) and Bland-Altman analysis. RESULTS: A total of 61.1% of the sample (n=22) displayed a MRI-PDFF ≥ 5.6%; QUS cut-off values were TAI=0.625 (AUROC 0.90, confidence interval [CI] 0.77-1.00), TSI=91.95 (AUROC 0.99, CI 0.98-1.00) and EzHRI=1.215 (AUROC 0.98, CI 0.94-1.00). Inter-rater reliability was good-to-excellent for EzHRI (ICC 0.91, 95% C.I. 0.82-0.95) and TAI (ICC 0.94, 95% C.I. 0.88-0.97) and moderate to good for TSI (ICC 0.73; 95% C.I. 0.53-0.85). CONCLUSION: Our results suggest that QUS can be used to reliably assess the presence and degree of pediatric hepatic steatosis.

Effects of mealtime assistance in the nutritional rehabilitation of eating disorders.

PURPOSE: The aim of the study was to examine the effects of meal supervision, provided by health professionals, volunteers or family members, on anthropometric, nutritional, psychological, and behavioural outcomes in patients with eating disorders (EDs). METHODS: The present systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The last search was conducted in three databases (PubMed, Scopus, and the Cochrane library). Inclusion criteria considered paediatric and adult patients suffering from EDs, regardless of ethnicity, and treated in different therapeutic settings. The quality of the studies was evaluated using the Newcastle Ottawa Scale (NOS) adapted for cross-sectional studies and Version 2 of the Cochrane risk-of-bias assessment tool for randomised trials. RESULTS: 3282 articles were retrieved, out of which only 6 met the eligibility criteria. A marked heterogeneity in definitions and approaches to supervised mealtime was observed. This variability emerged in the methodologies used in the supervised meal, and in the reference values for the outcome measures that were used, such as the analysis of different parameters. Based on these observations, mealtime assistance provided to patients with EDs shows an overall positive effect on eating behaviour and dysfunctional attitudes. Future research should be prompted to provide a thorough definition of a structured procedure for meal assistance to be potentially and systematically included in the nutritional rehabilitation protocols for patients with EDs. LEVEL OF EVIDENCE: Level IV systematic reviews of uncontrolled trials.

SARS-CoV-2 Spike Protein Mutations and Escape from Antibodies: A Computational Model of Epitope Loss in Variants of Concern.

The SARS-CoV-2 spike (S) protein is exposed on the viral surface and is the first point of contact between the virus and the host. For these reasons it represents the prime target for Covid-19 vaccines. In recent months, variants of this protein have started to emerge. Their ability to reduce or evade recognition by S-targeting antibodies poses a threat to immunological treatments and raises concerns for their consequences on vaccine efficacy. To develop a model able to predict the potential impact of S-protein mutations on antibody binding sites, we performed unbiased multi-microsecond molecular dynamics of several glycosylated S-protein variants and applied a straightforward structure-dynamics-energy based strategy to predict potential changes in immunogenic regions on each variant. We recover known epitopes on the reference D614G sequence. By comparing our results, obtained on isolated S-proteins in solution, to recently published data on antibody binding and reactivity in new S variants, we directly show that modifications in the S-protein consistently translate into the loss of potentially immunoreactive regions. Our findings can thus be qualitatively reconnected to the experimentally characterized decreased ability of some of the Abs elicited against the dominant S-sequence to recognize variants. While based on the study of SARS-CoV-2 spike variants, our computational epitope-prediction strategy is portable and could be applied to study immunoreactivity in mutants of proteins of interest whose structures have been characterized, helping the development/selection of vaccines and antibodies able to control emerging variants.

Computational Studies of SARS-CoV-2 3CLpro: Insights from MD Simulations.

