Impact of immune parameters and immune dysfunctions on the prognosis of patients with chronic lymphocytic leukemia

SIMPLE SUMMARY: In chronic lymphocytic leukemia (CLL), immune alterations—affecting both the innate and adaptive immunity—are very common. As a clinical consequence, patients with CLL frequently present with autoimmune phenomena, increased risk of infections and second malignancies. The aim of this review article is to present available data on CLL-associated alterations of immune parameters that correlate with known prognostic markers and with clinical outcome. Also, data on the impact of immune-related clinical manifestations on the prognosis of patients with CLL will be discussed. ABSTRACT: Chronic lymphocytic leukemia (CLL) is characterized by a wide spectrum of immune alterations, affecting both the innate and adaptive immunity. These immune dysfunctions strongly impact the immune surveillance, facilitate tumor progression and eventually affect the disease course. Quantitative and functional alterations involving conventional T cells, γδ T cells, regulatory T cells, NK and NKT cells, and myeloid cells, together with hypogammaglobulinemia, aberrations in the complement pathways and altered cytokine signature have been reported in patients with CLL. Some of these immune parameters have been shown to associate with other CLL-related characteristics with a known prognostic relevance or to correlate with disease prognosis. Also, in CLL, the complex immune response dysfunctions eventually translate in clinical manifestations, including autoimmune phenomena, increased risk of infections and second malignancies. These clinical issues are overall the most common complications that affect the course and management of CLL, and they also may impact overall disease prognosis

Impact of immune parameters and immune dysfunctions on the prognosis of patients with chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is characterized by a wide spectrum of immune alterations, affecting both the innate and adaptive immunity. These immune dysfunctions strongly impact the immune surveillance, facilitate tumor progression and eventually affect the disease course. Quantitative and functional alterations involving conventional T cells, γδ T cells, regulatory T cells, NK and NKT cells, and myeloid cells, together with hypogammaglobulinemia, aberrations in the complement pathways and altered cytokine signature have been reported in patients with CLL. Some of these immune parameters have been shown to associate with other CLL‐related characteristics with a known prognostic relevance or to correlate with disease prognosis. Also, in CLL, the complex immune response dysfunctions eventually translate in clinical manifestations, including autoimmune phenomena, increased risk of infections and second malignancies. These clinical issues are overall the most common complications that affect the course and management of CLL, and they also may impact overall disease prognosis

Inner approximated reachability analysis

International audienceComputing a tight inner approximation of the range of a function over some set is notoriously di cult, way beyond obtaining outer approximations. We propose here a new method to compute a tight inner approximation of the set of reachable states of non-linear dynamical systems on a bounded time interval. This approach involves a ne forms and Kaucher arithmetic, plus a number of extra ingredients from set-based methods. An implementation of the method is discussed, and illustrated on representative numerical schemes, discrete-time and continuous-time dynamical systems

External gap progression after cyclic fatigue of adhesive overlays and crowns made with high translucency zirconia or lithium silicate

Objectives: To evaluate three-dimensional external gap progression after chewing simulation of high translucency zirconia (HTZ) and zirconia-reinforced lithium silicate (ZLS) applied on endodontically treated teeth with different preparation designs. Materials and Method: Endodontically treated molars were prepared with low-retentive (adhesive overlay) and high-retentive (full crown) designs above cementum-enamel junction and restored with HTZ and ZLS. Micro-computed tomography analysis was assessed before and after chewing simulation to evaluate three-dimensionally the external gap progression. Results were statistically analyzed with two-way ANOVA and post-hoc Tukey test. Results: High-retentive preparation design had a significantly inferior gap progression compared to the overlay preparation (p < 0.01); ZLS exhibited a significant inferior gap progression compared to HTZ (p < 0.01). Conclusions: High-retentive preparations restored with ZLS seem to better perform in maintaining the sealing of the external margin after cyclic fatigue. Clinical significance: The clinician should pay attention to the proper combination of preparation designs and ceramic material selection for an endodontically treated molar restoration. HTZ seems to perform worse than lithium silicate in terms of marginal sealing, still showing lacks in resistance to cyclic fatigue when adhesive preparations are performed

Cancer incidence in Italian contaminated sites

INTRODUCTION: The incidence of cancer among residents in sites contaminated by pollutants with a possible health impact is not adequately studied. In Italy, SENTIERI Project (Epidemiological study of residents in National Priority Contaminated Sites, NPCSs) was implemented to study major health outcomes for residents in 44 NPCSs. METHODS: The Italian Association of Cancer Registries (AIRTUM) records cancer incidence in 23 NPCSs. For each NPCSs, the incidence of all malignant cancers combined and 35 cancer sites (coded according to ICD-10), was analysed (1996-2005). The observed cases were compared to the expected based on age (5-year period,18 classes), gender, calendar period (1996-2000; 2001-2005), geographical area (North-Centre and Centre-South) and cancer sites specific rates. Standardized Incidence Ratios (SIR) with 90% Confidence Intervals were computed. RESULTS: In both genders an excess was observed for overall cancer incidence (9% in men and 7% in women) as well as for specific cancer sites (colon and rectum, liver, gallblad-der, pancreas, lung, skin melanoma, bladder and Non Hodgkin lymphoma). Deficits were observed for gastric cancer in both genders, chronic lymphoid leukemia (men), malignant thyroid neoplasms, corpus uteri and connective and soft-tissue tumours and sarcomas (women). DISCUSSION: This report is, to our knowledge, the first one on cancer risk of residents in NPCSs. The study, although not aiming to estimate the cancer burden attributable to the environment as compared to occupation or life-style, supports the credibility of an etiologic role of environmental exposures in contaminated sites. Ongoing analyses focus on the interpretation of risk factors for excesses of specific cancer types overall and in specific NPCSs in relation to the presence of carcinogenic pollutants

