Evaluation of the microbiota-sparing properties of the anti-staphylococcal antibiotic afabicin.

BACKGROUND: Antibiotic use is associated with collateral damage to the healthy microbiota. Afabicin is a first-in-class prodrug inhibitor of the FabI enzyme that, when converted to the pharmacologically active agent afabicin desphosphono, demonstrates a staphylococcal-specific spectrum of activity. An expected benefit of highly targeted antibiotics such as afabicin is microbiome preservation. OBJECTIVES: To compare the effects of oral treatment with afabicin and standard-of-care antibiotics upon the murine gut microbiota, and to assess the effects of oral afabicin treatment on the human gut microbiota. METHODS: Gut microbiota effects of a 10 day oral course of afabicin treatment were monitored in mice and compared with clindamycin, linezolid and moxifloxacin at human-equivalent dose levels using 16S rDNA sequencing. Further, the gut microbiota of healthy volunteers was longitudinally assessed across 20 days of oral treatment with afabicin 240 mg twice daily. RESULTS: Afabicin treatment did not significantly alter gut microbiota diversity (Shannon H index) or richness (rarefied Chao1) in mice. Only limited changes to taxonomic abundances were observed in afabicin-treated animals. In contrast, clindamycin, linezolid and moxifloxacin each caused extensive dysbiosis in the murine model. In humans, afabicin treatment was not associated with alterations in Shannon H or rarefied Chao1 indices, nor relative taxonomic abundances, supporting the findings from the animal model. CONCLUSIONS: Oral treatment with afabicin is associated with preservation of the gut microbiota in mice and healthy subjects.

A project to identify the best practices and health performance objectives for building construction and renovation.

The 2014-2018 National Prevention Plan (NPP), in order to promote a correct relationship between health and the environment, indicated, among the central objectives, the definition of guidelines to promote the building hygiene codes in an eco-compatible way, but also to develop specific skills on the subject of confined environments and residential construction in the operators of the Regional Health Services. The CCM2015 Project has therefore set itself the goal of taking stock of the best health practices available today in terms of sustainability and eco-compatibility in the buildings' construction and renovation actions. All this in order to define updated health performance targets to be made available to the competent Authorities, to adapt the current legislation at national, regional and local level, and finally to define the contents of a continuing education (training courses) capable to support operators in risk assessment related to the built environment and in the definition of effective preventive measures.

Epithelial-Mesenchymal Transition in a Case of Metastatic Thyroid Carcinoma in a Brown Bear (Ursus arctos).

A 20-year-old male brown bear (Ursus arctos) with a 20 × 25 cm necrotic mass adjacent to the trachea was diagnosed as having an anaplastic thyroid carcinoma. Metastases were observed in the lungs and one adrenal gland and, histologically, these had anaplastic and follicular carcinoma patterns, respectively. E-cadherin labelling was observed in the adrenal mass only, while N-cadherin immunolabelling was detected in the thyroid gland and lung masses. Thyroid-specific markers (thyroid transcription factor-1, thyroglobulin) were expressed in the adrenal gland metastasis. This case illustrates an example of a primary epithelial-mesenchymal transition (EMT) enabling metastasis to distant organ sites, followed by a mesenchymal-epithelial transition within the adrenal gland microenvironment, allowing invasion and reacquisition of thyroid epithelial cell features. EMTs help to understand the phenomenon of carcinoma cell plasticity in enabling colonization and growth of metastases.

European all-cause excess and influenza-attributable mortality in the 2017/18 season: should the burden of influenza B be reconsidered?

