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HER2 sstatus and molecular subtypes of breast carcinoma in Central Vietnam
Full text linkBackground. Breast cancer is the most commonly occurring cancer in the females and the leading cause of cancer deaths in Vietnamese women. Beside the traditional histopathological classification according to the WHO, the genetic and molecular findings in the last decades have introduced a new nomenclature to identify of breast cancers oriented mostly to the functional characteristics of the neoplastic cells and the needs of therapy. Based on these criteria, breast cancers are divided into five main groups according to the expression levels of biomarkers such as estrogen (ER), progesterone receptors (PR), proliferation index (Ki67) and human epidermal growth factor receptor 2 (HER2). Among them, HER2 protein overexpression and gene amplification have a particularly important role to play in the classification of molecular subtypes. It is also a significant biomarker which has prognostic and predictive value and is a goal of targeted therapy. The aim of this study was to identify the prevalence rate of HER2 gene amplification or overexpression in the local Vietnamese population, and determine the molecular subtypes of breast cancer.
Materials and methods. Paraffin tissue blocks from 88 Vietnamese women diagnosed consecutively with invasive primary breast carcinoma during a period of 12 months, from April 2016 to April 2017. These blocks underwent immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) and dual in situ hybridization (DISH) for the assessment of HER2 status. HER2 positive includes the HER2 (3+) score in IHC or the HER2 gene amplification in FISH. The IHC for ER, PR and Ki67 were also evaluated to determine molecular subtypes. The analyses were based on the guideline of ASCO/CAP 2013.
Results. The median age of patients was 52.5. By using IHC, 30.7 % of tumours were strongly expressed in (3+) score the HER2 protein. The HER2 equivocal results occupied 9.1%. Gene amplification by FISH was found in 25% of tumours with an equivocal score in IHC. The prevalence rate of HER2 positive was 32.9%. The concordance between IHC and DISH assay were 100% in case of IHC positive or negative. In case HER2 results by using immunohistochemistry technique were equivocal, DISH was able to identify 2 cases (25% of cases) as positive. The concordance between FISH and DISH in the equivocal cases was 100%. Luminal B subtype accounted for the highest proportion, at 37.5% whereas luminal A was the lowest, at 18.2%. The HER2 enriched and triple negative subtype occupied 22.7% and 21.6%, respectively. A significant relationship was found between HER2 status as well as molecular subtypes and some clinicopathological characteristics and biomarkers.
Conclusion. HER2 gene amplification was found in 32.9% of Vietnamese breast cancers. This prevalence was considerably higher than in published studies on women from Western countries. Luminal B subtype was the most frequent, at 37.5% while the uncommon belonged to luminal A, at 18.2%. The HER2 enrich and triple negative subtypes were fairly higher than that in literature. HER2 status as well as molecular classification had prognostic and therapeutical significance
A Cross-sectional study of diverse bacterial and fungal communities in different body habitats in Sardinian centenarians
Full text linkMicrobes in the human body co-evolved with the host during the aging process, adapting to the aging-related niche alternation, however, the full view of the human microbiota variation related to aging is still unknown. Besides, the gut microbiota has been proposed as a promising determinant for human health. Using centenarians as a model for extreme aging may help to understand the correlation of gut microbiota with healthy-aging and longevity. By recruiting the young, elderly and centenarians in Sardinia, Italy, we obtained an integrated view of the spatial distribution of microbiota in the human body across a wide age range and determined the compositional and functional differences in gut microbiota associated with populations of different age in Sardinia. We found that the distribution and correlation of bacteria and fungi community in Sardinians were driven by body sites. In each different age groups, both the bacterial and fungal communities in the skin were significantly different in structure, but not in the oral. The gut bacterial communities in the centenarians clustered separately from the young and elderly which had overlapped clustering, while the fungal communities in gut can’t be separated by the age groups. Moreover, our data revealed that gut microbiota of the healthy elderly and young Sardinians also shared similar