Digital Orthopantomography vs Cone Beam Computed Tomography-Part 1: Detection of Periapical Lesions.

AIM: Digital orthopantomography (OPT) is usually the first examination step in supervising an incoming patient. Cone beam computed tomography (CBCT) is the most refined and affordable method to search for different dental lesions. The aim of this paper is to evaluate the effectiveness of OPT and CBCT in detecting periapical lesions in different dental groups. MATERIALS AND METHODS: An OPT and a CBCT scan of the dental arches of 45 patients were examined. The presence of AP was pointed out for OPT and CBCT. Sensitivity, specificity, predictive values, and accuracy were calculated for OPT, using CBCT as the reference standard. RESULTS: OPT showed low sensitivity (40.0), positive predictive value (90.4), negative predictive value (90.0), accuracy (90.0), and high specificity (99.2). It was found to have higher sensitivity in the lower front and premolar areas, while the lowest was found in the upper molar area. CONCLUSIONS: OPT can be used for endodontic diagnosis in the lower central and premolar sections, but CBCT plays a decisive role in the evaluation of molar areas and in the endodontic treatment planning, when a close relationship between apex and important anatomical structures exists. CLINICAL SIGNIFICANCE: CBCT exposes the patient to higher doses of radiations when compared with OPT, but CBCT, with its more selective sensitivity and the possibility to offer a three-dimensional (3D) rendering of dental and periodontal structures, is an elective choice for uncertain cases and for specific dental areas.

Digital Orthopantomography vs Cone Beam Computed Tomography-Part 2: A CBCT Analysis of Factors Influencing the Prevalence of Periapical Lesions.

AIM: Cone beam computed tomography (CBCT) is the most refined and affordable method available today for the examination of an incoming patient for different dental pathologies. The aim of this paper is to evaluate the significance of some factors influencing the prevalence of apical periodontitis. MATERIALS AND METHODS: An ortopantomography (OPT) and CBCT scan of the dental arches were examined for each of the selected 45 patients. The presence of apical periodontitis (AP) was compared for CBCT and OPT examination. Sensitivity, specificity, predictive values, and accuracy were calculated for CBCT, using OPT as a reference. The impact of protective/risk factors on the development of AP was examined. RESULTS: CBCT showed higher sensitivity (250%), predictive values (111%), accuracy (111%), and specificity (101%) than OPT. It was found to have higher sensitivity in all the dentition areas, especially where empty anatomical spaces or more radiotransparent structures have a strict relationship with the tooth apex and periapical structures like upper front area, premolar areas, and, especially, in the upper molar area. The prevalence of AP increased from 16 to 17% in the case of insufficient conservative restoration or 25% in the case of microleakage, 35-42% in the case of prosthetic restoration, 56-67% for posts, and 60 and 85%, respectively, for inadequate endodontic treatment and missed canals. CONCLUSION: CBCT plays a decisive role in the evaluation of molar areas and in the endodontic treatment planning, when a close relationship between the apex and important anatomical structures exists. Different risk factors with different relevance are identified. CLINICAL SIGNIFICANCE: As CBCT-examined results show, coronal restorations are moderate-risk factors, while insufficient endodontic treatments and posts are high-risk factors for the development of AP.

The Role of Pharmacists in Counteracting Vaccine Hesitancy: Effectiveness of the 2019 Carnia Project in Improving Adherence to Influenza Vaccination among Target Population.

Vaccine hesitancy has been included among the top ten threats to global health by the World Health Organization. Pharmacists can play a pivotal role in removing the individual barrier to vaccination, because of the relationship of trust they have with citizens and their ease of access. The aim of this study was to examine the impact of a pharmacy-based intervention to support the 2019 influenza vaccination campaign conducted in the Carnia district through one-to-one counseling. We analyzed data collected by pharmacists between 22 October 2019 and 20 January 2020, and trends in vaccination adherence in the context of the Local Health Authority and the entire province of Udine since 2016. The results showed that 77.2% of people who had not received an influenza vaccination in the previous year changed their minds about vaccination after receiving counseling. The pharmacy-based intervention improved influenza vaccination adherence in the target district (+13.4%), even when compared to the neighboring district of Gemona or considering the data in the broader local and provincial context, and this effect was particularly pronounced among those aged 65 to 74 years (p < 0.01). Considering these findings, pharmacies should be more effectively involved in the provision of public health services aimed at improving accessibility, timeliness, and equity.

