MicroRNA-551b expression profile in low and high-grade cervical intraepithelial neoplasia

OBJECTIVE: To evaluate the expression of microRNA (miR)-551b in patients with low and high grade cervical intraepithelial neoplasia (CIN) and to find an association with high-risk Human Papillomavirus (HR-HPV) infection-related prognostic biomarkers. PATIENTS AND METHODS: The expression level of miR-551b was determined in 50 paraffin-embedded cervical specimens (10 normal squamous epithelium, 18 condylomas, 8 CIN1, and 14 CIN2-3) using quantitative Real-time polymerase chain reaction (qRT-PCR). χ2-test compared miR-551b expression in different diagnosis groups. An Ordered Logistic Regression and a Probit correlation were made to correlate miR-551b expression levels with the cervical tissue histological findings. The immunohistochemical distribution of p16 and Ki-67 according to histopathological findings was also assessed. RESULTS: The distribution of the miR-551b expression profile was significantly lower in CIN1-3 samples compared to other histological diagnosis groups (condyloma and negative). The expression levels were inversely correlated to the cervical pathological grade, from negative to CIN2-3. A 1% increase in miR-551b expression level produced an increase of 19% to the probability of a minor histological grade diagnosis in a range from negative to CIN2-3 and an increase of 13% to the probability of a negative histological grade diagnosis. Among the cases with miR-551b expression < 0.02 (considered as cut-off value) a significant statistical correlation was found between p16 and Ki-67 expression and the diagnosis of CIN2-3. CONCLUSIONS: O ur d ata s howed a s ignificant inverse correlation between miR-551b expression and the histological grading of the lesions, suggesting a tumor suppressive function in the different stages of cervical dysplasia

Afatinib in the first-line treatment of patients with non-small cell lung cancer: clinical evidence and experience

Epidermal growth factor receptor (EGFR) gene mutations identify a molecularly defined subset of non-small cell lung cancer (NSCLC) patients who display an excellent sensitivity to EGFR tyrosine kinase inhibitors (TKIs). First-generation reversible EGFR TKIs, gefitinib and erlotinib have been proven to improve the objective response rate and to prolong the progression-free survival compared with standard chemotherapy in large phase III trials. Unfortunately, virtually all patients develop resistance to treatment, usually within 9–12 months. Afatinib is an irreversible ErbB family inhibitor initially designed to overcome the development of resistance. Compared with gefitinib in a first-line setting, afatinib prolonged progression-free survival and time to treatment failure, without impacting on overall survival in the general population of EGFR-mutant patients. However, afatinib has been shown to prolong overall survival in the subset of patients with an EGFR exon 19 deletion compared with chemotherapy. The aim of this review is to summarize the clinical evidence available to date and to critically discuss the place in therapy of afatinib in the rapidly expanding landscape of EGFR-mutant NSCLC first-line therapy

Prognostic factors facilitating multiple food allergies and atopiv march occurrence in children with Non-IgE mediated gastrointestinal Food Allergy: results of two years follow up of the NIGEFA project

Objectives and Study: Non-IgE mediated gastrointestinal food allergies (non-IgE-GIFA) are an increasing problem in pediatric gastroenterology clinical practice. These conditions include food protein-induced: enterocolitis syndrome (FPIES), enteropathy (FPE), allergic proctocolitis (FPIAP), and motility disorders (FPIMD). The NIGEFA project is focused on the investigation of main clinical features, prognostic factors (presence atopic dermatitis (AD), multiple food allergies, diagnostic delay, and familial history of allergy), and natural history (atopic march (AM) prevalence and timing of immune tolerance acquisition). Methods: Prospective observational study evaluating children with non-IgE-GIFA diagnosed according to standard criteria observed at a tertiary center for pediatric gastroenterology and allergy (both sexes, aged <36 m, follow up 12 m after diagnosis). Main anamnestic, demographic, and clinical data were collected from all enrolled patients. Immune tolerance acquisition was evaluated by the result of oral food challenge. Results: A total of 100 patients were enrolled: 58% male, mean age at diagnosis (SD) 8.5(8.8) m. Non-IgE-GIFA conditions were: FPE (44%), FPIES (11%), FPIAP (18%), FPIMD (27%). Mean diagnostic delay was 5.3 (7.4) m. Multiple non-IgE-GIFA were observed in 47% at baseline. Familial history of allergy was observed in 64% of subjects. Presence of AD before the onset of non-IgE-GIFA was observed in 40% of subjects. The overall rate of immune tolerance acquisition at 12 m was 27%, with a higher rate in FPIAP (44%) compared with FPIMD (29.6%), FPE (22.7%) and FPIES (9.1%) subjects (p<0.05). The rate of immune tolerance acquisition at 12 m was significantly lower in children with familial history of allergy (-48%, estimated risk ratio (RR)0.52 (95% CI 0.28 to 0.99, p<0.05)) and in those with multiple non-IgE-GIFA (-61%, RR at 12 m 0.39 (95% CI 0.18 to 0.85, p<0.05)). At 12 m follow up, the rate of subjects presenting AM was 24% with no difference among the 4 disease groups. The occurrence of AM was significantly higher in subjects with multiple (38%) vs. mono non-IgE-GIFA (11%) (p<.001) at baseline, with an estimated RR of 3.38 (95% CI 1.47 to 7.81, p<0.01) at 12 m. Moreover, for every 1-month of diagnostic delay there was an increase of 1.04 RR(95% CI 1.01 to 1.07) of AM occurrence at 12 m. No associations with other potential predictors (sex, familial allergy risk, AD before the onset of GIFA, type of non-IgE-GIFA) were found. Conclusions: These data shed lights on prognostic factors and natural history of non-IgE-GIFA suggesting the importance of early diagnosis in preventing the occurrence of AM occurrence in these patients. Contac

