Impact of the environment on the health: From theory to practice.

The Erice 56 Charter titled "Impact of the environment on the health: from theory to practice" was unanimously approved at the end of the 56th course of the "International School of Epidemiology and Preventive Medicine G. D'Alessandro" held from 3rd to November 7, 2019 in Erice - Sicily (Italy) and promoted by the Study Group of "Environment and Health" of the Italian Society of Hygiene, Preventive Medicine and Public Health. The course, that included lectures, open discussions and guided working groups, was aimed to provide a general training on epidemiological and toxicological aspects of the environmental health impact, to be used by public health professionals for risk assessment, without forgetting the risk communications. At the end of the course 12 key points were agreed among teachers and students: they underlined the need of specific training and research, in the perspective of "One Health" and "Global Health", also facing emerging scientific and methodological issues and focusing on communication towards stakeholders. This Discussion highlight the need to improve knowledge of Health and Environment topic in all sectors of health and environmental prevention and management.

From building regulations and local health rules to the new local building codes: a national survey in Italy on the prescriptive and performance requirements for a new performance approach.

BACKGROUND: World Health Organization has highlighted the need to strengthen the relationship between health and built environment factors, such as inappropriate housing conditions. Building Regulations and Local Health Rules provide safety and building hygiene in construction practices. Currently the Italian Government is giving rise to a Building Regulation Type and the paper aims to verify the present contents of recent innovative Local Health Rules and Building Regulations of several Italian municipalities for supporting the performance approach of the future Building Regulations including hygienic issues. METHODS: The analysis examines both Building Regulations and Local Health Rules of a sample of about 550 cities, analysing some specific fields of interest: urban field, outdoor issues, housing features, housing restrictions, and qualitative aspects. RESULTS: The analysis focuses on some specific aspects defining the general data reported in Building Regulations and Local Health Rules, in particular around surfaces, heights, lighting and aeration ratio, basements and semi-basements, gas radon, building greenery, etc. CONCLUSION: The investigation permitted to have a wide vision on the present State of the Art in order to highlight some innovative aspects and design approaches of Building Regulations and Local Health Rules. New perspectives in the new regulations should have a performance approach, starting also from the recent SARS-CoV-2 pandemic.

A proposal of hygienic and sanitary standards for the new Building Code in Italy.

The traditional emphasis of Public Health on the type and quality of housing today merges with other wider determinants of health such as: the neighbourhood, the community and the "place" where a home is located, but also the policies that make access to a healthy home within everyone's reach. At the neighbourhood scale, context-related aspects heavily influence the internal quality and real usability of the buildings themselves, with particular reference to factors such as the quality of the site, the relationship between the building and the context, the presence and quality of the greenery and open spaces surrounding the building, as well as all measures that make it possible to reduce the building's impact on the environment, to protect it against environmental pollution, and to manage the building in an integrated manner for maintenance purposes. Creating healthy living environments means referring to the different dimensions mentioned above, and this not only requires the attention of Public Health operators, but also implies an integration of vision and objectives among various professional skills and competences that puts health at the center of all policies. This proposal, which starts from the analysis of existing local hygiene regulations and scientific literature, aims to take stock of a number of areas considered fundamental for the assessment of building hygiene aspects, with particular reference to the eco-sustainability of buildings and adaptation to climate change. The aspects identified can be considered as a starting point for the preparation of integrated building and hygiene regulations based on documented effective practices for the protection of Public Health.

Strategies for Disease Prevention and Health Promotion in Urban Areas: The Erice 50 Charter.