metabolic functional profiles, while a distinct cluster is found in centenarians. Within the centenarian group, the gut microbiota is correlated with health status of the host. The centenarians have higher diversity of core microbiota species and microbes genes compared with that in young and elderly. The enrichment of Methanobrevibacter and Bifidobacterium were detected in Sardinian centenarians, which were also verified in a bigger centenarian cohort in Bologna, Italy. Moreover, potential metabolic functional analysis revealed that the gut microbiota in the centenarian group had significantly lower capability to digest complex carbohydrates but had enhanced fermentation capability via glycolysis. Gene pathways involved in amino acid biosynthesis are lower abundance, while menaquinol biosynthesis is higher abundance in the centenarians compared with that of the young and elderly. Our study indicates that the critical role aging plays in shaping human microbiota is habitat dependent, further suggesting the diverse degree of niche alternation caused by aging in different body habitats, emphasizing the importance of integrating the potential confounding factors into the microbiota studies. Sardinian centenarians’ specific gut microbiota may hold promising clues for the future research to identify the possible causative relationship between gut microbiota and longevity in human
Use of by-products in dairy sheep nutrition
Full text linkThis thesis aimed to evaluate the effects of the dietary inclusion of three by-products in sheep diets:
Tomato pomace (TP) is the by-product derived from process of tomato juice, grape marc (GM) derived from winemaking and exhausted myrtle berries (EMB) derived from production of liqueur called Mirto rosso (red myrtle).
This study is divided in 4 main chapters.
Chapter 1 reports the literature on amounts, chemical composition and fatty acid profile of by-products from tomato, wine and myrtle industries. Their use in ruminant nutrition and the effects on milk yield and composition and the biological effects have been discussed. Furthermore, the bioactive compounds, as polyphenol, identified in these by-products have been reported.
In the others chapters of the thesis are reported: the study of the effects of use of small amounts of dried tomato pomace, grape pomace and exhausted myrtle berries on milk yield and composition, and blood biochemical parameters (Chapter 2); the additional information on nutrient and polyphenol composition of the by-products from tomato, wine and myrtle industries in order to supplement existing feedstuff tables (Chapter 2); the effects of tomato pomace, grape pomace and exhausted myrtle berries on oxidative status of animals and milk (Chapter 3); the effects of these by-products on milk fatty acid profile (Chapter 3); and, finally, the effects of by-products on rumen microbiome and fermentation parameters (Chapter 4)
Oxidative stress in early stages of Chronic Obstructive Pulmonary Disease
No full textChronic obstructive pulmonary disease (COPD) is a common respiratory condition characterized by an irreversible or partial irreversible airway obstruction. Since oxidative stress and inflammation play an important role in the pathophysiology of the disease, our target was to evaluate biomarkers index of these conditions in order to find out one or more biomarkers that can predict the onset and the progression of the pathology.
We analyzed oxidative stress and inflammation biomarkers in 29 mild COPD, 14 moderate COPD and in 43 healthy controls. Results obtained show the decrease of PSH levels in COPD patients from the early stage of COPD and the increase is higher with COPD progression. Furthermore, COPD patients presented high ADMA/arginine ratio, low levels of global DNA methylation, high levels of kynurenine and kyn/trp ratio and low levels of tryptophan compared to healthy controls. In addition, the alterations of these biomarkers are further greater with the progression of the disease.
Concluding, our results underline the importance of oxidative stress in COPD presence and severity. Indeed, our data show the alteration of the pathways analyzed due principally to oxidative stress. So, it might be interesting to increase the number of subjects of the study and to include patients with severe form of COPD to fully characterized the impact of oxidative stress in this pathology
L'Impresa nella disciplina Iva tra diritto comunitario e nazionale
No full textMuovendo dalla premessa che la fattispecie dell’impresa dal punto di vista fiscale è armonizzata solo con riguardo all’imposta sul valore aggiunto, il progetto opera un’analisi del decreto n.633/1972 facendo riferimento alla normativa comunitaria ed alla giurisprudenza della Corte di Giustizia.