Effect of ω-3 and ω-9 fatty acid rich oils on lipoxygenases and cyclooxygenases enzymes and on the growth of a mammary adenocarcinoma model

Background Nutritional factors play a major role in cancer initiation and development. Dietary polyunsaturated fatty acids (PUFAs) have the ability to induce modifications in the activity of lipoxygenase (LOX) and cyclooxygenase (COX) enzymes that affect tumour growth. We studied the effect of two diets enriched in 6% Walnut and Peanut oils that are rich in ω-3 and ω9 PUFAs respectively on a murine mammary gland adenocarcinoma as compared with the control (C) that received commercial diet. Results Peanut oil enriched diet induced an increase in membrane arachidonic acid (AA) content and the cyclooxygenase enzyme derived 12-HHT (p < 0.05) and simultaneously showed decrease in 12-LOX, 15-LOX-2, 15-LOX-1 and PGE activities (p < 0.05) that corresponded to higher apoptosis and lower mitosis seen in this group (p < 0.05). Furthermore, Peanut oil group showed lower T-cell infiltration (p < 0.05), number of metastasis (p < 0.05) and tumour volume (p < 0.05) and longer survival rate compared to other groups. Conclusions The results of the present study showed that Peanut oil-enriched diet protects against mammary cancer development by modulating tumour membrane fatty acids composition and LOX and COX enzyme activities.Fil: Comba, Andrea. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Biología Celular; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Cátedra de Histología,embriología y Genética I; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Maestri, Damian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Berra, María Alejandra. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Biología Celular; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Cátedra de Histología,embriología y Genética I; ArgentinaFil: Garcia, Carolina Paola. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Biología Celular; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Cátedra de Histología,embriología y Genética I; ArgentinaFil: Das, Undurti N.. Jawaharlal Nehru Technological University; India. Undurti Narasimha Das; Estados Unidos. Krishna Institute of Medical Sciences; IndiaFil: Eynard, Aldo Renato. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Biología Celular; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Cátedra de Histología,embriología y Genética I; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Pasqualini, María Eugenia. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Biología Celular; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Cátedra de Histología,embriología y Genética I; Argentin

Angular Forces Around Transition Metals in Biomolecules

Quantum-mechanical analysis based on an exact sum rule is used to extract an semiclassical angle-dependent energy function for transition metal ions in biomolecules. The angular dependence is simple but different from existing classical potentials. Comparison of predicted energies with a computer-generated database shows that the semiclassical energy function is remarkably accurate, and that its angular dependence is optimal.Comment: Tex file plus 4 postscript figure

Long-term bond strength and endogenous enzymatic activity of a chlorhexidine-containing commercially available adhesive

10siObjectives: The aim of this study was to investigate, by the means of microtensile bond strength (μTBS) test, gelatin and in situ zymography, the influence of 0.2% CHX contained within a commercially available adhesive on long-term bond strength and endogenous enzymatic activity. Methods: Non-carious teeth were subjected to μTBS test (N = 15 for each group) and stressed until failure. μTBS was evaluated immediately and after 12-month storage in artificial saliva at 37 °C. Dentin powder was obtained from additional teeth (N = 7) for gelatin zymography, while for in situ zymography, 3 teeth for each group were selected. Gelatin and in situ zymography were performed in dentin powder and slices of dentin, respectively, to assess the ability of 0.2% CHX blended within the adhesive to inhibit endogenous enzymatic activity. Results: μTBS bond strength was higher in the CHX-containing groups, immediately as well as after aging. The bond strength significantly decreased after 12-month aging. The activation of endogenous MMPs was found to be related to the presence of CHX within the adhesive system and the bonding strategy employed. Conclusions: Under this perspective 0.2% CHX blended within Peak Universal adhesive monomer seems to in- crease immediate bond strength, to preserve bond strength over time and to efficiently inhibit endogenous enzymatic activity in dentin. Hence, blending the CHX in low concentrations within the adhesive could be recommended as a feasible technique in every-day clinical practice. Clinical significance: Using CHX-containing adhesives could be recommended due to several benefits: it seems to increase the longevity of the hybrid layer; the inhibitor appears to be efficiently delivered to the dentinal substrate and to inhibit endogenous enzymatic activity, without prolonging chair time.openopenMaravić, Tatjana; Comba, Allegra; Cunha, Sandra Ribeiro; Angeloni, Valeria; Cadenaro, Milena; Visinitini, Erika; Navarra, Chiara Ottavia; Salgarello, Stefano; Breschi, Lorenzo*; Mazzoni, AnnalisaMaravić, Tatjana; Comba, Allegra; Cunha, Sandra Ribeiro; Angeloni, Valeria; Cadenaro, Milena; Visinitini, Erika; Navarra, Chiara Ottavia; Salgarello, Stefano; Breschi, Lorenzo; Mazzoni, Annalis