The Erice 50 Charter titled "Strategies for Diseases Prevention and Health Promotion in Urban Areas" was unanimously approved at the conclusion of the 50th Residential Course "Urban Health. Instruments for promoting health and for assessing hygienic and sanitary conditions in urban areas", held from 29th March to 2nd April 2017 in Erice, at the "Ettore Majorana" Foundation and Centre for Scientific Culture and promoted by the International School of Epidemiology and Preventive Medicine "G. D'Alessandro" and the Study Group "Building Hygiene" of the Italian Society of Hygiene, Preventive Medicine and Public Health (SItI). At the conclusion of the intense learning experience during the Course, with more than 20 lectures, workshops and long-lasting discussions between Professors and Students, the participants identified the major points connecting urban features and Public Health, claiming the pivotal role of urban planning strategies for the management of Diseases Prevention and Health Promotion activities. The Erice 50 Charter is configured as a Decalogue for Healthy Cities and as a Think Tank for designing effective strategic actions and best practices to develop urban regeneration interventions and improve the urban quality of contemporary cities. The Decalogue is structured into the following key strategic objectives: 1. Promoting urban planning interventions that address citizens towards healthy behaviours; 2. Improving living conditions in the urban context; 3. Building an accessible and inclusive city, with a special focus on the frail population; 4. Encouraging the foundation of resilient urban areas; 5. Supporting the development of new economies and employment through urban renewal interventions; 6. Tackling social inequalities; 7. Improving stakeholders' awareness of the factors affecting Public Health in the cities; 8. Ensuring a participated urban governance; 9. Introducing qualitative and quantitative performance tools, capable of measuring the city's attitude to promote healthy lifestyles and to monitor the population's health status; 10. Encouraging sharing of knowledge and accessibility to informations. Finally, all the participants underlined that a multidisciplinary team, composed of Physicians specialized in Hygiene, Preventive Medicine, Public Health and Technicians as Architects, Urban planners and Engineers, is needed to deepen the research topic of Urban Health.

The Effect of High-Mobility Group Box 1 in Rat Steatotic and Nonsteatotic Liver Transplantation From Donors After Brain Death.

High-mobility group box 1 (HMGB1) has been described in different inflammatory disorders, and the deleterious effects of brain death (BD) may counteract the protection conferred by ischemic preconditioning (IP), the only surgical strategy that is being applied in clinical liver transplantation. Our study examined how HMGB1 may affect preconditioned and unpreconditioned steatotic and nonsteatotic liver grafts from donors after BD (DBDs) for transplantation. HMGB1 was pharmacologically modulated in liver grafts from DBDs, and HMGB1-underlying mechanisms were characterized. We found that BD decreased HMGB1 in preconditioned and unpreconditioned livers and was associated with inflammation and damage. Exogenous HMGB1 in DBDs activates phosphoinositide-3-kinase and Akt and reduces hepatic inflammation and damage, increasing the survival of recipients. Combination of IP and exogenous HMGB1 shows additional benefits compared with HMGB1 alone. This study provides new mechanistic insights into the pathophysiology of BD-derived liver graft damage and contributes to the development of novel and efficient strategies to ultimately improve liver graft quality.

[Exceptions to hygienic requirements of dwellings in building restoration and indemnity for abuses in Italy]. / Le deroghe ai requisiti igienico-sanitari nel recupero e nelle sanatoria di civili abitazioni in Italia.

Building restoration represents a fundamental tool to combine the population needs for housing with soil saving. Old buildings offer great possibilities, if we consider that 20% of residential buildings in Italy have been constructed before the beginning of XX century. In order to understand the public health impact of exemptions from hygienic requirements of dwellings, as well as indemnity for abuses, the authors analyse the national legislation on this topic. There is a strong need to update health standards and to rationalize and simplify the regulations, as a fundamental tool for the protection of public health in indoor environment.

Inhibition of lysozyme by taurine dibromamine.

Hypobromous acid (HOBr) is a powerful oxidant produced by stimulated neutrophils and eosinophils. Taurine, a non-protein amino acid present in high amounts in the leukocytes, reacts instantaneously with HOBr leading to their haloamine derivative taurine dibromamine (Tau-NBr2). Lysozyme is a bactericidal enzyme also present in leukocytes and in secretory fluids. The inhibition of lysozyme is a pathway for bacterial proliferation in inflammatory sites. Here, we investigated the inhibition of the enzymatic activity of lysozyme when it was submitted to oxidation by Tau-NBr2. We found that the oxidation of lysozyme by Tau-NBr2 decreased its enzymatic activity in 80%, which was significant higher compared to the effect of its precursor HOBr (30%). The study and comparison of Tau-NBr2 and HOBr regarding the alterations provoked in the intrinsic fluorescence, synchronous fluorescence, resonance light scattering and near and far-UV circular dichroism spectra of lysozyme and oxidized lysozyme revealed that tryptophan residues in the active site of the protein were the main target for Tau-NBr2 and could explain its efficacy as inhibitor of lysozyme enzymatic activity. This property of Tau-NBr2 may have pathological significance, since it can be easily produced in the inflammatory sites.

Antibacterial activity of alkyl gallates against Xanthomonas citri subsp. citri.

