Monoamine transporters in female human reproduction.

The present study explored the gene and protein expression of the monoamine transporters in human endometrium throughout the menstrual cycle, in early decidua and in placentas from normal as well as preeclamptic pregnancies using in-situ hybridization, real time-PCR, immunohistochemistry and primary tissue cultures. Four distinguishable patterns were observed in the endometrium over the menstrual cycle: (1) epithelial expression of norepinephrine transporter (NET) mRNA, (2) Stromal co- expression of vesicular monoamine transporter 2 (VMAT2) and plasma membrane monoamine transporter (PMAT) mRNAs with maximal intensity in the proliferative phase; (3) increasing epithelial expression of VMAT2 mRNA with a maximum in the late secretory phase; (4) stromal expression of extra-neuronal monoamine transporter (EMT) mRNA with a peak in the early secretory phase. The presence of functional EMT and VMAT2 transporter proteins throughout the menstrual cycle was shown by uptake of radiolabelled histamine. A similar expression pattern of monoamine transporters was seen in normal and preeclamptic placentas. In particular, NET mRNA was detected in the chorionic and anchoring villi while EMT mRNA was expressed in scattered cells in placental vessels as well as in intralobular septa cells. Serotonin transporter (SERT) mRNA was mainly detected in the chorionic villi. VMAT2 mRNA was detected in the deeper layers of the placenta bed biopsies in trophoblast cells. A small number of cells in the intima layer of some placental vessels showed mRNA expression of the organic cation transporters 1 and 2 (OCT1 and OCT2). Although the expression pattern was similar, a significantly lower gene expression of NET and EMT was found in placentas obtained from preeclamptic versus normal pregnancies. Our results suggest that monoamine transports may have specific functions in female human reproduction by maintaining adequate levels of extra cellular monoamines. Their presence and dynamic expression suggests an important role during the menstrual cycle and pregnancy. Moreover a defective gene expression or function of the monoamine transporters might be determinant in the onset of preeclampsia and its alteration in the vascular bed. Knowledge of the regulation of monoamine metabolism in the endometrium, decidua and placenta will increase the understanding of infertility problems and may offer new pharmacological approaches to optimise assisted reproduction and treatment of preeclampsia

Neuroscience, Accountability and Individual Boundaries

Cognitive neuroscience holds the promise of explaining operations of the mind in terms of the physical operations of the brain. It is claimed that brain imaging technique

Neuroscienze e genetica comportamentale nel processo penale italiano. Casi e prospettive

Since 2009 three Italian criminal cases involving neuroscientific and behavioral genetics evidence have been brought to the public attention. In these cases, the judge took the results of the tests into great consideration in order to reach a final decision on the accused person’s insanity and criminal responsibility. The possibility to deeply investigate the mechanisms at the basis of a person’s behavior is undeniably attractive.Analyzing what has happened so far, however, raises various thorny questions. Some of them can be summarized as follows: a) from a procedural point of view, what way should the neuroscientific and behavioral genetic evidence pass through? B) Once this evidence is brought in front of a judge or a jury, what contribution does it offer in comparison with the traditional psychiatric analysis and other forensic sciences? C) May neuroscience and behavioral genetics be helpful during the offenders’ post-sentence treatment and, if so, why such cases are not known yet? This article aims to face these questions and pose the basis for some initial answers through the analysis of the recent Italian case law and a comparison with the US criminal systemDal 2009 a oggi sono stati oggetto di cronaca ben tre casi giudiziari nell’ambito dei quali la perizia psichiatrica ha riportato i risultati di indagini neuroscientifiche e di genetica comportamentale, che sono poi stati valutati dal giudice ai fini della imputabilità e/o della determinazione della pena. La possibilità di indagare più a fondo quali meccanismi siano in grado di spiegare il comportamento umano, e di trarne conclusioni utili in ambito sociale e giuridico, è innegabilmente attraente.Un’analisi di quanto finora accaduto, tuttavia, rivela la presenza di molte questioni spinose. In particolare: a) Da un punto di vista procedurale, quale può essere la via d’ingresso nel processo penale per la prova neuroscientifica e di genetica comportamentale? b) Una volta presentate a un giudice o a una giuria, cosa possono aggiungere la neuroscienza e la genetica comportamentale alla spiegazione del comportamento umano rispetto a quanto offerto fino a oggi dalla psichiatria e dalle altre scienze forensi? c) Possono le neuro-tecniche essere di aiuto nella fase di esecuzione della pena, e come mai fino a ora non si ha notizia di casi in cui ciò sia avvenuto? Il presente contributo si propone, attraverso l’analisi della casistica italiana e alcuni cenni comparatistici con il sistema e la casistica statunitense, di approfondire le questioni alla base di queste domande e di porre le basi per alcune prime risposte