Given the enormous social and health impact of the pandemic triggered by severe acute respiratory syndrome 2 (SARS-CoV-2), the scientific community made a huge effort to provide an immediate response to the challenges posed by Coronavirus disease 2019 (COVID-19). One of the most important proteins of the virus is an enzyme, called 3CLpro or main protease, already identified as an important pharmacological target also in SARS and Middle East respiratory syndrome virus (MERS) viruses. This protein triggers the production of a whole series of enzymes necessary for the virus to carry out its replicating and infectious activities. Therefore, it is crucial to gain a deeper understanding of 3CLpro structure and function in order to effectively target this enzyme. All-atoms molecular dynamics (MD) simulations were performed to examine the different conformational behaviors of the monomeric and dimeric form of SARS-CoV-2 3CLpro apo structure, as revealed by microsecond time scale MD simulations. Our results also shed light on the conformational dynamics of the loop regions at the entry of the catalytic site. Studying, at atomic level, the characteristics of the active site and obtaining information on how the protein can interact with its substrates will allow the design of molecules able to block the enzymatic function crucial for the virus.

Macular degeneration: peculiar sunlight exposure in an agricultural worker.

BACKGROUND: Occupational exposure to sunlight, in particular to blue light (wavelength of 380-550 nm), is a risk factor for several pathologies, including chronic retinal photochemical damage and, more specifically, age-related macular degeneration (AMD). Moreover, in addition to the effect of blue light, there is evidence about the role of near ultraviolet light (UV-A) as a risk factor for AMD since, given the wavelength, a precise "turning point" between effect and no effect is not definable. METHODS AND RESULTS: This work reports the case of a woman employed in the agricultural sector from 15 to 25 years of age, with no significant occupational exposure to other risk factors for AMD, who later developed this pathology. The case is of particular interest given that she worked as a "mondina", a task involving the transplanting of young rice seedlings into water-flooded fields and manual weed control. This practice, although replaced by the introduction of pesticides, entailed the exposure to sunlight reflection on the water surface in addition to direct exposure to natural light. CONCLUSION: This brief case-report points out that occupational exposure to the short wavelength component of visible light and UV-A deserve further attention regarding preventive measures and the adoption of adequate personal protective equipment, in particular in productive sectors involving lengthy eye exposure to solar radiation and to the reflectance of surrounding surfaces. Furthermore, the cases of AMD and cataract should receive a complete and accurate occupational anamnesis for a more proper recognition of the possible role of occupational solar radiation exposure in the induction of the disease.

Control measurements for lasers in physiotherapy.

OBJECTIVES: In physical rehabilitation, is diffused the skin irradiation with near infrared laser at a fluence below 140 J/cm2, achieving a bio-stimulating effect that is due to the absorption of radiation in mitochondria rather than the simple heating of tissues. METHODS: In order to deliver radiation without thermal damage of the skin, are used radiation pulses which duration does not allow heat accumulation and propagation far from the irradiated target; this requires laser sources with average power below 10 W implying a safety classification as "potentially dangerous for eye and skin", or "class 4" according to the applicable international standards. In this paper, 6 laser therapy devices, of 5 different manufactures and models have been analyzed from the point of view of actual radiation output and user safety. In each case, one or more of the characteristic declared by the manufacturer in the user manual have been found different from the actual measured value. RESULTS: The actual accessible energy levels have been found to be complying with risk class 3B. The impact of the new version of the Standard IEC 60825-1 (2014), is also discussed, considering in particular the possible classification in the new class 1C, and the maximum permissible levels for pulsed lasers. CONCLUSIONS: An extension of the measurement protocols is proposed in order to assure effective and safe use of laser in physical therapy.

Oro-dental manifestations of eating disorders: a systematic review.

