Knoop microhardness and FT-Raman evaluation of composite resins: influence of opacity and photoactivation source

The aim of this study was to evaluate the degree of conversion by Knoop microhardness (KHN) and FT-Raman spectroscopy (FTIR) of one nanofilled (Filtek Supreme-3M-ESPE [FS]) and one microhybrid composite (Charisma-Heraeus-Kulzer [CH]), each with different opacities, namely enamel, dentin, and translucent, which were photo-activated by a quartz-tungsten-halogen lamp (QTH) and a light-emitting diode (LED). Resin was bulk inserted into a disc-shaped mold that was 2.0 mm thick and 4 mm in diameter, obtaining 10 samples per group. KHN and FTIR values were analyzed by two-way ANOVA and Tukey's tests (&#945; = 0.05). Nanofilled resin activated by a LED presented higher microhardness values than samples activated by a QTH for dentin opacity (p < 0.05). The microhybrid resin showed no differences in KHN or FTIR values with different activation sources or opacity. The nanofilled dentin and enamel resins showed lower FTIR values than the translucent resin. The KHN values of the translucent resins were not influenced by the light source

Caveolin 1 expression favors tumor growth and is associated with poor survival in primary lung adenocarcinomas

Despite the consolidated clinico-pathological correlates of Caveolin 1 expression in non–small cell lung cancer, the available data on the role of Caveolin 1 in relation to proliferation, migration..

COVID-19 and Breast Cancer: Analysis of Surgical Management of a Large Referral Center during the 2020-2021 Pandemic Period

Background: Coronavirus disease-19 (COVID-19) has spread worldwide since December 2019 and was officially declared a pandemic in March 2020. Due to the rapid transmission and the high fatality rate, drastic emergency restrictions were issued, with a negative impact on routine clinical activities. In particular, in Italy, many authors have reported a reduction in the number of breast cancer diagnoses and critical problems in the management of patients who accessed the breast units during the dramatic first months of the pandemic. Our study aims to analyze the global impact of COVID-19 in the two years of the pandemic (2020&ndash;2021) on the surgical management of breast cancer by comparing them with the previous two years. Methods: In our retrospective study, we analyzed all cases of breast cancer diagnosed and surgically treated at the breast unit of &ldquo;Citt&agrave; della Salute e della Scienza&rdquo; in Turin, Italy, making a comparison between the 2018&ndash;2019 pre-pandemic period and the 2020&ndash;2021 pandemic period. Results: We included in our analysis 1331 breast cancer cases surgically treated from January 2018 to December 2021. A total of 726 patients were treated in the pre-pandemic years and 605 in the pandemic period (&minus;121 cases, 9%). No significant differences were observed regarding diagnosis (screening vs. no screening) and timing between radiological diagnosis and surgery for both in situ and invasive tumors. There were no variations in the breast surgical approach (mastectomy vs. conservative surgery), while a reduction in axillary dissection compared to the sentinel lymph node in the pandemic period was observed (p-value &lt; 0.001). Regarding the biological characteristics of breast cancers, we observed a greater number of grades 2&ndash;3 (p-value = 0.007), pT stage 3&ndash;4 breast cancer surgically treated without previous neoadjuvant chemotherapy (p-value = 0.03), and a reduction in luminal B tumors (p-value = 0.007). Conclusions: Overall, we report a limited reduction in surgical activity for breast cancer treatment considering the entire pandemic period (2020&ndash;2021). These results suggest a prompt resumption of surgical activity similar to the pre-pandemic period

Ki-67 proliferation index but not mitotic thresholds integrates the molecular prognostic stratification of lower grade gliomas