The E-Cultural Adaption Framework (E-CAF) : adapting the local travel interface for Egyptian consumers

Although the Internet has become a global medium, which companies use to access individuals worldwide, it is argued in this thesis that cultural issues still need to be taken into account when designing Web sites. In fact, international marketers agree that culture in terms of consumers‘ values and beliefs remains a significant constraint for reaching international consumers. Professional analysts and designers generally agree that well-designed user interfaces improve the performance and appeal of the Web and help in reaching large numbers of consumers across cultures. Therefore, one way of improving the user-interface is by paying attention to users' culture, which means developing culturally adapted Web sites. The Web localisation literature addresses the users' ultural concerns by utilising some of the popular cultural models like those of Hofstede and Hall; however these tools are not appropriate for handling the cultural values affecting the online behaviour of consumers. Effective Web localisation can be achieved through an appropriate cultural framework that incorporates the cultural values that affect the online behaviour of consumers. This thesis introduces the electronic cultural adaption framework or E-CAF, as a structure for adapting local Web interfaces. The E-CAF, constructed for the travel domain, uses six cultural dimensions derived from the observation of behaviour and identifies unique cultural variables that affect online consumer behaviour. The E-CAF is constructed using grounded theory methodology and is then evaluated as a tool for adapting local Web interfaces. This includes discussing the applicability of the E-CAF as a tool for identifying online marketing strategies suitable for targeting consumers across cultures and using the E-CAF to assess and evaluate the cultural adaptation of three Egyptian local travel interfaces. Finally, the E-CAF is utilized as a means for developing questions that can help designers to collect the clients' designing requirements. This helps the designers to build an effective local interface based on an understanding of each client‘s special design requirements.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Stima dei danni da vento ai soprassuoli forestali in Regione Toscana a seguito dell'evento del 5 marzo 2015

Il vento è uno dei maggiori fattori di disturbo per le foreste europee e i cambiamenti climatici hanno provocato un aumento di eventi estremi negli ultimi anni. La regione Toscana tra il 4 e il 5 marzo 2015 è stata colpita da una tempesta di vento che ha provocato notevoli danni ai soprassuoli forestali. L’obiettivo di questo lavoro è di sviluppare una metodologia speditiva per la mappatura delle aree danneggiate in termini di superfici interessate, numero di piante atterrate e volume legnoso a terra. Il contributo illustra a tal fine l’utilizzo di dati telerilevati e in particolare le potenzialità dei dati Airborne Laser Scanning (ALS)

An international network (PlaNet) to evaluate a human placental testing platform for chemicals safety testing in pregnancy

tThe human placenta is a critical life-support system that nourishes and protects a rapidly growing fetus; aunique organ, species specific in structure and function. We consider the pressing challenge of providingadditional advice on the safety of prescription medicines and environmental exposures in pregnancy andhow ex vivo and in vitro human placental models might be advanced to reproducible human placentaltest systems (HPTSs), refining a weight of evidence to the guidance given around compound risk assess-ment during pregnancy. The placental pharmacokinetics of xenobiotic transfer, dysregulated placentalfunction in pregnancy-related pathologies and influx/efflux transporter polymorphisms are a few caveatsthat could be addressed by HPTSs, not the specific focus of current mammalian reproductive toxicologysystems. An international consortium, “PlaNet”, will bridge academia, industry and regulators to con-sider screen ability and standardisation issues surrounding these models, with proven reproducibilityfor introduction into industrial and clinical practice