In primo luogo la ricerca si sofferma sulla direttiva n.2006/112/CE combinandone la disciplina con le pronunce della Corte di Giustizia UE succedutesi negli anni in modo da tracciare i concetti fondamentali posti a base del tributo nell’ordinamento comunitario. L’elaborato muove poi un’analisi sulla legittimità e sulla coerenza sistematica dell’ordinamento nazionale rispetto al modello comunitario con l’intento di individuare le nozioni e le fonti della normativa interna non armonizzate rispetto al contenuto della direttiva.
La ricerca poi si focalizza sullo studio del concetto di impresa (commerciale ed agricola) ai fini della soggettività Iva operando una comparazione tra la disciplina nazionale (art.4 del d.p.r. n.633/1972) e la normativa oltre che la giurisprudenza di fonte comunitaria. Nell’ambito della disamina sul soggetto passivo Iva particolare attenzione viene rivolta al regime Iva applicabile agli enti pubblici in generale e, nel caso specifico, alle attività espletate in veste di pubblica autorità sottolineando le differenze esistenti tra diritto nazionale e comunitario nella classificazione dell’attività di un ente come di pubblica autorità.
Ulteriore analisi riguarda la riconducibilità alla nozione di attività economica, con conseguente assoggettamento ad Iva, delle cessioni di energia da fonte rinnovabile poste in essere: a) dalle distinte categorie dell’imprenditore agricolo; b) dal soggetto persona fisica che produce elettricità per scopi personali; c) dal soggetto persona fisica che produce energia in eccesso rispetto ai suoi bisogni; d) nell’esercizio di un’attività d’impresa.
Ultimo aspetto concerne l’analisi del regime fiscale della gestione collettiva del risparmio operando una comparazione tra il regime di esenzione previsto dalla normativa nazionale (art.10 del d.p.r. n.633/1972) e quello derivante dall’art.13 della VI direttiva. Per la disamina della disciplina applicabile si opera uno studio delle pronunce della Corte di Giustizia UE che appaiono improntate, rispetto al disposto della normativa, ad un sostanziale restringimento del regime di esenzione Iva per i servizi ritenuti non strettamente riconducibili alla gestione patrimoniale
Phenotypic and molecular characterization of extraintestinal pathogenic <i>Escherichia coli</i> and other Gram-negative invasive bacteria in Mozambique
No full textThere is limited information is available regarding the population structure of extraintestinal pathogenic Escherichia coli (ExPEC), and other Gram-negative bacteria (GNB) and their susceptibility profile in Africa, although the increasing prevalence of Extended Spectrum β-lactamases (ESBL), Plasmid mediated β-lactamases (AmpC) and Carbapenemase producing bacteria. Characterization of Gram-negative bacteria pathogens (GNBP) is pivotal in selection of empiric antimicrobials, while awaiting bacterial culture results with suspected invasive bacterial and infection preventive measures worldwide. In the majority of low-income countries like Mozambique, despite the increasing of GNB that produces ESBLs, Plasmid mediated β-lactamases (AmpC) and Carbapenemase and their association with high morbidity-mortality, not all antibiotics agents are available to treat these pathogens and most clinical diagnostic laboratories may not attempt to detect these three major groups of enzymes leading to difficulties in the hospital control of resistant microorganisms and antibiotics misuse. The overall purpose of this study was to evaluate the epidemiology and antimicrobial resistance of ExPEC and other GNB associated with invasive infections such as urinary tract infection, intra-abdominal infection, osteomyelitis, soft-tissue infection, pneumonia, sepsis, meningitis and other infections in Mozambique, through phenotypic and molecular approach. From February 2016 to July of 2018, mainly in Hospital Central of Maputo (HCM) and in other four hospitals: Hospital General of Macamo (HGM), Hospital General of José Macamo (HJM) Hospital Provincial of Quelimane (HPQ) and Hospital Central of Quelimane (HCQ) (n=159) samples were collected. Bacterial identification was done using matrix-assisted laser desorption ionization-time of flight (MALDI-TOF). Antibiotic Susceptibility Testing (AST) was done phenotypically by VITEK 2 compact system (bioMérieux) and by genotypic approaches through PCR (n=77) and Whole Genome Sequencing (WGS) (n=82) DNA of Gram-negative bacteria extracted using Wizard® Genomic DNA Purification Kit (Promega). Full genome sequences of the isolates were obtained using WGS technology and were analyzed in silico for molecular characterization. To our best knowledge, this is the first depth study of ExPEC and other GNB based on WGS in Mozambique. Overall, 159 GNB were isolated, of which 81% were from the main Departments of HCM (Pediatric, Medicine, Surgery and Gynecology and Obstetrics) and 19% from other hospitals (HGM and HJM, and HPQ and HCQ), in particular from Pediatric Departments. Of the 128 GNB from HCM, 59% were isolated from blood and 38% and 2% from pus and cerebrospinal fluid (CSF), respectively.