OBJECTIVES: Weekly monitoring of European all-cause excess mortality, the EuroMOMO network, observed high excess mortality during the influenza B/Yamagata dominated 2017/18 winter season, especially among elderly. We describe all-cause excess and influenza-attributable mortality during the season 2017/18 in Europe. METHODS: Based on weekly reporting of mortality from 24 European countries or sub-national regions, representing 60% of the European population excluding the Russian and Turkish parts of Europe, we estimated age stratified all-cause excess morality using the EuroMOMO model. In addition, age stratified all-cause influenza-attributable mortality was estimated using the FluMOMO algorithm, incorporating influenza activity based on clinical and virological surveillance data, and adjusting for extreme temperatures. RESULTS: Excess mortality was mainly attributable to influenza activity from December 2017 to April 2018, but also due to exceptionally low temperatures in February-March 2018. The pattern and extent of mortality excess was similar to the previous A(H3N2) dominated seasons, 2014/15 and 2016/17. The 2017/18 overall all-cause influenza-attributable mortality was estimated to be 25.4 (95%CI 25.0-25.8) per 100,000 population; 118.2 (116.4-119.9) for persons aged 65. Extending to the European population this translates into over-all 152,000 deaths. CONCLUSIONS: The high mortality among elderly was unexpected in an influenza B dominated season, which commonly are considered to cause mild illness, mainly among children. Even though A(H3N2) also circulated in the 2017/18 season and may have contributed to the excess mortality among the elderly, the common perception of influenza B only having a modest impact on excess mortality in the older population may need to be reconsidered.

Temporal variation in the effect of heat and the role of the Italian heat prevention plan.

OBJECTIVES: The aim of the article is to evaluate the temporal change in the effect of heat on mortality in Italy in the last 12 years after the introduction of the national heat plan. STUDY DESIGN: Time series analysis. METHODS: Distributed lag non-linear models were used to estimate the association between maximum apparent temperature and mortality in 23 Italian cities included in the national heat plan in four study periods (before the introduction of the heat plan and three periods after the plan was in place between 2005 and 2016). The effect (relative risks) and impact (attributable fraction [AF] and number of heat-related deaths) were estimated for mild summer temperatures (20th and 75th percentile maximum apparent temperature [Tappmax]) and extreme summer temperatures (75th and 99th percentile Tappmax) in each study period. A survey of the heat preventive measures adopted over time in the cities included in the Italian heat plan was carried out to better describe adaptation measures and response. RESULTS: Although heat still has an impact on mortality in Italian cities, a reduction in heat-related mortality is observed progressively over time. In terms of the impact, the heat AF related to extreme temperatures declined from 6.3% in the period 1999-2002 to 4.1% in 2013-2016. Considering the entire temperature range (20th vs 99th percentile), the total number of heat-related deaths spared over the entire study period was 1900. CONCLUSIONS: Considering future climate change and the health burden associated to heat waves, it is important to promote adaptation measures by showing the potential effectiveness of heat prevention plans.

Role of circulating endothelial progenitor cells in the reparative mechanisms of stable ischemic myocardium.

BACKGROUND: Mobilization of endothelial progenitor cells (EPCs) into circulation from bone marrow in patients with acute myocardial infarction has strong scientific evidence; less is known about EPC mobilization in patients with stable coronary artery disease (CAD). The aim of this study was to investigate the association of stable ischemic heart disease with EPC levels in tissue and blood. METHODS: Fifty-five consecutive patients admitted to a single treatment center for valve or coronary artery bypass grafting (CABG) surgeries were included in the study. Blood samples were collected in the morning before surgery and analyzed by flow-cytometry to determine peripheral EPC levels (EPC/ml). Tissue EPC (CD34+VEGFR2+) levels were assessed on a right atrial appendage segment. RESULTS: Mean age was 76±5years, 48% were men, and 53% had CAD The number of CD34+ VEGFR2+ cells in the tissue of patients with CAD was significantly higher (p<0.005) and circulating EPC showed a tendency to be reduced by approximately 20% in peripheral blood of patients with CAD when compared to those without CAD. CONCLUSION: Patients with stable CAD had higher EPC density values (EPC/mm2) and were more likely to have lower EPC blood levels when compare with normal controls.

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.

Targeting MT1-MMP as an ImmunoPET-Based Strategy for Imaging Gliomas.

