A singular case of cavernous internal carotid artery aneurysm in patient with cavernous sinus syndrome and bacterial meningitis

AbstractWe report the uncommon case of an acute cavernous sinus syndrome in a patient who was consequently discovered to have both a cavernous internal carotid artery aneurysm and bacterial meningitis. Which came first, the chicken or the egg? Which of the two, the aneurysm or the meningitis, gave rise to the patient’s symptoms? We briefly reviewed the literature of similar cases and tried to analyze the possible pathophysiological relationship between these findings. Moreover, this case highlights the importance of a multidisciplinary management of these patients to better decide between a medical and a surgical and/or endovascular treatment

DNA Damage Regulates the Functions of the RNA Binding Protein Sam68 through ATM-Dependent Phosphorylation

Simple Summary Alterations of the complex network of interactions between the DNA damage response pathway and RNA metabolism have been described in several tumors, and increasing efforts are devoted to the elucidation of the molecular mechanisms involved in this network. Previous large-scale proteomic studies identified the RNA binding protein Sam68 as a putative target of the ATM kinase. Herein, we demonstrate that ATM phosphorylates Sam68 upon DNA damage induction, and this post-translational modification regulates both the signaling function of Sam68 in the initial phase of the DNA damage response and its RNA processing activity. Thus, our study uncovers anew crosstalk between ATM and Sam68, which may represent a paradigm for the functional interaction between the DDR pathway and RNA binding proteins, and a possible actionabletarget in human cancers. Cancer cells frequently exhibit dysregulation of the DNA damage response (DDR), genomic instability, and altered RNA metabolism. Recent genome-wide studies have strongly suggested an interaction between the pathways involved in the cellular response to DDR and in the regulation of RNA metabolism, but the molecular mechanism(s) involved in this crosstalk are largely unknown. Herein, we found that activation of the DDR kinase ATM promotes its interaction with Sam68, leading to phosphorylation of this multifunctional RNA binding protein (RBP) on three residues: threonine 61, serine 388 and serine 390. Moreover, we demonstrate that ATM-dependent phosphorylation of threonine 61 promotes the function of Sam68 in the DDR pathway and enhances its RNA processing activity. Importantly, ATM-mediated phosphorylation of Sam68 in prostate cancer cells modulates alternative polyadenylation of transcripts that are targets of Sam68, supporting the notion that the ATM-Sam68 axis exerts a multifaceted role in the response to DNA damage. Thus, our work validates Sam68 as an ATM kinase substrate and uncovers an unexpected bidirectional interplay between ATM and Sam68, which couples the DDR pathway to modulation of RNA metabolism in response to genotoxic stress

Fine-needle aspiration accuracy in the diagnosis of primary epithelioid angiosarcoma of the adrenal gland: a case report and review of the literature

Primary epithelioid angiosarcoma of the adrenal gland is extremely rare. Only 37 cases have been reported in the scientific literature.Here we describe the case of a 55-year-old woman affected by metastatic angiosarcoma in the right adrenal gland, who died few days after the histological diagnosis made by fine-needle aspiration (FNA). This is the second case of primary epithelioid angiosarcoma diagnosed by FNA among scientific articles published in English in PubMed. Microscopically, the tumor showed a predominant epithelioid differentiation, thus making the diagnostic process more difficult than usual. Immunohistochemical examination revealed positive reactivity for cytokeratin, CD31, and CD34. The literature shows that epithelioid adrenal angiosarcoma has poor clinical outcome, especially when metastatic at presentation

TERT Promoter Mutations Differently Correlate with the Clinical Outcome of MAPK Inhibitor-Treated Melanoma Patients

Resistance is a major challenge in the management of mitogen-activated protein kinase inhibitor (MAPKi)-treated metastatic melanoma. Tumor genetic alterations can cause MAPK pathway reactivation, leading to lack of response and poor outcome. Characterization of the mutational profile in patients with melanoma might be crucial for patient-tailored treatment choices. Mutations in the promoter region of the telomerase reverse transcriptase gene (TERTprom) lead to increased TERT expression and telomerase activity and are frequent in BRAFV600 mutant melanoma. Reportedly, TERTprom, and BRAFV600 mutations cooperate in driving cancer progression and aggressiveness. We evaluated the effect of the TERTprom status on the clinical outcome in 97 MAPKi-treated melanoma patients. We observed that patients with the c.-146C > T mutation showed a significantly worse progression-free survival (PFS) compared to those carrying the c.-124C > T mutation and a two-fold increased risk of progression (median 5.4 vs. 9.5 months; hazard ratio (HR) 1.9; 95% confidence interval (CI) 1.2-3.2; p = 0.013). This trend was also observed for the overall survival (OS); melanoma patients with the c.-146C > T mutation showed a poorer prognosis compared to those with the c.-124C > T mutation (median 13.3 vs. 25.5 months; HR 1.9, 95% CI 1.1-3.3, p = 0.023). Our results disclose a different correlation of the two TERTprom mutations with MAPKi-treated melanoma patient outcome, highlighting a different impact of the pathway blockade

Standardization proposal of soft tissue artefact description for data sharing in human motion measurements

