Awareness towards Chikungunya virus infection risk by general practitioners in Rome: a questionnaire based survey before the 2017 outbreak

Autochthonous cases of Chikungunya (CHIKV) have been recently detected in Rome. A survey was conduct- ed prior to the 2017 outbreak to assess knowledge, attitude, and practices towards CHIKV infections on 103 randomly selected general practitioners (GPs), practicing in the centre of Rome. Only 24.3% were aware of CHIKV and completed the interview. Among completers, the knowledge of basic elements of CHIKV in- fection was insufficient. Only two thirds of them were able to identify possible CHIKV cases in hypothetical clinical scenarios presented by the interviewer. Our study highlights the need to improve GP knowledge to- wards CHIKV, as a necessary step to establish an efficacious epidemic surveillance

A clustering approach and a rule of thumb for risk aggregation

The problem of establishing reliable estimates or bounds for the (T)VaR of a joint risk portfolio is a relevant subject in connection with the computation of total economic capital in the Basel regulatory framework for the finance sector as well as with the Solvency regulations for the insurance sector. In the computation of total economic capital, a financial institution faces a considerable amount of model uncertainty related to the estimation of the interdependence amongst the marginal risks. In this paper, we propose to apply a clustering procedure in order to partition a risk portfolio into independent subgroups of positively dependent risks. Based on available data, the portfolio partition so obtained can be statistically validated and allows for a reduction of capital and the corresponding model uncertainty. We illustrate the proposed methodology in a simulation study and two case studies considering an Operational and a Market Risk portfolio. A rule of thumb stems from the various examples proposed: in a mathematical model where the risk portfolio is split into independent subsets with comonotonic dependence within, the smallest VaR-based capital estimate (at the high regulatory probability levels typically used) is produced by assuming that the infinite-mean risks are comonotonic and the finite-mean risks are independent. The largest VaR estimate is instead generated by obtaining the maximum number of independent infinite-mean sums

Vertebral Augmentation for Neoplastic Lesions with Posterior Wall Erosion and Epidural Mass

BACKGROUND AND PURPOSE: The presence of a cortical erosion of the posterior wall or an epidural mass is commonly considered a contraindication to performing a vertebral augmentation, considering the perceived increased risk of an epidural cement leak. Our aim was to assess technical and clinical complications of vertebral augmentation procedures performed for pain palliation and/or stabilization of neoplastic lytic vertebral body lesions, with cortical erosion of the posterior wall, often associated with a soft-tissue epidural mass. MATERIALS AND METHODS: In 48 patients, we performed retrospective vertebral augmentation assessment on 70 consecutive levels with cortical erosion of the posterior wall, as demonstrated by preprocedural CT/MR imaging. An epidural mass was present in 31/70 (44.3%) levels. Cavity creation was performed with Coblation Wands before cement injection in 59/70 levels. Injection of high-viscosity polymethylmethacrylate was performed under real-time continuous fluoroscopic control. Postprocedural CT of the treated levels was performed in all cases. Clinical follow-up was performed at 1 and 4 weeks postprocedurally. RESULTS: In 65/70 (92.8%) levels, the vertebral augmentation resulted in satisfactory polymethylmethacrylate filling of the lytic cavity and adjacent trabecular spaces in the anterior half of the vertebral body. An epidural leak of polymethylmethacrylate occurred in 10/70 (14.2%) levels, causing radicular pain in 3 patients, which spontaneously resolved within 1 week in 2 patients, while 1 patient with a T1–T2 foraminal leak developed severe weakness of the intrinsic hand muscles and a permanent motor deficit. CONCLUSIONS: In our series of vertebral augmentation of neoplastic lytic vertebral lesions performed for palliation of pain and/or stabilization, we observed a polymethylmethacrylate epidural leak in only 14.2% of levels, despite the presence of cortical erosion of the posterior wall and an epidural mass, with an extremely low rate of clinical complications. Our data seem to justify use of vertebral augmentation in patients with intractable pain or those at risk for vertebral collapse

Which factors can influence post-operative renal function preservation after nephron-sparing surgery for kidney cancer: a critical review

