Histopathological determinants of autofluorescence patterns in oral carcinoma

Biological tissues (including oral mucosa) can absorb and re-emit specific light wavelengths, detectable through spectrophotometric devices. Such a phenomenon is known as \u201cautofluorescence\u201d (AF). Several devices evaluating tissue AF have been developed and commercialized in the last two decades. Among these, the VELscope\uae system has been proposed as a visual diagnostic aid for potentially malignant disorders and malignant lesions of the oral mucosa. In the present pilot study, we investigated which are the main histopathological features possibly related to variations in AF patterns in a set of 20 oral squamous cell verrucous carcinoma. Among all the histological features investigated, only the mean width of keratin was significantly different between hypofluorescent and hyperfluorescent carcinomas. The results of the present study demonstrate that AF features of oral malignant lesions are significantly associated with the width of their keratin layer

Cutting edge: extracellular high mobility group box-1 protein is a proangiogenic cytokine.

The chromosomal high mobility group box-1 (HMGB1) protein acts as a proinflammatory cytokine when released in the extracellular environment by necrotic and inflammatory cells. In the present study, we show that HMGB1 exerts proangiogenic effects by inducing MAPK ERK1/2 activation, cell proliferation, and chemotaxis in endothelial cells of different origin. Accordingly, HMGB1 stimulates membrane ruffling and repair of a mechanically wounded endothelial cell monolayer and causes endothelial cell sprouting in a three-dimensional fibrin gel. In keeping with its in vitro properties, HMGB1 stimulates neovascularization when applied in vivo on the top of the chicken embryo chorioallantoic membrane whose blood vessels express the HMGB1 receptor for advanced glycation end products (RAGE). Accordingly, RAGE blockade by neutralizing Abs inhibits HMGB1-induced neovascularization in vivo and endothelial cell proliferation and membrane ruffling in vitro. Taken together, the data identify HMGB1/RAGE interaction as a potent proangiogenic stimulus

Cognitive reserve index and functional and cognitive outcomes in severe acquired brain injury: A pilot study

Background: Many variables affect outcome after brain injury. Cognitive reserve (CR) is a subjective factor that reflects a set of personal characteristics and that differentiates individuals. It may influence an individual’s capacity to react to brain injury. Objective: To study the effects of cognitive reserve on functional and cognitive outcome at the end of rehabilitation, in patients with severe acquired brain injury (sABI), by means of the Cognitive Reserve Index questionnaire (CRIq). Methods: We report a retrospective study of a continuous series of sABI patients on first admission to a rehabilitation center. Disability and cognitive outcomes were recorded. Results: In the 94 patients enrolled, the assessments after rehabilitation showed a significant gain measured with the disability Rating Scale for patients with a higher CR (CRIq≥ 85). A significant negative correlation was found: between CRIq scores and the interval elapsing before first access to neuropsychological assessment, between CRIq scores, especially level of education, and tests that measure the same domain (attention). Conclusions: Improvements in overall and cognitive disability emerged, but CR did not seem to substantially influence outcome in this sample of patients. This result may be partly due to the clinical severity of the population studied and the sample’s dimension, although quantitatively representative of the population

Nomophobia in healthcare: an observational study between nurses and students

BACKGROUND AND AIM: The abuse of technical devices can be considered a form of addiction that is defined in current literature as Nomophobia. The phenomenon appears to be quite widespread among nurses and nursing students, and nomophobic behaviours of professionals can lead to a reduction in the quality of the care provided. The aim of this study is to investigate the situation in a University and in a hospital in northern Italy and evaluate the levels of nomophobia among nurses and students. METHODS: An observational study was conducted with a questionnaire using a sample of nursing students and nurses.  Both of the studies had the common goal of investigating the levels of nomophobia and   evaluate the comparison between the two groups. RESULTS: In general, neither nurses nor students seem to demonstrate nomophobia's critical levels. The comparison of the daily use of the smartphone between nurses and students shows that the frequent use of students is balanced by the nurses' daily trend line that progressively decreases. Both nurses and students affirm to use their smartphones at work with a certain frequency although, especially among the students, it is usually for appropriate and justified reasons. CONCLUSIONS: It is necessary to consider the development of an educational project that regulates the use of smartphones, explaining the meaning of nomophobia, right from the first year of the University experience so as to correctly address the students'  (and future professionals') behaviours  to make them aware of the misuse of mobile phones, especially in the clinical setting that can easily cause distractions and consequently irreversible  errors

The usefulness of Moynihan questionnaire in the evaluation of knowledge on healthy diet of patients undergoing cardiology rehabilitation

