A novel diagnostic method to detect truncated neurofibromin in neurofibromatosis 1.

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic condition caused by dominant loss-of-function mutations of the tumor suppressor gene NF1 that encodes neurofibromin, a negative regulator of RAS activity. Mutation analysis of NF1 located at 17q11.2 has been hampered by the large size of the gene, the high rate of new mutations, the lack of mutational clustering, and the presence of several homologous loci. To date, about 80% of the reported NF1 mutations are predicted to result in protein truncation, but very few studies have correlated the causative NF1 mutation with its effect at the protein level. We evaluated a novel diagnostic method to detect truncated forms of neurofibromin in a large cohort of unrelated subjects suspected of having NF1, according to the NIH consensus criteria. Western blot analysis was carried out on protein extracts from patients' leukocytes to highlight the possible presence of altered neurofibromin as a result of mutations in NF1. Truncated neurofibromin was identified in 274/336 patients (81%), confirming the usefulness and reproducibility of the proposed diagnostic approach. Our methodology can be routinely applied in the diagnostic setting, thanks to its simplicity and reliability. Combined with molecular approaches, it may increase the accuracy and efficiency of NF1 genetic testing. We evaluated a novel diagnostic method to detect truncated forms of neurofibromin in patients fulfilling the clinical criteria for Neurofibromatosis 1. Western blot analysis identified truncated neurofibromin in 274/336 patients (81%). Our results indicate that the proposed technique is cheap and reliable, and could ideally be performed as a preliminary biochemical screening before molecular analysis of the NF1 gene.

Work-related upper limb disorders and risk assessment among automobile manufacturing workers: A retrospective cohort analysis.

OBJECTIVE: To estimate the three-year cumulative risk of work-related upper limb disorders (WRULDs) in a cohort of automotive industry workers and to provide a first test of the ability of the European Assembly Worksheet (EAWS) methodology to predict WRULDs. METHODS: 292 workers were investigated by reviewing workers' medical records during the period from 2012-2015 to determine their exposure to biomechanical overload according to EAWS risk scores (0-25, low risk, Green zone; 26-50, medium risk, Yellow zone; >50, High risk; Red zone). RESULTS: The risks were 0.83%, 5.71%, and 11.88% for the Control (unexposed), Green and Yellow Groups, respectively. Only the comparison between the Yellow/Control Groups was significant (p = 0.0014). In total, we observed 17 cases of musculoskeletal disorders (MSDs) (14 symptomatic and 3 cases detected by physical examination). CONCLUSIONS: The EAWS is a useful tool for the preliminary risk assessments of biomechanical overload among automotive industry workers. The finding of mainly non-specific disorders highly suggests that health surveillance should aim to identify not only full-blown diseases but also symptomatic cases.

Prevalence of latent tuberculosis infection and associated risk factors among 1557 nursing students in a context of low endemicity.

INTRODUCTION: The risk of tuberculosis (TBC) in nurses is related to its incidence in the general population. Nursing students involved in clinical training could be exposed to occupational risks similar to those of healthcare workers (HCWs). To better understand the epidemiology of nosocomial TBC among nurses in a context of low endemicity, we recruited a cohort of young nursing trainees at the Second University of Naples. METHODS: A screening programme for LTBI in nursing students was conducted between January 2012 and December 2013, at the Second University of Naples, with clinical evaluations, tuberculin skin test (TST) and, in positive TST student, the interferon-g release assays (IGRA). Putative risk factors for LTBI were assessed by a standardized questionnaire. RESULTS: 1577 nursing students attending the Second University of Naples have been submitted to screening programme for TBC. 1575 have performed TST as first level test and 2 Quantiferon test (QFT). 19 students were TST positive and continued the diagnostic workup practicing QFT, that was positive in 1 student. Of the 2 subjects that have practiced QFT as first level test only 1 was positive. In 2 students positive to QFT test we formulated the diagnosis of LTBI by clinical and radiographic results. CONCLUSION: The prevalence of LTBI among nursing students in our study resulted very low. In countries with a low incidence of TBC, the screening programs of healthcare students can be useful for the early identification and treatment of the sporadic cases of LTBI.

Tuberculin skin test and Quantiferon test agreement and influencing factors in tuberculosis screening of healthcare workers: a systematic review and meta-analysis.

OBJECTIVE: A systematic review and meta-analysis was conducted to evaluate the agreement between Tuberculin Skin Test (TST) and Quantiferon (QFT) in screening for tuberculosis (TB) infection among healthcare workers (HCWs) and to estimate associations between TST and QFT agreement and variables of interest, such as Bacillus Calmette-Guérin (BCG) vaccination and incidence of TB. METHODS: Cross-sectional and longitudinal studies on HCWs, published in English until October 2013, comparing TST and QFT results, were selected. For each study Cohen's κ value and a 95% confidence interval were calculated. Summary measures and indexes of heterogeneity between studies were calculated. RESULTS: 29 studies were selected comprising a total of 11,434 HCWs. Cohen's κ for agreement between TST and QFT for 24 of them was 0.28 (95% CI 0.22 to 0.35), with the best value in high TB incidence countries and the lowest rate of BCG vaccination. CONCLUSION: Currently, there is no gold standard for TB screening and the most-used diagnostic tools show low agreement. For evidence-based health surveillance in HCWs, occupational physicians need to consider a number of factors influencing screening results, such as TB incidence, vaccination status, age and working seniority.

Prevalence of latent tuberculosis infection and associated risk factors among 3,374 healthcare students in Italy.

INTRODUCTION: The risk of tuberculosis (TB) in healthcare personnel (HCP) is related to its incidence in the general population. Healthcare students involved in clinical training could be exposed to occupational risks similar to those that HCP face. The prevalence of latent tuberculosis infection (LTBI) among undergraduate healthcare students with different working seniority in Italy was analysed. METHODS: A cross-sectional study under a screening programme for LTBI among undergraduate and postgraduate students attending Medical School at the Second University of Naples was conducted between January 2012 and December 2013 with clinical evaluations, tuberculin skin testing (TST) and, in positive TST students, Interferon-γ release assays (IGRA). Putative risk factors for LTBI were assessed by means of a standardised questionnaire. RESULTS: 3,374 students attending the Medical School of the Second University of Naples were submitted to a screening programme for TBC. 3,331 performed TST as a first-level test and 43 performed a Quantiferon test (QFT). 128 students were TST-positive and continued the diagnostic work with QFT, which was positive in 34 students. Of the 43 subjects who took the QFT as a first-level test only 1 was positive. In 35 students positive to the QFT test we formulated the diagnosis of LTBI by clinical and radiographic results. A correlation was found between age, non-Italian born persons, studying age, post-medical school status and LTBI. CONCLUSIONS: The prevalence of LTBI among healthcare students in our study was very low. In countries with a low incidence of TB, the screening programmes of healthcare students can be useful for early identification and treatment of sporadic cases of LTBI.