Soft tissue artefact (STA) represents one of the main obstacles for obtaining accurate and reliable skeletal kinematics from motion capture. Many studies have addressed this issue, yet there is no consensus on the best available bone pose estimator and the expected errors associated with relevant results. Furthermore, results obtained by different authors are difficult to compare due to the high variability and specificity of the phenomenon and the different metrics used to represent these data. Therefore, the aim of this study was twofold: firstly, to propose standards for description of STA; and secondly, to provide illustrative STA data samples for body segments in the upper and lower extremities and for a range of motor tasks specifically, level walking, stair ascent, sit-to-stand, hip- and knee-joint functional movements, cutting motion, running, hopping, arm elevation and functional upper-limb movements. The STA dataset includes motion of the skin markers measured in vivo and ex vivo using stereophotogrammetry as well as motion of the underlying bones measured using invasive or bio-imaging techniques (i.e., X-ray fluoroscopy or MRI). The data are accompanied by a detailed description of the methods used for their acquisition, with information given about their quality as well as characterization of the STA using the proposed standards. The availability of open-access and standard-format STA data will be useful for the evaluation and development of bone pose estimators thus contributing to the advancement of three-dimensional human movement analysis and its translation into the clinical practice and other applications

The Role of Carbon Dioxide Laser Therapy in Penile Kaposi’s Sarcoma: A Case Series of Three HIV-Negative HHV-8-Positive Patients

Kaposi’s sarcoma (KS) is a rare tumor of vascular origin. It is quite common in HIV patients. It is rarely located on the glans penis, especially in HIV-negative patients (just some tens in the literature). Owing to the rarity of the disease, both the real impact on survival and the most suitable therapy are not known. However, in this 3-patient case series, carbon dioxide laser therapy was effective both for local control and survival. In fact, two late relapses but no disease-related death were recorded. Probably, KS in HIV-negative patients is a slowly progressive disease, not so aggressive as in HIV-positive patients. Laser therapy is easy, fast, and cheap, and may treat the disease radically. If these data are confirmed by further studies, in the foreseeable future, laser therapy may become the gold standard for treating HIV-negative patients affected by penile KS

SIAMOC position paper on gait analysis in clinical practice: General requirements, methods and appropriateness. Results of an Italian consensus conference

Gait analysis is recognized as a useful assessment tool in the field of human movement research. However, doubts remain on its real effectiveness as a clinical tool, i.e. on its capability to change the diagnostic-therapeutic practice. In particular, the conditions in which evidence of a favorable cost-benefit ratio is found and the methodology for properly conducting and interpreting the exam are not identified clearly. To provide guidelines for the use of Gait Analysis in the context of rehabilitation medicine, SIAMOC (the Italian Society of Clinical Movement Analysis) promoted a National Consensus Conference which was held in Bologna on September 14th, 2013. The resulting recommendations were the result of a three-stage process entailing i) the preparation of working documents on specific open issues, ii) the holding of the consensus meeting, and iii) the drafting of consensus statements by an external Jury. The statements were formulated based on scientific evidence or experts' opinion, when the quality/quantity of the relevant literature was deemed insufficient. The aim of this work is to disseminate the consensus statements. These are divided into 13 questions grouped in three areas of interest: 1) General requirements and management, 2) Methodological and instrumental issues, and 3) Scientific evidence and clinical appropriateness. SIAMOC hopes that this document will contribute to improve clinical practice and help promoting further research in the field

Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires

The production of tt‾ , W+bb‾ and W+cc‾ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓν , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of $t\overline{t}$, $W+b\overline{b}$ and $W+c\overline{c}$ is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 $\pm$ 0.02 \mbox{fb}^{-1}. The $W$ bosons are reconstructed in the decays $W\rightarrow\ell\nu$, where $\ell$ denotes muon or electron, while the $b$ and $c$ quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions

Physics case for an LHCb Upgrade II - Opportunities in flavour physics, and beyond, in the HL-LHC era

The LHCb Upgrade II will fully exploit the flavour-physics opportunities of the HL-LHC, and study additional physics topics that take advantage of the forward acceptance of the LHCb spectrometer. The LHCb Upgrade I will begin operation in 2020. Consolidation will occur, and modest enhancements of the Upgrade I detector will be installed, in Long Shutdown 3 of the LHC (2025) and these are discussed here. The main Upgrade II detector will be installed in long shutdown 4 of the LHC (2030) and will build on the strengths of the current LHCb experiment and the Upgrade I. It will operate at a luminosity up to 2×1034 cm−2s−1, ten times that of the Upgrade I detector. New detector components will improve the intrinsic performance of the experiment in certain key areas. An Expression Of Interest proposing Upgrade II was submitted in February 2017. The physics case for the Upgrade II is presented here in more depth. CP-violating phases will be measured with precisions unattainable at any other envisaged facility. The experiment will probe b → sl+l−and b → dl+l− transitions in both muon and electron decays in modes not accessible at Upgrade I. Minimal flavour violation will be tested with a precision measurement of the ratio of B(B0 → μ+μ−)/B(Bs → μ+μ−). Probing charm CP violation at the 10−5 level may result in its long sought discovery. Major advances in hadron spectroscopy will be possible, which will be powerful probes of low energy QCD. Upgrade II potentially will have the highest sensitivity of all the LHC experiments on the Higgs to charm-quark couplings. Generically, the new physics mass scale probed, for fixed couplings, will almost double compared with the pre-HL-LHC era; this extended reach for flavour physics is similar to that which would be achieved by the HE-LHC proposal for the energy frontier

LHCb upgrade software and computing : technical design report

This document reports the Research and Development activities that are carried out in the software and computing domains in view of the upgrade of the LHCb experiment. The implementation of a full software trigger implies major changes in the core software framework, in the event data model, and in the reconstruction algorithms. The increase of the data volumes for both real and simulated datasets requires a corresponding scaling of the distributed computing infrastructure. An implementation plan in both domains is presented, together with a risk assessment analysis