Body composition with dual energy X-ray absorptiometry : from basics to new tools

Dual-energy X-ray absorptiometry (DXA) in nowadays considered one of the most versatile imaging techniques for the evaluation of metabolic bone disorders such as osteoporosis, sarcopenia and obesity. The advantages of DXA over other imaging techniques are the very low radiation dose, its accuracy and simplicity of use. In addition, fat mass (FM) and lean mass (LM) values by DXA shows very good accuracy compared to that of computed tomography and magnetic resonance imaging. In this review we will explain the technical working principles of body composition with DXA, together with the possible limitations and pitfalls that should be avoided in daily routine to produce high-quality DXA examinations. We will also cover the current clinical practical application of whole body DXA values, with particular emphasis on the use of LM indices in the diagnostic workup of reduced muscle mass, sarcopenia and osteosarcopenic obesity according to the most recent guidelines. The possible use of adipose indices will be considered, such as the fat mass index (FMI) or the android/gynoid ratio, as well as lipodystrophy indices and the evaluation of visceral adipose tissue (VAT). Whenever available, we will provide possible cut-off diagnostic values for each of these LM and FM indices, according to current literature and guidelines

Hypoxia shapes autophagy in LPS-activated dendritic cells

During their lifespan, dendritic cells (DCs) are exposed to different pO2 levels that affect their differentiation and functions. Autophagy is one of the adaptive responses to hypoxia with important implications for cell survival. While the autophagic machinery in DCs was shown to impact signaling of TLRs, its regulation by the MD-2/TLR4 ligand LPS is still unclear. The aim of this study was to evaluate whether LPS can induce autophagy in DCs exposed to either aerobic or hypoxic conditions. Using human monocyte-derived DCs and the combination of immunofluorescence confocal analysis, measure of mitochondrial membrane potential, Western blotting, and RT-qPCR, we showed that the ability of LPS to modulate autophagy was strictly dependent upon pO2 levels. Indeed, LPS inhibited autophagy in aerobic conditions whereas the autophagic process was induced in a hypoxic environment. Under hypoxia, LPS treatment caused a significant increase of functional lysosomes, LC3B and Atg protein upregulation, and reduction of SQSTM1/p62 protein levels. This selective regulation was accompanied by activation of signalling pathways and expression of cytokines typically associated with DC survival. Bafilomycin A1 and chloroquine, which are recognized as autophagic inhibitors, confirmed the induction of autophagy by LPS under hypoxia and its impact on DC survival. In conclusion, our results show that autophagy represents one of the mechanisms by which the activation of the MD-2/TLR4 ligand LPS promotes DC survival under hypoxic conditions

Investigation of VOCs associated with different characteristics of breast cancer cells

The efficacy of breath volatile organic compounds (VOCs) analysis for the screening of patients bearing breast cancer lesions has been demonstrated by using gas chromatography and artificial olfactory systems. On the other hand, in-vitro studies suggest that VOCs detection could also give important indications regarding molecular and tumorigenic characteristics of tumor cells. Aim of this study was to analyze VOCs in the headspace of breast cancer cell lines in order to ascertain the potentiality of VOCs signatures in giving information about these cells and set-up a new sensor system able to detect breast tumor-associated VOCs. We identified by Gas Chromatography-Mass Spectrometry analysis a VOCs signature that discriminates breast cancer cells for: i) transformed condition; ii) cell doubling time (CDT); iii) Estrogen and Progesterone Receptors (ER, PgR) expression, and HER2 overexpression. Moreover, the signals obtained from a temperature modulated metal oxide semiconductor gas sensor can be classified in order to recognize VOCs signatures associated with breast cancer cells, CDT and ER expression. Our results demonstrate that VOCs analysis could give clinically relevant information about proliferative and molecular features of breast cancer cells and pose the basis for the optimization of a low-cost diagnostic device to be used for tumors characterization

Studying a Masonry Sail Vault by Antonio da Sangallo the Elder in the Fortezza Vecchia in Livorno

The present contribution aims to illustrate some first results obtained from ongoing research on a 16th-century masonry sail vault in the Fortezza Vecchia (the Old Fortress) in Livorno (Italy). A multidisciplinary research is currently ongoing. The information collected by means of geometric surveys and experimental tests are being used as input data for the different analytical and numerical models expressly developed to study the vault’s structural response. The structural analysis has been performed using two analytical models set within the framework of limit analysis. The first considers the vault as a thin shell, and suitable sets of statically admissible stresses are built; the second model is a modern reinterpretation of Durand-Claye’s method for domes. As an additional term of comparison, numerical analyses are carried out by means of FE models. The study is still under development, and a first set of results has been obtained by limiting the analysis to vertical loads accounting for the self-weight of the vault and that of the overlying soil layer

Forecasting Effusive Dynamics and Decompression Rates by Magmastatic Model at Open-vent Volcanoes

Effusive eruptions at open-conduit volcanoes are interpreted as reactions to a disequilibrium induced by the increase in magma supply. By comparing four of the most recent effusive eruptions at Stromboli volcano (Italy), we show how the volumes of lava discharged during each eruption are linearly correlated to the topographic positions of the effusive vents. This correlation cannot be explained by an excess of pressure within a deep magma chamber and raises questions about the actual contributions of deep magma dynamics. We derive a general model based on the discharge of a shallow reservoir and the magmastatic crustal load above the vent, to explain the linear link. In addition, we show how the drastic transition from effusive to violent explosions can be related to different decompression rates. We suggest that a gravity-driven model can shed light on similar cases of lateral effusive eruptions in other volcanic systems and can provide evidence of the roles of slow decompression rates in triggering violent paroxysmal explosive eruptions, which occasionally punctuate the effusive phases at basaltic volcanoes

