Invasive intraneural interfaces: foreign body reaction issues

Intraneural interfaces are stimulation/registration devices designed to couple the peripheral nervous system (PNS) with the environment. Over the last years, their use has increased in a wide range of applications, such as the control of a new generation of neural-interfaced prostheses. At present, the success of this technology is limited by an electrical impedance increase, due to an inflammatory response called foreign body reaction (FBR), which leads to the formation of a fibrotic tissue around the interface, eventually causing an inefficient transduction of the electrical signal. Based on recent developments in biomaterials and inflammatory/fibrotic pathologies, we explore and select the biological solutions that might be adopted in the neural interfaces FBR context: modifications of the interface surface, such as organic and synthetic coatings; the use of specific drugs or molecular biology tools to target the microenvironment around the interface; the development of bio-engineered-scaffold to reduce immune response and promote interface-tissue integration. By linking what we believe are the major crucial steps of the FBR process with related solutions, we point out the main issues that future research has to focus on: biocompatibility without losing signal conduction properties, good reproducible in vitro/in vivo models, drugs exhaustion and undesired side effects. The underlined pros and cons of proposed solutions show clearly the importance of a better understanding of all the molecular and cellular pathways involved and the need of a multi-target action based on a bio-engineered combination approach

Decoding Information From Neural Signals Recorded Using Intraneural Electrodes: Toward the Development of a Neurocontrolled Hand Prosthesis

The possibility of controlling dexterous hand prostheses by using a direct connection with the nervous system is particularly interesting for the significant improvement of the quality of life of patients, which can derive from this achievement. Among the various approaches, peripheral nerve based intrafascicular electrodes are excellent neural interface candidates, representing an excellent compromise between high selectivity and relatively low invasiveness. Moreover, this approach has undergone preliminary testing in human volunteers and has shown promise. In this paper, we investigate whether the use of intrafascicular electrodes can be used to decode multiple sensory and motor information channels with the aim to develop a finite state algorithm that may be employed to control neuroprostheses and neurocontrolled hand prostheses. The results achieved both in animal and human experiments show that the combination of multiple sites recordings and advanced signal processing techniques (such as wavelet denoising and spike sorting algorithms) can be used to identify both sensory stimuli (in animal models) and motor commands (in a human volunteer). These findings have interesting implications, which should be investigated in future experiments. © 2006 IEEE

INFLAMMATION AND VENTRICULAR-VASCULAR COUPLING IN HYPERTENSIVE PATIENTS WITH METABOLIC SYNDROME

Abstract Background and aims Metabolic syndrome (MetS) is currently considered to raise the risk for type 2 diabetes and cardiovascular events. It has been suggested that part of this risk excess may be due to a cluster of additional factors associated with MetS. We aimed to investigate the role of inflammation on the ventricular-vascular coupling in patients with MetS. Methods and results We enrolled a total of 227 hypertensive patients (106 with MetS and 121 without MetS) matched for age and gender. Aortic pulse wave velocity (aPWV), intima-media thickness (IMT) and high sensitivity C-reactive protein (CRP) increased according to the number of MetS components. Patients with MetS showed increased aPWV (11.5 ± 3.7 vs. 10.3 ± 2.5 m/s, P = 0.03) compared with controls. In a model adjusted for age, sex, heart rate and mean blood pressure, aPWV resulted increased in patients with CKD (beta 1.29 m/s, 95%CI 0.61–1.96 m/s, P P = 0.005). After additional adjustment for CRP and IMT, the slope of aPWV was respectively reduced by 16% and 62%, suggesting that inflammation and intima-media thickening could contribute to aortic stiffening in patients with MetS. In these patients, aPWV was also associated with left-ventricular mass index (beta 0.79 g/m 2.7 , 95%CI 0.05–1.52 g/m 2.7 , P = 0.05). Conclusion MetS is characterized by an inflammation-dependent acceleration in cardiovascular ageing. This pattern of pathophysiological abnormalities may contribute to amplify the burden of cardiovascular risk in patients with MetS

Changing Epidemiology of Extended-Spectrum β-Lactamases in Argentina: Emergence of CTX-M-15

