Mutant p53 inhibits miRNA biogenesis by interfering with the microprocessor complex.

Downregulation of microRNAs (miRNAs) is commonly observed in cancers and promotes tumorigenesis suggesting that miRNAs may function as tumor suppressors. However, the mechanism through which miRNAs are regulated in cancer, and the connection between oncogenes and miRNA biogenesis remain poorly understood. The TP53 tumor-suppressor gene is mutated in half of human cancers resulting in an oncogene with gain-of-function activities. Here we demonstrate that mutant p53 (mutp53) oncoproteins modulate the biogenesis of a subset of miRNAs in cancer cells inhibiting their post-transcriptional maturation. Interestingly, among these miRNAs several are also downregulated in human tumors. By confocal, co-immunoprecipitation and RNA-chromatin immunoprecipitation experiments, we show that endogenous mutp53 binds and sequesters RNA helicases p72/82 from the microprocessor complex, interfering with Drosha-pri-miRNAs association. In agreement with this, the overexpression of p72 leads to an increase of mature miRNAs levels. Moreover, functional experiments demonstrate the oncosuppressive role of mutp53-dependent miRNAs (miR-517a, -519a, -218, -105). Our study highlights a previously undescribed mechanism by which mutp53 interferes with Drosha-p72/82 association leading, at least in part, to miRNA deregulation observed in cancer.

Prevalence of HIV-1 infection in 18 year old men in Tuscany. The Toscana Collaborative Group.

BACKGROUND: The main route of transmission of the human immunodeficiency virus type 1 (HIV-1) is sexual contact. A high proportion of young adults is exposed to this mode of transmission. Therefore it is important to assess the level of HIV-1 prevalence among 18 year olds in Italy. METHODS: Available blood samples taken at the physical examination of the military draft visit in Tuscany, Italy, have been tested in an anonymous unlinked fashion for HIV-1 infection in 1990 and 1991. RESULTS: In the 2 years, 4478 and 4959 men were tested, respectively, representing 91.7% of all subjects included in the draft lists. Prevalence of HIV-1 infection was 1.12 per 1000 (95%CI: 0.36-2.61 per 1000) in 1990 and 0.20 per 1000 (95% CI: 0.01-1.12) in 1991. CONCLUSIONS: Prevalence of HIV-1 infection in the 18 year old male population in Tuscany is close to or below 1/1000. Evidence of the presence of HIV-1 infection in this population should prompt the implementation of adequate prevention programmes among adolescents.

Central nervous system involvement during infection by Phlebovirus toscana of residents in natural foci in central Italy (1977-1988).

Central nervous system (CNS) involvement was detected during infection caused by the sand fly-transmitted Phlebovirus Toscana. One hundred fifty-five cases of Toscana virus-associated meningitis or meningoencephalitis were identified in a survey that lasted ten years, conducted in two regions of central Italy. Diagnosis was performed by different serologic tests. A combination of hemagglutination-inhibition and plaque-reduction neutralization or indirect immunofluorescence for IgM, and enzyme-linked immunosorbent assays for IgM were considered the most suitable tests for the diagnosis of Toscana virus infection. A few strains of Toscana virus were isolated from the cerebrospinal fluid of seropositive patients. Toscana virus-associated CNS disease occurred during the summer, reaching a peak value in August, when the maximum activity of the sand fly vector occurs and virus isolates are obtained in their natural foci. The results suggest that Toscana virus should be considered as a possible cause of CNS disease in Mediterranean countries where sand flies of the genus Phlebotomus are known to be present.

On the measurement of horizontal inequity in the delivery of health care.

This paper offers a critical appraisal of the various methods used to date to investigate inequity in the delivery of health care. It concludes that none of the methods used to date is particularly well equipped to provide unbiassed estimates of the extent of inequity. It also concludes that Le Grand's (1978) approach is likely to point towards inequity favouring the rich even when none exists. The paper offers an alternative approach, which builds on the approaches to date but seeks to overcome their deficiencies.