BACKGROUND: Eating disorders (EDs) pose a significant risk to health, especially when not diagnosed early. For several years EDs and oral health has been extensively studied, and now it is quite clear the existence of a correlation between specific oral manifestations and these disorders. While these oral signs could potentially aid early diagnosis of EDs, their identification and the eventual establishment of a correlation is currently heavily limited to the clinician's experience. The present systematic review critically examines existing literature, offering an updated overview of oro-dental manifestations associated with EDs. METHOD: MEDLINE (via PubMed), Web of Science, Scopus, and grey literature were searched, and relevant epidemiological comparative studies were screened using the Rayyan software. No limitations have been imposed on the research regarding oro-dental outcomes, encompassing all medically diagnosed EDs. The quality of the studies was valuated using AXIS appraisal tool for cross-sectional studies. RESULT: Out of 3990 studies, 32 fulfilled the eligibility criteria and were included in the synthesis. The identified eating disorders include Anorexia Nervosa, Bulimia Nervosa and/or Eating Disorders Not Otherwise Specified, predominantly among female subjects, primarily originating from Europe. The evaluated oro-dental outcomes include dental erosion, caries, saliva assessment, hygiene-periodontal parameters, and mucosal tissue appearance. The association with erosion is confirmed while gingival recession, dentinal hypersensitivity, salivary flow thresholds and aspects relating to oral pathology are receiving increasing support from emerging evidence. DISCUSSION: This trend emphasizes the critical role of the complete intraoral examination to detect significant oro-dental signs that may indicate the onset of an ED.

The article is a review of existing studies that explores the link between eating disorders and oral health issues. It found that people with eating disorders, including anorexia nervosa and bulimia nervosa, may experience dental problems such as tooth erosion, cavities, and altered saliva production. The review findings emphasize the importance of dental care providers recognizing these signs early and suggests better training for dental professionals. By doing so, they can help diagnose eating disorders sooner and recommend appropriate treatment. This approach aims to improve patients' overall wellbeing by addressing both the oral health issues and the underlying eating disorders, making it essential for patients and medical teams to be aware of the interconnectedness between oral health and eating disorders.

Food Compass and the challenge of sustainability on the route towards healthful diets.

In order to tackle the global increase in overweight and obesity prevalence, several nutrient profiling systems have been developed; among others, Food Compass Score (FCS) has been designed to encompass multiple domains of food healthfulness. However, environmental sustainability of healthy diets is another crucial dimension which should not be overlooked in the context of human health. The aim of the present study is to assess the association between healthiness and environmental sustainability of food items, using the FCS and Agribalyse databases, respectively. A total of 806 matching food items were identified, grouped in 12 food categories; within each category, differences in median Z-scores between FCS and Single Environmental Footprint (EF) Score were assessed. While Fruits, Legumes and Nuts, Mixed foods, Meat Poultry and Eggs (MPE), Savory and Sweets, and Vegetables showed statistically significant differences (all p < 0.001), Beverages (p = 0.361), Dairy (p = 0.092), Fats and Oils (p = 0.594), Grains (p = 0.436), Sauce and Condiments (p = 0.093), and Seafood (p = 0.241) had similar Food Compass and Single EF Z-scores distributions. These findings underscore a relevant lack of difference between healthfulness and environmental impact of some prominent food categories, such as Grains and Seafood. Therefore, we suggest matching nutrient profiling systems with adequate environmental sustainability indices.

[Experimental evaluation of the occupational exposure to static magnetic fields on a 3 T magnetic resonance scanner]. / Valutazione sperimentale dell'esposizione lavorativa ai compi magnetici statici prodotti da una risonanza magnetica da 3 T.

