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The early diagnosis and treatment of individuals harboring M. tuberculosis is key to ensuring the effectiveness of health programs aimed at the elimination of tuberculosis (TB). Monitoring for TB also has other important health care implications for the related immune pathology caused by the chronic inflammatory response to M. tuberculosis. Moreover, the recent introduction of biologic therapies for the treatment of several immune-mediated inflammatory diseases has shown unexpected high frequencies of reactivation of latent TB. The present cross-sectional study is aimed at estimating the prevalence of latent tuberculosis infection (LTBI) in different groups of subjects, either undergoing a routine program of screening for TB or a clinical monitoring of autoimmune or lung disorders, by analyzing their immune response in vitro to a pool of different M. tuberculosis antigens through an IFN-gamma-release assay (IGRA). We consecutively tested 1,644 subjects including health care workers (931), healthy immigrants from different countries (93), patients with a diagnosis of psoriasis (405), patients with lung inflammatory disease (60) or lung neoplasia (32) and a group of HIV-1 infected Italian subjects (120). The prevalence of IGRAs positive responses among health care workers was 8.9 percent. In comparison, significantly higher frequencies were found in healthy immigrant subjects (33.3%), similar to those found in inflammatory broncho-pneumopathies (34.5%) or lung cancer (29.6%). Interestingly, an unexpected high prevalence was also found in patients affected by psoriasis (18.0%), while HIV-infected subjects had values comparable to those of health care workers (10.8%). An age cut-off was determined and applied for each group by receiver operating characteristic (ROC) curves in order to perform the statistical analysis among age-comparable groups. Multivariate analysis showed that the age and clinical conditions such as having a diagnosis of psoriasis or a lung inflammatory disease were independent risk factors for developing an IGRA positive response. This study highlights an unprecedented high prevalence of IGRA positive responses among patients affected by psoriasis and emphasizes the need for a preliminary assessment of LTBI before the administration of any biologic therapy based on cytokine antagonists such as anti-TNF-alpha. Moreover, screening for LTBI should be routinely performed in the presence of a chronic pulmonary disease.

Background: Involvement of various gene mutations in hypertension have been already reported, including GST (detoxification Phase II enzymes), with contrasting results. This study analyzes a possible association between GSTM1-null and GSTT1-null polymorphisms and the hypertension status in a very old population (>80 years)., Methods: 354 old patients were collected (255 were hypertensive and 99 were not)., Results: GSTM1-null individuals (n=156) were significantly associated with increased risk of hypertension [OR=2.25 (1.36-3.72); p=0.005]. This association was confirmed both in 115 male and 239 female subjects. In contrast, no significant association was observed [p=0.52, OR=1.24 (0.67-2.29)] in the 57 hypertensive GSTT1-null genotypes vs 198 wild-type individuals. The above mentioned significances were obtained by multivariate logistic regression analysis after adjusting for confounder variables. Alcohol consumption and/or smoke habits were not significantly different between the two groups, as well as gender, marital status, education, number of concomitant diseases, and presence of cardiovascular diseases. No synergistic association was observed for the combined null genotypes of GSTT1 and GSTM1., Conclusions: The knowledge of GSTM1 variant status seems to be potentially useful to predict a possible hypertensive status after 80 years of age. This study underlines a possible importance of the GSTM1 enzyme for blood pressure regulation.

Background: Literature data report an association between some vitamin D receptor (VDR) polymorphisms and different kinds of tumours, including malignant melanoma (MM). Only three VDR polymorphisms (FokI, TaqI and A-1012G) have been investigated in association with the presence of cutaneous MM or the development of metastases., Objectives: The present paper analyses for the first time the association between BsmI polymorphism and MM prevalence together with Breslow thickness. In addition, the FokI single nucleotide polymorphism was also determined., Methods: One hundred and one patients with MM and 101 healthy donors matched for age and sex were enrolled. Molecular VDR typing was performed by means of restriction fragment length polymorphism analysis., Results: All cases and controls were in Hardy-Weinberg equilibrium for BsmI, FokI and A-1012G. Significant associations were found between the BsmI bb genotype frequency and MM (P = 0.02) along with Breslow thickness (P = 0.001). This same behaviour was not observed for the FokI or A-1012G polymorphisms. Multivariate logistic regression analysis confirmed these significant results after correction for age, gender, skin type and MM localization., Conclusions: Although the biological meaning of the effects exerted by BsmI polymorphism is still under debate, the statistical association found in the present study suggests that further work should be done to verify this variant as a possible risk marker for MM and its aggressiveness, also considering that the real association may be due to other unknown genes linked to the BsmI b allele.

Background: The association between head and neck squamous cell carcinoma (HNSCC) and allelic variants of glutathione S-transferase M1 (GSTM1) and -T1 (GSTT1) is currently controversial. The present study investigates the prevalences of GSTT1 and GSTM1 polymorphism in a cohort of 100 head and neck cancer patients, 100 healthy donors and 200 controls with non-neoplastic head and neck diseases from Italian Lazio Region., Methods: The patients with benign head and neck pathologies, as well as the healthy donors were matched for age, sex, cigarette smoke (yes/no) and alcohol consumption (yes/no). Molecular definition of GSTT1 and GSTM1 genotype has been performed by means of allele-specific PCR technique., Results: A significant association between head and neck cancer and GSTM1 null genotype was observed both considering benign disease controls (p=0.001, OR=2.613; 95% C.I.=1.48-4.62), and healthy donors (p=0.0003, OR=3.35; 95% C.I. 1.69-6.67) while no significant association was found with GSTT1 null genotype (p>or=0.14). No interactive association was observed when combining the different genotypes of the two polymorphisms. These results were confirmed after correction for daily number of cigarettes and period of tobacco exposure., Conclusions: The present study confirms a role for genetic alterations of GSTM1 detoxifying enzyme as a risk factor for the development of HNSCC in patients from the Italian Lazio Region, independently of age, sex and other confounding variables.

Objective: In addition to the previous classification of chronic lung disease (CLD) O2 dependency at 36 weeks of postmenstrual age, a new definition of CLD has recently been proposed: new bronchopulmonary-dysplasia (BPD). This uses total duration of O2 supplementation and positive pressure requirements to delineate three degrees of severity (mild, moderate, and severe) according to the respiratory status at 36 weeks postmenstrual age. We analyzed the balance of serum proinflammatory and profibrotic/angiogenic cytokine concentrations in relation to CLD and the new BPD definition., Design and Setting: Descriptive study in a third-level neonatal ICU., Patients: Thirty-one preterm neonates with a gestational age of 24-29 weeks were studied to evaluate their serum cytokine concentration; they were previously enrolled in a randomized clinical trial to compare the effects of high-frequency oscillatory ventilation vs. intermittent mandatory ventilation in terms of pulmonary mechanics and lung cytokines. Serum samples were collected on days 1, 3, and 5 after birth until extubation to detect the levels of three proinflammatory cytokines plus four profibrotic/angiogenic cytokines, and correlations were examined to old CLD and new BPD. Ventilation treatments were distributed homogeneously between the groups and did not interfere with the results presented here., Results and Conclusions: Old CLD development, mainly corresponding to the moderate/severe forms of new BPD, was associated with increased proinflammatory and profibrotic/angiogenic cytokines, while mild forms of new BPD were characterized only by increases in profibrotic/angiogenic cytokines, suggesting a different balance of two pathogenic mechanisms in different phases of the disease.