The use of ESEM-EDX as an innovative tool to analyze the mineral structure of peri-implant human bone

This study aimed to investigate the mineralization and chemical composition of the bone-implant interface and peri-implant tissues on human histological samples using an environmental scanning electron microscope as well as energy-dispersive x-ray spectroscopy (ESEM-EDX) as an innovative method. Eight unloaded implants with marginal bone tissue were retrieved after four months from eight patients and were histologically processed and analyzed. Histological samples were observed under optical microscopy (OM) to identify the microarchitecture of the sample and bone morphology. Then, all samples were observed under ESEM-EDX from the coronal to the most apical portion of the implant at 500x magnification. A region of interest with bone tissue of size 750 7 500 microns was selected to correspond to the first coronal and the last apical thread (ROI). EDX microanalysis was used to assess the elemental composition of the bone tissue along the thread interface and the ROI. Atomic percentages of Ca, P, N, and Ti, and the Ca/N, P/N and Ca/P ratios were measured in the ROI. Four major bone mineralization areas were identified based on the different chemical composition and ratios of the ROI. Area 1: A well-defined area with low Ca/N, P/N, and Ca/P was identified as low-density bone. Area 2: A defined area with higher Ca/N, P/N, and Ca/P, identified as new bone tissue, or bone remodeling areas. Area 3: A well-defined area with high Ca/N, /P/N, and Ca/P ratios, identified as bone tissue or bone chips. Area 4: An area with high Ca/N, P/N, and Ca/P ratios, which was identified as mature old cortical bone. Bone Area 2 was the most represented area along the bone-implant interface, while Bone Area 4 was identified only at sites approximately 1.5 mm from the interface. All areas were identified around implant biopsies, creating a mosaic-shaped distribution with well-defined borders. ESEM-EDX in combination with OM allowed to perform a microchemical analysis and offered new important information on the organic and inorganic content of the bone tissue around implants

Ultrasonographic evaluation of three approaches for botulinum toxin injection into tibialis posterior muscle in chronic stroke patients with equinovarus foot: An observational study

Spastic equinovarus (SEV) foot deformity is commonly observed in patients with post-stroke spasticity. Tibialis posterior (TP) is a common target for botulinum toxin type-A (BoNT-A) injection, as a first-line treatment in non-fixed SEV deformity. For this deep muscle, ultrasonographic guidance is crucial to achieving maximum accuracy for the BoNT-A injection. In current clinical practice, there are three approaches to target the TP: an anterior, a posteromedial, and a posterior. To date, previous studies have failed to identify the best approach for needle insertion into TP. To explore the ultrasonographic characteristics of these approaches, we investigated affected and unaffected legs of 25 stroke patients with SEV treated with BoNT-A. We evaluated the qualitative (echo intensity) and quantitative (muscle depth, muscle thickness, overlying muscle, subcutaneous tissue, cross-sectional area) ultrasound characteristics of the three approaches for TP injection. In our sample, we observed significant differences among almost all the parameters of the three approaches, except for the safety window. Moreover, our analysis showed significant differences in cross-sectional area between treated and untreated. Advantages and disadvantages of each approach were investigated. Our findings can thus provide a suitable reference for clinical settings, especially for novice operators

Immunotherapy in the Treatment of Metastatic Melanoma: Current Knowledge and Future Directions

Melanoma is one of the most immunologic malignancies based on its higher prevalence in immune-compromised patients, the evidence of brisk lymphocytic infiltrates in both primary tumors and metastases, the documented recognition of melanoma antigens by tumor-infiltrating T lymphocytes and, most important, evidence that melanoma responds to immunotherapy. The use of immunotherapy in the treatment of metastatic melanoma is a relatively late discovery for this malignancy. Recent studies have shown a significantly higher success rate with combination of immunotherapy and chemotherapy, radiotherapy, or targeted molecular therapy. Immunotherapy is associated to a panel of dysimmune toxicities called immune-related adverse events that can affect one or more organs and may limit its use. Future directions in the treatment of metastatic melanoma include immunotherapy with anti-PD1 antibodies or targeted therapy with BRAF and MEK inhibitors

