Novel PTCH1 Mutations in Patients with Keratocystic Odontogenic Tumors Screened for Nevoid Basal Cell Carcinoma (NBCC) Syndrome

Keratocystic odontogenic tumors (KCOTs) are cystic tumors that arise sporadically or associated with nevoid basal cell carcinoma syndrome (NBCCS). NBCCS is a rare autosomal dominantly inherited disease mainly characterized by multiple basal cell carcinomas, KCOTs of the jaws and a variety of other tumors. PTCH1 mutation can be found both in sporadic or NBCCS associated KCOTs. The aim of the current study was to assess whether a combined clinical and bio-molecular approach could be suitable for the detection of NBCCS among patients with a diagnosis of keratocystic odontogenic tumors (KCOTs). The authors collected keratocystic odontogenic tumors recorded in the database of the Pathology Department of the University of Modena and Reggio Emilia during the period 1991-2011. Through interviews and examinations, family pedigrees were drawn for all patients affected by these odontogenic lesions. We found out that 18 of the 70 patients with KCOTs and/or multiple basal cell carcinomas actually met the clinical criteria for the diagnosis of NBCCS. A wide inter- and intra-familial phenotypic variability was evident in the families. Ameloblastomas (AMLs) were reported in two probands that are also carriers of the PCTH1 germline mutations. Nine germline mutations in the PTCH1 gene, 5 of them novel, were evident in 14 tested probands. The clinical evaluation of the keratocystic odontogenic tumors can be used as screening for the detection of families at risk of NBCCS. Keratocystic odontogenic lesions are uncommon, and their discovery deserves the search for associated cutaneous basal cell carcinomas and other benign and malignant tumors related to NBCCS.     

Observed Touch on a Non-Human Face Is Not Remapped onto the Human Observer's Own Face

Visual remapping of touch (VRT) is a phenomenon in which seeing a human face being touched enhances detection of tactile stimuli on the observer''s own face, especially when the observed face expresses fear. This study tested whether VRT would occur when seeing touch on monkey faces and whether it would be similarly modulated by facial expressions. Human participants detected near-threshold tactile stimulation on their own cheeks while watching fearful, happy, and neutral human or monkey faces being concurrently touched or merely approached by fingers. We predicted minimal VRT for neutral and happy monkey faces but greater VRT for fearful monkey faces. The results with human faces replicated previous findings, demonstrating stronger VRT for fearful expressions than for happy or neutral expressions. However, there was no VRT (i.e. no difference between accuracy in touch and no-touch trials) for any of the monkey faces, regardless of facial expression, suggesting that touch on a non-human face is not remapped onto the somatosensory system of the human observer.     

Transfer factor with anti-EBV activity as an adjuvant therapy for nasopharyngeal carcinoma: A pilot study

Overall survival of nasopharyngeal carcinoma (NPC) at UICC stage IV still remains unsatisfactory even with combination chemotherapy (CT) and radio-therapy (RT). In view of the association of reactivation of Epstein-Barr virus (EBV) with the development and recurrence of NPC, immunotherapy in the form of transfer factor (TF) with specific activity against EBV (TF-B1) was suggested as an adjuvant to a combination of CT and RT in order to improve survival. In the present study, 6 UICC Stage IV patients received TF-B1 and another 6 patients matched for disease stage were given TF prepared from peripheral blood leucocytes (TF-PBL). Results were compared with another 18 patients matched by age, sex, and stage of disease who received standard therapy without TF during the same period (C group). After a median follow up of 47.5 months, the survival for the TF-B1 group was found to be significantly better (P=<0.05) than the PBL and C group. While the 8 patients with distant metastasis (DM), not treated with TF-B1 (6 in the control and 2 in the PBL group), died due to progressive disease (average survival being 14.3 months), both patients with DM in the TF-B1 group had complete remission: one died of tuberculosis after surviving for 3.5 years and another is still alive, disease free, after 4.2 years. Although the series involved a small number of cases, the apparent effect of adjuvant immunotherapy in the form of TF with anti-EBV activity is of considerable interest.     

Stereotactic radiotherapy for bone oligometastases

About 60–90% of cancer patients are estimated to develop bone metastases, particularly in the spine.Bone scintigraphy, computed tomography (CT ) and magnetic resonance imaging (MRI ) are currently used to assess metastatic bone disease; positron emission tomography/computed tomography (PET-CT ) has become more widespread in clinical practice because of its high sensitivity and specificity with about 95% diagnostic accuracy. The most common and well-known radiotracer is 18F-fluorodeoxyglucose (¹⁸FDG); several other PET-radiotracers are currently under investigation for different solid tumors, such as ¹¹C or ¹⁸FDG-choline and prostate specific membrane antigen (PSMA)-PET/CT for prostate cancer. In treatment planning, standard and investigational imaging modalities should be registered with the planning CT so as to best define the bone target volume. For target volume delineation of spine metastases, the International Spine Radiosurgery Consortium (ISRC ) of North American experts provided consensus guidelines. Single fraction stereotactic radiotherapy (SRT ) doses ranged from 12 to 24 Gy; fractionated SRT administered 21–27 Gy in 3 fractions or 20–35 Gy in 5 fractions. After spine SRT, less than 5% of patients experienced grade ≥ 3 acute toxicity. Late toxicity included the extremely rare radiation-induced myelopathy and a 14% risk of de novo vertebral compression fractures.     