Eradication of therapy-resistant human prostate tumors using an ultrasound-guided site-specific cancer terminator virus delivery approach.

Intratumoral injections of a replication-incompetent adenovirus (Ad) expressing melanoma differentiation-associated gene-7/interleukin-24 (Ad.mda-7), a secreted cytokine displaying cancer-selective, apoptosis-inducing properties, profoundly inhibits prostate cancer (PC) growth in immune-incompetent animals. In contrast, Ad.mda-7 is ineffective in PCs overexpressing antiapoptotic proteins such as Bcl-2 or Bcl-x(L). However, intratumoral injections of a conditionally replication-competent Ad (CRCA) in which expression of the adenoviral E1A gene is driven by the cancer-specific promoter of progression-elevated gene-3 (PEG-3) and which simultaneously expresses mda-7/interleukin (IL)-24 in the E3 region of the Ad (Ad.PEG-E1A-mda-7), a cancer terminator virus (CTV), is highly active in these cells. A major challenge for gene therapy is systemic delivery of nucleic acids directly into an affected tissue. Ultrasound (US) contrast agents (microbubbles-MBs) are viable candidates for gene delivery/therapy. Here, we show that MB/Ad.mda-7 complexes targeted to DU-145 cells using US dramatically reduced tumor burden in xenografted nude mice. Additionally, US-guided MB/CTV delivery completely eradicated not only targeted DU-145/Bcl-x(L)-therapy-resistant tumors, but also nontargeted distant tumors (established in the opposite flank), thereby implementing a cure. These findings highlight potential therapeutic applications of this novel image-guided gene therapy technology for advanced PC patients with metastatic disease.

A Micro-computed Tomography Evaluation of the Shaping Ability of Two Nickel-titanium Instruments, HyFlex EDM and ProTaper Next.

INTRODUCTION: The aim of this study was to evaluate and compare, by means of micro-computed tomography imaging, the shaping ability of ProTaper Next (PTN) and the novel HyFlex EDM (HFEDM) instruments. METHODS: Forty teeth were randomly divided into 2 groups and prepared with PTN or HFEDM. Root canal transportation and centering ratio were evaluated in mesiodistal and buccolingual directions at 5 levels (at the midpoint of the apical, middle, and coronal thirds and at the boundaries between them). Variations in volume, surface, and cross-sectional shape were measured for the apical, middle, and coronal thirds. The null hypotheses were that no differences existed between the 2 groups. The D'Agostino-Pearson test (α = .05) was conducted to assess the normality of the data sets. The distributions were compared by using the Mann-Whitney test (α = .05). RESULTS: Statistically significant differences (P < .005) were recorded only for buccolingual canal transportation and centering ratio at the section between the middle and coronal thirds, where HFEDM files were superior. CONCLUSIONS: HFEDM and PTN files were similarly effective, and both safely prepared the root canals, respecting their original anatomies. HFEDM files performed better in terms of buccolingual canal transportation and centering ratio at the section between the middle and coronal thirds.

Expression of cell-cycle-regulated proteins pRb2/p130, p107, p27(kip1), p53, mdm-2, and Ki-67 (MIB-1) in prostatic gland adenocarcinoma.