Artificial neural network analysis of bone quality DXA parameters response to teriparatide in fractured osteoporotic patients

Teriparatide is a bone-forming therapy for osteoporosis that increases bone quantity and texture, with uncertain action on bone geometry. No data are available regarding its influence on bone strain. To investigate teriparatide action on parameters of bone quantity and quality and on Bone Strain Index (BSI), also derived from DXA lumbar scan, based on the mathematical model finite element method. Forty osteoporotic patients with fractures were studied before and after two years of daily subcutaneous 20 mcg of teriparatide with dual X-ray photon absorptiometry to assess bone mineral density (BMD), hip structural analysis (HSA), trabecular bone score (TBS), BSI. Spine deformity index (SDI) was calculated from spine X-ray. Shapiro-Wilks, Wilcoxon and Student's t test were used for classical statistical analysis. Auto Contractive Map was used for Artificial Neural Network Analysis (ANNs). In the entire population, the ameliorations after therapy regarded BSI (-13.9%), TBS (5.08%), BMD (8.36%). HSA parameters of femoral shaft showed a worsening. Dividing patients into responders (BMD increase >10%) and non-responders, the first presented TBS and BSI ameliorations (11.87% and -25.46%, respectively). Non-responders presented an amelioration of BSI only, but less than in the other subgroup (-6.57%). ANNs maps reflect the mentioned bone quality improvements. Teriparatide appears to ameliorate not only BMD and TBS, but also BSI, suggesting an increase of bone strength that may explain the known reduction in fracture risk, not simply justified by BMD increase. BSI appears to be a sensitive index of TPD effect. ANNs appears to be a valid tool to investigate complex clinical systems

Immune-modulating effects of bevacizumab in metastatic non-small-cell lung cancer patients

The mPEBev is an anticancer regimen which combines a chemotherapy doublet, based on cisplatin and oral etoposide (mPE), with bevacizumab (mPEBev), a mAb targeting the vasculo-endothelial growth factor (VEGF). In previous studies, this regimen showed powerful anti-angiogenetic effects and significant antitumor activity in metastatic non-small-cell lung cancer (mNSCLC) patients. We also recorded the best benefit in patients exhibiting low-systemic inflammatory profile at baseline. On these bases, we hypothesized that mPEBev antitumor activity could be partially related to bevacizumab-associated immunological effects. For this reason, we performed an immunological monitoring in 59 out of 120 stage IIIb-IV NSCLC patients enrolled in the BEVA2007 phase II trial, who received fractioned cisplatin (30 mg/sqm days 1-3q21) and oral etoposide (50 mg, days 1-15q21) (mPE doublet) ±bevacizumab. In this group of patients, 12 received the mPE doublet alone and 47 the doublet in combination with bevacizumab (5 mg/kg on the day 3q21; mPEBev regimen). Blood cell counts, serum analysis, multiplex cytokine assay and immunocytofluorimetric analysis, performed on baseline and post-treatment on blood samples from these patients, revealed that bevacizumab addition to the doublet decreased levels of pro-angiogenic (VEGF, Angiostatin-1 and Follistatin) and inflammatory cytokines (interferon (IFN)γ, IL4 and IL17), improved in vivo and in vitro cytotoxic T-lymphocytes (CTL) response and promoted dendritic cell activation. These results suggest that the mPEBev regimen improve the micro-environmental conditions for an efficient antigen-specific CTL response, making it a feasible candidate regimen to be assessed in combination with immune-checkpoint inhibitors in NSCLC patients

Assessment of DXA derived bone quality indexes and bone geometry parameters in early breast cancer patients: A single center cross-sectional study

Background: Bone mineral density (BMD) lacks sensitivity in individual fracture risk assessment in early breast cancer (EBC) patients treated with aromatase inhibitors (AIs). New dual-energy X-ray absorptiometry (DXA) based risk factors are needed. Methods: Trabecular bone score (TBS), bone strain index (BSI) and DXA parameters of bone geometry were evaluated in postmenopausal women diagnosed with EBC. The aim was to explore their association with morphometric vertebral fractures (VFs). Subjects were categorized in 3 groups in order to evaluate the impact of AIs and denosumab on bone geometry: AI-naive, AI-treated minus (AIDen-) or plus (AIDen+) denosumab. Results: A total of 610 EBC patients entered the study: 305 were AI-naive, 187 AIDen-, and 118 AIDen+. In the AI-naive group, the presence of VFs was associated with lower total hip BMD and T-score and higher femoral BSI. As regards as bone geometry parameters, AI-naive fractured patients reported a significant increase in femoral narrow neck (NN) endocortical width, femoral NN subperiosteal width, intertrochanteric buckling ratio (BR), intertrochanteric endocortical width, femoral shaft (FS) BR and endocortical width, as compared to non-fractured patients. Intertrochanteric BR and intertrochanteric cortical thickness significantly increased in the presence of VFs in AIDen- patients, not in AIDen+ ones. An increase in cross-sectional area and cross-sectional moment of inertia, both intertrochanteric and at FS, significantly correlated with VFs only in AIDen+. No association with VFs was found for either lumbar BSI or TBS in all groups. Conclusions: Bone geometry parameters are variably associated with VFs in EBC patients, either AI-naive or AI treated in combination with denosumab. These data suggest a tailored choice of fracture risk parameters in the 3 subgroups of EBC patients