The plant-pathogenic bacterium Xanthomonas citri subsp. citri is the causal agent of Asiatic citrus canker, a serious disease that affects all the cultivars of citrus in subtropical citrus-producing areas worldwide. There is no curative treatment for citrus canker; thus, the eradication of infected plants constitutes the only effective control of the spread of X. citri subsp. citri. Since the eradication program in the state of São Paulo, Brazil, is under threat, there is a clear risk of X. citri subsp. citri becoming endemic in the main orange-producing area in the world. Here we evaluated the potential use of alkyl gallates to prevent X. citri subsp. citri growth. These esters displayed a potent anti-X. citri subsp. citri activity similar to that of kanamycin (positive control), as evaluated by the resazurin microtiter assay (REMA). The treatment of X. citri subsp. citri cells with these compounds induced altered cell morphology, and investigations of the possible intracellular targets using X. citri subsp. citri strains labeled for the septum and centromere pointed to a common target involved in chromosome segregation and cell division. Finally, the artificial inoculation of citrus with X. citri subsp. citri cells pretreated with alkyl gallates showed that the bacterium loses the ability to colonize its host, which indicates the potential of these esters to protect citrus plants against X. citri subsp. citri infection.

Protocatechuic acid alkyl esters: hydrophobicity as a determinant factor for inhibition of NADPH oxidase.

This study presents the increased efficiency of NADPH oxidase inhibition produced by esterification of protocatechuic acid (P0). Alkyl esters bearing chain lengths of 4 (P4), 7 (P7) and 10 (P10) carbons were synthesized and their oxidation potential, hydrophobicity, antiradical activity, inhibition of superoxide anion (O2°(-)), and the abilities to affect hypochlorous acid (HOCl) production by leukocytes and inhibit myeloperoxidase (MPO) chlorinating activity were studied. The increased hydrophobicity (logP, 0.81-4.82) of the esters was not correlated with a significant alteration in their oxidation potential (0.222-0.298 V). However, except for P10, the esters were ~ 2-fold more effective than the acid precursor for the scavenging of DPPH and peroxyl radicals. The esters were strong inhibitors of O2°(-) released by activated neutrophils (PMNs) and peripheral blood mononuclear cells (PBMCs). A correlation was found between the carbon chain length and the relative inhibitory potency. P7, the most active ester, was ~ 10-fold more efficient as NADPH oxidase inhibitor than apocynin. The esters strongly inhibited the release of HOCl by PMNs, which was a consequence of the inhibition of NADPH oxidase activity in these cells. In conclusion, as effective inhibitors of NADPH oxidase, the esters of protocatechuic acid are promising drugs for treatment of chronic inflammatory diseases. Moreover, this is the first demonstration that, besides the redox active moiety, the hydrophobicity can also be a determinant factor for the design of NADPH oxidase inhibitors.

Alkyl hydroxybenzoic acid derivatives that inhibit HIV-1 protease dimerization.

The therapeutic potential of gallic acid and its derivatives as anti-cancer, antimicrobial and antiviral agents is well known. We have examined the mechanism by which natural gallic acid and newly synthesized gallic acid alkyl esters and related protocatechuic acid alkyl esters inhibit HIV-1 protease to compare the influence of the aromatic ring substitutions on inhibition. We used Zhang-Poorman's kinetic analysis and fluorescent probe binding to demonstrate that several gallic and protecatechuic acid alkyl esters inhibited HIV-1 protease by preventing the dimerization of this obligate homodimeric aspartic protease rather than targeting the active site. The tri-hydroxy substituted benzoic moiety in gallates was more favorable than the di-substituted one in protocatechuates. In both series, the type of inhibition, its mechanism and the inhibitory efficiency dramatically depended on the length of the alkyl chain: no inhibition with alkyl chains less than 8 carbon atoms long. Molecular dynamics simulations corroborated the kinetic data and propose that gallic esters are intercalated between the two N- and C-monomer ends. They complete the ß-sheet and disrupt the dimeric enzyme. The best gallic ester (14 carbon atoms, K(id) of 320 nM) also inhibited the multi-mutated protease MDR-HM. These results will aid the rational design of future generations of non-peptide inhibitors of HIV-1 protease dimerization that inhibit multi-mutated proteases. Finally, our work suggests the wide use of gallic and protocatechuic alkyl esters to dissociate intermolecular ß-sheets involved in protein-protein interactions.