BACKGROUND: A critical challenge in the management of Glioblastoma Multiforme (GBM) tumors is the accurate diagnosis and assessment of tumor progression in a noninvasive manner. We have identified Membrane-type 1 matrix metalloproteinase (MT1-MMP) as an attractive biomarker for GBM imaging since this protein is actively involved in tumor growth and progression, correlates with tumor grade and is closely associated with poor prognosis in GBM patients. Here, we report the development of an immunoPET tracer for effective detection of MT1-MMP in GBM models. METHODS: An anti-human MT1-MMP monoclonal antibody (mAb), LEM2/15, was conjugated to p-isothiocyanatobenzyl-desferrioxamine (DFO-NCS) for 89Zr labeling. Biodistribution and PET imaging studies were performed in xenograft mice bearing human GBM cells (U251) expressing MT1-MMP and non-expressing breast carcinoma cells (MCF-7) as negative control. Two orthotopic brain GBM models, patient-derived neurospheres (TS543) and U251 cells, with different degrees of blood-brain barrier (BBB) disruption were also used for PET imaging experiments. RESULTS: 89Zr labeling of DFO-LEM2/15 was achieved with high yield (>90%) and specific activity (78.5 MBq/mg). Biodistribution experiments indicated that 89Zr-DFO-LEM2/15 showed excellent potential as a radiotracer for detection of MT1-MMP positive GBM tumors. PET imaging also indicated a specific and prominent 89Zr-DFO-LEM2/15 uptake in MT1-MMP+ U251 GBM tumors compared to MT1-MMP- MCF-7 breast tumors. Results obtained in orthotopic brain GBM models revealed a high dependence of a disrupted BBB for tracer penetrance into tumors. 89Zr-DFO-LEM2/15 showed much higher accumulation in TS543 tumors with a highly disrupted BBB than in U251 orthotopic model in which the BBB permeability was only partially increased. Histological analysis confirmed the specificity of the immunoconjugate in all GBM models. CONCLUSION: A new anti MT1-MMP-mAb tracer, 89Zr-DFO-LEM2/15, was synthesized efficiently. In vivo validation showed high-specific-contrast imaging of MT1-MMP positive GBM tumors and provided strong evidence for utility of MT1-MMP-targeted immunoPET as an alternate to nonspecific imaging of GBM.

Jaagsiekte Sheep Retrovirus Can Reach Peyer's Patches and Mesenteric Lymph Nodes of Lambs Nursed by Infected Mothers.

Ovine pulmonary adenocarcinoma (OPA) is a contagious lung cancer of sheep caused by jaagsiekte sheep retrovirus (JSRV). It is generally accepted that transmission by the respiratory route occurs under natural conditions. However recent studies strongly indicate that JSRV can also be transmitted to lambs perinatally via colostrum and milk (C/M). The aim of this work was to confirm that C/M can transmit JSRV infection to lambs under natural conditions and investigate the initial events associated with this transmission route. We have analyzed the presence of JSRV in C/M samples from 22 naturally infected, asymptomatic ewes throughout a lactation period, and in various tissues collected from a group of 36 of their lambs that were fed naturally. The lambs were euthanized at 12, 24, 48, and 72 hours and at 5 and 10 days after birth. We detected JSRV-provirus by PCR in the somatic C/M cells from 10/22 ewes (45.45%). The virus was also detected in 9/36 lambs (25%). JSRV-infected cells, with lymphoreticular-like morphology, were observed by immunohistochemistry (IHC) and in situ hybridization (ISH) in Peyer's patches (PP) from the small intestine of the youngest lambs and in mesenteric lymph nodes (MLN) from lambs older than 72 hours. The virus was also detected by PCR in white blood cells (WBC) in 2/36 lambs (5.5%). These results confirm colostral transmission of JSRV to lambs under natural conditions. Infected lymphoreticular cells contained in C/M appear to be involved. These cells can cross the intestinal barrier of newborn lambs, reach the MLN and enter into circulation.