A multicenter survey, carried out in 2010 in Argentina, showed an increased prevalence of extended-spectrum p-lactamase (ESBL)-producing enterobacteria, with some changes in the molecular epidemiology of circulating ESBLs. While enzymes of the CTX-M-2 group remain endemic, the emergence of CTX-M-15 and of enzymes of the CTX-M-8 and CTX-M-9 groups was observed. The CTX-M-15-positive isolates represented 40% of CTX-M producers and included representatives of Escherichia coli ST131 and Klebsiella pneumoniae ST11.Fil: Sennati, S.. Università degli Studi di Siena; ItaliaFil: Santella, G.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; ArgentinaFil: Di Conza, José Alejandro. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Pallecchi, L.. Università degli Studi di Siena; ItaliaFil: Pino, Marylú. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Ghiglione, Barbara. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Rossolini, G.M.. Università degli Studi di Siena; ItaliaFil: Radice, Marcela Alejandra. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Gutkind, Gabriel Osvaldo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Analysis of HDL-microRNA panel in heterozygous familial hypercholesterolemia subjects with LDL receptor null or defective mutation

In the last years increasing attention has been given to the connection between genotype/phenotype and cardiovascular events in subjects with familial hypercholesterolemia (FH). MicroRNAs (miRs) bound to high-density lipoprotein (HDL) may contribute to better discriminate the cardiovascular risk of FH subjects. Our aim was to evaluate the HDL-miR panel in heterozygous FH (HeFH) patients with an LDLR null or defective mutation and its association with pulse wave velocity (PWV). We evaluated lipid panel, HDL-miR panel and PWV in 32 LDLR null mutation (LDLR-null group) and 35 LDLR defective variant (LDLR-defective group) HeFH patients. HDL-miR-486 and HDL-miR-92a levels were more expressed in the LDLR-null group than the LDLR-defective group. When we further stratified the study population into three groups according to both the LDLR genotype and history of ASCVD (LDLR-null/not-ASCVD, LDLR-defective/not-ASCVD and LDLR/ASCVD groups), both the LDLR/ASCVD and the LDLR-null/not-ASCVD groups had a higher expression of HDL-miR-486 and HDL-miR-92a than the LDLR-defective/not-ASCVD group. Finally, HDL-miR-486 and HDL-miR-92a were independently associated with PWV. In conclusion, the LDLR-null group exhibited HDL-miR-486 and HDL-miR-92a levels more expressed than the LDLR-defective group. Further studies are needed to evaluate these HDL-miRs as predictive biomarkers of cardiovascular events in FH

Does sonification of action simulation training impact corticospinal excitability and audiomotor plasticity?

© The Author(s) 2021. Sonification is a sensory augmentation strategy whereby a sound is associated with, and modulated by, movement. Evidence suggests that sonification could be a viable strategy to maximize learning and rehabilitation. Recent studies investigated sonification of action observation, reporting beneficial effects, especially in Parkinson’s disease. However, research on simulation training—a training regime based on action observation and motor imagery, in which actions are internally simulated, without physical execution—suggest that action observation alone is suboptimal, compared to the combined use of action observation and motor imagery. In this study, we explored the effects of sonified action observation and motor imagery on corticospinal excitability, as well as to evaluate the extent of practice-dependent plasticity induced by this training. Nineteen participants were recruited to complete a practice session based on combined and congruent action observation and motor imagery (AOMI) and physical imitation of the same action. Prior to the beginning, participants were randomly assigned to one of two groups, one group (nine participants) completed the practice block with sonified AOMI, while the other group (ten participants) completed the practice without extrinsic auditory information and served as control group. To investigate practice-induced plasticity, participants completed two auditory paired associative stimulation (aPAS) protocols, one completed after the practice block, and another one completed alone, without additional interventions, at least 7 days before the practice. After the practice block, both groups significantly increased their corticospinal excitability, but sonification did not exert additional benefits, compared to non-sonified conditions. In addition, aPAS significantly increased corticospinal excitability when completed alone, but when it was primed by a practice block, no modulatory effects on corticospinal excitability were found. It is possible that sonification of combined action observation and motor imagery may not be a useful strategy to improve corticospinal, but further studies are needed to explore its relationship with performance improvements. We also confirm the neuromodulatory effect of aPAS, but its interaction with audiomotor practice remain unclear

Comparison of direct and indirect methods to maximise the detection of Babesia caballi and Theileria equi infections in Central Southern Italy