[Environmental, social and demographic characteristics of children and adolescents, resident in different Italian areas]. / Caratteristiche demografiche, sociali e stili di vita della popolazione infantile in varie aree geografiche italiane.

The second phase of the SIDRIA study provides important information regarding the family characteristics of Italian children (6-7 years old) and adolescents (13-14 years old), and the frequency of risk factors for asthma and allergies, allowing comparisons between study areas according to differences in latitude (North, Centre, South) and urbanization level (metropolitan areas, with at least 500,000 inhabitants, and other areas). Parental education level was higher in metropolitan and central areas. The frequency of children and adolescents born abroad, and the percentage of mothers and fathers employed were higher outside metropolitan areas and there was an increase from the South to the North of Italy. This trend was paralleled by an increase in maternal age at child's birth and in the frequency of low birth weight and day care attendance. The frequency of breastfeeding was greater in children than in adolescents; the opposite was registered for passive smoking, with a frequency of exposure higher in adolescents than in children, especially in the Northern and Central areas, even if the proportion of subjects having at least one parent who smokes was still high in both age groups. The prevalence of overweight children was striking, especially in the South where physical activity was less frequent and children had the unhealthy habit of consuming a lot of snacks and carbonated beverages. Frequency of exposure to traffic in the area of residence was particularly high, especially in the metropolitan areas.

[Frequency of asthma and allergies in Italian children and adolescents: results from SIDRIA-2]. / La prevalenza di asma e allergie nei bambini e adolescenti italiani: i risultati del progetto SIDRIA-2.

The present study investigated the prevalences of asthma, allergic rhinitis (both to pollen and to other causes) and eczema in Italian children (6-7 yr old) and adolescents (13-14 yr old) in the second phase of SIDRIA (2002), aiming also to highlight geographical differences in the prevalence of the studied diseases. Prevalence of lifetime asthma is 9.3% in children and 10.3% in adolescents; lifetime prevalences of allergic rhinitis and eczema are 12.3% and 15.9% in children, 20.9% and 11.9% in adolescents. In both age groups, prevalence of lifetime asthma and lifetime and past 12 months wheezing was greater in central than in northern and southern areas. A similar situation was also seen for allergic rhinitis but not for eczema whose prevalence decreased between North to South of Italy. An excess in prevalence of lifetime asthma and rhinitis was found in metropolitan areas compared to other areas; prevalence of eczema did not show any difference by urbanization level. Prevalence of asthma and, only in children, prevalence of rhinitis symptoms was greater in males than in females. On the contrary, prevalence of eczema and, only in adolescents, prevalence of rhinitis symptoms was greater in females. Prevalence of childhood asthma, allergic rhinitis and eczema in Italy ranks intermediate with respect to other countries participating in ISAAC phase three.

Mould/dampness exposure at home is associated with respiratory disorders in Italian children and adolescents: the SIDRIA-2 Study.

AIMS: To report on the relation between home mould and/or dampness exposure and respiratory disorders in a large sample of children and adolescents in Italy, accounting for age at time of exposure. METHODS: 20,016 children (mean age 7 years) and 13,266 adolescents (mean age 13 years) completed questionnaires on indoor exposures and respiratory symptoms/diseases. Statistical analyses were adjusted for sex, age, questionnaire's compiler, area of residence, season of interview, parental educational status, family history of asthma, rhinitis, eczema, chronic obstructive pulmonary disease, presence of gas water heaters, passive smoking, pets, and active smoking (only for adolescents). Population attributable risk % (PAR) was also computed. RESULTS: Asthma was more strongly related to only early than to only current exposure, both in children (OR 1.80, 95% CI 1.41 to 2.30) and adolescents (OR 1.89, 95% CI 1.38 to 2.59). The same result was found for rhino-conjunctivitis (OR 1.46, 95% CI 1.17 to 1.82), in children, and for wheeze among adolescents (OR 1.56, 95% CI 1.15 to 2.11). In children, wheeze (OR 1.98, 95% CI 1.47 to 2.66) and eczema (OR 1.44, 95% CI 1.09 to 1.91) were more strongly related to mould/dampness when exposed both early and currently; the same occurred in adolescents for rhino-conjunctivitis (1.78, 95% CI 1.30 to 2.45). Although persistent cough/phlegm was significantly related to mould/dampness exposure in children, regardless of exposure timing, no significant association between mould/dampness exposure and eczema or cough/phlegm was found among adolescents. PAR estimates were higher for only early than only current exposures. Avoiding early only exposure would abate wheeze by 6%, asthma or cough/phlegm by 7%, rhino-conjunctivitis in children by 4%, and in adolescents, asthma by 6%, and wheeze by 4%. CONCLUSIONS: Respiratory disorders such as wheeze and asthma can often be explained by exposure to home mould/dampness, especially early in life. The association seems more evident in children than in adolescents. These findings may suggest the need for environmental prevention strategies.

