Presence of papillomavirus sequences in condylomatous lesions of the mamillae and in invasive carcinoma of the breast

BACKGROUND: Viruses including Epstein–Barr virus (EBV), a human equivalent of murine mammary tumour virus (MMTV) and human papillomavirus (HPV) have been implicated in the aetiology of human breast cancer. We report the presence of HPV DNA sequences in areolar tissue and tumour tissue samples from female patients with breast carcinoma. The presence of virus in the areolar–nipple complex suggests to us a potential pathogenic mechanism. METHODS: Polymerase chain reaction (PCR) was undertaken to amplify HPV types in areolar and tumour tissue from breast cancer cases. In situ hybridisation supported the PCR findings and localised the virus in nipple, areolar and tumour tissue. RESULTS: Papillomavirus DNA was present in 25 of 29 samples of breast carcinoma and in 20 of 29 samples from the corresponding mamilla. The most prevalent type in both carcinomas and nipples was HPV 11, followed by HPV 6. Other types detected were HPV 16, 23, 27 and 57 (nipples and carcinomas), HPV 20, 21, 32, 37, 38, 66 and GA3-1 (nipples only) and HPV 3, 15, 24, 87 and DL473 (carcinomas only). Multiple types were demonstrated in seven carcinomas and ten nipple samples. CONCLUSIONS: The data demonstrate the occurrence of HPV in nipple and areolar tissues in patients with breast carcinoma. The authors postulate a retrograde ductular pattern of viral spread that may have pathogenic significance

World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions

BACKGROUND: To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. METHODS: In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40-80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. FINDINGS: Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0·685 (95% CI 0·629-0·741) to 0·833 (0·783-0·882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40-64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt. INTERPRETATION: We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide. FUNDING: World Health Organization, British Heart Foundation (BHF), BHF Cambridge Centre for Research Excellence, UK Medical Research Council, and National Institute for Health Research

End-tidal arterial CO2 partial pressure gradient in patients with severe hypercapnia undergoing noninvasive ventilation

BACKGROUND: Patients with severe hypercapnia represent a particularly serious condition in an emergency department (ED), requiring immediate attention. Noninvasive ventilation (NIV) is an integral part of the treatment for acute respiratory failure. The present study aimed to validate the measurement of end-tidal CO(2) (EtCO(2)) as a noninvasive technique to evaluate the effectiveness of NIV in acute hypercapnic respiratory failure. METHODS: Twenty consecutive patients admitted to the ED with severe dyspnea were enrolled in the study. NIV by means of bilevel positive airway pressure, was applied to the patients simultaneously with standard medical therapy and continued for 12 hours; the arterial blood gases and side-stream nasal/oral EtCO(2) were measured at subsequent times: T0 (admission to the ED), T1h (after 1 hour), T6h (after 6 hours), and T12h (after 12 hours) during NIV treatment. RESULTS: The arterial CO(2) partial pressure (PaCO(2))–EtCO(2) gradient decreased progressively, reaching at T6h and T12h values lower than baseline (P < 0.001), while arterial pH increased during the observation period (P < 0.001). A positive correlation was found between EtCO(2) and PaCO(2) values (r = 0.89, P < 0.001) at the end of the observation period. CONCLUSION: In our hypercapnic patients, the effectiveness of the NIV was evidenced by the progressive reduction of the PaCO(2)–EtCO(2) gradient. The measurement of the CO(2) gradient could be a reliable method in monitoring the effectiveness of NIV in acute hypercapnic respiratory failure in the ED

Grammatiche della forma per la città del nostro tempo

La ricerca del Gruppo Urbanformgrammars si focalizza sul rapporto tra architettura e città. Assumendo questo orizzonte problematico si è sviluppato nel Novecento il contributo più rilevante del pensiero architettonico italiano. Ad esso il gruppo si vuole riallacciare guardando al fenomeno della città contemporanea per riconoscere, insieme alla crisi della sua forma, le potenzialità che da essa derivano

CityNature 5. Corso di Laurea Magistrale in Architettura. Dipartimento di Scienze dell’Ingegneria Civile e dell’architettura. Politecnico di Bari

Si tratta della pubblicazione di un progetto redatto da alcuni docenti del Corso di Laurea Magistrale in Architettura del Politecnico di Bari in occasione del workshop "Expo dopo Expo"

A Herpesviral induction of RAE-1 NKG2D ligand expression occurs through release of HDAC mediated repression.