Plant tolerance to mercury in a contaminated soil is enhanced by the combined effects of humic matter addition and inoculation with arbuscular mycorrhizal fungi.

In a greenhouse pot experiment, lettuce plants (Lactuca sativa L.) were grown in a Hg-contaminated sandy soil with and without inoculation with arbuscular mycorrhizal fungi (AMF) (a commercial inoculum containing infective propagules of Rhizophagus irregularis and Funneliformis mosseae) amended with different rates of a humic acid (0, 1, and 2 g kg(-1) of soil), with the objective of verifying the synergistic effects of the two soil treatments on the Hg tolerance of lettuce plants. Our results indicated that the plant biomass was significantly increased by the combined effect of AMF and humic acid treatments. Addition of humic matter to soil boosted the AMF effect on improving the nutritional plant status, enhancing the pigment content in plant leaves, and inhibiting both Hg uptake and Hg translocation from the roots to the shoots. This was attributed not only to the Hg immobilization by stable complexes with HA and with extraradical mycorrhizal mycelium in soil and root surfaces but also to an improved mineral nutrition promoted by AMF. This work indicates that the combined use of AMF and humic acids may become a useful practice in Hg-contaminated soils to reduce Hg toxicity to crops.

Mid-infrared Mueller ellipsometer with pseudo-achromatic optical elements.

The purpose of this article is to present a new broadband Mueller ellipsometer designed to work in the mid-infrared range, from 3 to 14 µm. The Mueller ellipsometer, which can be mounted in reflection or in transmission configuration, consists of a polarization state generator (PSG), a sample holder, and a polarization state analyzer (PSA). The PSG consists of one linear polarizer and a retarder sequentially rotated to generate a set of four optimal polarization states. The retarder consists of a biprism made of two identical Fresnel rhombs disposed symmetrically and joined by an optical contact, giving the ensemble a "V" shape. Retardation is induced by the four total internal reflections that the beam undergoes when it propagates through the biprism. Total internal reflection allows the generation of a quasi-achromatic retardation. The PSA is identical to the PSG, but with its optical elements mounted in reverse order. After a measurement run, the instrument yields a set of sixteen independent values, which is the minimum amount of data required to calculate the Mueller matrix of the sample. The design of the Mueller ellipsometer is based on the optimization of an objective criterion that allows for minimizing the propagation of errors from raw data to the Mueller matrix of the sample. The pseudo-achromatic optical elements ensure a homogeneous quality of the measurements for all wavelengths. The performance of the Mueller ellipsometer, in terms of precision and accuracy, is discussed and illustrated with a few examples.

Sum decomposition of Mueller-matrix images and spectra of beetle cuticles.

Spectral Mueller matrices measured at multiple angles of incidence as well as Mueller matrix images are recorded on the exoskeletons (cuticles) of the scarab beetles Cetonia aurata and Chrysina argenteola. Cetonia aurata is green whereas Chrysina argenteola is gold-colored. When illuminated with natural (unpolarized) light, both species reflect left-handed and near-circularly polarized light originating from helicoidal structures in their cuticles. These structures are referred to as circular Bragg reflectors. For both species the Mueller matrices are found to be nondiagonal depolarizers. The matrices are Cloude decomposed to a sum of non-depolarizing matrices and it is found that the cuticle optical response, in a first approximation can be described as a sum of Mueller matrices from an ideal mirror and an ideal circular polarizer with relative weights determined by the eigenvalues of the covariance matrices of the measured Mueller matrices. The spectral and image decompositions are consistent with each other. A regression-based decomposition of the spectral and image Mueller matrices is also presented whereby the basic optical components are assumed to be a mirror and a circular polarizer as suggested by the Cloude decomposition. The advantage with a regression decomposition compared to a Cloude decomposition is its better stability as the matrices in the decomposition are determined a priori. The origin of the depolarizing features are discussed but from present data it is not possible to conclude whether the two major components, the mirror and the circular polarizer are laterally separated in domains in the cuticle or if the depolarization originates from the intrinsic properties of the helicoidal structure.