In vitro effect of natural and semi-synthetic carbohydrate polymers on Chlamydia trachomatis infection.

The effect of different natural and semi-synthetic polysaccharides on Chlamydia trachomatis multiplication in Hela 229 cells was evaluated. Some neutral, negatively and positively charged carbohydrates were able, in a dose-dependent fashion, to inhibit chlamydial infection by interfering mainly with the adsorption process. The inhibiting compounds, whose effect was shown within the concentration range of 8-200 micrograms/ml, were in order of action: dextran sulphate > glyloid sulphate 4327 > glycogen sulphate 4427 > arabic gum = glyloid > chitosan > glycogen. Data obtained suggested that antichlamydial activity was not only related to the electric charge of these molecules but could also be attributed to other features of their polymeric backbone. Since carbohydrate polymers have also been shown to inhibit the early stages of infection by viral agents causing sexually transmitted diseases, the employment of these molecules for prevention or treatment of mixed viral-C. trachomatis infections can be hypothesized.

[Clinico-diagnostic considerations on various cases of lymphogranuloma venereum]. / Considerazioni clinico-diagnostiche su alcuni casi di linfogranuloma venereo.

The authors report some recently observed cases of lymphogranuloma venereum and focus their attention on the complex approach to clinical and laboratory diagnosis. Furthermore they underline the importance and the spread of this disease in new geographical area, such as Europe.

Role of leuprolide acetate depot in hysteroscopic surgery: a controlled study.

OBJECTIVE: To evaluate leuprolide acetate (LA) depot (Enantone Depot, Takeda, Italy) when administered preoperatively in hysteroscopic surgery. DESIGN: Prospective, comparative study. SETTING: University Clinic of Obstetrics and Gynecology. PATIENTS: One hundred ninety-three patients (114 pretreated with LA depot and 79 controls) who underwent hysteroscopic surgery for uterine septa (group A), submucous fibroids (group B), and abnormal uterine bleeding (group C). RESULTS: In groups B and C there was a significant reduction in the operating time, bleeding during the operation, and the amount of distention medium required after LA depot administration, but no significant differences in surgical feasibility or efficacy were found in group A patients after treatment. CONCLUSION: Preoperative treatment with LA depot is effective in making hysteroscopic surgery easier.

Operative laparoscopy for tubal pathology.

Tubal pathology has represented in the last years, the main indication to operative laparoscopy, mainly as a consequence of the widespread use of this technique in the treatment of the ectopic pregnancy. Furthermore, operative laparoscopy has been widely applied to the treatment of the distal tubal pathology for infertility, when IVF/ET failed or was not accepted. The Authors discuss the rationale for these applications of operative laparoscopy and also the possibility of performing by laparoscopy demolitive interventions on the tubes.

Operative laparoscopy for uterine pathology.

In the first years of its use, operative laparoscopy for uterine pathology was employed in the surgical treatment of myomas and in the correction of uterine retroversion (hysteropexy). More recently the technique has been employed for the laparoscopically assisted hysterectomy or for subtotal laparoscopical hysterectomy using the Semm Kit. Also radical hysterectomy has been performed in advanced centers by laparoscopy. In this paper, the Authors discuss the indications, the counterindications, the risks and complications of the operative laparoscopy in the different forms of ovarian pathology.

Operative laparoscopy for pelvic and extrapelvic pathology.

The treatment of pelvic adhesions has been the first and more successful indication for operative laparoscopy. Frequently this intervention is the first step of others laparoscopic procedures. The different modalities of these interventions, i.e. by electrocautery or by scissor, or by laser are discussed. Among indications of operative laparoscopy for pelvic pathology the treatment of endometrial implants has been considered. In this paper less frequent indications for operative laparoscopy as pelvic abscess, or complementary operation as appendicectomy and colecistectomy are also discussed.