Representações sociais do suicídio na adolescência

Em Portugal, dados recentes da Direção-Geral de Saúde (2013), apontam para um aumento do número de suicídios nos últimos anos e revelam que nos adolescentes o suicídio é a segunda causa de morte. Os comportamentos suicidas nos adolescentes constituem, assim, um importante problema de saúde pública. Face ao exposto, a finalidade deste projeto é conhecer as representações sociais do suicídio juvenil, recolher informações acerca do contacto ou vivência dos adolescentes com o suicídio e as suas opiniões acerca das ajudas disponíveis face à ideação suicida. Foi realizado um estudo exploratório, numa escola do centro do país e a amostra incluiu 82 adolescentes com idades compreendidas entre os 14 e 19 anos que frequentam o ensino secundário. Para a recolha dos dados foi utilizado um questionário aferido e validado para adolescentes - Questionário Suicídio Juvenil – Representações Sociais dos Adolescente (Henriques, Rothes, Vila, Monteiro & Oliveira, 2008). Recorreu-se ao SPSS (IBM 22) com recurso ao teste U de MannWhitney,e ao teste rho de Spearman para o tratamento dos dados. Entre os vários resultados obtidos salienta-se que apesar de em baixa percentagem, existe um número significativo de adolescentes que apresenta ideação suicida e que já tentou o suicídio. Os adolescentes atribuem ao suicídio causas tais como, escape de problemas, bullying, problemas amorosos e fatores biológicos. Verifica-se ainda uma relação entre o contacto com o suicídio e a ideação suicida. Desta forma, realça-se a importância de desenvolver um estudo mais alargado sobre esta problemática e consequentemente a “psicoeducação” acerca do suicídio junto dos adolescentes, adotando-se uma intervenção precoce de forma a promover a saúde mental dos adolescentes.ABSTRACT In Portugal, recent data from the Directorate General of Health (2013), pointing to an increase in the number of suicides in recent years and that reveal in adolescents suicide is the second leading cause of death. The suicidal behaviors in adolescents are, therefore, an important public health problem. In view of the above, the purpose of this project is to understand the social representations of youth suicides, collect information about the contact or experience of adolescents with the suicide and their views about the aid available to suicidal ideation. It was carried out an exploratory study, in a school in the center of the country and the sample included 82 adolescents aged between 14 and 19 years attending secondary education. For the collection of data was used a questionnaire measured and validated for adolescents - Questionnaire Youth Suicides - Social Representations of Adolescent (Henriques, Rothes, Vila, Monteiro & Oliveira, 2008). We used SPSS (IBM 22) using the Mann-Whitney U test, and the test Spearman's rho for the treatment of the data. Between the various results obtained enhance that although in low percentage, there is a significant number of adolescents with suicidal ideation and that already tried to commit suicide. The adolescents attach to suicide causes such as, exhaust problems, bullying, problems loving and biological factors. There is also a relationship between the contact with suicide and suicidal ideation. Thus, enhance the importance of developing a study more extended on this issue and therefore the "psychoeducation" about committing suicide together of adolescents, adopting an early intervention in order to promote the mental health of adolescents

Body mass index in HER2-negative metastatic breast cancer treated with first-line paclitaxel and bevacizumab