The most frequent isolates in HCM were K. pneumoniae (27%), followed by ExPEC and Acinetobacter spp. both with 20%. Other GNB as Pseudomonas spp., P. mirabilis, Enterobacter spp., Salmonella spp., M. morgani, K. oxytoca, K. variicola, and S. maltophilia were less observed (ranging from 8% to 1%). The Acinetobacter spp. included (n=23) A. baumanni, and (n=1) A. complex; Pseudomonas spp. included (n=17) P. aeruginosa, (n=1) P. otitidis and (n=1) P. stutzeri; Enterobacter spp. included (n=4) E. complex and (n=1) E. cloacae; and Salmonella spp. included, (n=2) Salmonella enterica serovar Typhimurium (S. Typhimurium), and (n=1) S. Isangi. From other hospitals, seven GNB from blood samples were isolated, including (n=2) Salmonella spp. (n=8) S. Typhimurium and (n=1) Salmonella enterica serovar Thompson, (4) E. coli and K. pneumoniae, (3) E. cloacae, (2) P. aeruginosa, (n=2) A. baumanni and A. complex, (n=1) S. complex, S. marcescens and P. septica only in Pediatric departments. Among ExPEC and other GNB, the resistance to the commonly antibiotics, including penicillins, cephalosporins, trimethoprim-sulfamethoxazole, gentamicin and ciprofloxacin used in Mozambique is high and being associated with different mechanisms, including narrow β-lactamases (TEM-1B, OXA-1), ESBL (CTX-M-9, 15, -27, -88), AmpC (CMY-2 and DHA-13) and carbapenemases (NDM-5, OXAs, NDM and VIM). These mechanisms were found associated with others depending on the species, namely: chromosomal mutations Fluoroquinolone mutations in gyrA, parC and parE, acrR, ompK36, ompK37 and ramR; efflux pumps oqxA and oqxB, aminoglycosides and fluoroquinolones genes [aac(6')-Iaa, aac(6')Ib-cr, aac(6')-Ian, aac(6')-IIC, aac(3)-Ia, aac(3)-IIa, aac(3)-IId, aph(3')-Ia, aph(3'')-I, aph(6)-Id and ant(2'')-Ia, 16S rRNA methylases (rmtB)], sulphonamides (sul1 and sul2), phenicols (catA1, catA2, catA3, catB3, catB7, cmlA1 and floR), macrolides [mdf(A), mph(A), mph(E) and msr(E) and ereA), tetracycline [tet(A)/(B), tet(D), tet(J) and tet(39)], fosfomycin (fosA), rifampicin (ARR-2 and ARR-3), plasmid mediated quinolone resistance (qnrB1, qnrB6 and qnrD1), colistin (mcr-9) and dfr genes, mainly belonging to class 1 and 2 integrons (dfrA1, drfrA5, dfrA7, dfrA8, dfrA12, dfrA14, dfrA17, dfrA16, dfrA19, dfrA27) encoding resistance to trimethoprim-sulfamethoxazole.
