Pathological Investigation of Congenital Bicuspid Aortic Valve Stenosis, Compared with Atherosclerotic Tricuspid Aortic Valve Stenosis and Congenital Bicuspid Aortic Valve Regurgitation

Congenital bicuspid aortic valve (CBAV) is the main cause of aortic stenosis (AS) in young adults. However, the histopathological features of AS in patients with CBAV have not been fully investigated.We examined specimens of aortic valve leaflets obtained from patients who had undergone aortic valve re/placement at our institution for severe AS with CBAV (n = 24, CBAV-AS group), severe AS with tricuspid aortic valve (n = 24, TAV-AS group), and severe aortic regurgitation (AR) with CBAV (n = 24, CBAV-AR group). We compared the histopathological features among the three groups. Pathological features were classified using semi-quantitative methods (graded on a scale 0 to 3) by experienced pathologists without knowledge of the patients' backgrounds. The severity of inflammation, neovascularization, and calcium and cholesterol deposition did not differ between the CBAV-AS and TAV-AS groups, and these four parameters were less marked in the CBAV-AR group than in the CBAV-AS (all p<0.01). Meanwhile, the grade of valvular fibrosis was greater in the CBAV-AS group, compared with the TAV-AS and CBAV-AR groups (both p<0.01). In AS patients, thickness of fibrotic lesions was greater on the aortic side than on the ventricular side (both p<0.01). Meanwhile, thickness of fibrotic lesions was comparable between the aortic and ventricular sides in CBAV-AR patients (p = 0.35).Valvular fibrosis, especially on the aortic side, was greater in patients with CBAV-AS than in those without, suggesting a difference in the pathogenesis of AS between CBAV and TAV

Experimental setup and procedure for the measurement of the 7Be(n,p)7Li reaction at n_TOF

Following the completion of the second neutron beam line and the related experimental area (EAR2) at the n_TOF spallation neutron source at CERN, several experiments were planned and performed. The high instantaneous neutron flux available in EAR2 allows to investigate neutron induced reactions with charged particles in the exit channel even employing targets made out of small amounts of short-lived radioactive isotopes. After the successful measurement of the 7Be(n,) cross section, the 7Be(n,p)7Li reaction was studied in order to provide still missing cross section data of relevance for Big Bang Nucleosynthesis (BBN), in an attempt to find a solution to the cosmological Lithium abundance problem. This paper describes the experimental setup employed in such a measurement and its characterization.Séptimo Programa Marco de la Comunidad Europea de la Energía Atómica (Euratom)-Proyecto CHANDA (No. 605203)Narodowe Centrum Nauki (NCN)-UMO-2012/04/M/ST2/00700-UMO-2016/22/M/ST2/00183Croatian Science Foundation-HRZZ 168

Preconditioning of low-frequency repetitive transcranial magnetic stimulation with transcranial direct current stimulation: evidence for homeostatic plasticity in the human motor cortex

Recent experimental work in animals has emphasized the importance of homeostatic plasticity as a means of stabilizing the properties of neuronal circuits. Here, we report a phenomenon that indicates a homeostatic pattern of cortical plasticity in healthy human subjects. The experiments combined two techniques that can produce long-term effects on the excitability of corticospinal output neurons: transcranial direct current stimulation (TDCS) and repetitive transcranial magnetic stimulation (rTMS) of the left primary motor cortex. "Facilitatory preconditioning" with anodal TDCS caused a subsequent period of 1 Hz rTMS to reduce corticospinal excitability to below baseline levels for >20 min. Conversely, "inhibitory preconditioning" with cathodal TDCS resulted in 1 Hz rTMS increasing corticospinal excitability for at least 20 min. No changes in excitability occurred when 1 Hz rTMS was preceded by sham TDCS. Thus, changing the initial state of the motor cortex by a period of DC polarization reversed the conditioning effects of 1 Hz rTMS. These preconditioning effects of TDCS suggest the existence of a homeostatic mechanism in the human motor cortex that stabilizes corticospinal excitability within a physiologically useful range

Maternally inherited genetic variants of CADPS2 are present in Autism Spectrum Disorders and Intellectual Disability patients.