Artificial intelligence applications and cataract management: A systematic review

Artificial intelligence (AI)-based applications exhibit the potential to improve the quality and efficiency of patient care in different fields, including cataract management. A systematic review of the different applications of AI-based software on all aspects of a cataract patient's management, from diagnosis to follow-up, was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. All selected articles were analyzed to assess the level of evidence according to the Oxford Centre for Evidence-Based Medicine 2011 guidelines, and the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation system. Of the articles analyzed, 49 met the inclusion criteria. No data synthesis was possible for the heterogeneity of available data and the design of the available studies. The AI-driven diagnosis seemed to be comparable and, in selected cases, to even exceed the accuracy of experienced clinicians in classifying disease, supporting the operating room scheduling, and intraoperative and postoperative management of complications. Considering the heterogeneity of data analyzed, however, further randomized controlled trials to assess the efficacy and safety of AI application in the management of cataract should be highly warranted

Continental-Scale Partitioning of Fire Emissions During the 1997 to 2001 El Niño/La Niña Period

During the 1997 to 1998 El Niño, drought conditions triggered widespread increases in fire activity, releasing CH_4 and CO_2 to the atmosphere. We evaluated the contribution of fires from different continents to variability in these greenhouse gases from 1997 to 2001, using satellite-based estimates of fire activity, biogeochemical modeling, and an inverse analysis of atmospheric CO anomalies. During the 1997 to 1998 El Niño, the fire emissions anomaly was 2.1 ± 0.8 petagrams of carbon, or 66 ± 24% of the CO_2 growth rate anomaly. The main contributors were Southeast Asia (60%), Central and South America (30%), and boreal regions of Eurasia and North America (10%)

X-ray Near Field Speckle: Implementation and Critical Analysis

We have implemented the newly-introduced, coherence-based technique of x-ray near-field speckle (XNFS) at 8-ID-I at the Advanced Photon Source. In the near field regime of high-brilliance synchrotron x-rays scattered from a sample of interest, it turns out, that, when the scattered radiation and the main beam both impinge upon an x-ray area detector, the measured intensity shows low-contrast speckles, resulting from interference between the incident and scattered beams. We built a micrometer-resolution XNFS detector with a high numerical aperture microscope objective and demonstrate its capability for studying static structures and dynamics at longer length scales than traditional far field x-ray scattering techniques. Specifically, we characterized the structure and dynamics of dilute silica and polystyrene colloidal samples. Our study reveals certain limitations of the XNFS technique, which we discuss.Comment: 53 pages, 16 figure

Case report of an atypical early onset X-linked retinoschisis in monozygotic twins

Background: X-linked Retinoschisis (XLRS) is one of the most common macular degenerations in young males, with a worldwide prevalence ranging from 1:5000 to 1:20000. Clinical diagnosis of XLRS can be challenging due to the highly variable phenotypic presentation and limited correlation has been identified between mutation type and disease severity or progression. Case presentation: We report the atypical early onset of XLRS in 3-month-old monozygotic twins. Fundus examination was characterized by severe bullous retinal schisis with pre-retinal and intraretinal haemorrhages. Molecular genetic analysis of the RS1 was performed and the c.288G &gt; A (p. Trp96Ter) mutation was detected in both patients. Conclusions: Early onset XLRS is associated with a more progressive form of the disease, characterized by large bullous peripheral schisis involving the posterior pole, vascular abnormalities and haemorrhages. The availability of specific technology permitted detailed imaging of the clinical picture of unusual cases of XLRS. The possible relevance of modifying genes should be taken into consideration for the future development of XLRS gene therapy

Evaluation of an image analysis device (APAS) for screening urine cultures

While advancements have been made in some areas of pathology with diagnostic materials being screened using image analysis technologies, the reporting of cultures from agar plates remains a manual process. We compared the results for 2,163 urine cultures read by a reference panel of microbiologists, by the routine laboratory process, and by an automated plate reading system, APAS (LBT Innovations Ltd., South Australia). APAS detected colonies with a sensitivity of 99.1% and a specificity of 99.3% on blood agar, while on MacConkey agar, the colony detection sensitivity was 99.4% with a specificity of 99.3%. The device's ability to enumerate growth had an accuracy of 89.2%, and the morphological identification of colonies showed a high level of performance for the colony types typical of Escherichia coli and other enteric bacilli. On blood agar, lactose-fermenting colonies were morphologically identified with a sensitivity of 98.9%, while on MacConkey agar they were identified with a sensitivity of 99.2%. In this first clinical evaluation, APAS demonstrated high performance in the detection, enumeration, and colony classification of isolates compared with that for conventional plate-reading methods. The device found all cases reported by the laboratory and detected the most commonly encountered organisms found in urinary tract infections.John Glasson, Rhys Hill, Michael Summerford, Steven Gigli