NONO regulates the intra-S-phase checkpoint in response to UV radiation.

The main risk factor for skin cancer is ultraviolet (UV) exposure, which causes DNA damage. Cells respond to UV-induced DNA damage by activating the intra-S-phase checkpoint, which prevents replication fork collapse, late origin firing and stabilizes fragile sites. Recently, the 54-kDa multifunctional protein NONO was found to be involved in the non-homologous end-joining DNA repair process and in poly ADP-ribose polymerase 1 activation. Interestingly, NONO is mutated in several tumour types and emerged as a crucial factor underlying both melanoma development and progression. Therefore, we set out to evaluate whether NONO could be involved in the DNA-damage response to UV radiations. We generated NONO-silenced HeLa cell clones and found that lack of NONO decreased cell growth rate. Then, we challenged NONO-silenced cells with exposure to UV radiations and found that NONO-silenced cells, compared with control cells, continued to synthesize DNA, failed to block new origin firing and impaired CHK1S345 phosphorylation showing a defective checkpoint activation. Consistently, NONO is present at the sites of UV-induced DNA damage where it localizes to RAD9 foci. To position NONO in the DNA-damage response cascade, we analysed the loading onto chromatin of various intra-S-phase checkpoint mediators and found that NONO favours the loading of topoisomerase II-binding protein 1 acting upstream of the ATM and Rad3-related kinase activity. Strikingly, re-expression of NONO, through an sh-resistant mRNA, rescued CHK1S345 phosphorylation in NONO-silenced cells. Interestingly, NONO silencing affected cell response to UV radiations also in a melanoma cell line. Overall, our data uncover a new role for NONO in mediating the cellular response to UV-induced DNA damage.

Monoterpenoids glycosides content from two Mediterranean populations of Crucianella maritima L.

In this study, the iridoidic content of two accessions of Crucianella maritima L., one from Sardinia and the second from Latium, was examined and compared. From a qualitative point of view, the iridoidic pattern of the two samples was similar, since the same compounds (asperuloside, asperulosidic acid and deacetyl asperulosidic acid) were isolated. Asperuloside was the main compound in both accessions. Asperulosidic acid was the second compound in the accession from Sardinia, while the accession from Latium exhibited a similar amount of asperulosidic acid and deacetyl asperulosidic acid. These iridoids can be considered as chemotaxonomic markers for parts of the Rubiaceae family, in particular for the Rubioideae subfamily to which C. maritima belongs.

Phytochemical pattern of Gentiana species of Appennino in central Italy.

The molecular pattern of two Gentiana species, G. dinarica and G. lutea, present in a protected area of Appennino Centrale in Italy, was examined. Results were compared with literature data, examining the differences between the two species.

Improved diagnosis of central venous catheter-related bloodstream infections using the HB&L UROQUATTRO™ system.

The diagnosis of catheter-related bloodstream infections (CRBSIs) in febrile patients with indwelling central venous catheters (CVCs) needs improvement. To diagnose CRBSIs more efficiently, we have developed a novel culture approach using the catheter tips removed from febrile patients. CVCs and blood cultures from 1,070 patients with only CVC-related infections were obtained over a period of 3 years (January 2009 to December 2011). The CVCs were evaluated by a semi-quantitative catheter culture method according to Maki's method and by our novel method, which is based on the use of the HB&L UROQUATTRO™ system (Alifax, Padova, Italy). Using our new method, 571 (571/1,070) of the infections were confirmed as CRBSIs. The remaining 487 patients had infections that were associated with hematologic malignancies, neutropenia, prior exposure to antibiotics, and a decreased CVC removal rate. Twelve samples were identified as false-positives. The percentage of patients with CRBSIs confirmed using the HB&L UROQUATTRO™ system was 53.36 % versus 34.95 % (p-value 0.004) using Maki's method (374/1,070 CVC Maki-positive samples). Our results indicate that our new culture method allows for an improved CRBSI diagnosis rate. A significant number of tip cultures (18.41 %) tested positive for CRBSIs using our system but were negative when tested using Maki's method. Moreover, the use of the HB&L UROQUATTRO™ system allowed us to significantly reduce diagnosis time; a negative CRBSI diagnosis could be made within 6 h and a positive diagnosis could be made within 22-28 h.

Role of the quantiferon-TB test in ruling out pleural tuberculosis: a multi-centre study.