PURPOSE: The quest for prognostic molecular markers in prostatic carcinoma is still in progress. Many proteins have already been screened by immunohistochemistry with the aim to find the most reliable indicator of progressive disease. In this study, we evaluated the expression of pRb2/p130, p107, p27(kip1), p53, mdm-2, and Ki-67 (MIB-1) by immunohistochemistry in 24 prostate carcinomas compared with the paired expression of normal prostates. EXPERIMENTAL DESIGN: Expression of the different proteins in normal and pathological specimens was evaluated by the Wilcoxon test. A matrix of correlation (Spearman coefficient) was used to evaluate the possible association in expression among the different proteins. Logistic regression analysis was used to test the multivariable prognostic value of the levels of protein expression for the probability of disease development. RESULTS: p53 and Ki-67 (MIB-1) showed a higher expression in cancer than in normal tissue (P = 0.006 and <0.001, respectively). pRb2/p130, p107, and p27(kip1) showed an overall lower expression in cancer, but the difference between cytoplasmic and nuclear expression was always higher for cancer (Ps, from <0.001 to 0.016). mdm-2 expression was lower in cancer, but the difference between cytoplasmic and nuclear expression was not significant (P = 0.571) when compared with that in normal tissue. A positive correlation between p27 and pRb2/p130 levels expressed, in normal and cancer counterparts in the same sample, as the difference between cytoplasmic and nuclear protein concentrations (P = 0.045) was found. Additionally, p107 expression showed an inverse correlation with Ki-67 (MIB-1) expression in the most aggressive tumors (P = 0.046). Logistic regression output showed that Ki-67 (MIB-1) and pRb2/p130 (expressed as differences between cytoplasmic and nuclear concentrations) were the variables associated with a higher risk of cancer. The highest value was reported for Ki-67 (MIB-1) (odds ratio, 2.11), followed by pRb2/p130 (odds ratio, 1.01). pRb2/p130 alone was associated with a sensitivity (rate of cases having a posterior probability of disease >/=0.5) of 61% with a false positive rate of 22%. Ki-67 (MIB-1) alone yielded a sensitivity of 69% and a false positive rate of 14%. The combined model (Ki-67 + pRb2/p130) yielded a sensitivity of 83% with a false positive rate of 17%. Interestingly, one specimen in which we also found a high-grade prostatic intraepithelial neoplasia showed the progressive loss of pRb2/p130 from normal prostatic cells to prostatic intraepithelial neoplasia cells, suggesting that in prostatic cancer, lack of expression of the tumor suppressor gene pRb2/p130 could be involved in the progression of the disease, from an early stage. CONCLUSIONS: This study showed that all of the proteins but mdm-2 were expressed at a different rate in normal and pathological prostate specimens. Multivariate analysis showed that pRb2/p130 and p107 may be involved in the pathogenesis and progression of prostate cancers, and that the expression of the retinoblastoma-related protein pRb2/p130 along with Ki-67 (MIB-1), expressed as differences between cytoplasmic and nuclear concentrations, could be considered new parameters to be evaluated in discriminating patients at a higher risk for prostate cancer.

Microbubble-assisted p53, RB, and p130 gene transfer in combination with radiation therapy in prostate cancer.

Combining radiation therapy and direct intratumoral (IT) injection of adenoviral vectors has been explored as a means to enhance the therapeutic potential of gene transfer. A major challenge for gene transfer is systemic delivery of nucleic acids directly into an affected tissue. Ultrasound (US) contrast agents (microbubbles) are viable candidates to enhance targeted delivery of systemically administered genes. Here we show that p53, pRB, and p130 gene transfer mediated by US cavitation of microbubbles at the tumor site resulted in targeted gene transduction and increased reduction in tumor growth compared to DU-145 prostate cancer cell xenografts treated intratumorally with adenovirus (Ad) or radiation alone. Microbubble-assisted/US-mediated Ad.p53 and Ad.RB treated tumors showed significant reduction in tumor volume compared to Ad.p130 treated tumors (p<0.05). Additionally, US mediated microbubble delivery of p53 and RB combined with external beam radiation resulted in the most profound tumor reduction in DU-145 xenografted nude mice (p<0.05) compared to radiation alone. These findings highlight the potential therapeutic applications of this novel image-guided gene transfer technology in combination with external beam radiation for prostate cancer patients with therapy resistant disease.

Cadmium induces p53-dependent apoptosis in human prostate epithelial cells.

Cadmium, a widespread toxic pollutant of occupational and environmental concern, is a known human carcinogen. The prostate is a potential target for cadmium carcinogenesis, although the underlying mechanisms are still unclear. Furthermore, cadmium may induce cell death by apoptosis in various cell types, and it has been hypothesized that a key factor in cadmium-induced malignant transformation is acquisition of apoptotic resistance. We investigated the in vitro effects produced by cadmium exposure in normal or tumor cells derived from human prostate epithelium, including RWPE-1 and its cadmium-transformed derivative CTPE, the primary adenocarcinoma 22Rv1 and CWR-R1 cells and LNCaP, PC-3 and DU145 metastatic cancer cell lines. Cells were treated for 24 hours with different concentrations of CdCl(2) and apoptosis, cell cycle distribution and expression of tumor suppressor proteins were analyzed. Subsequently, cellular response to cadmium was evaluated after siRNA-mediated p53 silencing in wild type p53-expressing RWPE-1 and LNCaP cells, and after adenoviral p53 overexpression in p53-deficient DU145 and PC-3 cell lines. The cell lines exhibited different sensitivity to cadmium, and 24-hour exposure to different CdCl(2) concentrations induced dose- and cell type-dependent apoptotic response and inhibition of cell proliferation that correlated with accumulation of functional p53 and overexpression of p21 in wild type p53-expressing cell lines. On the other hand, p53 silencing was able to suppress cadmium-induced apoptosis. Our results demonstrate that cadmium can induce p53-dependent apoptosis in human prostate epithelial cells and suggest p53 mutation as a possible contributing factor for the acquisition of apoptotic resistance in cadmium prostatic carcinogenesis.