Despite several molecular signatures for “lower grade diffuse gliomas” (LGG) have been identified, WHO grade still remains a cornerstone of treatment guidelines. Mitotic count bears a crucial role in its definition, although limited by the poor reproducibility of standard Hematoxylin & Eosin (H&E) evaluation. Phospho-histone-H3 (PHH3) and Ki-67 have been proposed as alternative assays of cellular proliferation. Therefore in the present series of 141 LGG, the molecular characterization (namely IDH status, 1p/19q co-deletion and MGMT promoter methylation) was integrated with the tumor “proliferative trait” (conventional H&E or PHH3-guided mitotic count and Ki-67 index) in term of prognosis definition. Exclusively high PHH3 and Ki-67 values were predictor of poor prognosis (log rank test, P = 0.0281 for PHH3 and P = 0.032 for Ki-67), unlike standard mitotic count. Based on Cox proportional hazard regression analyses, among all clinical (age), pathological (PHH3 and Ki-67) and molecular variables (IDH, 1p/19q codeletion and MGMT methylation) with a prognostic relevance at univariate survival analysis, only IDH expression (P = 0.001) and Ki-67 proliferation index (P = 0.027) proved to be independent prognostic factors. In addition, stratifying by IDH expression status, high Ki-67 retained its prognostic relevance uniquely in the IDH negative patient (P = 0.029) doubling their risk of death (hazard ratio = 2.27). Overall, PHH3 immunostaining is the sole reliable method with a prognostic value to highlight mitotic figures in LGG. Ki-67 proliferation index exceeds PHH3 mitotic count as a predictor of patient's prognosis, and should be integrated with molecular markers in a comprehensive grading system for LGG

Activation of P2X7 and P2Y11 purinergic receptors inhibits migration and normalizes tumor-derived endothelial cells via cAMP signaling

Purinergic signaling is involved in inflammation and cancer. Extracellular ATP accumulates in tumor interstitium, reaching hundreds micromolar concentrations, but its functional role on tumor vasculature and endothelium is unknown. Here we show that high ATP doses (>20 μM) strongly inhibit migration of endothelial cells from human breast carcinoma (BTEC), but not of normal human microvascular EC. Lower doses (1–10 mm result ineffective. The anti-migratory activity is associated with cytoskeleton remodeling and is significantly prevented by hypoxia. Pharmacological and molecular evidences suggest a major role for P2X7R and P2Y11R in ATP-mediated inhibition of TEC migration: selective activation of these purinergic receptors by BzATP mimics the anti-migratory effect of ATP, which is in turn impaired by their pharmacological or molecular silencing. Downstream pathway includes calcium-dependent Adenilyl Cyclase 10 (AC10) recruitment, cAMP release and EPAC-1 activation. Notably, high ATP enhances TEC-mediated attraction of human pericytes, leading to a decrease of endothelial permeability, a hallmark of vessel normalization. Finally, we provide the first evidence of in vivo P2X7R expression in blood vessels of murine and human breast carcinoma. In conclusion, we have identified a purinergic pathway selectively acting as an antiangiogenic and normalizing signal for human tumor-derived vascular endothelium

Impacto da osteoporose em implantes dentários: uma revisão sistemática.