Introduction: The aim of this article was to compare different surgical approaches to perform nephron-sparing surgery (NSS) in terms of preservation of renal function. Material and methods: We critically reviewed the literature from January 2000 to December 2020 including studies comparing different surgical techniques. Results: A total of 51 studies met the inclusion criteria. Functional outcomes were evalutated in terms of percentual change of estimated glomerular filtration rate (eGFR) and impaired renal function (IRF) on scintigraphy. In cases with a mean age <60 years, the mean decrease in eGFR after NSS was 11.7% and that of IRF 10.0%, whereas higher changes were found in cases with a mean age ≥60 years. For open NSS, the mean eGFR and IRF changes were 15.3% and 21.1%, respectively; using the laparoscopic approach, the mean percentual eGFR and IRF changes were 13.9% and 11.1%, respectively; in robotic cases, the mean eGFR and IRF changes were 10.8% and 13.1%, respectively. In cases performed with global ischemia, the mean eGFR and IRF changes were 12.7% and 15.1%, respectively. Similar results were found distinguishing ischemia time ≤20 and >20 minutes, whereas using the off-clamp technique the mean decreases in eGFR and IRF were only 4.2% and 6%, respectively. Conclusions: Patients' age, tumor size, off-clamp technique, and robot-assisted approach were significant independent predictive factors able to influence renal function changes after NSS. A lower reduction of eGFR and IRF after NSS was reported in patients aged <60 years, submitted to a robot-assisted procedure, and using selective and cold ischemia <20 minutes or an off-clamp technique

Obese mice exposed to psychosocial stress display cardiac and hippocampal dysfunction associated with local brain-derived neurotrophic factor depletion

Introduction: Obesity and psychosocial stress (PS) co-exist in individuals of Western society. Nevertheless, how PS impacts cardiac and hippocampal phenotype in obese subjects is still unknown. Nor is it clear whether changes in local brain-derived neurotrophic factor (BDNF) account, at least in part, for myocardial and behavioral abnormalities in obese experiencing PS. Methods: In adult male WT mice, obesity was induced via a high-fat diet (HFD). The resident-intruder paradigm was superimposed to trigger PS. In vivo left ventricular (LV) performance was evaluated by echocardiography and pressure-volume loops. Behaviour was indagated by elevated plus maze (EPM) and Y-maze. LV myocardium was assayed for apoptosis, fibrosis, vessel density and oxidative stress. Hippocampus was analyzed for volume, neurogenesis, GABAergic markers and astrogliosis. Cardiac and hippocampal BDNF and TrkB levels were measured by ELISA and WB. We investigated the pathogenetic role played by BDNF signaling in additional cardiac-selective TrkB (cTrkB) KO mice. Findings: When combined, obesity and PS jeopardized LV performance, causing prominent apoptosis, fibrosis, oxidative stress and remodeling of the larger coronary branches, along with lower BDNF and TrkB levels. HFD/PS weakened LV function similarly in WT and cTrkB KO mice. The latter exhibited elevated LV ROS emission already at baseline. Obesity/PS augmented anxiety-like behaviour and impaired spatial memory. These changes were coupled to reduced hippocampal volume, neurogenesis, local BDNF and TrkB content and augmented astrogliosis. Interpretation: PS and obesity synergistically deteriorate myocardial structure and function by depleting cardiac BDNF/TrkB content, leading to augmented oxidative stress. This comorbidity triggers behavioral deficits and induces hippocampal remodeling, potentially via lower BDNF and TrkB levels. Fund: J.A. was in part supported by Rotary Foundation Global Study Scholarship. G.K. was supported by T32 National Institute of Health (NIH) training grant under award number 1T32AG058527. S.C. was funded by American Heart Association Career Development Award (19CDA34760185). G.A.R.C. was funded by NIH (K01HL133368-01). APB was funded by a Grant from the Friuli Venezia Giulia Region entitled: “Heart failure as the Alzheimer disease of the heart; therapeutic and diagnostic opportunities”. M.C. was supported by PRONAT project (CNR). N.P. was funded by NIH (R01 HL136918) and by the Magic-That-Matters fund (JHU). V.L. was in part supported by institutional funds from Scuola Superiore Sant'Anna (Pisa, Italy), by the TIM-Telecom Italia (WHITE Lab, Pisa, Italy), by a research grant from Pastificio Attilio Mastromauro Granoro s.r.l. (Corato, Italy) and in part by ETHERNA project (Prog. n. 161/16, Fondazione Pisa, Italy). Funding source had no such involvement in study design, in the collection, analysis, interpretation of data, in the writing of the report; and in the decision to submit the paper for publication

