The Development of Nociceptive Network Activity in the Somatosensory Cortex of Freely Moving Rat Pups

Cortical perception of noxious stimulation is an essential component of pain experience but it is not known how cortical nociceptive activity emerges during brain development. Here we use continuous telemetric electrocorticogram (ECoG) recording from the primary somatosensory cortex (S1) of awake active rat pups to map functional nociceptive processing in the developing brain over the first 4 weeks of life. Cross-sectional and longitudinal recordings show that baseline S1 ECoG energy increases steadily with age, with a distinctive beta component replaced by a distinctive theta component in week 3. Event-related potentials were evoked by brief noxious hindpaw skin stimulation at all ages tested, confirming the presence of functional nociceptive spinothalamic inputs in S1. However, hindpaw incision, which increases pain sensitivity at all ages, did not increase S1 ECoG energy until week 3. A significant increase in gamma (20-50 Hz) energy occurred in the presence of skin incision at week 3 accompanied by a longer-lasting increase in theta (4-8 Hz) energy at week 4. Continuous ECoG recording demonstrates specific postnatal functional stages in the maturation of S1 cortical nociception. Somatosensory cortical coding of an ongoing pain "state" in awake rat pups becomes apparent between 2 and 4 weeks of age

Papel etiológico de los virus en la enfermedad periodontal

El objetivo de esta revisión es presentar la evidencia disponible que relaciona la infección por virus con el desarrollo de periodontitis. Esta relación se ha visto con los virus de la familia herpes, sobretodo el citomegalovirus humano (CMV) y el virus Epstein-Barr (VEB), así como con el virus de la inmunodeficiencia humana (HIV). Las infecciones por herpesvirus generalmente sucede en dos fases, durante la primoinfección la clínica suele ser leve o asintomática y a esta le sigue una fase asintomática en la que el virus se encuentra en estado de latencia. Dicho estado se verá interrumpido esporádicamente por periodos de activación en los que se produce una replicación viral y posiblemente se dé una manifestación de la enfermedad que explicaría, en parte, el progreso en episodios de la enfermedad periodontal. De hecho, algunas de las causas que llevan a la reactivación del virus también se consideran factores de riesgo de la enfermedad periodontal y podrían relacionar a ambas patologías. The purpose of this review is to evaluate the evidence supporting the hypothesis that viral infection plays a role in the development of periodontitis. This relationship has been found mainly with the herpesvirus family, especially with human cytomegalovirus (CMV) and with Epstein-Barr virus (EBV), but also with human immunodeficiency virus (HIV). The herpesvirus infection generally involves a mild or asymptomatic primary phase followed by an asymptomatic latent phase interrupted sporadically by periods of activation, where viral replication and possibly clinical disease become manifest and which will in part, explain the episodic progressive nature of human periodontitis. In fact, herpesvirus reactivation is triggered by a number of immunosuppressing factors, some of which have also been shown to be risk indicators of periodontal disease and which could relate both patologies

Experimental Validation of the Innovative Thermal Energy Storage Based on an Integrated System "Storage Tank/Steam Generator"

Abstract In the past years, an innovative thermal energy storage system at high temperature (up to 550C) for CSP plants was proposed by ENEA and Ansaldo Nucleare: a single storage tank integrated with a steam generator immersed in the heat storage medium. The idea is based on the exploitation of the thermophysical characteristics of the heat storage medium (a binary mixture of salts of NaNO3 at 60% and KNO3 at 40%) in order to maintain over time, in the single tank, a thermal stratification of the fluid. The thermal stratification is able to trigger, in the immersed steam generator, the natural circulation, shell side and downwards, of the hot molten salt cooled down by the water that flows upwards tube side, thus heating up and producing superheated steam. The advantages of such a system are: - efficient performances; - simple implementation; - compactness: - modularity; - and, overall, contained costs: only one storage tank instead of the two tanks and only one heat exchanger instead of the three exchangers of the classic configuration; reduced quantity of salt; minimization of piping, valves and other components. The technical feasibility of the proposed system, together with the stability over time of the stratification in temperature of the storage medium, have been already verified and assessed. This report has the aim of presenting the experimental results obtained by ENEA in the Casaccia Research Centre (Rome, Italy), with a small scale test section consisting of a 300 kWth steam generator inserted in a 8 m3 storage tank with molten salt at high temperature. The reported results relate to the behaviour of the system in steady state conditions, and show its promising performances