The recent postponement until 31 October 2013 of the deadline for transposition of the EU Directive 2004/40/EC, concerning the minimum health requirementsfor the exposure of workers to the risks arising from electromagnetic fields between 0 and 300 GHz, keeps on suspending the Italian law which was aimed to implement the EU regulations on the occupational exposure to electromagnetic fields, including those generated by Magnetic Resonance Imaging (MRI) units. Waiting for the revision of the exposure limits proposed by the EU Directive taking into account results from new studies and evolution of knowledge, the time-weighted values of static magnetic field proposed by the Italian Ministry of Health (D.M 02/08/91) still survive as limits for worker's exposure. The comparison between the proposed thresholds and the time required to position patients allows to calculate how long the MRI staff can stay at different values of static magnetic field, i.e. the maximum workload of each worker. In order to evaluate more accurately how many time the members of MRI staff are near the magnet bore and the real value of worker's exposure to the static magnetic field during the handling of patients, a teslameter Metrolab THM1176-PDA was used. Personal exposure measurements on the radiologists and the radiographers who worked on a 3 T GE Healthcare Discovery 750 MR were carried out during the positioning of self-sufficient and collaborative patients. The sensor was worn at the chest level on the side that was nearest to the magnet bore. Results show wide variations occurring between individual working procedures concerning the handling of patients, especially during the initial position phase. The mean values of the time spent by radiographers inside the magnet room (B > 0.5 mT) to place the patient and to take him outside at the end of the exam were respectively 220 and 127 seconds. The mean value of the time spent by radiologists was 162 seconds when they had to insert a peripheral vein access (arm) and inject contrast medium. The time fraction spent in magnetic flux density above 200 mT was near 31% for radiographers and about 7% for radiologists. The maximum of the static magnetic field recorded was 1550 mT for radiographers and 409 mT for radiologists. The measuring system has proven to be useful in evaluating the compliance with time weighted exposure limit stated by Italian law and also to find the maximum magnetic flux density to which the staff is actually exposed. This is the quantity of significance in evaluating workers' exposure following international guidelines.

The role of neighborhood inequalities on diabetes prevention care: a mini-review.

An emerging research niche has focused on the link between social determinants of health and diabetes mellitus, one of the most prevalent non-communicable diseases in modern society. The aim of the present mini-review is to explore and summarize current findings in this field targeting high-income countries. In the presence of disadvantaged neighborhood factors (including socioeconomic status, food environment, walkability and neighborhood aesthetics), diabetes prevention and care are affected at a multidimensional level. The vast majority of the included studies suggest that, besides individual risk factors, aggregated neighborhood inequalities should be tackled to implement effective evidence-based policies for diabetes mellitus.

Dynapenia, Muscle Quality, and Hepatic Steatosis in Patients with Obesity and Sarcopenic Obesity.

Accumulating evidence supports a connection between sarcopenic obesity (SO) and NAFLD. The extent to which fatty liver contributes to impaired muscle contractility is not yet well established. The aim of our study was to investigate the effect of NAFLD on dynapenia in patients with SO. In this study, 71 non-diabetic subjects (age 55 (7.8) years, BMI 35.2 kg/m2 (32.6-38.8)) were classified as having SO and non-sarcopenic obesity (NSO). SO patients displayed worse serum lipid profiles, higher body fat, and lower skeletal muscle mass (both total and appendicular) than NSO patients, despite the absence of any significant differences in body weight, glycometabolic parameters, and hepatic steatosis prevalence. A positive correlation between disposition index and muscle quality index (MQI) (r = 0.393, p = 0.013) emerged after controlling for menopause and body fat percentage. Based on multiple linear regression analysis, MQI was significantly positively associated with the disposition index (ß: 0.059, SE: 0.002, p = 0.006) after adjustment for menopause, body fat percentage, and the presence of hepatic steatosis according to the hepatorenal index (HRI). Similar findings emerged when including liver enzyme levels in place of hepatic steatosis. Muscle quality was positively associated with ß-cell function corrected for insulin resistance among patients with obesity and sarcopenic obesity, irrespective of the presence of fatty liver disease.

Digital Anthropometry: A Systematic Review on Precision, Reliability and Accuracy of Most Popular Existing Technologies.

Digital anthropometry (DA) has been recently developed for body composition evaluation and for postural analysis. The aims of this review are to examine the current state of DA technology, as well as to verify the methods for identifying the best technology to be used in the field of DA by evaluating the reliability and accuracy of the available technologies on the market, and lay the groundwork for future technological developments. A literature search was performed and 28 studies met the inclusion criteria. The reliability and accuracy of DA was high in most studies, especially in the assessment of patients with obesity, although they varied according to the technology used; a good correlation was found between DA and conventional anthropometry (CA) and body composition estimates. DA is less time-consuming and less expensive and could be used as a screening tool before more expensive imaging techniques or as an alternative to other less affordable techniques. At present, DA could be useful in clinical practice, but the heterogeneity of the available studies (different devices used, laser technologies, population examined, etc.) necessitates caution in the interpretation of the obtained results. Furthermore, the need to develop integrated technologies for analyzing body composition according to multi-compartmental models is increasingly evident.

