RESTITUTIO AD INTEGRUM IN A CASE OF ONJ RELATED TO BEVACIZUMAB

Aim. Bevacizumab is a humanized recombinant monoclonal antibody that blocks vascular endothelial growth factor (VEGF). The activity of VEGF is the ability to promote the vascular endothelial cells proliferation inducing the formation of new blood vessels. Bevacizumab is used in the treatment of selected advanced colon, lung, renal and central nervous system tumours and plays a developing role in the management of breast and ovarian cancers. It is also injected intraocularly for treatment of macular degeneration. Recently, bevacizumab has been reported as responsible of drug-related osteonecrosis of the jaw (ONJ), showing a histological pattern similar to bisphosphonate-related ONJ. Moreover, it may increase the risk for osteonecrosis of the jaw when administered in isolation or when given concurrently with bisphosphonates. Materials and methods. Only few case reports in literature have been reported describing ONJ after bevacizumab administration. In June 2011, a 57-year-old female patient was referred to our department for pain in the left posterior mandibular region. She reported the following anamnestic data: in 2002, for the diagnosis of breast cancer, she underwent to left quadrantectomy and radiant treatment; from October 2010, she was receiving multimodal chemotherapy containing bevacizumab. No previous treatment with bisphosphonates, or other known local and systemic risk factors were reported. Intraoral examination showed a painful area of bone exposure in the left posterior lingual mandible. The surrounding soft tissue was erythematous with purulent discharge and with swelling of the extraoral soft tissue of the left mandible. After interaction with her oncologist, bevacizumab has been suspended and systemic antibiotic (ampicillina/sulbactam intramuscularly twice daily for 8 days and metronidazole 250mg per os twice daily for 8 days), local antiseptics (chlorhexidine 0.2% mouth rinses and 0.5% chlorhexidine gel) were administered. Results. After 15 days, she showed a complete healing after spontaneous sequestration of a necrotic bone fragment. Conclusions. The antiangiogenic and antiresorptive effects of bevacizumab are dose-dependent and time-dependent. Probably this implies that angiogenesis, bone remodelling and healing processes should restart after drug cessation. The present case supports the necessity to apply BRONJ prevention protocol also in patients in therapy with bevacizumab

Set-based Inverse Kinematics Control of an Anthropomorphic Dual Arm Aerial Manipulator

The paper presents a multiple task-priority inverse kinematics algorithm for a dual-arm aerial manipulator. Both tasks defined as equality constraints and inequality constraints are handled by means of a singularity robust method based on the Null-Space based Behavioral control. The proposed schema is constituted by the inverse kinematics control, that receives the desired behavior of the system and outputs the reference values for the motion variables, i.e. the UAV pose and the arm joints position, and a motion control, that computes the vehicle thrusts and the joint torques. The method has been experimentally validated on a system composed by an underactuated aerial hexarotor vehicle equipped with two lightweight 4-DOF manipulators, involved in operations requiring the coordination of the two arms and the vehicle

Imaging performance of phase-contrast breast computed tomography with synchrotron radiation and a CdTe photon-counting detector

Purpose: Within the SYRMA-CT collaboration based at the ELETTRA synchrotron radiation (SR) facility (Trieste, Italy) the authors investigated the imaging performance of the phase-contrast computed tomography (CT) system dedicated to monochromatic in vivo 3D imaging of the female breast, for breast cancer diagnosis. Methods: Test objects were imaged at 38 keV using monochromatic SR and a high-resolution CdTe photon-counting detector. Signal and noise performance were evaluated using modulation transfer function (MTF) and Noise Power Spectrum (NPS). Phase-contrast CT images as well as images obtained after the application of a phase-retrieval algorithm were evaluated. The contrast to noise ratio (CNR) and the capability of detecting test microcalcification clusters and soft masses were explored. Results: For a voxel size of (60 \u3bcm)3, phase-contrast images showed higher spatial resolution (6.7 mm-1 at 10% MTF) than corresponding phase retrieval images (2.5 mm-1). Phase retrieval produced a reduction of the noise level as well as an increase of the CNR by more than one order of magnitude, compared to raw phase-contrast images. CaCO3 microcalcifications with a diameter down to 130 \u3bcm were detected both in phase-contrast and in phase retrieval images of the test object. Conclusions: The investigation on test objects indicates that breast CT with a monochromatic SR source is technically feasible in terms of spatial resolution, image noise and contrast, for in vivo 3D imaging with a dose comparable to that of two-view mammography. Phase-retrieved images showed the best performance in the trade-off between spatial resolution and image noise