Natural Killer (NK) cells are essential for control of viral infection and cancer. NK cells express NKG2D, an activating receptor that directly recognizes NKG2D ligands. These are expressed at low level on healthy cells, but are induced by stresses like infection and transformation. The physiological events that drive NKG2D ligand expression during infection are still poorly understood. We observed that the mouse cytomegalovirus encoded protein m18 is necessary and sufficient to drive expression of the RAE-1 family of NKG2D ligands. We demonstrate that RAE-1 is transcriptionally repressed by histone deacetylase inhibitor 3 (HDAC3) in healthy cells, and m18 relieves this repression by directly interacting with Casein Kinase II and preventing it from activating HDAC3. Accordingly, we found that HDAC inhibiting proteins from human herpesviruses induce human NKG2D ligand ULBP-1. Thus our findings indicate that virally mediated HDAC inhibition can act as a signal for the host to activate NK-cell recognition

A Herpesviral induction of RAE-1 NKG2D ligand expression occurs through release of HDAC mediated repression.

Natural Killer (NK) cells are essential for control of viral infection and cancer. NK cells express NKG2D, an activating receptor that directly recognizes NKG2D ligands. These are expressed at low level on healthy cells, but are induced by stresses like infection and transformation. The physiological events that drive NKG2D ligand expression during infection are still poorly understood. We observed that the mouse cytomegalovirus encoded protein m18 is necessary and sufficient to drive expression of the RAE-1 family of NKG2D ligands. We demonstrate that RAE-1 is transcriptionally repressed by histone deacetylase inhibitor 3 (HDAC3) in healthy cells, and m18 relieves this repression by directly interacting with Casein Kinase II and preventing it from activating HDAC3. Accordingly, we found that HDAC inhibiting proteins from human herpesviruses induce human NKG2D ligand ULBP-1. Thus our findings indicate that virally mediated HDAC inhibition can act as a signal for the host to activate NK-cell recognition

La maieutica della città. Contributi sul progetto urbano e architettonico

Il volume raccoglie una serie di contributi di vari autori sul tema del progetto urbano a cui è stato chiesto di chiarire il loro rapporto con la forma della città consolidata e il suo portato nella contemporaneità. La città vista non tanto o solo come opera d’arte collettiva, ma in quanto espressione di una volontà di condivisione del vivere in una comunità che in essa si riconosce e si esprime anche attraverso le forme urbane. Se è vero l’assunto che le diverse collettività nei secoli hanno saputo dare vita a forme e precise relazioni gerarchiche tra le parti, che consolidatesi nel tempo hanno fornito risposte convincenti al tema dell’abitare, forse è ancora possibile fare dell’esperienza costruita, materia viva del pensiero d’architettura del nostro tempo. Le nostre città, che dalla metà del Novecento hanno conosciuto grandi cambiamenti, hanno bisogno di essere ripensate, di ripopolarsi di nuove architetture e spazi pubblici carichi di significato e capaci di rispondere alle nuove urgenze imposteci dalla situazione ambientale, sociale ed economica. Il lavoro sulla città consolidata è l’orizzonte in cui l’architettura contemporanea ha cominciato a muoversi ormai da qualche tempo. È quindi questo un campo di ricerca e sperimentazione per nuove strutture della scena urbana. Riqualificare, rigenerare, costruire sul costruito, riciclo urbano, consumo zero, sono tutte formule lessicali che, da punti di vista diversi e con sfumature diverse, indicano la stessa situazione e l’intento di occuparsi di quelle aree che la voracità dei processi di urbanizzazione dell’ultimo mezzo secolo, ha lasciato irrisolto o vago o chiaramente sgradevole. Rimediare a smagliature e disturbi visivi, come incidenti e aporie disseminate dal rapido susseguirsi delle trasformazioni, è uno dei compiti che gli architetti dovranno affrontare nel prossimo futuro, forse il più cospicuo.The volume collects a series of contributions on the topic of urban design by various authors, who were asked to clarify their relationship with the shape of the city and its impact on the contemporary world. The city seen not so much or only as a collective work of art, but as an expression of a desire to share life in a community that recognizes itself in it and also expresses itself through urban forms. If the assumption is true that the different communities over the centuries have been able to give life to forms and precise hierarchical relationships between the parts, which, consolidated over time, have provided convincing answers to the theme of living, perhaps it is still possible to have a constructed experience, living material of the architectural thought of our time. Our cities, which have experienced great changes since the mid-twentieth century, need to be rethought, to be repopulated with new architecture and public spaces full of meaning and capable of responding to the new urgencies imposed on us by the environmental, social and economic situation. Work on the consolidated city is the horizon in which contemporary architecture has begun to move for some time now. This is therefore a field of research and experimentation for new structures of the urban scene. Redevelop, regenerate, build on buildings, urban recycling, zero consumption, are all lexical formulas which, from different points of view and with different nuances, indicate the same situation and the intent to deal with those areas that the voracity of urbanization processes of the last half century, has left unresolved or vague or plainly unpleasant. Remediating stretch marks and visual disturbances, such as accidents and aporias spread by the rapid succession of transformations, is one of the tasks that architects will have to face in the near future, perhaps the most conspicuous