How Much Do Front-Of-Pack Labels Correlate with Food Environmental Impacts?

Nutrient profiling and front-of-pack labeling (FOPL) have been developed to categorize food products as more or less healthy based on their nutrient content and to easily communicate this information to consumers. The goal is to change individual food choices toward a healthier diet. Since global climate change has recently become an urgent matter, this paper also aims to investigate the correlations between different food health scales, including some FOPLs currently adopted by one or more countries, and several sustainability indicators. For this purpose, a food sustainability composite index has been developed to summarize environmental indicators and compare food scales. Results indicate, as expected, that well-known healthy and sustainable diets are strongly correlated with both environmental indicators and the composite index, while FOPLs based on portions or on 100 g show moderate and weak correlation values, respectively. Within-category analysis has not found any associations that explain these results. Hence, 100 g standard, on which FOPLs are usually developed, seems not to be the ideal basis for developing a label that aspires to communicate healthiness and sustainability in a unique format, as required by the need for simple messaging. On the contrary, FOPLs based on portions appear to be more likely to achieve this goal.

Conformational Behavior of SARS-Cov-2 Spike Protein Variants: Evolutionary Jumps in Sequence Reverberate in Structural Dynamic Differences.

SARS-CoV-2 has evolved rapidly in the first 3 years of pandemic diffusion. The initial evolution of the virus appeared to proceed through big jumps in sequence changes rather than through the stepwise accumulation of point mutations on already established variants. Here, we examine whether this nonlinear mutational process reverberates in variations of the conformational dynamics of the SARS-CoV-2 Spike protein (S-protein), the first point of contact between the virus and the human host. We run extensive microsecond-scale molecular dynamics simulations of seven distinct variants of the protein in their fully glycosylated state and set out to elucidate possible links between the mutational spectrum of the S-protein and the structural dynamics of the respective variant, at global and local levels. The results reveal that mutation-dependent structural and dynamic modulations mostly consist of increased coordinated motions in variants that acquire stability and in an increased internal flexibility in variants that are less stable. Importantly, a limited number of functionally important substructures (the receptor binding domain, in particular) share the same time of movements in all variants, indicating efficient preorganization for functional regions dedicated to host interactions. Our results support a model in which the internal dynamics of the S-proteins from different strains varies in a way that reflects the observed random and non-stepwise jumps in sequence evolution, while conserving the functionally oriented traits of conformational dynamics necessary to support productive interactions with host receptors.

Molecular mechanisms of chaperone-directed protein folding: Insights from atomistic simulations.

Molecular chaperones, a family of proteins of which Hsp90 and Hsp70 are integral members, form an essential machinery to maintain healthy proteomes by controlling the folding and activation of a plethora of substrate client proteins. This is achieved through cycles in which Hsp90 and Hsp70, regulated by task-specific co-chaperones, process ATP and become part of a complex network that undergoes extensive compositional and conformational variations. Despite impressive advances in structural knowledge, the mechanisms that regulate the dynamics of functional assemblies, their response to nucleotides, and their relevance for client remodeling are still elusive. Here, we focus on the glucocorticoid receptor (GR):Hsp90:Hsp70:co-chaperone Hop client-loading and the GR:Hsp90:co-chaperone p23 client-maturation complexes, key assemblies in the folding cycle of glucocorticoid receptor (GR), a client strictly dependent upon Hsp90/Hsp70 for activity. Using a combination of molecular dynamics simulation approaches, we unveil with unprecedented detail the mechanisms that underpin function in these chaperone machineries. Specifically, we dissect the processes by which the nucleotide-encoded message is relayed to the client and how the distinct partners of the assemblies cooperate to (pre)organize partially folded GR during Loading and Maturation. We show how different ligand states determine distinct dynamic profiles for the functional interfaces defining the interactions in the complexes and modulate their overall flexibility to facilitate progress along the chaperone cycle. Finally, we also show that the GR regions engaged by the chaperone machinery display peculiar energetic signatures in the folded state, which enhance the probability of partial unfolding fluctuations. From these results, we propose a model where a dynamic cross-talk emerges between the chaperone dynamics states and remodeling of client-interacting regions. This factor, coupled to the highly dynamic nature of the assemblies and the conformational heterogeneity of their interactions, provides the basis for regulating the functions of distinct assemblies during the chaperoning cycle.