BACKGROUND: The aim of study was to test the usefulness of Moynihan questionnaire in the evaluation of knowledge on healthy diet of patients undergoing cardiology rehabilitation. METHODS: We enrolled 51 patients (pts): 41 men and 10 women, mean age 67.97 +/-11.2 years. The case study included: 21 pts that underwent coronary bypass surgery, 16 pts replaced plastic tube, 14 pts had surgery for the other reasons. All pts underwent nutritional investigation by a dietitian. Anthropometric and biochemical parameters were detected and, by the end, the Moynihan questionnaire was administrated. Pts underwent nutritional coaching, and questionnaire and dietary assessment were rechecked after 3 months. RESULTS: At baseline, the mean Questionnaire score was 22.4 +/- 3.2 points, decreased to 20.6 +/-3.1 points after 3 months (p<0.05). A detailed analysis of the questions showed that the major informations gaps were related to consumption of fruits and vegetables, consumption of fat and salt. In addition pts have acquired more general knowledge about food composition. CONCLUSIONS: The Moynihan questionnaire is an useful instrument of evaluation of dietary knowledge even in selected patients population. In the present study involving patients after cardiac surgery the main difficulties were related to high age of pts, the low cultural level and, mainly, to the post-surgery stress. However, an increase of correct answers as well as an increased knowledge about food composition were detected after educational intervention performed by the dietitian

Correlation between autofluorescence intensity and histopathological features in non-melanoma skin cancer: An ex vivo study

Non-melanoma skin cancer (NMSC) is the most common malignant tumor affecting fair-skinned people. Increasing incidence rates of NMSC have been reported worldwide, which is an important challenge in terms of public health management. Surgical excision with pre-operatively identified margins is one of the most common and effective treatment strategies. Incomplete tumor removal is associated with a very high risk of recurrence and re-excision. Biological tissues can absorb and re-emit specific light wave-lengths, detectable through spectrophotometric devices. Such a phenomenon is known as autofluorescence (AF). AF spectroscopy has been widely explored for non-invasive, early detection of NMSC as well as for evaluation of surgical margins before excision. Fluorescence-aided diagnosis is based on differences in spectral characteristics between healthy and neoplastic skin. Understanding the biological basis of such differences and correlating AF intensity to histological features could improve the diagnostic accuracy of skin fluorescence spectroscopy. The primary objective of the present pre-clinical ex vivo study is to investigate the correlation between the intensity of cutaneous AF and the histopathological features of NMSC. Ninety-eight lesions suggestive for NMSCs were radically excised from 75 patients (46 M; 29 F; mean age: 79 years). After removal, 115 specific reference points on lesions (\u201ccases\u201d; 59 on BBC, 53 on SCC and 3 on other lesions) and on peri-lesional healthy skin (controls; 115 healthy skin) were identified and marked through suture stitches. Such reference points were irradiated at 400\u2013430 nm wavelength, and resulting emission AF spectra were acquired through spectrophotometry. For each case, AFIR (autofluorescence intensity ratio) was measured as the ratio between the number of photons emitted at a wavelength ranging between 450 and 700 nm (peak: 500 nm) in the healthy skin and that was captured in the pathological tissue. At the histological level, hyperkeratosis, neoangiogenesis, cellular atypia, epithelial thickening, fibrosis and elastosis were quantified by light microscopy and were assessed through a previously validated grading system. Statistical correlation between histologic variables and AFIR was calculated through linear regression. Spectrometric evaluation was performed on 230 (115 cases + 115 controls) reference points. The mean AFIR for BCC group was 4.5, while the mean AFIR for SCC group was 4.4 and the fluorescence peaks at 500 nm were approximately 4 times lower (hypo-fluorescent) in BCCs and in SCCs than in healthy skin. Histological variables significantly associated with alteration of AFIR were fibrosis and elastosis (p < 0.05), neoangiogenesis, hyperkeratosis and epithelial thickening. Cellular atypia was not significantly associated with alteration of AFIR. The intensity of fluorescence emission in neoplastic tissues was approximately 4 times lower than that in healthy tissues. Histopathological features such as hyperkeratosis, neoangiogenesis, fibrosis and elastosis are statistically associated with the decrease in AFIR. We hypothesize that such tissue alterations are among the possible biophysical and biochemical bases of difference in emission AF between neoplastic and healthy tissue. The results of the present evaluation highlighted the possible usefulness of autofluorescence as diagnostic, non-invasive and real-time tool for NMSCs

Synchronous and metachronous colorectal liver metastases: Impact of primary tumor location on patterns of recurrence and survival after hepatic resection