open22siIntellectual disability (ID) and autism spectrum disorders (ASDs) are complex neuropsychiatric conditions, with overlapping clinical boundaries in many patients. We identified a novel intragenic deletion of maternal origin in two siblings with mild ID and epilepsy in the CADPS2 gene, encoding for a synaptic protein involved in neurotrophin release and interaction with dopamine receptor type 2 (D2DR). Mutation screening of 223 additional patients (187 with ASD and 36 with ID) identified a missense change of maternal origin disrupting CADPS2/D2DR interaction. CADPS2 allelic expression was tested in blood and different adult human brain regions, revealing that the gene was monoallelically expressed in blood and amygdala, and the expressed allele was the one of maternal origin. Cadps2 gene expression performed in mice at different developmental stages was biallelic in the postnatal and adult stages; however, a monoallelic (maternal) expression was detected in the embryonal stage, suggesting that CADPS2 is subjected to tissue- and temporal-specific regulation in human and mice. We suggest that CADPS2 variants may contribute to ID/ASD development, possibly through a parent-of-origin effect.openBonora E;Graziano C;Minopoli F;Bacchelli E;Magini P;Diquigiovanni C;Lomartire S;Bianco F;Vargiolu M;Parchi P;Marasco E;Mantovani V;Rampoldi L;Trudu M;Parmeggiani A;Battaglia A;Mazzone L;Tortora G;Maestrini E;Seri M;Romeo G;IMGSACBonora E;Graziano C;Minopoli F;Bacchelli E;Magini P;Diquigiovanni C;Lomartire S;Bianco F;Vargiolu M;Parchi P;Marasco E;Mantovani V;Rampoldi L;Trudu M;Parmeggiani A;Battaglia A;Mazzone L;Tortora G;Maestrini E;Seri M;Romeo G;IMGSA

Estimation of the variance in any point of an electron-density map for any space group

In a recent paper [Giacovazzo & Mazzone (2011). Acta Cryst. A67, 210-218] a mathematical expression of the variance at any point of the unit cell has been described. The formulas were derived in P1 for any type of Fourier synthesis (observed, difference and hybrid) under the following hypothesis: the current phases are distributed on the trigonometric circle about the correct values according to von Mises distributions. This general hypothesis allows the variance expressions to be valid at any stage of the phasing process. In this paper the method has been extended to any space group, no matter whether centric or acentric. The properties of the variance generated by space-group symmetry are described; in particular it is shown that the variance is strictly connected with the implication transformations, which are basic for Patterson deconvolution. General formulas simultaneously taking into account phase uncertainty and measurement errors have been obtained, valid no matter what the quality of the model

Cerebellum to motor cortex paired associative stimulation induces bidirectional STDP-like plasticity in human motor cortex

The cerebellum is crucially important for motor control and adaptation. Recent non-invasive brain stimulation studies have indicated the possibility to alter the excitability of the cerebellum and its projections to the contralateral motor cortex, with behavioral consequences on motor control and adaptation. Here we sought to induce bidirectional spike-timing dependent plasticity (STDP)-like modifications of motor cortex (M1) excitability by application of paired associative stimulation (PAS) in healthy subjects. Conditioning stimulation over the right lateral cerebellum (CB) preceded focal transcranial magnetic stimulation (TMS) of the left M1 hand area at an interstimulus interval of 2 ms (CB→M1 PAS(2 ms)), 6 ms (CB→M1 PAS(6 ms)) or 10 ms (CB→M1 PAS(10 ms)) or randomly alternating intervals of 2 and 10 ms (CB→M1 PAS(Control)). Effects of PAS on M1 excitability were assessed by the motor-evoked potential (MEP) amplitude, short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and cerebellar-motor cortex inhibition (CBI) in the first dorsal interosseous muscle of the right hand. CB→M1 PAS(2 ms) resulted in MEP potentiation, CB→M1 PAS(6 ms) and CB→M1 PAS(10 ms) in MEP depression, and CB→M1 PAS(Control) in no change. The MEP changes lasted for 30-60 min after PAS. SICI and CBI decreased non-specifically after all PAS protocols, while ICF remained unaltered. The physiological mechanisms underlying these MEP changes are carefully discussed. Findings support the notion of bidirectional STDP-like plasticity in M1 mediated by associative stimulation of the cerebello-dentato-thalamo-cortical pathway and M1. Future studies may investigate the behavioral significance of this plasticity

Transcranial magnetic stimulation as a new tool to control pain perception.