Diagnosing pleural tuberculosis (plTB) might be difficult due to limited sensitivity of conventional microbiology tools. As M. tuberculosis (MTB)-specific T cells are recruited into pleural space in plTB, their detection may provide useful clinical information. To this aim, in addition to standard diagnostic tests, we used the QuantiFERON-TB Gold In-Tube (QFT-IT) test in blood and pleural effusion (PE) samples from 48 patients with clinical suspicion of plTB, 18 (37.5%) of whom had confirmed plTB. Four of them (22.2%) tested positive with a nucleic acid amplification test for MTB. The tuberculin skin test was positive in most confirmed plTB cases (88.9%). Positive QFT-IT tests were significantly more frequent in patients with confirmed plTB, as compared to patients with an alternative diagnosis, both in blood (77.7 vs 36.6%, p=0.006) and in PE samples (83.3% vs 46.6%, p=0.02). In addition, both blood and PE MTB-stimulated IFN-gamma levels were significantly higher in plTB patients (p=0.03 and p=0.0049 vs non-plTB, respectively). In blood samples, QFT-IT had 77.8% sensitivity and 63.3% specificity, resulting in 56.0% positive (PPV) and 82.6% negative (NPV) predictive values. On PE, QFT-IT sensitivity was 83.3% and specificity 53.3% (PPV 51.7% and NPV 84.2%). The optimal AUC-derived cut-off for MTB-stimulated pleural IFN-gamma level was 3.01 IU/mL (77.8% sensitivity, 80% specificity, PPV 68.4% and NPV 82.8%). These data suggest that QFT-IT might have a role in ruling out plTB in clinical practice.

Pulmonary sarcoidosis in a patient with psoriatic arthritis during infliximab therapy.

The occurrence of sarcoidosis during anti-TNF-alpha therapy has occasionally been published. We report the case of a psoriasis patient who developed pulmonary sarcoidosis during a cycle of therapy with infliximab.

Percutaneous management of complications of tuberculous spondylodiscitis: short- to medium-term results.

PURPOSE: Psoas abscesses are the most frequent complication of tuberculosis with skeletal involvement. The aim of this paper is to report our experience with the systematic application of percutaneous drainage to tuberculous psoas abscesses. MATERIALS AND METHODS: Between January 1997 and December 2005, 23 patients (14 men and nine women; age range 21-48 years), after a previous study with computed tomography (CT) and/or magnetic resonance (MR) imaging, underwent percutaneous drainage of a tuberculous fluid collection in the psoas muscles. Follow-up consisted of monthly clinical and laboratory assessment, and plain chest radiography and spinal CT every 6-12 months. RESULTS: Spondylodiscitis involved the thoracolumbar spine. Fluid collections were bilateral in 14 cases and communicating in ten of these. Maximum transverse diameter was 7 cm, whereas longitudinal diameter was 14 cm. Placement of the drainage catheter was successful in all cases, and the catheter was left in place for 5-36 (mean 18.4) days. Symptom regression occurred immediately after drainage of the fluid collection. The drainage procedure was curative in 100% of cases. Dislodgement of the drainage catheter occurred in two cases as a result of excessive traction during dressing removal. CONCLUSIONS: A serious complication of bone tuberculosis, psoas abscesses, can be effectively treated by percutaneous drainage, leading to immediate pain resolution. The drainage catheter requires daily monitoring to identify when it can be safely removed without risk of recurrence.

Polymorphisms in the genes of the urokinase plasminogen activation system in relation to colorectal cancer.

BACKGROUND: Extracellular matrix degradation, mediated by the urokinase plasminogen activation (uPA) system, is a critical step in tumor invasion and metastasis. High tumor levels of uPA and its inhibitor PAI-1 have been correlated with poor cancer prognosis. We examined four single nucleotide polymorphisms (SNPs) with a potential effect on expression of genes in the uPA system for their role in colorectal cancer susceptibility and prognosis. PATIENTS AND METHODS: We genotyped the SNPs in 308 Swedish incident colorectal cancer patients with up to 16 years of follow-up and in 585 age- and sex-matched controls. We evaluated the associations between genotypes and colorectal cancer and Dukes' stage. Survival probabilities were compared between different subgroups. RESULTS: Patients with PAI-1 -675 5G/5G genotype had better survival than patients with 4G/4G or 4G/5G genotypes when they had Dukes' stage A or B tumors (P = 0.023 and P = 0.015, respectively). No statistically significant association was observed between the SNPs and the risk of colorectal cancer or Dukes' stage. CONCLUSIONS: Our results suggest a role for the PAI-1 genotype in colorectal cancer prognosis, but further studies are needed to evaluate the impact of our finding in the clinic.

The combined use of VIGI@ct (bioMérieux) and fluorescent amplified length fragment polymorphisms in the investigation of potential outbreaks.