Impairment of the autophagic flux in astrocytes intoxicated by trimethyltin

Autophagy is a lysosomal catabolic route for protein aggregates and damaged organelles which in different stress conditions, such as starvation, generally improves cell survival. An impairment of this degradation pathway has been reported to occur in many neurodegenerative processes. Trimethyltin (TMT) is a potent neurotoxin present as an environmental contaminant causing tremors, seizures and learning impairment in intoxicated subjects. The present data show that in rat primary astrocytes autophagic vesicles (AVs) appeared after few hours of TMT treatment. The analysis of the autophagic flux in TMT-treated astrocytes was consistent with a block of the late stages of autophagy and was accompanied by a progressive accumulation of the microtubule associated protein light chain 3 (LC3) and of p62/SQSTM1. Interestingly, an increased immunoreactivity for p62/SQSTM1 was also observed in hippocampal astrocytes detected in brain slices of TMT-intoxicated rats. The time-lapse recordings of AVs in EGFP-mCherry-LC3B transfected astrocytes demonstrated a reduced mobility of autophagosomes after TMT exposure respect to control cells. The observed block of the autophagic flux cannot be overcome by known autophagy inducers such as rapamycin or 0.5mM lithium. Although ineffective when used at 0.5mM, lithium at higher concentrations (2mM) was able to protect astrocyte cultures from TMT toxicity. This effect correlated well with its ability to determine the phosphorylation/inactivation of glycogen kinase synthase-3β (GSK-3β)

Identification of inversion domains in KTiOPO4 via resonant X-ray diffraction

A novel method is presented for the identification of the absolute crystallographic structure in multi-domain polar materials such as ferroelectric KTiOPO4. Resonant (or `anomalous') X-ray diffraction spectra collected across the absorption K edge of Ti (4.966 keV) on a single Bragg reflection demonstrate a huge intensity ratio above and below the edge, providing a polar domain contrast of ~270. This allows one to map the spatial domain distribution in a periodically inverted sample, with a resolution of ~1 µm achieved with a microfocused beam. This non-contact, non-destructive technique is well suited for samples of large dimensions (in contrast with traditional resonant X-ray methods based on diffraction from Friedel pairs), and its potential is particularly relevant in the context of physical phenomena connected with an absence of inversion symmetry, which require characterization of the underlying absolute atomic structure (such as in the case of magnetoelectric coupling and multiferroics)

An unusual cause of gross hematuria, improved by recumbency

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An innovative concept of a thermal energy storage system based on a single tank configuration using stratifying molten salts as both heat storage medium and heat transfer fluid, and with an integrated steam generator

Abstract The proposed innovative thermal energy storage system is based on a single tank containing a mixture of nitrate salts (60% NaNO3 and 40% KNO3 in weight; this mixture gradually changes from solid to liquid in the temperature range between about 220 °C and 240 °C, becoming completely melted above this temperature), with an integrated steam generator directly contained inside it. The system is operated exploiting the thermal stratification of the salts mixture in the temperature range between 550 °C (hot temperature) and 290 °C (cold temperature). The experimental work conducted at ENEA has revealed that the thermal stratification of the molten salts mixture can be maintained quite constant for several hours and the presence of the integrated steam generator actively guarantees and maintains the stratification during the operation time, avoiding mixing of the stratified layers. The single-tank system with stratification of the molten salts and an integrated steam generator is an important improvement in terms of efficiency, reliability and cost reduction, with respect to the two-tank thermal energy storage system. This report has the aim of giving an overview of this new technology but, given the fact that the experimental activities are still ongoing, the description of the system remains at a qualitative level. The complete set of experimental results will be presented in the future when the Projects that are framework of this research will have been completed

HBV vaccination with Fendrix is effective and safe in pre-dialysis CKD population

Background: Patients with chronic kidney disease have a poor response to hepatitis B vaccine due to the immunodeficiency conferred from chronic uremia. A recombinant HB vaccine containing an improved adjuvant system AS04 (HBV-AS04) has been manufactured but scarce evidence exists on HBV-AS04 use among patients with CKD. Aim: To assess efficacy and safety of an adjuvanted recombinant vaccine (HBV-AS04) in a large cohort of CKD patients at pre-dialysis stage (with susceptibility to HBV infection). Methods: Patients were prospectively enrolled to receive four 20-mcg doses of HBV-AS04 by intramuscular route (deltoid muscle) at months 1, 2, 3, and 4. Anti-HBs surface antibody concentrations were tested at intervals of 1, 2, 3, 4, and 12 months. Multivariate analyses were performed to assess the parameters, which predicted immunologic response to HBV-AS04 vaccine. Results: One hundred and seven patients were included and 102 completed the study. At completion of vaccine schedule, the frequency of responders (anti-HBs titers 65 10 mIU/mL) was 95% (97/102) (mean anti-HBs antibody titers, 688.9 \ub1 385 mIU/mL), according to per-protocol analysis. Serum haemoglobin levels were greater in responder than non- or low-responder patients to HBV-AS04 (P = 0.04) and this was confirmed by multivariate analysis. The seroprotection rate at month 50 was 88% (30/34) with lower anti-HBs antibody titers (218.5 \ub1 269.6 mIU/mL, P = 0.001). No major side effects were observed. Conclusions: Our prospective study performed in a real-world setting showed a high immunogenicity and safety of HBV-AS04 vaccine in patients with CKD not yet on maintenance dialysis. Studies provided with longer follow-ups are under way to assess the durability of seroprotection in responders

Electric field control of the magnetic chiralities in ferroaxial multiferroic RbFe(MoO4)2

