Comparison of different microbiological procedures for the diagnosis of Pneumocystis jirovecii pneumonia on bronchoalveolar-lavage fluid

Background: The current diagnostic gold standard for Pneumocystis jirovecii is represented by microscopic visualization of the fungus from clinical respiratory samples, as bronchoalveolar-lavage fluid, defining "proven" P. jirovecii pneumonia, whereas qPCR allows defining "probable" diagnosis, as it is unable to discriminate infection from colonization. However, molecular methods, such as end-point PCR and qPCR, are faster, easier to perform and interpret, thus allowing the laboratory to give back the clinician useful microbiological data in a shorter time. The present study aims at comparing microscopy with molecular assays and beta-D-glucan diagnostic performance on bronchoalveolar-lavage fluids from patients with suspected Pneumocystis jirovecii pneumonia. Bronchoalveolar-lavage fluid from eighteen high-risk and four negative control subjects underwent Grocott-Gomori's methenamine silver-staining, end-point PCR, RT-PCR, and beta-D-glucan assay.Results: All the microscopically positive bronchoalveolar-lavage samples (50%) also resulted positive by end-point and real time PCR and all, but two, resulted positive also by beta-D-glucan quantification. End-point PCR and RT-PCR detected 10 (55%) and 11 (61%) out of the 18 samples, respectively, thus showing an enhanced sensitivity in comparison to microscopy. All RT-PCR with a Ct <27 were confirmed microscopically, whereas samples with a Ct >= 27 were not.Conclusions: Our work highlights the need of reshaping and redefining the role of molecular diagnostics in a peculiar clinical setting, like P. jirovecii infection, which is a rare but also severe and rapidly progressive clinical condition affecting immunocompromised hosts that would largely benefit from a faster diagnosis. Strictly selected patients, according to the inclusion criteria, resulting negative by molecular methods could be ruled out for P. jirovecii pneumonia

Anti-HPV vaccination in women treated for HPV-related lesions: effective vaccination strategy for achieving HPV-related diseases control

Human Papillomavirus (HPV) vaccination is able to reduce the risk of relapse in women undergoing surgery for HPVrelated lesions. The surgical treatment of these lesions can correlate with a greater risk of preterm parts. The extension of the recommendation of HPV vaccination to patients treated for a previous HPV-related lesion would entail a lower expense for the Health System. Therefore, an increase in the use of HPV vaccination is desirable also in this target population as well as the implementation of a care pathway dedicated to women treated for HPV lesions that includes vaccination in the prevention activities of relapses

Development of a Nomogram Predicting the Risk of Persistence/Recurrence of Cervical Dysplasia

Background: Cervical dysplasia persistence/recurrence has a great impact on women's health and quality of life. In this study, we investigated whether a prognostic nomogram may improve risk assessment after primary conization. Methods: This is a retrospective multi-institutional study based on charts of consecutive patients undergoing conization between 1 January 2010 and 31 December 2014. A nomogram assessing the importance of different variables was built. A cohort of patients treated between 1 January 2015 and 30 June 2016 was used to validate the nomogram. Results: A total of 2966 patients undergoing primary conization were analyzed. The median (range) patient age was 40 (18-89) years. At 5-year of follow-up, 6% of patients (175/2966) had developed a persistent/recurrent cervical dysplasia. Median (range) recurrence-free survival was 18 (5-52) months. Diagnosis of CIN3, presence of HR-HPV types, positive endocervical margins, HPV persistence, and the omission of HPV vaccination after conization increased significantly and independently of the risk of developing cervical dysplasia persistence/recurrence. A nomogram weighting the impact of all variables was built with a C-Index of 0.809. A dataset of 549 patients was used to validate the nomogram, with a C-index of 0.809. Conclusions: The present nomogram represents a useful tool for counseling women about their risk of persistence/recurrence after primary conization. HPV vaccination after conization is associated with a reduced risk of CIN2+

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Surface-associated Motility in Bacillus subtilis

Motility of the Gram-positive bacterium Bacillus subtilis on solid surface

Surface-Associated Flagellum Formation and Swarming Differentiation in Bacillus subtilis Are Controlled by the ifm Locus