Treatment for chronic pain is frequently unsuccessful or characterized by side-effects. The high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has been suggested in the management of refractory chronic pain. Various studies have shown that HF-rTMS sessions of long-duration applied at primary motor cortex induce pain relief through mechanisms of plastic changes. Efficacy of rTMS mostly depends on stimulation parameters, but this aspect requires better characterization. A rationale to target other cortical areas exists. Current data are promising, but a careful analysis of stimulation settings and maintenance treatment design are need

Design and Development of an Affordable Haptic Robot with Force-Feedback and Compliant Actuation to Improve Therapy for Patients with Severe Hemiparesis

The study describes the design and development of a single degree-of-freedom haptic robot, Haptic Theradrive, for post-stroke arm rehabilitation for in-home and clinical use. The robot overcomes many of the weaknesses of its predecessor, the TheraDrive system, that used a Logitech steering wheel as the haptic interface for rehabilitation. Although the original TheraDrive system showed success in a pilot study, its wheel was not able to withstand the rigors of use. A new haptic robot was developed that functions as a drop-in replacement for the Logitech wheel. The new robot can apply larger forces in interacting with the patient, thereby extending the functionality of the system to accommodate low-functioning patients. A new software suite offers appreciably more options for tailored and tuned rehabilitation therapies. In addition to describing the design of the hardware and software, the paper presents the results of simulation and experimental case studies examining the system\u27s performance and usability

Management of women aged 25-34 with diagnosis of ASCUS in the screening center of Latina.

In cervical cancer screening program of Latina (Italy) the hr-HPV as primary test is performed only on women aged 35-64 while women aged 25-34 are invited to perform PapTest. The aim of this study was to evaluate the impact of the application of the PapTest in women aged 25-34 and to evaluate the management of ASCUS. Women aged 25-34 were invited to perform PapTest according to the Italian guidelines; women with diagnosis of LSIL+ were referred to colposcopy while women with diagnosis of ASCUS were referred to hr-HPV test and only women resulted positive were referred to colposcopy. The 4.0% of women resulted positive to PapTest and the referral rate to colposcopy was 3.5%. The PPV value for CIN2+ at colposcopy was 7.2% and the Detection Rate (DR) for CIN2+ was 2.40‰. The ASCUS category was diagnosed in 41.8% of women resulted positive to PapTest and between them the 70.6% resulted positive to the hr-HPV test. The referral rate to colposcopy of women resulted positive to hr-HPV test was 1.1%. The PPV for CIN2+ at colposcopy and the DR of CIN2+ was 8.4% and 0.96‰ respectively. Between women with diagnosis of ASCUS, only 6 women showed a CIN2+ lesion (4 CIN2 and 2 CIN3). The present study showed that this algorithm, applied to women aged 25-34, obtained a good performance in term of test specificity (98%) and confirm that the application of hr-HPV test in the management of ASCUS leads to a decreased of inappropriate colposcopy due to transitory infection in young women

Information processing of social exclusion: Links with bullying, moral disengagement and guilt

The Social Information Processing (SIP) theory and the Social Cognitive Theory of Moral Agency were integrated to investigate the associations between SIP and bullying, guilt, and moral disengagement. Participants were 341 children and early adolescents (Mage = 11.14). Two social exclusion vignettes were administered to assess three SIP steps (step 2: Attribution of hostile intent; step 3: Selection of antisocial goals, and step 4: Generation of aggressive responses). Guilt was assessed through five vignettes. A self-report measure was used to assess moral disengagement and peer nominations were used to assess bullying perpetration. Moderated mediation analyses were performed to test the hypotheses. Findings indicated that attribution of hostile intent was associated with selection of antisocial goals, which in turn, was associated with the generation of aggressive responses among participants with high levels of bullying and low levels of guilt and moral disengagement. Results are discussed in terms of their theoretical and practical relevance.publishedVersio