The Enfacement Illusion Is Not Affected by Negative Facial Expressions

Enfacement is an illusion wherein synchronous visual and tactile inputs update the mental representation of one’s own face to assimilate another person’s face. Emotional facial expressions, serving as communicative signals, may influence enfacement by increasing the observer’s motivation to understand the mental state of the expresser. Fearful expressions, in particular, might increase enfacement because they are valuable for adaptive behavior and more strongly represented in somatosensory cortex than other emotions. In the present study, a face was seen being touched at the same time as the participant’s own face. This face was either neutral, fearful, or angry. Anger was chosen as an emotional control condition for fear because it is similarly negative but induces less somatosensory resonance, and requires additional knowledge (i.e., contextual information and social contingencies) to effectively guide behavior. We hypothesized that seeing a fearful face (but not an angry one) would increase enfacement because of greater somatosensory resonance. Surprisingly, neither fearful nor angry expressions modulated the degree of enfacement relative to neutral expressions. Synchronous interpersonal visuo-tactile stimulation led to assimilation of the other’s face, but this assimilation was not modulated by facial expression processing. This finding suggests that dynamic, multisensory processes of self-face identification operate independently of facial expression processing.     

Persistence of Enterococcus faecalis in aquatic environments via surface interactions with copepods

Several human pathogens and fecal-pollution indicators may persist as viable organisms in natural environments, owing to their ability to activate different types of survival strategies. These strategies include adhesion on both abiotic and biotic surfaces and the entrance to the so-called viable but nonculturable (VBNC) state. In an 18-month survey for the detection of enterococci in both lake water and seawater, C. Signoretto et al. (Appl. Environ. Microbiol. 70:6892-6896, 2004) have shown that Enterococcus faecalis was detected mostly bound to plankton and in the VBNC state. In the present study, we show that in vitro adhesion of E. faecalis to copepods accelerated the entry of cells into the VBNC state relative to that of planktonic bacteria. VBNC E. faecalis cells maintained their adhesive properties to copepods and chitin (the main component of the copepod carapace), though to a reduced extent in comparison with growing cells. Sugar competition experiments showed interference with adhesion to both copepods and chitin by GlcNAc and only to copepods by D-mannose. Four enterococcal cell wall proteins present in both growing and VBNC cells and lipoteichoic acid were shown to be capable of binding chitin. The results indicate that copepods may represent an additional environmental reservoir of enterococci, thus suggesting the advisability of redesigning the protocols currently used for microbial detection during the evaluation of the microbiological quality of environmental samples.     

Substrate specificity of protein tyrosine phosphatases 1B, RPTPα, SHP-1, and SHP-2

We determined the substrate specificities of the protein tyrosine phosphatases (PTPs) PTP1B, RPTPα, SHP-1, and SHP-2 by on-bead screening of combinatorial peptide libraries and solution-phase kinetic analysis of individually synthesized phosphotyrosyl (pY) peptides. These PTPs exhibit different levels of sequence specificity and catalytic efficiency. The catalytic domain of RPTPα has very weak sequence specificity and is approximately 2 orders of magnitude less active than the other three PTPs. The PTP1B catalytic domain has modest preference for acidic residues on both sides of pY, is highly active toward multiply phosphorylated peptides, but disfavors basic residues at any position, a Gly at the pY-1 position, or a Pro at the pY+1 position. By contrast, SHP-1 and SHP-2 share similar but much narrower substrate specificities, with a strong preference for acidic and aromatic hydrophobic amino acids on both sides of the pY residue. An efficient SHP-1/2 substrate generally contains two or more acidic residues on the N-terminal side and one or more acidic residues on the C-terminal side of pY but no basic residues. Subtle differences exist between SHP-1 and SHP-2 in that SHP-1 has a stronger preference for acidic residues at the pY-1 and pY+1 positions and the two SHPs prefer acidic residues at different positions N-terminal to pY. A survey of the known protein substrates of PTP1B, SHP-1, and SHP-2 shows an excellent agreement between the in vivo dephosphorylation pattern and the in vitro specificity profiles derived from library screening. These results suggest that different PTPs have distinct sequence specificity profiles and the intrinsic activity/specificity of the PTP domain is an important determinant of the enzyme's in vivo substrate specificity.