DNA damage response at telomeres boosts the transcription of SARS-CoV-2 receptor ACE2 during aging

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19), known to be more common in the elderly, who also show more severe symptoms and are at higher risk of hospitalization and death. Here, we show that the expression of the angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 cell receptor, increases during aging in mouse and human lungs. ACE2 expression increases upon telomere shortening or dysfunction in both cultured mammalian cells and in vivo in mice. This increase is controlled at the transcriptional level, and Ace2 promoter activity is DNA damage response (DDR)-dependent. Both pharmacological global DDR inhibition of ATM kinase activity and selective telomeric DDR inhibition by the use of antisense oligonucleotides prevent Ace2 upregulation following telomere damage in cultured cells and in mice. We propose that during aging telomere dysfunction due to telomeric shortening or damage triggers DDR activation and this causes the upregulation of ACE2, the SARS-CoV-2 cell receptor, thus contributing to make the elderly more susceptible to the infection

Sfrp1 deficiency makes retinal photoreceptors prone to degeneration

Millions of individuals worldwide suffer from impaired vision, a condition with multiple origins that often impinge upon the light sensing cells of the retina, the photoreceptors, affecting their integrity. The molecular components contributing to this integrity are however not yet fully understood. Here we have asked whether Secreted Frizzled Related Protein 1 (SFRP1) may be one of such factors. SFRP1 has a context-dependent function as modulator of Wnt signalling or of the proteolytic activity of A Disintegrin And Metalloproteases (ADAM) 10, a main regulator of neural cell-cell communication. We report that in Sfrp1^{-/-} mice, the outer limiting membrane (OLM) is discontinuous and the photoreceptors disorganized and more prone to light-induced damage. Sfrp1 loss significantly enhances the effect of the Rpe6^{Leu450Leu} genetic variant -present in the mouse genetic background- which confers sensitivity to light-induced stress. These alterations worsen with age, affect visual function and are associated to an increased proteolysis of Protocadherin 21 (PCDH21), localized at the photoreceptor outer segment, and N-cadherin, an OLM component. We thus propose that SFRP1 contributes to photoreceptor fitness with a mechanism that involves the maintenance of OLM integrity. These conclusions are discussed in view of the broader implication of SFRP1 in neurodegeneration and aging

Squamous cell carcinoma of the lower lip: FAS/FASL expression, lymphocyte subtypes and outcome.

Squamous cell carcinoma (SCC) of the lip is a relatively common malignancy of the head and neck region. Tumour thickness, grading and perineural invasion are significant prognostic indicators. However, there is still the need of new reliable biological markers able to predict the prognosis of the single cases with an unfavourable biological behaviour unpredictable by the classic clinical-pathological parameters. 32 cases of (SCC) of the lower lip were analysed for their clinicopathologic features, and immunohistochemical expression of Fas/FasL in neoplastic cells and in inflammatory infiltrate. Moreover the density and phenotype of tumour-infiltrating lymphocytes (TIL) were analysed. The results were related with the follow-up of the patients ranging from 2 to 6 years. The cases with over-expression of Fas/FasL in neoplastic cells and Fas+ in T cells preferentially showed a more aggressive clinical behaviour (p<0.01). Moreover we found an alteration of the normal expression of CD4 and CD8 lymphocyte types in ten cases. This data suggest that the Fas/FasL pathway is involved in the close relation between neoplastic cells and T cells and so in the biological behaviour of these tumours

Electrocardiogram analysis in Anderson-Fabry disease: a valuable tool for progressive phenotypic expression tracking