Searching for feasible stationary states in reaction networks by solving a Boolean constraint satisfaction problem.

We analyze the solutions, on single network instances, of a recently introduced class of constraint-satisfaction problems (CSPs), describing feasible steady states of chemical reaction networks. First, we show that the CSPs generalize the scheme known as network expansion, which is recovered in a specific limit. Next, a full statistical mechanics characterization (including the phase diagram and a discussion of the physical origin of the phase transitions) for network expansion is obtained. Finally, we provide a message-passing algorithm to solve the original CSPs in the most general form.

Cystic gastrointestinal stromal tumors of the pancreas simulating cystoadenocarcinoma. Report of three cases and short review of the literature.

Gastrointestinal stromal tumors (GISTs) represent a distinct subset of mesenchymal tumours of the gastrointestinal tract. They are more common in the stomach and small intestine, and are characterized by the proliferation of spindle or epithelioid cells and by the expression of CD117. Extra-gastrointestinal stromal tumors are rare and only 13 cases of pancreatic GISTs have been reported in the literature, only 1 of which presented as a cystic lesion. Mutational analysis of KIT and Platelet derived growth factor receptor-α genes was performed only in two out of the 13 cases. We report 3 cases of cystic GISTs of the pancreas, radiologically mimicking a cystoadenocarcinoma. Routine histopathology and molecular characterization of the tumours have been performed. In two of them, molecular analysis showed unusual genetic alterations (the internal repeat of codon 502 and 503 in exon 9 of the KIT gene and the KIT exon 9 single nucleotide substitution c.1427G⟩T). Pancreatic GIST should be included in the differential diagnosis of both cystic and solid masses of the pancreas. The diagnosis should be accomplished by a combination of radiology, histology, immunohistochemistry and molecular biology. The evaluation of CD117 expression and the sequence analysis of KIT and Platelet derived growth factor receptor-α gene is mandatory for therapy.

Solitary tumours associated with Jaagsiekte retrovirus in sheep are heterogeneous and contain cells expressing markers identifying progenitor cells in lung repair.

Ovine pulmonary adenocarcinoma (OPA) is a naturally occurring lung cancer of sheep caused by jaagsiekte sheep retrovirus (JSRV). This study examines immunohistochemically solitary lung nodules considered as early OPA lesions from 11 sheep infected naturally by JSRV. All 11 neoplastic nodules exhibited features of adenocarcinoma and in four of them mesenchymal growth was also observed. Both types of lesion were labelled with antibody specific for JSRV-Env. In two cases infiltrating lymphoreticular cells also contained JSRV-Env. All tumours had a high Ki67 labelling index and variably contained cells expressing CC10 (a marker of Clara cells (CCs)), SPC (a marker of type II pneumocytes), p63 and keratin 14 (markers for stem/progenitor cells of the lung airway epithelia). Tumours with mesenchymal growth had intense expression of vimentin and desmin, weak expression of smooth muscle actin and did not express pancytokeratin and p63. Both epithelial and mesenchymal proliferations did not express the stem cell markers CD90 and CD117, but some tumour infiltrating cells expressed CD133. Solitary OPA tumours can therefore be adenocarcinomas or mixed tumours and have a heterogeneous cellular composition, containing groups of cells expressing markers that characterize local progenitor cells involved in lung repair.

ESX-1-induced apoptosis is involved in cell-to-cell spread of Mycobacterium tuberculosis.

Apoptosis modulation is a procedure amply utilized by intracellular pathogens to favour the outcome of the infection. Nevertheless, the role of apoptosis during infection with Mycobacterium tuberculosis, the causative agent of human tuberculosis, is subject of an intense debate and still remains unclear. In this work, we describe that apoptosis induction in host cells is clearly restricted to virulent M. tuberculosis strains, and is associated with the capacity of the mycobacteria to secrete the 6 kDa early secreted antigenic target ESAT-6 bothunder in vitro and in vivo conditions. Remarkably, only apoptosis-inducing strains are able to propagate infection into new cells, suggesting that apoptosis is used by M. tuberculosis as a colonization mechanism. Finally, we demonstrate that in vitro modulation of apoptosis affects mycobacterial cell-to-cell spread capacity, establishing an unambiguous relationship between apoptosis and propagation of M. tuberculosis. Our data further indicate that BCG and MTBVAC vaccines are inefficient in inducing apoptosis and colonizing new cells, correlating with the strong attenuation profile of these strains previously observed in vitro and in vivo.