Several GNB including ExPEC, K. pneumoniae, P. mirabilis, K. oxytoca, and E. complex, harbored the ESBL CTX-M-15 downstream of ISEcp1 on IncF and A/C plasmids, that plays an important role in the dissemination of resistance genes among GNB in HCM.
The presence of pandemic or/and emerging ExPEC (mainly ST131, ST69, ST410, ST405, ST38), K. pneumoniae, K. oxytoca, E. cloacae ST84, P. mirabilis, A. baumanii and P. aeruginosa carrying CTX-M-15 and ISEcp1 linked to IncF, A/C and Col plasmids represent a high risk for the country due to rapidly dissemination and evolution of diverse multiresistant plasmids and also for treatment failure with antibiotics. Additionally, the detection of the hypervirulent and hypermucoviscous K. pneumoniae ST23 constitutes a worrisome situation due to its ability to generate invasive community-acquired infections. Therefore, prudent use of antibiotics is advocated, and a systematic national surveillance system of antibiotic resistance is urgently need to overcome the dissemination of ESBL, AmpC, and carbapenemases containing GNB in Mozambique. The presence of E. coli ST405 and ST410 carrying carbapenemase (NDM-5) and AmpC (CMY-2), respectively, both located on IncF plasmid highlight the need of strict adherence to infection prevention and control policies by healthcare workers to prevent further dissemination within HCM.
Early detection of ESBL, AmpC and carbapenemase genes would be important for the reduction of mortality rate and spread of MDR organisms in studied hospitals. Although the study found evidence of antimicrobial resistance of ExPEC and other GNB, the data collected did not represent the complete picture of the situation in the whole studied hospitals due to small number of samples related to blood and CFS culture contaminations
Why a <i>Learning City</i> could be a <i>Healthy City</i>?<br/> Why and how to bypass the rhetoric of <i>innovative learning spaces</i>, using the construct of the [urban] <i>capability</i> [sensitive design] <i>approach</i>
No full textThis research aims to demonstrate if and how a Learning City can exist, and satisfy the requirement of a Healthy City, trying to give an operational meaning to this word beyond the current definitions and guidelines (OMS, OECD, UNESCO, ONU, MIUR) reflecting on the educational potential of space. The results of the research demonstrate a "healthy city” is above all a fully, inclusive and enabling, innovative and safe "usable and used" city by all its inhabitants. A malleable and transformable urban environment, not only a container of health or learning, but also as an instrument that creates them and allows the people to be not only recipients, but co-authors of their own processes of development and well-being in the full sense, in an emancipatory perspective.
The research is therefore inscribed in the broad debate on what it means to be a "healthy city" as well as the particularly effervescent "innovative" learning spaces, "re-organizing” the priorities of the urban agenda. The research approach aims to overcome the limits inherent in the disciplinary and academic fields, often characterised by fragmentation and isolation, by moving onto other disciplinary domains, especially in the pedagogical sciences; re-center the city around the theme of learning, beyond the enclosures / standards/ disciplinary and exclusion devices produced by the contemporary city, from the beginning of the modern city. At the same time, the rhetoric of the Innovative Learning Spaces is replaced with projects / processes (of space and learning) based on the "Capability Approach" as a founding paradigm of the spatial and pedagogical choices (with the perspective for lifelong/wide/deep learning).