AIM: To assess the failure and bone-to-implant contact rate of dental implants placed on osteoporotic subjects. METHODS: Extensive examination strategies were created to classify studies for this systematic review. MEDLINE (via PubMed) and EMBASE database were examined for studies in English up to and including May 2014. The examination presented a combination of the MeSH words described as follow: "osteoporosis" or "osteopenia" or "estrogen deficiency" AND "implant" or "dental implant" or "osseointegration". Assessment of clinical and/or histological peri-implant conditions in osteoporosis subjects treated with titanium dental implants. The examination included a combination of the MeSH terms described as follow: "osteoporosis" or "osteopenia" or "estrogen deficiency" AND "implant" or "dental implant" or "osseointegration". RESULTS: Of 943 potentially eligible articles, 12 were included in the study. A total of 133 subjects with osteoporosis, 73 subjects diagnosed with osteopenia and 708 healthy subjects were assessed in this systematic review. In these subjects were installed 367, 205, 2981 dental implants in osteoporotic, osteopenic and healthy subjects, respectively. The failure rate of dental implant was 10.9% in osteoporotic subjects, 8.29% in osteopenic and 11.43% in healthy ones. Bone-to-implant contact obtained from retrieved implants ranged between 49.96% to 47.84%, for osteoporosis and non-osteoporotic subjects. CONCLUSION: Osteoporotic subjects presented higher rates of implant loss, however, there is a lower evidence to strengthen or refute the hypothesis that osteoporosis may have detrimental effects on bone healing. Consequently, final conclusions regarding the effect of osteoporosis in dental implant therapy cannot be made at this time. There are no randomized clinical trial accessible for evaluation and the retrospective nature of the evaluated studies shall be taken in account when interpreting this study.OBJETIVO: Avaliar a falha e a taxa de contato osso-implante de implantes dentários colocados em indivíduos osteoporóticos. MÉTODOS: Estratégias de exame extensas foram criadas para classificar os estudos para esta revisão sistemática.&nbsp;O banco de dados MEDLINE (&nbsp;via&nbsp;PubMed) e EMBASE foram examinados para estudos em inglês até maio de 2014. O exame apresentou uma combinação das palavras MeSH descritas a seguir: "osteoporose" ou "osteopenia" ou "deficiência de estrogênio" AND "implante" ou "implante dentário" ou "osseointegração".&nbsp;Avaliação das condições clínicas e / ou histológicas do peri-implante em indivíduos com osteoporose tratados com implantes dentários de titânio.&nbsp;O exame incluiu uma combinação dos termos MeSH descritos a seguir: "osteoporose" ou "osteopenia" ou "deficiência de estrogênio" AND "implante" ou "implante dentário" ou "osseointegração". RESULTADOS: Dos 943 artigos potencialmente elegíveis, 12 foram incluídos no estudo.&nbsp;Um total de 133 indivíduos com osteoporose, 73 indivíduos com diagnóstico de osteopenia e 708 indivíduos saudáveis ​​foram avaliados nesta revisão sistemática.&nbsp;Nesses sujeitos foram instalados 367, 205, 2981 implantes dentários em indivíduos osteoporóticos, osteopênicos e saudáveis, respectivamente.&nbsp;A taxa de falha do implante dentário foi de 10,9% nos indivíduos osteoporóticos, 8,29% nos osteopênicos e 11,43% nos saudáveis.&nbsp;O contato osso-implante obtido a partir de implantes recuperados variou entre 49,96% a 47,84%, para osteoporose e indivíduos não osteoporóticos. CONCLUSÃO: Os indivíduos osteoporóticos apresentaram maiores taxas de perda de implantes, no entanto, há uma evidência menor para fortalecer ou refutar a hipótese de que a osteoporose possa ter efeitos prejudiciais na cicatrização óssea.&nbsp;Consequentemente, as conclusões finais sobre o efeito da osteoporose na terapia com implantes dentários não podem ser feitas no momento.&nbsp;Não existem ensaios clínicos randomizados acessíveis para avaliação e a natureza retrospectiva dos estudos avaliados deve ser levada em consideração na interpretação deste estudo

Immune inflammation indicators in anal cancer patients treated with concurrent chemoradiation: training and validation cohort with online calculator (ARC: Anal Cancer Response Classifier)

Background: In anal cancer, there are no markers nor other laboratory indexes that can predict prognosis and guide clinical practice for patients treated with concurrent chemoradiation. In this study, we retrospectively investigated the influence of immune inflammation indicators on treatment outcome of anal cancer patients undergoing concurrent chemoradiotherapy. Methods: All patients had a histologically proven diagnosis of squamous cell carcinoma of the anal canal/margin treated with chemoradiotherapy according to the Nigro's regimen. Impact on prognosis of pre-treatment systemic index of inflammation (SII) (platelet x neutrophil/lymphocyte), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were analyzed. Results: A total of 161 consecutive patients were available for the analysis. Response to treatment was the single most important factor for progression-free survival (PFS) and overall survival (OS). At univariate analysis, higher SII level was significantly correlated to lower PFS (p&lt;0.01) and OS (p=0.046). NLR level was significantly correlated to PFS (p=0.05), but not to OS (p=0.06). PLR level significantly affected both PFS (p&lt;0.01) and OS (p=0.02). On multivariate analysis pre-treatment, SII level was significantly correlated to PFS (p=0.0079), but not to OS (p=0.15). We developed and externally validated on a cohort of 147 patients a logistic nomogram using SII, nodal status and pre-treatment Hb levels. Results showed a good predictive ability with C-index of 0.74. An online available calculator has also been developed. Conclusion: The low cost and easy profile in terms of determination and reproducibility make SII a promising tool for prognostic assessment in this oncological setting