[Appraisal of the optical diagnostic technique for cervical intra-epithelial neoplasia by polarimetric imaging "Polcolpo". Comparison with colposcopic and histological diagnoses by biopsy]. / Étude prospective comparant les performances de la colposcopie classique à la colposcopie guidée par polarimétrie sur la détection des néoplasies intra-épithéliales du col utérin.

OBJECTIVES: The main objective of this study was to compare the performances of polarimetric imaging and standard colposcopy for the detection of CIN. MATERIALS AND METHODS: We performed a monocentric prospective clinical study. The standard colposcopic diagnosis obtained during a first consultation was compared to the diagnosis provided by polarimetric imaging in a second consultation. In addition to the biopsies guided by classical or polarimetric colposcopy, a systematic biopsy taken at a predefined location allowed to calculate the specificities and sensitivities of both techniques. RESULTS: One hundred and forty-one patients were included, all of them with anomalous Pap smears. Sixty-seven cone biopsies were taken, 69 % of which were eventually diagnosed with CIN2+ lesions. The sensitivities and specificities were found to be equal for standard and polarimetric colposcopies. CONCLUSION: We could not demonstrate any improvement of the diagnostic performances with polarimetric colposcopy alone. However, for both healthy and pathological cervices, we observed interesting polarimetric responses involving other characteristics than those we initially assumed, and which will be taken into account in a future study.

Bovine rod rhodopsin. 1. Bleaching by luminescence in vitro by recombination of radicals from polyunsaturated fatty acids.

Rod outer segments of photoreceptors are characterized by rhodopsin, a membrane protein surrounded by phospholipids containing a very high concentration of polyunsaturated fatty acids. These fatty acids can propagate free radicals, initiated by peroxidation, whose recombination is eventually associated with light emission as chemiluminescence. The results reported here indicate that this effect produces an isomerization of the retinal (bleaching effect) of the rhodopsin, similar to that induced by light in normal vision. In vitro experiments on detergent-suspended rod outer segments (RdOS) from bovine eyes, using an enzymatic source of radicals, xanthine/xanthine oxidase, were carried out. The results indicate that the proposed mechanism is likely, because they can show the bleaching of rhodopsin in RdOS, owing to its extraordinary sensitivity. Thus this mechanism is, also, a possible explanation for anomalous visual effects such as light flashes (phosphene-like) perceived by humans. The functionality of the rhodopsin in the RdOS was first tested by visible light. Rhodopsin reactivation after bleaching was obtained by adding cis-retinal to the suspension, demonstrating the reversibility of the bleaching process. A special experimental system was developed to observe the bleaching from luminescence by radical recombination, avoiding physical contact between the rod outer segment suspension and the radicals to prevent radical-induced damage and modifications of the delicate structure of the rod outer segment.

Optimal fluxes, reaction replaceability, and response to enzymopathies in the human red blood cell.

Characterizing the capabilities, key dependencies, and response to perturbations of genome-scale metabolic networks is a basic problem with important applications. A key question concerns the identification of the potentially most harmful reaction knockouts. The integration of combinatorial methods with sampling techniques to explore the space of viable flux states may provide crucial insights on this issue. We assess the replaceability of every metabolic conversion in the human red blood cell by enumerating the alternative paths from substrate to product, obtaining a complete map of he potential damage of single enzymopathies. Sampling the space of optimal steady state fluxes in the healthy and in the mutated cell reveals both correlations and complementarity between topologic and dynamical aspects.