The coupling of magnetic chiralities to the ferroelectric polarisation in multiferroic RbFe(MoO$_4$)$_2$ is investigated by neutron spherical polarimetry. Because of the axiality of the crystal structure below $T_\textrm{c}$ = 190 K, helicity and triangular chirality are symmetric-exchange coupled, explaining the onset of the ferroelectricity in this proper-screw magnetic structure - a mechanism that can be generalised to other systems with "ferroaxial" distortions in the crystal structure. With an applied electric field we demonstrate control of the chiralities in both structural domains simultaneously.Comment: 5 pages, 4 figure

Nuove terapie per l’epatite C nei pazienti nefropatici cronici

Gli studi effettuati nell\u2019ultima decade hanno evidenziato il ruolo sfavorevole che svolge l\u2019infezione da virus dell\u2019epatite C sulla sopravvivenza dei pazienti nefropatici (particolarmente i pazienti in dialisi ed i portatori di trapianto renale). In aggiunta, l\u2019infezione da virus dell\u2019epatite C sembra essere associata ad un aumentato rischio di nefropatia cronica nella popolazione adulta generale. Pertanto, c\u2019\ue8 urgente bisogno di terapie antivirali efficaci e sicure in questi pazienti. Recenti studi randomizzati e controllati hanno mostrato che la terapia antivirale basata su interferone peghilato e ribavirina pu\uf2 essere efficace (frequenza della risposta virale protratta, circa il 70%), e ben tollerata quando \ue8 usata da medici esperti in pazienti appropriati. Da qualche anno \ue8 iniziata la commercializzazione dei farmaci ad azione anti-virale diretta nella popolazione adulta con funzione renale normale, ma l\u2019uso di questi farmaci nei nefropatici cronici \ue8 ancora allo stato iniziale. Sono stati negli ultimi mesi pubblicati alcuni studi; il primo ha riguardato il trattamento antivirale di HCV nei pazienti (n=224) con malattia renale cronica (CKD stadio 4/ 5) che hanno ricevuto terapia con grazoprevir (inibitore di HCV NS3/4A) ed elbasvir (inibitore di HCV NS5A) per 12 settimane. La frequenza di SVR12 \ue8 stata pari a 94.3% (115/122); nessuno dei pazienti del gruppo di studio ha interrotto precocemente la terapia antivirale per eventi avversi. Il secondo studio riguarda la combinazione antivirale 3D (ombitasvir/paritaprevir/ritonavir/dasabuvir con e senza ribavirina) che \ue8 stata somministrata a 20 pazienti con malattia renale cronica (CKD, stadio 4/5, genotipo 1), la frequenza di SVR12 era 90% (18/20). Non sono stati riportati eventi avversi che hanno necessitato un\u2019interruzione precoce della terapia antivirale. Esistono inoltre alcuni studi preliminari riguardo la terapia antivirale sofosbuvir/simeprevir (n=38) in pazienti con malattia renale cronica di stadio 4/5; la frequenza di SVR12 era 89% (34/38). Altri studi clinici, di fase 2 o 3, basati sui farmaci ad azione antivirale diretta sono in corso. In conclusione, i nuovi farmaci ad azione anti-virale diretta promettono di eradicare l\u2019infezione da virus dell\u2019epatite C nei pazienti con insufficienza renale. Restano da chiarire alcuni punti cruciali quali il costo dei nuovi farmaci, che \ue8 un problema non trascurabile anche per i paesi industrializzati. Anche le interazioni tra farmaci sono un argomento di rilevanza clinica visto che i pazienti nefropatici cronici hanno una frequenza elevata di co-morbilit\ue0.Recent evidence has been accumulated showing a negative impact of chronic hepatitis C virus infection on survival in patients with chronic kidney disease. Moreover, it appears that anti-HCV positive status has been associated with an increased risk of developing chronic kidney disease in the adult general population. These reports have emphasized the need for safe and effective therapies for hepatitis C virus infection in the chronic kidney disease population. Treatment of HCV has made considerable progress with the approval of interferon-free, direct-acting antiviral drug-based combination therapies among patients with intact kidneys; but a paucity of information exists regarding chronic kidney disease patients. The first published report on the antiviral treatment of hepatitis C among patients with chronic kidney disease (stage 4-5) and HCV genotype 1 concerns the combination of grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A inhibitor); excellent safety and efficacy (sustained viral response, 94.3% 115/122) have been reached. In another study, the 3-D regimen (ombitasvir/ paritaprevir/ ritonavir/ dasabuvir with or without ribavirin) has been administered to CKD (stage 4-5) patients with genotype 1 (n=20); the rate of sustained viral response was excellent (90%, 18/20) and no patients discontinued treatment due to adverse events. Preliminary data on the combined treatment of sofosbuvir (NS5B inhibitor) and simeprevir (NS3/4A inhibitor) has given a viral response of 89% (34/38), but the size of the study group (n=38 patients with end-stage renal disease) was small. Thus, the evidence in the medical literature concerning use of DAAs in CKD population is encouraging even if it has a preliminary nature. Also, several points need to be addressed regarding the use of DAAs in CKD population including their impact on survival, costs, and drug-drug interactions