BackgroundElectrocardiogram (ECG) has proven to be useful for early detection of cardiac involvement in Anderson-Fabry disease (AFD); however, little evidence is available on the association between ECG alterations and the progression of the disease.Aim and MethodsTo perform a cross sectional comparison of ECG abnormalities throughout different left ventricular hypertrophy (LVH) severity subgroups, providing ECG patterns specific of the progressive AFD stages. 189 AFD patients from a multicenter cohort underwent comprehensive ECG analysis, echocardiography, and clinical evaluation.ResultsThe study cohort (39% males, median age 47 years, 68% classical AFD) was divided into 4 groups according to different degree of left ventricular (LV) thickness: group A &amp; LE; 9 mm (n = 52, 28%); group B 10-14 mm (n = 76, 40%); group C 15-19 mm (n = 46, 24%); group D &amp; GE; 20 mm (n = 15, 8%). The most frequent conduction delay was right bundle branch block (RBBB), incomplete in groups B and C (20%,22%) and complete RBBB in group D (54%, p &lt; 0.001); none of the patients had left bundle branch block (LBBB). Left anterior fascicular block, LVH criteria, negative T waves, ST depression were more common in the advanced stages of the disease (p &lt; 0.001). Summarizing our results, we suggested ECG patterns representative of the different AFD stages as assessed by the increases in LV thickness over time (Central Figure). Patients from group A showed mostly a normal ECG (77%) or minor anomalies like LVH criteria (8%) and delta wave/slurred QR onset + borderline PR (8%). Differently, patients from groups B and C exhibited more heterogeneous ECG patterns: LVH (17%; 7% respectively); LVH + LV strain (9%; 17%); incomplete RBBB + repolarization abnormalities (8%; 9%), more frequently associated with LVH criteria in group C than B (8%; 15%). Finally, patients from group D showed very peculiar ECG patterns, represented by complete RBBB + LVH and repolarization abnormalities (40%), sometimes associated with QRS fragmentation (13%).ConclusionsECG is a sensitive tool for early identification and long-term monitoring of cardiac involvement in patients with AFD, providing "instantaneous pictures" along the natural history of AFD. Whether ECG changes may be associated with clinical events remains to be determined

An ESPRESSO view of HD 189733 system. Broadband transmission spectrum, differential rotation, and system architecture

The development of state-of-the-art spectrographs has ushered in a new era in the detection and characterization of exoplanetary systems. Our objective is to utilize the high-resolution and precision capabilities of the ESPRESSO instrument to detect and measure the broad-band transmission spectrum of HD 189733b's atmosphere. Additionally, we aim to employ an improved Rossiter-McLaughlin model to derive properties related to the velocity fields of the stellar surface and to constrain the orbital architecture. Our results demonstrate a high degree of precision in fitting the observed radial velocities during transit using the improved modeling of the Rossiter-McLaughlin effect. We tentatively detect the effect of differential rotation with a confidence level of $93.4 \%$ when considering a rotation period within the photometric literature values, and $99.6\%$ for a broader range of rotation periods. For the former, the amplitude of differential rotation ratio suggests an equatorial rotation period of $11.45\pm 0.09$ days and a polar period of $14.9\pm 2$. The addition of differential rotation breaks the latitudinal symmetry, enabling us to measure the true spin-orbit angle $\psi \approx 13.6 \pm 6.9 ^\circ$ and the stellar inclination axis angle $i_{\star} \approx 71.87 ^{+6.91^\circ}_{-5.55^\circ}$. Moreover, we determine a sub-solar amplitude of the convective blueshift velocity $V_{CB}$ $\approx$ $-211 ^{+69} _{-61}$ m$\,$s$^{-1}$, which falls within the expected range for a K-dwarf host star and is compatible with both runs. Finally, we successfully retrieved the transmission spectrum of HD 189733b from the high-resolution ESPRESSO data. We observe a significant decrease in radius with increasing wavelength, consistent with the phenomenon of super-Rayleigh scattering