On the measurement of inequalities in health.

This paper offers a critical appraisal of the various methods employed to date to measure inequalities in health. It suggests that only two of these--the slope index of inequality and the concentration index--are likely to present an accurate picture of socioeconomic inequalities in health. The paper also presents several empirical examples to illustrate of the dangers of using other measures such as the range, the Lorenz curve and the index of dissimilarity.

Awareness of health risks at the workplace and of risks of contracting communicable diseases including those related to food hygiene, among seafarers.

BACKGROUND: The awareness of health risks on board ships in terms of knowledge of dangers and discomfort at the workplace, and of risks of contracting communicable diseases including those related to food hygiene was assessed in a sample of workers of an Italian shipping company. Analysis was performed on crew members and on ashore personnel of the same firm to assess possible differences in risk perception. MATERIALS AND METHODS: The study was conducted by proposing an anonymous questionnaire to the crew members of 9 tankers and to the office staff of the shipping company Finaval S.p.A., which has its headquarters in Rome. RESULTS: People living ashore have a better knowledge of infectious risks than seafarers. Both ashore workers and seafarers have a reasonable awareness of blood-borne and sexually-transmitted diseases. Seafarers are more concerned about the risks of psychological problems due to isolation than are office personnel. The risk of not being adequately cared for in case of disease or injury on board is also perceived as a major problem by seafarers. Ashore personnel, eating raw fish more than their mates on board, are at a greater risk of communicable gastrointestinal diseases. CONCLUSIONS: Seafarers should be the target of specific informative campaigns about health risks, possible consequences, and how to minimize exposure to them during travel/life at sea.

Survey on HIV risk perception and sexual behaviours among seafarers.

Because the nature of their work seafarers spend long periods of time away from their families and therefore represent a group at risk for sexually transmitted diseases, including HIV infection. This paper reports the results of a survey to evaluate awareness and knowledge of the risk of HIV infection among seafarers. Risky behaviours for HIV transmission were also assessed. The survey was conducted using anonymous questionnaires on 197 workers of 9 vessels and 26 office employees of an Italian shipping company (FINAVAL S.p.A., Rome). The respondents considered HIV/AIDS as one of the diseases with a high risk of transmission. Most respondents had a good general knowledge of HIV/AIDS and on the ways of its transmission. However, there is still lack of knowledge on the basics of this disease. On the other hand, in spite of knowledge and awareness about the risks of the disease, only 56.35% of the interviewed crewmembers used protection in sexual intercourse with occasional partners. Compared to data available in literature, the percentage of self-protecting people is increasing, but the number of seafarers exposing themselves to risky behaviours is still high. As expected, condoms are used with regular partners with lower frequency compared to occasional intercourse. The results of this survey indicate that adequate prevention campaigns and major attention paid to seafarers health is useful for stimulating responsible conduct for the prevention of infectious diseases, including HIV infection. Nevertheless, it is still necessary to increase information about the risk of sexually transmitted diseases and how to reduce it.

Polaronic and nonadiabatic phase diagram from anomalous isotope effects.

Isotope effects (IEs) are powerful tools to probe directly the dependence of many physical properties on lattice dynamics. In this Letter we investigate the onset of anomalous IEs in the spinless Holstein model by employing the dynamical mean field theory. We show that the isotope coefficients of the electron effective mass and of the dressed phonon frequency are sizable also far away from the polaronic crossover and mark the importance of nonadiabatic lattice fluctuations. We draw a nonadiabatic phase diagram in which we identify a novel crossover, not related to polaronic features, where the IEs attain their largest anomalies.

Equity and efficiency in Italian health care.