Even with good surveillance programmes, hospital-acquired infections (HAIs) are not always recognized and this may lead to an outbreak. In order to reduce this risk, we propose a model for prompt detection of HAIs, based on the use of a real-time epidemiological information system called VIGI@ct (bioMèrieux, Las Balmas, France) and on the rapid confirmation or exclusion of the genetic relationship among pathogens using fluorescent amplified length fragment polymorphism (f-AFLP) microbial fingerprinting. We present the results of one year's experience with the system, which identified a total of 306 suspicious HAIs. Of these, 281 (92%) were 'confirmed' by clinical evidence, 16 (5%) were considered to be simple colonization and the latter nine (3%) were archived as 'not answered' because of the absence of the physician's cooperation. There were seven suspected outbreaks; of these, f-AFLP analysis confirmed the clonal relationship among the isolates in four cases: outbreak 1 (four isolates of Pseudomonas aeruginosa), outbreak 2 (three Escherichia coli isolates), outbreak 6 (two Candida parapsilosis isolates) and outbreak 7 (30 ESbetaL-producing Klebsiella pneumoniae subsp. pneumoniae). Based on our results, we conclude that the combination of VIGI@ct and f-AFLP is useful in the rapid assessment of an outbreak due to Gram-positive or Gram-negative bacteria and yeasts.

Number of siblings and the risk of solid tumours: a nation-wide study.

We analysed the effects of number of siblings on the risk of solid tumours using the Swedish Family-Cancer Database, including population-based information on over 11 million individuals and more than 178,000 cancer patients diagnosed between 1958 and 2004. Incidence rate ratios (RRs), estimated by Poisson regression models, were adjusted for age, sex, birth cohort, area of residence and socioeconomic status. Having eight or more siblings vs none increased the risk of stomach cancer (RR=1.83, 95% confidence interval (CI), 1.44-2.34). Anal cancer diagnosed before age 40 showed the strongest association with the total siblings (RR=3.27, 95% CI, 2.04-5.26 for five or more siblings vs none). Endometrial (RR=0.76, 95% CI, 0.70-0.82), testicular (RR=0.71, 95% CI, 0.62-0.82), skin cancer (RR=0.82, 95% CI, 0.69-0.97) and melanoma (RR=0.72, 95% CI, 0.65-0.79) showed strong decreased risks for five or more siblings vs none. Prostate cancer risk for those with five or more older siblings vs none was 1.38 (95% CI, 1.23-1.55). Having five or more younger siblings was most strongly associated with stomach cancer (RR=1.59, 95% CI, 1.29-1.95) and melanoma (RR=0.68, 95% CI, 0.59-0.79). We conclude that sibship characteristics are strong correlates of cancer risk at several sites; plausible interpretations include socioeconomic status.

History of cirrhosis and risk of digestive tract neoplasms.

BACKGROUND: Cirrhosis is strongly related to liver cancer. Data on the possible association between cirrhosis and risk at other cancer sites are scanty. PATIENTS AND METHODS: We analysed data from a network of case-control studies conducted in Italy between 1983 and 1997, including patients with cancers of the oral cavity and pharynx (520), oesophagus (405), stomach (731), colon (943), rectum (613), liver (425), gallbladder (63) and pancreas (395). The controls were 4297 patients admitted to hospitals for acute non-neoplastic conditions. RESULTS: After strict allowance for alcohol drinking, tobacco smoking and history of hepatitis, the multivariate odds ratios for a history of cirrhosis were 4.7 [95% confidence interval (CI) 2.2-9.8] for neoplasms of the oral cavity and pharynx, 2.6 (95% CI 1.2-5.7) for the oesophagus, 1.0 (95% CI 0.4-2.5) for the stomach, 1.0 (95% CI 0.4-2.4) for the colon, 1.7 (95% CI 0.7-4.1) for the rectum, 20.5 (95% CI 12.3-34.2) for the liver, 2.1 (95% CI 0.3-16.8) for the gallbladder and 0.9 (95% CI 0.3-3.0) for the pancreas. CONCLUSIONS: Our study confirms and further quantifies the increased risk of liver cancer in cirrhotic patients and is compatible with an increased risk of oral, pharyngeal and oesophageal cancers.

[Evaluation of central venous catheters by endocavitary ECG]. / Registrazione elettrocardiografica intratoracica (EC-ECG) per valutare il catetere venoso centrale.

Jugular vein catheterization (JVC) is adopted for blood access in patients with acute renal failure, chronic renal failure and when patients demonstrate traditional vascular access (VA) failure. We believe that the best technique, first described by Serafini et al, to establish the position of a central venous catheter (CVC) is endocavitary electrocardiography (EC-ECG) and its use is recommended in all uremic patients requiring hemodialysis (HD). This technique uses the tip of the CVC as a reference point in standard electrocardiography. From 2001 to March 2004, we successfully applied this CVC technique in 33 patients requiring HD. The EC-ECG technique is a method that complies with the Food and Drug Administration guidelines regarding catheter tip location in uremic patients.

