Study of Patients Self-Training Influence on Peripheral Neuropathies Diseases Diagnosis through D.I.T.A Device.

In our daily life, the sight and the sense of touch play a fundamental role in objects recognitions. This process is helped by the experience: if a subject has already seen or already touched an object in the past, he will recognize it more easily in the future. Following this assumption, the authors of this paper wanted to investigate if the experience can influence the results of a clinical examination where the subject has an active role. The attention was focused on the peripheral neuropathies diagnosis since they require an accurate assessment of several parameters including the tactile sensitivity trend. In other words, if the tests encompass an active role of the subjects, one of the main uncertainties is the self-training that influences the subject responses. This work focuses on the study of this self-training using the D.I.T.A device (Dynamic Investigation Test-rig on hAptics). Results clearly show a fundamental role of priming during "haptic modality": expert subjects, previously experienced with the tests, demonstrated better recognition of the encountered stimuli, compared to novices. Moreover, the results show that the maximum difference between the two groups of subjects is in the first part of the test. An ANOVA analysis was carried out to demonstrate that also the errors between the pins-arrays are affected by the priming.

Frequent detection of high human papillomavirus DNA loads in oral potentially malignant disorders.

Human papillomavirus (HPV) is estimated to be the cause of 40--80% of the squamous cell carcinoma of the oropharynx but only of a small fraction of the oral cavity cancers. The prevalence of oral HPV infection has significantly increased in the last decade, raising concerns about the role of HPV in progression of oral potentially malignant disorders (OPMD) toward squamous cell carcinomas. We sought to study HPV infection in patients with oral lesions, and in control individuals, using non-invasive and site-specific oral brushing and sensitive molecular methods. HPV DNA positivity and viral loads were evaluated in relation to patient data and clinical diagnosis. We enrolled 116 individuals attending Dental Clinics: 62 patients with benign oral lesions (e.g. fibromas, papillomatosis, ulcers) or OPMD (e.g. lichen, leukoplakia) and 54 controls. Oral cells were collected with Cytobrush and HPV-DNA was detected with quantitative real-time PCR for the more common high-risk (HR) and low-risk (LR) genotypes. HPV detection rate, percentage of HR HPVs and HPV-DNA loads (namely HPV16 and in particular, HPV18) were significantly higher in patients than in controls. Lichen planus cases had the highest HPV-positive rate (75.0%), hairy leukoplakia the lowest (33.3%). This study detected unexpectedly high rates of HPV infection in cells of the oral mucosa. The elevated HR HPV loads found in OPMD suggest the effectiveness of quantitative PCR in testing oral lesions. Prospective studies are needed to establish whether elevated viral loads represent a clinically useful marker of the risk of malignant progression.

Development and validation of a tactile sensitivity scale for peripheral neuropathy screening.

One of the difficult of the hands peripheral neuropathy screening uncertainty is that the current diagnosis is based not on assessments obtained by accurate and repeatable devices, but mostly on the clinical examination. So, in this paper the authors present a tactile pins-array scale determined with well-defined parameters assessed by non-invasive DITA device (Dynamic Investigation Test-rig on hAptics). This high resolution scale permits to screen the gradual tactile sensory deficit of patients affected by neuropathic diseases. The work has started with an experiment on healthy subjects penalizing their bare finger tactile sensitivity with five different pins-arrays. So, a pins-array scale divided in six levels (grouped in three ranges: low, uncertain and normal tactile sensitivity) was created. The scale was validated with a pilot study on six subjects affected by neuropathic disease. Results show an important role of the scale, supporting the clinical screening and reducing the uncertainty.

HPV16 E5 affects the KGFR/FGFR2b-mediated epithelial growth through alteration of the receptor expression, signaling and endocytic traffic.

The E5 oncoprotein of the human papillomavirus type 16 (HPV16 E5) cooperates in cervical carcinogenesis and in epithelial transformation deregulating cell growth, survival and differentiation through the modulation of growth factor receptors. Among the epithelial receptor tyrosine kinases, the keratinocyte growth factor receptor/fibroblast growth factor receptor 2b (KGFR/FGFR2b) is a major paracrine mediator of epithelial homeostasis and appears to have an unique and unusual role in epithelial tissues, exerting a tumor-suppressive function in vitro and in vivo. With the aim to better elucidate the molecular events involved in the pathological activity of 16E5, we investigated if the viral protein would be able to affect the KGFR expression, signaling and turnover by interference with its degradative and recycling endocytic pathways. Quantitative reverse transcriptase-PCR and biochemical approaches on human keratinocytes transfected with 16E5-HA showed that E5 protein is able to induce KGFR down-modulation at both transcript and protein levels. Immunofluorescence microscopy in double-transfected cells expressing both E5 and KGFR revealed that the viral protein alters the receptor endocytic trafficking and triggers its endosomal sorting to the indirect juxtanuclear recycling pathway. The shift from lysosomal degradation to recycling at the plasma membrane correlates with a reduced phosphorylation of the fibroblast growth factor receptor substrate-2α tyrosine 196, the major docking site for Grb2-Cbl complexes responsible for receptor ubiquitination and degradation. 5'-Bromo-deoxyuridine incorporation assay demonstrated that expression of 16E5 induces a decrease in the growth response to the receptor ligands as a consequence of KGFR down-modulation, suggesting that 16E5 might have a role on HPV infection in perturbing the KGFR-mediated physiological behavior of confluent keratinocytes committed to differentiation.