New Advances in Metabolic Syndrome, from Prevention to Treatment: The Role of Diet and Food.

The definition of metabolic syndrome (MetS) has undergone several changes over the years due to the difficulty in establishing universal criteria for it. Underlying the disorders related to MetS is almost invariably a pro-inflammatory state related to altered glucose metabolism, which could lead to elevated cardiovascular risk. Indeed, the complications closely related to MetS are cardiovascular diseases (CVDs) and type 2 diabetes (T2D). It has been observed that the predisposition to metabolic syndrome is modulated by complex interactions between human microbiota, genetic factors, and diet. This review provides a summary of the last decade of literature related to three principal aspects of MetS: (i) the syndrome's definition and classification, pathophysiology, and treatment approaches; (ii) prediction and diagnosis underlying the biomarkers identified by means of advanced methodologies (NMR, LC/GC-MS, and LC, LC-MS); and (iii) the role of foods and food components in prevention and/or treatment of MetS, demonstrating a possible role of specific foods intake in the development of MetS.

Indoor noise level measurements and subjective comfort: Feasibility of smartphone-based participatory experiments.

We designed and performed a participatory sensing initiative to explore the reliability and effectiveness of a distributed network of citizen-operated smartphones in evaluating the impact of environmental noise in residential areas. We asked participants to evaluate the comfort of their home environment in different situations and at different times, to select the most and least comfortable states and to measure noise levels with their smartphones. We then correlated comfort ratings with noise measurements and additional contextual information provided by participants. We discuss how to strengthen methods and procedures, particularly regarding the calibration of the devices, in order to make similar citizen-science efforts effective at monitoring environmental noise and planning long-term solutions to human well-being.

Modelling infrared radiation exposure by black body-like sources.

In this work, a method previously proposed in the literature (Sisto R, Pinto I, Stacchini N et al. Infrared radiation exposure in traditional glass factories. AIHAJ 2000; 61: 5-10) to evaluate the exposure to infrared (IR) radiation when the source can be approximated as a black body is implemented in a mathematical code developed in Matlab. Some practical situations are discussed. A comparison between the results obtained by a spectroradiometric technique and that obtained by using a broadband radiometer and the modelling of the source is shown. The IR radiation exposure evaluations in a cement industry and in a steel forge are shown and compared to the exposure limit values.

[Preliminary analysis of indoor pollution from nitrogen dioxide in an area of Northern Italy]. / Analisi preliminare dell'inquinamento indoor da biossido di azoto in un'area del Nord Italia.

OBJECTIVE: The aims of this work are to describe the annual mean concentration of NO2 and to identify the home features and "habits" of its occupants related to NO2 levels. Both indoor and outdoor NO2 concentrations were measured in 114 dwellings in Pavia (Northern Italy). DESIGN: The study is in the frame of European Community Respiratory Health Survey II. Data were collected in the period 2001-2002 during home visits by trained fieldworkers. PARTICIPANTS: 116 subjects gave the consent to home visits. MAIN OUTCOME MEASURE: NO2 concentration measured using passive samplers. RESULTS: Indoor NO2 concentration is in average 47.1 microg/m3 (+/- 24.5 microg/m3) and outdoor NO2 concentration is 44.3 microg/m3 (+/- 14.5 microg/m3). The gas oven is the only domestic gas appliance associate with high levels of NO2 when measuring in homes. The outdoor pollution affects NO2 indoor concentrations and contribute to store NO2 in homes. CONCLUSION: the study is the first step in the evaluation of NO2 exposure effect on respiratory health.