Background: Considerable differences in terms of prognosis exist between the right-sided (RCC) and the left-sided colon cancer (LCC). Aim of the work: In this study, we evaluated prognostic implications of primary tumor location (PTL) among patients who underwent curative-intent hepatectomy for synchronous (SM) and metachronous (MM) colorectal liver metastases (CRLM). Methods: The study population included all consecutive patients affected by CRLM scheduled for first liver resection at three Italian oncological centers. Results: A total of 204 patients who underwent CRLM resection were included, 50% with RCC. Synchronous lesions were prevalent (n=133, 65%). Median OS was respectively 40.3 months for SM-RCC, 53.5 months for SM-LCC, 64.5 months for MM-RCC and 81.6 months for MM-LCC. Patients with MM-LCC showed an OS better than patients with SM-RCC (p=0.008) and SM-LCC (p=0.002). PTL had no influence on RFS. RCC group had less recurrences (75% vs 86.5%), though further surgery with curative-intent was possible more in LCC group (29.3% vs 32.5%). Cox proportional hazards model analysis showed that age and the presence of SM vs MM was associated with a significantly higher hazard ratio (HR) for death (HR=1.024; 95%CI=1.005-1.043; p=0.011 and HR=2.010; 95%CI=1.328-3.043; p=0.001, respectively). Conclusions: We confirmed that patients with CRLM and right-sided primary colon cancer experience worse survival after hepatic resection. The timing of metastasis has been revealed as important prognostic factor

Optimizing PD-L1 evaluation on cytological samples from advanced non-small-cell lung cancer

Aim: Programmed cell death-ligand 1 (PD-L1) predicts response to immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC) patients. Most NSCLCs are diagnosed at an advanced stage and using minimally invasive diagnostic procedures that yield small biopsies or cytological samples. Methods: Cytological smears and paired histological samples from 52 advanced NSCLC patients were tested for PD-L1 expression by immunocyto/histochemistry (ICC/IHC) and for PD-L1 gene status by FISH. Results: PD-L1 was overexpressed in 9/52 (17%) cytological samples and in seven (13.5%) matched biopsies. The concordance between immunocytochemistry and IHC was 92.3% (48/52; p < 0.001). The concordance between PD-L1 gene status on cytology and histology was 69.2% (18/26; p < 0.001). No correlation between IHC and fluorescence in situ hybridization results was found. Conclusion: Our data support the feasibility and reliability of PD-L1 protein and PD-L1 gene assessment on direct cytological smears from NSCLC patients whenever histological sample are inadequate

High levels of Notch intracellular cleaved domain are associated with stemness and reduced bevacizumab efficacy in patients with advanced colon cancer

δ-like ligand 4 (DLL4)-Notch signaling is associated with tumor resistance to anti-vascular endothelial growth factor (VEGF) therapy. Furthermore, Notch signaling is critical for the maintenance of colon cancer stem cells (CSCs), which are relevant in drug resistance and tumor angiogenesis. CD44 is a transmembrane glycoprotein and is considered a putative marker of CSCs. To assess the association of Notch intracellular cleaved domain (NICD), DLL4 and CD44 expression with the efficacy of anti‑angiogenic drugs, a series of samples derived from patients with advanced colon cancer enrolled in prospective clinical trials were analyzed. Histological samples from 51 primary tumors that originated from patients treated with bevacizumab‑based first‑line chemotherapy were analyzed by immunohistochemistry for NICD, DLL4 and CD44 expression, and CD31 for microvessel count. The expression levels of genes relevant for angiogenesis [angiopoietin (ANGPT)1, ANGPT2, fibroblast growth factor (FGF)1, FGF2, epidermal growth factor, placental growth factor, VEGFA and DLL4] were detected by reverse transcription-quantitative PCR using RNA extracte

The Bloom's syndrome helicase (BLM) interacts physically and functionally with p12, the smallest subunit of human DNA polymerase δ

Bloom's syndrome (BS) is a cancer predisposition disorder caused by mutation of the BLM gene, encoding a member of the RecQ helicase family. Although the phenotype of BS cells is suggestive of a role for BLM in repair of stalled or damaged replication forks, thus far there has been no direct evidence that BLM associates with any of the three human replicative DNA polymerases. Here, we show that BLM interacts specifically in vitro and in vivo with p12, the smallest subunit of human POL δ (hPOL δ). The hPOL δ enzyme, as well as the isolated p12 subunit, stimulates the DNA helicase activity of BLM. Conversely, BLM stimulates hPOL δ strand displacement activity. Our results provide the first functional link between BLM and the replicative machinery in human cells, and suggest that BLM might be recruited to sites of disrupted replication through an interaction with hPOL δ. Finally, our data also define a novel role for the poorly characterized p12 subunit of hPOL δ