In the III part of the work (chapter IV and V) explains the reasons why this could occur, opening learning spaces to the city and vice versa, from the perspective of widespread learning, with a series of reflections, ideas, research trails, case studies, and direct experience in the field as well as in the sphere of research & action. A possible methodology is introduced suggesting to elaborate the concept of "tactical counter-device" chosen as a tool that, by its nature, is able to “hack” and “dubug” space into an inclusive perspective, capacitative-enabling, "beta-permanent", open and incremental. Starting a new concept of learning, which guarantees different yet fair opportunities to all, ensuring everyone will have the chance to use and enjoy the city with respect to the development prospects chosen for each-ones own life and action projects, especially for all those categories of "disadvantaged" inhabitants to whom the city is hostile and inaccessible
Agriculture pollution in Lebanese rivers: influence of soil and sediment properties on pesticide persistence
Full text linkThe Beqaa region, crossed by Litani river, represents 47% of Lebanon's agricultural economy. The Litani, the largest river of Lebanon, suffers from different kinds of pollution including that caused by widely used pesticides in Beqaa valley. The herbicides fluazifop (FLP), terbuthylazine (TBZ) and triclopyr (TCP) are the most frequently used in Litani basin, therefore their sorption on sediment and soil samples taken from four sites along Litani river Berdaouni, Joub Jannine, Ammiq and Qaraoun, respectively, was investigated.The sorption data obtained for the three herbicides fitted well to Freundlich logarithmic equation both on sediment and soil samples, showing very low sorption coefficient (Kads) values. At pH values of sediments and soils, their colloidal component is negatively charged similarly to the FLP and TCP herbicides, therefore the very low sorption measured is attributable to negative sorption due to the repulsion between species with the same charge. TBZ instead at measured pH values of sediments and soils is in neutral form, therefore, the greatest adsorption observed for TBZ is probably due to a lipophilic effect that is more active for TBZ than for the other two herbicides. This agrees with the higher Kads values observed on samples more rich in organic matter. The low sorption and FLP, TBZ and TCP low degradability make them herbicides at high risk of leaching. The addition of biochar (BC) from coppiced woodlands, to soils and sediments increased considerably Kads values for all three herbicides. The BC effect was more evident on poorer samples in organic matter. These findings suggest that BC addition to Litani basin soil may be considered as an useful tool to prevent FLP, TBZ and TCP leaching in water
Parkinson's disease: Immune System, infections and Alpha-synuclein protein
Full text linkParkinson's disease (PD) is a neurodegenerative disorder and its etiology is unknown, but environmental factors are implicated in the development of this disease. In this project we want to analyze different roles played by α-syn, HSV-1 and Immune System in PD. We have investigated autoimmunity in PD through ELISA and a specific immune-stimulation using homologous peptides of HSV-1 and α-syn in PD patients VS HCs. Moreover with in vitro study we have investigated the potential role of α-syn as a antimicrobial peptide and could therefore contribute to α-syn aggregation, neuroinflammation, and widespread dopaminergic neuron death. Lastly we have analyzed the potential of circulating miRNAs as noninvasive diagnostic candidate biomarkers of PD patients and neuroinflammation. The obtained results are in line with the hypothesis of a possible involvement of the immune system, in particular autoimmunity, in the pathogenesis of Parkinson's disease, and that HSV-1 infections may lead to a progression of the disease. Concerning α-syn as a potential antimicrobial peptides further studies are needed to clarify the complexity of the functions of this protein. Regarding identification of miRNA we have highlighted different levels of expression of some miRNA, 155 and 146a, between patients with PD and healthy controls
Application of genomic tools to breeding and to genetic structure studies in livestock populations
Full text linkThis work is organized into a general introduction, four chapters of experimental contributions and general conclusions. Chapter 1 contains the general introduction, aiming to provide a synopsis about genetic application in animal science. Two main topics were debated in this thesis, modern genomic tools applied in animal breeding and animal biodiversity.
The first two experimental contributions (Chapters 2 and 3) concerned animal breeding programs, particularly the first and the last step: variance components and breeding values estimation, respectively. The contribution about variance components estimation was the result of my abroad period at the University of Georgia (USA). Chapter 3 deals with the estimation of heritability and genomic breeding values for milk fatty acid profile.
Regarding the animal biodiversity, two researches were carried out analyzing both cattle and sheep breeds farmed in Italy. Several statistical approaches were used to identify selection signatures in livestock. Chapter 4 analyzed genetic diversity among five cattle breeds: two purebreds and three crossbreeds raised in Sardinia. In the Chapter 5, in order to highlight genome regions that can differentiate livestock production, selection signatures were investigated among different productive aptitudes in the Italian ovine stock.
Finally, the general conclusions reported in Chapter 6 offered a short overview of the main results obtained during the PhD