: Equine piroplasmosis is a disease of equids, caused by tick-borne apicomplexan protozoan pathogens Babesia caballi and Theileria equi, which, according to the World Organisation for Animal Health (OIE), can be diagnosed by enzyme-linked immunosorbent assay (ELISA), immunofluorescent antibody test (IFAT) and polymerase chain reaction (PCR). The present study was conducted to evaluate and compare the assays available for the diagnosis of equine piroplasmosis. Data employed were obtained from 1300 blood samples collected between 2012-2014 from asymptomatic and symptomatic equines (horses and donkeys) of central-southern regions of Italy and analyzed by ELISA, IFAT, PCR (one commercial and one from literature) and blood smear microscopic examination. Statistical differences of the proportions of positivity for each parasite and group (asymptomatic and symptomatic) among the methods were verified by the z test to identify the most sensitive. The concordance between each pair of methods - for each parasite and within the groups - and trends in detection of suspect samples of four hypothetical diagnostic algorithms using serological and biomolecular assays were evaluated to identify the most suitable laboratory diagnostic workflow. The results of this study highlighted a lower capacity to detect suspect samples of commercial ELISA for B. caballi in all groups when compared to biomolecular methods and IFAT; and of the commercial PCRs in asymptomatic animals, identifying a PCR from literature and IFAT as the best choice for a combined diagnosis. For T. equi, IFAT detected more suspect samples than ELISA, even if the latter showed good performance and some samples were positive only by the ELISA and PCR, indicating that their simultaneous employment is still advantageous. Host-parasite interaction, amino-acid/genetic diversity and differences in detection limits among the assays could be among the reasons in explaining the present results. In view of further studies, ELISA should be used in combination with PCR, that should regularly be included in the laboratory diagnosis to maximise the detection of early infections and support the evaluation of pharmacological treatment

Analysis of gingival crevicular fluid biomarkers in patients with metabolic syndrome

Objectives: To assess associations between gingival crevicular fluid (GCF) markers in patients with metabolic syndrome, with or without concomitant periodontitis. Methods: A total of 95 patients with Metabolic Syndrome (MetS) had a periodontal examination and gingival crevicular fluid samples taken. Proteomic analysis of gingival crevicular fluid (GCF) was carried out by Human XL Cytokine protein arrays in 12 selected patients, followed by multiplex ELISA of 11 analytes in 95 participants. Results: Increased levels of Aggrecan, IL-6 and IL-8 were found in patients with periodontal health compared with moderate and severe periodontitis. The inverse stepwise association between severity of periodontitis and reduced Aggrecan levels was also observed at adjusted linear regression analysis. Diagnosis of diabetes was associated with higher GCF levels of IL-8 and MMP-8. Conclusion: Diabetes may affect GCF levels of cytokines, irrespective of periodontal status. Periodontal status may be associated with Aggrecan levels in the GCF of patients affected by metabolic syndrome. Clinical significance: Investigation of GCF biomarkers may potentially help have diagnostic potential in patients with MetS

Neutral Iron Emission Lines From The Day-side Of KELT-9b -- The GAPS Programme With HARPS-N At TNG XX

We present the first detection of atomic emission lines from the atmosphere of an exoplanet. We detect neutral iron lines from the day-side of KELT-9b (Teq $\sim$ 4, 000 K). We combined thousands of spectrally resolved lines observed during one night with the HARPS-N spectrograph (R $\sim$ 115, 000), mounted at the Telescopio Nazionale Galileo. We introduce a novel statistical approach to extract the planetary parameters from the binary mask cross-correlation analysis. We also adapt the concept of contribution function to the context of high spectral resolution observations, to identify the location in the planetary atmosphere where the detected emission originates. The average planetary line profile intersected by a stellar G2 binary mask was found in emission with a contrast of 84 $\pm$ 14 ppm relative to the planetary plus stellar continuum (40 $\pm$ 5$\%$ relative to the planetary continuum only). This result unambiguously indicates the presence of an atmospheric thermal inversion. Finally, assuming a modelled temperature profile previously published (Lothringer et al. 2018), we show that an iron abundance consistent with a few times the stellar value explains the data well. In this scenario, the iron emission originates at the $10^{-3}$-$10^{-5}$ bar level.Comment: Accepted for publication on ApJL; 19 pages, 4 figures, 3 table

Bilateral transcranial direct current stimulation reshapes resting-state brain networks: A Magnetoencephalography assessment

Transcranial direct current stimulation (tDCS) can noninvasively induce brain plasticity, and it is potentially useful to treat patients affected by neurological conditions. However, little is known about tDCS effects on resting-state brain networks, which are largely involved in brain physiological functions and in diseases. In this randomized, sham-controlled, double-blind study on healthy subjects, we have assessed the effect of bilateral tDCS applied over the sensorimotor cortices on brain and network activity using a whole-head magnetoencephalography system. Bilateral tDCS, with the cathode (−) centered over C4 and the anode (+) centered over C3, reshapes brain networks in a nonfocal fashion. Compared to sham stimulation, tDCS reduces left frontal alpha, beta, and gamma power and increases global connectivity, especially in delta, alpha, beta, and gamma frequencies. The increase of connectivity is consistent across bands and widespread. These results shed new light on the effects of tDCS and may be of help in personalizing treatments in neurological disorders