Design and characterization of superpotent bivalent ligands targeting oxytocin receptor dimers via a channel-like structure

Dimeric/oligomeric states of G-protein coupled receptors have been difficult to target. We report here bivalent ligands consisting of two identical oxytocin-mimetics that induce a three order magnitude boost in G-protein signaling of oxytocin receptors (OTRs) in vitro and a 100- and 40-fold gain in potency in vivo in the social behavior of mice and zebrafish. Through receptor mutagenesis and interference experiments with synthetic peptides mimicking transmembrane helices (TMH), we show that such superpotent behavior follows from the binding of the bivalent ligands to dimeric receptors based on a TMH1-TMH2 interface. Moreover, in this arrangement, only the analogues with a well-defined spacer length (∼25 Å) precisely fit inside a channel-like passage between the two protomers of the dimer. The newly discovered oxytocin bivalent ligands represent a powerful tool for targeting dimeric OTR in neurodevelopmental and psychiatric disorders and, in general, provide a framework to untangle specific arrangements of G-protein coupled receptor dimers

Brain hemodynamic intermediate phenotype links Vitamin B12 to cognitive profile of healthy and mild cognitive impaired subjects

Vitamin B12, folate, and homocysteine are implicated in pivotal neurodegenerative mechanisms and partake in elders' mental decline. Findings on the association between vitamin-related biochemistry and cognitive abilities suggest that the structural and functional properties of the brain may represent an intermediate biomarker linking vitamin concentrations to cognition. Despite this, no previous study directly investigated whether vitamin B12, folate, and homocysteine levels are sufficient to explain individual neuropsychological profiles or, alternatively, whether the activity of brain regions modulated by these compounds better predicts cognition in elders. Here, we measured the relationship between vitamin blood concentrations, scores at seventeen neuropsychological tests, and brain activity of sixty-five elders spanning from normal to Mild Cognitive Impairment. We then evaluated whether task-related brain responses represent an intermediate phenotype, providing a better prediction of subjects' neuropsychological scores, as compared to the one obtained considering blood biochemistry only. We found that the hemodynamic activity of the right dorsal anterior cingulate cortex was positively associated (p value < 0 05 cluster corrected) with vitamin B12 concentrations, suggesting that elders with higher B12 levels had a more pronounced recruitment of this salience network region. Crucially, the activity of this area significantly predicted subjects' visual search and attention abilities (p value = 0 0023), whereas B12 levels per se failed to do so. Our results demonstrate that the relationship between blood biochemistry and elders' cognitive abilities is revealed when brain activity is included into the equation, thus highlighting the role of brain imaging as intermediate phenotype.Vitamin B12, folate, and homocysteine are implicated in pivotal neurodegenerative mechanisms and partake in elders' mental decline. Findings on the association between vitamin-related biochemistry and cognitive abilities suggest that the structural and functional properties of the brain may represent an intermediate biomarker linking vitamin concentrations to cognition. Despite this, no previous study directly investigated whether vitamin B12, folate, and homocysteine levels are sufficient to explain individual neuropsychological profiles or, alternatively, whether the activity of brain regions modulated by these compounds better predicts cognition in elders. Here, we measured the relationship between vitamin blood concentrations, scores at seventeen neuropsychological tests, and brain activity of sixty-five elders spanning from normal to Mild Cognitive Impairment. We then evaluated whether task-related brain responses represent an intermediate phenotype, providing a better prediction of subjects' neuropsychological scores, as compared to the one obtained considering blood biochemistry only. We found that the hemodynamic activity of the right dorsal anterior cingulate cortex was positively associated (p value < 0 05 cluster corrected) with vitamin B12 concentrations, suggesting that elders with higher B12 levels had a more pronounced recruitment of this salience network region. Crucially, the activity of this area significantly predicted subjects' visual search and attention abilities (p value = 0 0023), whereas B12 levels per se failed to do so. Our results demonstrate that the relationship between blood biochemistry and elders' cognitive abilities is revealed when brain activity is included into the equation, thus highlighting the role of brain imaging as intermediate phenotype