Differential role of CD133 and CXCR4 in renal cell carcinoma.

The chemokine receptor CXCR4 and CD133, putative stem cell markers, were previously described in renal cancer (RCC). To evaluate the biological and prognostic role of CD133 and CXCR4 in RCC the expression was evaluated through qPCR and immunoblotting in human renal cancer cell lines (786-O, A498, ACHN, CAKI-1, SN12C, TK10, UO31) and patients biopsies. Renal cancer cells and surgical biopsies expressed functional CXCR4 while CD133 was not detectable. CXCR4 and CD133 expression was then evaluated in 240 renal cancer patients through immunohistochemistry. CXCR4 and CD133 were low in 19.1% and 59.6%; intermediate in 20% and 17.9%; high in 60.8% and 22.5% of the cases, respectively. CXCR4 was overexpressed in tumours (p= 0.02), while CD133 was over expressed in healthy tissues (p= 0.04). Disease free survival Kaplan Meier plots suggest that prognosis is unfavourable for patients whose primary tumours express CXCR4 (p= 0.0199) but nor CD133 (p= 0.151) neither the concomitant CXCR4-CD133 (p=0.848) high expression affected prognosis. Analysis of prognostic factors suggests that age, clinical presentation, AJCC stage and CXCR4 had a significant prognostic value at the univariate analysis. The CXCR4 predictive ability was confirmed at the multivariate analysis while no prognostic role was identified for CD133.Thus concomitant CD133 and CXCR4 evaluation is not worth in RCC patient while the CXCR4 prognostic role encourage CXCR4 antagonists as promising therapeutic option.

Vesicourethral anastomosis during radical retropubic prostatectomy: does the number of sutures matter?

OBJECTIVES: To prospectively evaluate the outcome of radical retropubic prostatectomy using three different techniques of vesicourethral anastomosis (VUA), with a different number of sutures used during this surgical step. METHODS: Three groups of patients who had undergone nerve-sparing radical retropubic prostatectomy were compared. Overall, 90 patients with localized prostate cancer were recruited. The patients were randomly assigned to undergo one of three different VUA techniques. The anastomotic sutures consisted of four or six monocryl 2-0 stitches. The "two-suture" anastomosis in group 1 was performed by passing two U-shaped horizontal stitches at the 6-o'clock and 12-o'clock positions. The following intraoperative and perioperative parameters were considered for the comparative analysis: time to perform VUA, blood loss, hospitalization, and time to drain removal. RESULTS: A statistically significant difference was found in terms of the mean time to anastomosis between groups 1 and 2 (3.61 +/- 1.14 versus 16.6 +/- 4.04, P <0.0001) and between groups 1 and 3 (3.61 +/- 1.14 versus 23.45 +/- 5.4, P <0.0001). No significant differences could be detected for blood loss, time to drain removal, or hospitalization. No significant difference was detected in terms of functional outcome (stricture rate, erectile function, and continence). CONCLUSIONS: The number of stitches used for VUA during radical retropubic prostatectomy did not influence the perioperative and postoperative parameters. The time to VUA was considerably lower using our "two-suture" technique.

Renal cell carcinoma with solitary toe metastasis.

Solitary metastases to the small bones and/or to the soft tissue of the hands and feet (acrometastases) are rare. We report a case of renal cell carcinoma (RCC) with big toe metastasis revealed before the primary tumor became apparent. The best treatment for a single metastasis is always surgical excision, regardless of the lesion being synchronous or metachronous. The biological behavior of metastatic RCC is unpredictable and only early diagnosis and treatment may favorably affect patient survival. Thus, metastatic RCC should be included in the differential diagnosis of all enlarging cutaneous nodules, wherever they develop.