Radiometric characterisation of more representative natural building materials in the province of Rome.

Natural building materials, characterised by middle-low-activity concentrations of primordial radionuclides ((40)K, (232)Th and (238)U series) are widely used in Italy. Since natural materials reflect the geological variability of their sites of origin, a systematic study was carried out in the province of Rome and the results are reported in this paper. In the present work, in order to evaluate average, minimum and maximum contents of primordial radionuclides, more representative lithologies outcropping on the territory of the province of Rome were identified and around 150 samples were collected. Also, these lithologies were characterised from a radioprotection point of view, by means of the evaluation of the index, I, when they are used as building materials. The results confirm the high-primordial radionuclide content within some materials used in Latium (central Italy). Although the study was carried out in a limited area, the results confirm considerable variation in the primordial radionuclide content depending on the sites of origin.

Hormone replacement therapy and risk of lymphomas and myelomas.

The relation between post-menopausal hormone replacement therapy (HRT) and lymphoid neoplasms was analysed using data from a case-control study conducted in northern Italy between 1983 and 1992. Cases included 26 incident, histologically confirmed, post-menopausal female patients of Hodgkin's Disease (HD), 145 non-Hodgkin's lymphomas (NHL) and 65 multiple myelomas (MM), between 45 and 79 years of age. The control group comprised 361 women (age range 45-79 years) admitted to the same network of hospitals for acute, non-neoplastic conditions. The multivariate odds ratio (OR) for ever HRT users was 0.7 [95% confidence interval (CI) 0.2-2.8] for HD, 0.7 (95% CI 0.3-1.4) for NHL, and 0.2 (95% CI 0.1-1.0) for MM. No clear pattern of association was found for duration or recently of use. Despite the relatively small number of cases, due to the rarity of the disease, and the low frequency of HRT use in this population, these findings provide additional information for any global risk-benefit assessment of HRT use.

Cholecystectomy and the risk of colorectal cancer in Italy.

In two case-control studies from Italy covering 3533 cases of colorectal cancer and 7062 hospital controls, the odds ratios were 1.04 after cholecystectomy for colorectal, 1.08 for colon and 1.03 for rectal cancers. The results did not differ significantly by gender, colon subsite or time since diagnosis.

Cigarette smoking and risk of Hodgkin's disease.

The role of cigarette smoking on the risk of Hodgkin's disease remains controversial. To provide further information on the issue, we analysed data of a case-control study from northern Italy. The cases were 158 patients with incident, histologically confirmed Hodgkin's disease, and the controls were 316 patients, frequency-matched to the cases by age, sex and study centre, and admitted to the same network of hospitals for acute, non-neoplastic, non-alcohol- or non-tobacco-related conditions. Compared with those who had never smoked, the multivariate odds ratio was 0.54 for former and 0.85 for current smokers. No trend in risk was found for either the number of cigarettes smoked or the duration of consumption. None of the estimates, or the corresponding trends in risk, was statistically significant. Our results are consistent with those of several studies indicating no direct association between cigarette smoking and risk of Hodgkin's disease.

Infections and atopy: an exploratory study for a meta-analysis of the "hygiene hypothesis".

BACKGROUND: According to the "hygiene hypothesis" selected allergic diseases could be prevented by exposure to infectious agents during early childhood. METHODS: This study was performed to assess the feasibility of a future meta-analysis on the "hygiene hypothesis" and atopic diseases. Differences concerning the potential association with a history of infectious events, in terms of magnitude and homogeneity of global risk estimates between the three major atopic diseases (i.e. atopic dermatitis, asthma and allergic rhinitis) were examined. We conducted a preliminary analysis on a sample of articles published on this topic and cited in a recent and authoritative review. RESULTS: The ranges of relative risks estimates (between 0.6 and 0.8) were similar for atopic dermatitis, allergic rhinitis and asthma. Compared with asthma and allergic rhinitis, reported global risk estimates were more stable for atopic dermatitis (lowest heterogeneity). Our analysis suggests that three main categories of indirect markers of exposure to infection can be identified: 1) geographical gradient, 2) indices of potential contact with infectious agents (such as number of siblings) and 3) history of infectious events. CONCLUSIONS: In this exploratory study, we chose articles cited in a single review and obtained a preliminary quantification of the association between infections and atopic diseases. The association with indirect markers of infection corresponded to 20% protection for atopic dermatitis, 30% for allergic rhinitis and 40% for asthma. In a subsequent meta-analysis, diseases should be considered separately and differences between types of exposures should be taken into account as one of the major end-points, with attention to time since exposure and disease onset.