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

La liberta' personale e le neuroscienze cognitive

L’emersione di nuove scoperte scientifiche e lo sviluppo di nuove tecnologie hanno portato a un ripensamento del tema della prova scientifica nel processo penale in prospettiva interdisciplinare. Se, da un lato, la ricostruzione probatoria dei fatti di reato è sempre più affidata ai risultati della prova tecnico-scientifica, dall’altro agli strumenti tradizionalmente noti se ne stanno affiancando di nuovi, la cui affidabilità e rilevanza è spesso controversa. La presente ricerca nasce dall’interesse verso il recente affacciarsi nel panorama giuridico di strumenti e prospettive scientifiche relativamente nuove, come le neuroscienze cognitive e le tecniche a esse collegate. Se, da un lato, vi è un grande interesse da parte di giuristi e scienziati ad approfondire il tema, dall’altro però l’indagine è ancora disorganica, dispersa tra tematiche diverse, con profili di approfondimento che mutano anche a seconda della prospettiva che si assume: nazionale o internazionale, giuridica o multidisciplinare. L’ambito di riferimento del presente lavoro, è quello dell’utilizzo delle neurotecniche nel processo penale. Si possono rilevare diversi piani sui quali si può condurre l’analisi: a) Un piano di tipo penale-sostanziale, con riferimento all’accertamento dell’imputabilità; b) Un piano di tipo procedurale, con riferimento all’ammissione della prova scientifica nel processo c) Un piano di tipo costituzionale, con riferimento alla protezione dei diritti fondamentali dell’imputato. Questi tre livelli sono, in realtà, strettamente interconnessi e la libertà personale è il presupposto e il punto di arrivo dell’indagine penale: la sua protezione o compressione costituiscono il fil rouge di tutti i piani di analisi, dal momento che la custodia cautelare e la pena detentiva sono una violazione, pur giustificata da esigenze di giustizia e di prevenzione, ma pur sempre violazione, della libertà personale di un essere umano. E va notato come, una volta che si sia assunta l’idea ampia di libertà personale che le corti costituzionali ormai hanno esplicitamente affermato (in Italia, si pensi alla sentenza n. 471 del 1990), potenziali altre violazioni ad essa, nella sua dimensione psicofisica, si possono riscontrare in altri momenti e per altre parti del processo, come per esempio, con riferimento alle modalità di escussione del teste /acquisizione della prova nel corso del processo. Da ciò discende la centralità, nel valutare il modo in cui alcune recenti scoperte scientifiche e le tecniche connesse possano incidere sul diritto penale, della protezione della libertà personale dell ’imputato e delle parti del processo, e di come essa sia regolata nei diversi sistemi e posta in evidenza nella casistica giudiziaria. Queste considerazioni sono centrali nella presente ricerca: partendo dal fatto che la libertà personale costituisce un presupposto condiviso nei contemporanei sistemi giuridici occidentali, si è mirato a osservare il modo in cui si atteggia il rapporto tra tale libertà dell’imputato (e delle altre parti nel processo) e il potere autoritativo dello stato nel processo penale, laddove le nuove tecniche neuroscientifiche hanno applicazione. L’analisi è stata condotta in una prospettiva comparata tra il sistema giuridicocostituzionale italiano e quello statunitense

Can We Finally 'See' Pain? Brain Imaging Techniques and Implications for the Law

The assessment of chronic pain is a highly unmet medical need. Chronic pain is also the subject of a large and costly category of legal claims. Yet, with pain cases, the jury always face a doubt: is the claimant faking or malingering? How can we be assured that the claimant is \u2018really\u2019 in pain? Most recently, several new neuroimaging technologies are promising to solve these questions, by rendering pain visible, measurable and, to some degree, verifiable. The results of these advancements have prompted us to think of pain in a different way, i.e. as an altered brain state in which functional connections are modified, with components of degenerative aspects. But, does this imply the stronger claim that these technologies allow us to \u2018know\u2019, or to literally \u2018see\u2019, the pain of others? Is the pain being objectified by these techniques? And if so, what might the law do differently, or do better

Monoamine transporters in human endometrium and decidua.

BACKGROUND Monoamines play important roles in decidualization, implantation, immune modulation and inflammation. Furthermore, monoamines are potent vasoactive mediators that regulate blood flow and capillary permeability. Regulation of the uterine blood flow is important both during menstruation and pregnancy. Adequate monoamine concentrations are essential for a proper implantation and physiological development of pregnancy. Unlike most transmitter substances, monoamines are recycled by monoamine transporters rather than enzymatically inactivated. Their intracellular fate is influenced by their lower affinity for inactivating enzymes than for vesicular transporters located in intracellular vesicles. Thus, cells are capable not only of recapturizing and degrading monoamines, but also of storing and releasing them in a controlled fashion. METHODS The general objective of the present review is to summarize the role of the monoamine transporters in the female human reproduction. Since the transporter proteins critically regulate extracellular monoamine concentrations, knowledge of their distribution and cyclic variation is of great importance for a deeper understanding of the contribution of monoaminergic mechanisms in the reproductive process. MEDLINE was searched for relevant publications from 1950 to 2007. RESULTS Two families of monoamine transporters, neuronal and extraneuronal monoamine transporters, are present in the human endometrium and deciduas. CONCLUSIONS New knowledge about monoamine metabolism in the endometrium during menstruation and pregnancy will increase understanding of infertility problems and may offer new pharmacological approaches to optimize assisted reproduction