Health care finance and provision in Italy is unusual by international standards: public financing relies heavily on both general taxation and social insurance, and although the vast majority of expenditure is publicly financed, the majority of care is provided by the private sector. The system suffers, however, from a chronic failure to control expenditures and its record on perinatal and infant mortality is poor. Hospitals in Italy have a low bed-occupancy rate by international standards and the per diem system of reimbursing private hospitals encourages unduly long stays. Costs per inpatient day are high by international standards, but costs per admission are close to the OECD average. Ambulatory care costs are extremely low, but this appears to be due to the fact that GPs see so many patients that their role is inevitably mainly administrative. Consumption of medicines is extremely high, but because the cost per item is low, expenditure per capita is not unduly high. Despite the emphasis on social insurance, the financing system appears to be progressive. There is evidence of inequalities in health in Italy, and some evidence that health care is not provided equally to those in the same degree of need.

[Acute viral hepatitis in the Florence area: II. Immunologic study]. / L'epatite virale acuta nell'area di Firenze: II--Studio immunologico.

Sera obtained from 302 patients with acute viral hepatitis were studied for the presence of organ and non organ specific autoantibodies and of circulating immune complexes (CIC). Autoantibodies were determined by indirect immunofluorescence techniques and CICs were detected by 125 J - C1q assay (C1qBA according to Zubler et al., 1976). A high prevalence of anti smooth muscle autoantibodies (SMA) was found in the sera of the patients. In particular, SMA were found in the sera from 44/73 (60.2%), 92/182 (50.55%) and 10/47 (21.3%) of A, B and nonA nonB hepatitis, respectively. The highest prevalence of SMA was observed within 10 days after the clinical onset of the disease in hepatitis A patients and within 10-15 days in nonA nonB hepatitis. The prevalence of SMA in hepatitis B is persistently high during the first two weeks of illness, then decreases and, about the 3rd week, increases again. CIC were detected in 156 sera from 302 patients (51.65%) affected by acute viral hepatitis. The prevalence of CIC was significantly higher in hepatitis A (78.08%) than in B and nonA nonB hepatitis (45.6% and 34.03% respectively). CIC were demonstrated in almost all the sera of hepatitis A patients admitted between the 6th and the 15th day after the onset of the disease. A strict connection was observed between SMA and CIC and, although to a lesser extent, between CIC and markers of A and B viruses. No significant connection between CIC and serum aminotransferase or bilirubin levels was noted. CIC screening was performed weekly for 1 month after admission in 225 patients with acute viral hepatitis. According to our data, the clearance of immune complexes from serum seems to occur more quickly in B and nonA nonB hepatitis than in virus A hepatitis.

[Acute viral hepatitis in the Florence area: I. Epidemiologic study]. / L'epatite virale acuta nell'area di firenze: I--Studio epidemiologico.

The sera of 401 patients admitted to the Department of Infectious Diseases [U.S.L. (Unità Sanitaria Locale) 10 D] in Florence in one year were screened for the presence of markers of hepatitis A and B viruses. On the basis of clinical and serological data, the diagnosis of viral hepatitis was confirmed for 302 patients. Among the se, 73 (24.18%) were affected by hepatitis A, 182 (60.26%) by hepatitis B and 47 (15.56%) by nonA nonB hepatitis. The prevalence of B nonA nonB hepatitis in 133 drug addicts was 69.37% and 25.51% respectively. A previous infection with hepatitis A virus, as demonstrated by the presence of anti A antibodies of the IgG idiotype in the sera, was demonstrated in 201 of 328 patients (62.03%) not affected by hepatitis A. Only 14% of them reported data related to a possible former acute hepatitis. Markers of B virus were found in 62 of 167 sera of patients (37.12%) not affected by acute B hepatitis or chronic HBsAg positive hepatitis. However the prevalence of virus B markers increases up to 50% in the sera of drug addicts. According to our data the spreading of virus hepatitis in the area of Florence is similar to that observed in other Regions of Central and Northern Italy with fairly good social and hygienic conditions. High prevalence of nonA nonB hepatitis and of HBsAg carriers among the drug addicts are noteworthy.