The evidence emerged from the TOURANDOT trial encourages evaluating the role of anthropometric determinants on treatment outcomes in HER2-negative metastatic breast cancer patients treated with bevacizumab-including regimens. We thus analyzed data from a subgroup of these patients from a larger cohort previously assessed for treatment outcomes. Patients were included in the present analysis if body mass index values had been recorded at baseline. Clinical benefit rates, progression free survival and overall survival were assessed for the overall study population and subgroups defined upon molecular subtype. One hundred ninety six patients were included (N:196). Body mass index showed no impact on clinical benefit rates in the overall study sample and in the luminal cancer subset (p = 0.12 and p = 0.79, respectively), but did so in the triple negative subgroup, with higher rates in patients with body mass index ≥25 (p = 0.03). In the overall study sample, body mass index did no impact progression free or overall survival (p = 0.33 and p = 0.67, respectively). Conversely, in triple negative patients, progression free survival was significantly longer with body mass index ≥25 (6 vs 14 months, p = 0.04). In this subset, overall survival was more favorable (25 vs 19 months, p = 0.02). The impact of the molecular subtype was confirmed in multivariate models including the length of progression free survival, and number of metastatic sites (p < 0.0001). Further studies are warranted to confirm our findings in more adequately sized, ad hoc, prospective studies

Novel highly potent and selective sigma1 receptor antagonists effectively block the binge eating episode in female rats

In this paper, the benzo-cracking approach was applied to the potent sigma1 (σ1) receptor antagonist 1 to afford the less conformationally constrained 1,3-dioxane derivatives 2 and 3. To evaluate the effect of the increase in the distance between the two hydrophobic structural elements that flank the basic function, the cis and trans diastereomers of 4 and 5 were also prepared and studied. Compounds 2 and 3 showed affinity values at the σ1 receptor significantly higher than that of the lead compound 1. In particular, 3 displayed unprecedented selectivity over the σ2 receptor, the phencyclidine site of the NMDA receptor, and opioid receptor subtypes, as well as over the dopamine transporter. Docking results supported the structure-activity relationship studies. Due to its interesting biological profile, derivative 3, selected for an in vivo study in a validated preclinical model of binge eating, was able to counteract the overeating of palatable food only in binging rats, without affecting palatable food intake in the control group and anxiety-like and depression-related behaviors in female rats. This result strengthened the involvement of the σ1 receptor in the compulsive-like eating behavior and supported the σ1 receptor as a promising target for the management of eating disorders

Tissue immune profile: a tool to predict response to neoadjuvant therapy in triple negative breast cancer

Abstract: Pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) can predict better survival outcomes in patients with early triple negative breast cancer (TNBC). Tumor infiltrating lymphocytes (TILs), Programmed Death-Ligand 1 (PD-L1), and Cluster of Differentiation 73 (CD73) are immune-related biomarkers that can be evaluated in the tumor microenvironment. We investigated if the contemporary expression of these biomarkers combined in a tissue immune profile (TIP) can predict pCR better than single biomarkers in TNBC. Tumor infiltrating lymphocytes (TILs), CD73 expression by cancer cells (CC), and PD-L1 expression by immune cells (IC) were evaluated on pre-NACT biopsies. We defined TIP positive (TIP+) as the simultaneous presence of TILS ≥ 50%, PD-L1 ≥ 1%, and CD73 ≤ 40%. To consider the effects of all significant variables on the pCR, multivariate analysis was performed. Akaike information criterion (AIC) and Bayesian information criterion (BIC) were used for model selection. We retrospectively analyzed 60 biopsies from patients with TNBC who received standard NACT. Pathological complete response was achieved in 23 patients (38.0%). Twelve (20.0%) cases resulted to be TIP+. The pCR rate was significantly different between TIP+ (91.7%) and TIP− (25.0%) (p < 0.0001). Using a multivariate analysis, TIP was confirmed as an independent predictive factor of pCR (OR 49.7 (6.30–392.4), p < 0.0001). Finally, we compared the efficacy of TIP versus each single biomarker in predicting pCR by AIC and BIC. The combined immune profile is more accurate in predicting pCR (AIC 68.3; BIC 74.5) as compared to single biomarkers. The association between TIP+ and pCR can be proposed as a novel link between immune background and response to chemotherapy in TNBC, highlighting the need to consider an immunological patients’ profile rather than single biomarkers