Knowledge of the highly regulated processes governing the production of flagella in Bacillus subtilis is the result of several observations obtained from growing this microorganism in liquid cultures. No information is available regarding the regulation of flagellar formation in B. subtilis in response to contact with a solid surface. One of the best-characterized responses of flagellated eubacteria to surfaces is swarming motility, a coordinate cell differentiation process that allows collective movement of bacteria over solid substrates. This study describes the swarming ability of a B. subtilis hypermotile mutant harboring a mutation in the ifm locus that has long been known to affect the degree of flagellation and motility in liquid media. On solid media, the mutant produces elongated and hyperflagellated cells displaying a 10-fold increase in extracellular flagellin. In contrast to the mutant, the parental strain, as well as other laboratory strains carrying a wild-type ifm locus, fails to activate a swarm response. Furthermore, it stops to produce flagella when transferred from liquid to solid medium. Evidence is provided that the absence of flagella is due to the lack of flagellin gene expression. However, restoration of flagellin synthesis in cells overexpressing σ(D) or carrying a deletion of flgM does not recover the ability to assemble flagella. Thus, the ifm gene plays a determinantal role in the ability of B. subtilis to contact with solid surfaces

LENTIVIRUS INFECTION IN AN AFRICAN LION - A CLINICAL, PATHOLOGICAL AND VIROLOGICAL STUDY

In May 1991, clinical, pathologic, and virologic investigations were carried out on an 8-yr-old male lion (Panthera lee), with recurrent infections, in captivity with two lionesses in the Zoological Garden of Pistoia, Tuscany, Italy. The lion had severe pneumonia, neutropenia, thrombocytopenia, and an increase in blood urea nitrogen and creatininemia; in spite of therapy, it died within 3 months. At necropsy, the animal had a lymphoma and other lesions similar to those described in feline immunodeficiency virus-infected cats. We identified FIV gag-sequence using PCR amplification of lymph node tissues

Il Locus IFM controlla la formazione di flagelli su superfici solide e il differenziamento swarming in Bacillus subtilis

Nel batterio Gram-positivo Bacillus subtilis la mobilità swarming su superfici solide è controllata dal locus ifm

HPV Vaccination in Women Treated for Cervical Intraepithelial Neoplasia: A Budget Impact Analysis

Human Papillomavirus (HPV) is the most common sexually transmitted infection. Its progression is related to the development of malignant lesions, particularly cervical intraepithelial neoplasias (CINs). CINs correlate with a higher risk of premature births, and their excisional and ablative treatment further increases this risk in pregnant women. These complications are also correlated with higher healthcare costs for their management. In Italy, more than 26,000 new cases of CINs are estimated to occur yearly and their economic burden is significant. Therefore, the management of these conditions is a public health priority. Since HPV vaccination is associated with a reduced risk of relapse in women surgically treated for HPV-related injuries, we estimated the economic impact of extending HPV vaccination to this target population. This strategy would result in a significant reduction in the general costs of managing these women, resulting in an overall saving for the Italian Health Service of €155,596.38 in 5 years. This lower cost is due not only to the reduced incidence of CINs following vaccination, but also to the lower occurrence of preterm births. Extending HPV vaccination to this target population as part of a care path to be offered to women treated for HPV injuries is therefore desirable

Swarming Differentiation and Swimming Motility in Bacillus subtilis Are Controlled by swrA, a Newly Identified Dicistronic Operon

The number and disposition of flagella harbored by eubacteria are regulated by a specific trait successfully maintained over generations. The genes governing the number of flagella in Bacillus subtilis have never been identified, although the ifm locus has long been recognized to influence the motility phenotype of this microorganism. The characterization of a spontaneous ifm mutant of B. subtilis, displaying diverse degrees of cell flagellation in both liquid and solid media, raised the question of how the ifm locus governs the number and assembly of functional flagella. The major finding of this investigation is the characterization of a newly identified dicistronic operon, named swrA, that controls both swimming motility and swarming differentiation in B. subtilis. Functional analysis of the swrA operon allowed swrAA (previously named swrA [D. B. Kearns, F. Chu, R. Rudner, and R. Losick, Mol. Microbiol. 52:357-369, 2004]) to be the first gene identified in B. subtilis that controls the number of flagella in liquid environments and the assembly of flagella in response to cell contact with solid surfaces. Evidence is given that the second gene of the operon, swrAB, is essential for enabling the surface-adhering cells to undergo swarming differentiation. Preliminary data point to a molecular interaction between the two gene products