Regenerative endodontic procedures (REPs) are biologically based procedures planned to replace damaged tissues, including dentinee and root structures, as well as cells of the pulp–dentine complex. ...Effective sterilization of the root canal is essential in REPs, and antibiotics have been widely used to disinfect root canals. The aim of this paper was to review the scientific literature on (i) Effectiveness of antibiotics used in REPs against bacteria implicated in endodontic disease; (ii) Scientific evidence supporting the use of topical antibiotics in REPs; (iii) Clinical implications of the use of antibiotics in REPs and the possible side effects; (iv) Effect of antibiotics on dental pulp stem cells; and (v) Ongoing research on the use of antibiotics in REPs. Antibiotics used in REPs are effective against bacteria implicated in endodontic infections. Triple antibiotic pastes with minocycline attain complete disinfection of immature teeth with necrotic pulps, without affecting SCAP. Experimental studies carried out in dogs support the use of antibiotics in REPs. Clinical studies report high success rates of RET using antibiotics as intracanal dressings. However, tooth discolouration is an important side effect of the use of TAP. An antibiotic paste containing only metronidazole and ciprofloxacin could be a good alternative to the use of TAP. The use of antibiotic‐containing scaffolds or clindamycin‐modified triple antibiotic (metronidazole, ciprofloxacin and clindamycin) polymer could be a biologically safe antimicrobial drug delivery system in REPs.
As the interface between the Sun's photosphere and corona, the chromosphere and transition region play a key role in the formation and acceleration of the solar wind. Observations from the Interface ...Region Imaging Spectrograph reveal the prevalence of intermittent small-scale jets with speeds of 80 to 250 kilometers per second from the narrow bright network lanes of this interface region. These jets have lifetimes of 20 to 80 seconds and widths of ≤300 kilometers. They originate from small-scale bright regions, often preceded by footpoint brightenings and accompanied by transverse waves with amplitudes of ~20 kilometers per second. Many jets reach temperatures of at least ~10(5) kelvin and constitute an important element of the transition region structures. They are likely an intermittent but persistent source of mass and energy for the solar wind.
Previous studies have found an association between the outcome of root canal treatment (RCT) and diabetic status. This systematic review and meta‐analysis aimed to analyse the potential relationship ...between diabetes and the occurrence of extracted root filled teeth (RFT). The clinical PICO question was as follows: in adult patients with RFT, does the absence or presence of diabetes influence the prevalence of RFT extraction? The key words used in the systematic search were as follows: (Diabetes OR Diabetes Mellitus OR Hyperglycaemia OR Diabetic) AND (Endodontic OR Endodontics OR Endodontic Treatment OR Root Canal Treatment OR Root Canal Preparation OR Root Canal Therapy OR Root Filled Teeth OR Endodontically Treated Teeth) AND (Extraction OR Retention OR Survival OR Success OR Failure OR Outcome). The primary outcome variable was odds ratio (OR) for the frequency of extracted RFT in diabetics and healthy subjects. The method of DerSimonian–Laird with random effects was used to calculate the overall OR. Three hundred titles were identified, and three studies achieved the inclusion criteria. Data from 54 936 root canal treatments, 50 301 in nondiabetic control subjects and 4635 in diabetic patients, were analysed. The calculated overall odds ratio (OR = 2.44; 95% CI = 1.54–3.88; P = 0.0001) implies that diabetics had a significantly higher prevalence of extracted RFT than healthy nondiabetic subjects. The results of available studies indicate a significant relationship between DM and increased frequency of nonretained root filled teeth. Diabetes mellitus should be considered an important preoperative prognostic factor in root canal treatment.
Spinal Muscular Atrophy (SMA) is a genetic neuromuscular disorder caused by reduction of the ubiquitously expressed protein Survival Motor Neuron (SMN). Low levels of SMN impact on spinal cord ...motoneurons (MNs) causing their degeneration and progressive muscle weakness and atrophy. To study the molecular mechanisms leading to cell loss in SMN-reduced MNs, we analyzed the NF-κB intracellular pathway in SMA models. NF-κB pathway activation is required for survival and regulates SMN levels in cultured MNs. Here we describe that NF-κB members, inhibitor of kappa B kinase beta (IKKβ), and RelA, were reduced in SMA mouse and human MNs. In addition, we observed that Gemin3 protein level was decreased in SMA MNs, but not in non-neuronal SMA cells. Gemin3 is a core member of the SMN complex responsible for small nuclear ribonucleoprotein biogenesis, and it regulates NF-κB activation through the mitogen-activated protein kinase TAK1. Our experiments showed that Gemin3 knockdown reduced SMN, IKKβ, and RelA protein levels, and caused significant neurite degeneration. Overexpression of SMN increased Gemin3 protein in SMA MNs, but did not prevent neurite degeneration in Gemin3 knockdown cells. These data indicated that Gemin3 reduction may contribute to cell degeneration in SMA MNs.
In the present work, we analyze multiwavelength observations from Hinode, Solar and Heliospheric Observatory (SOHO), and STEREO of the early phases of a coronal mass ejection (CME). We use Hinode/EIS ...and SOHO/UVCS high-resolution spectra to measure the physical properties of the CME ejecta as a function of time at 1.1 and 1.9 solar radii. Hinode/XRT images are used in combination with EIS spectra to constrain the high temperature plasma properties of the ejecta. SECCHI/EUVI, SECCHI/COR 1, SOHO/EIT, and SOHO/LASCO images are used to measure the CME trajectory, velocity, and acceleration. The combination of measurements of plane of the sky velocities from two different directions allows us to determine the total velocity of the CME plasma up to 5 solar radii. Plasma properties, dynamical status, thermal structure, and brightness distributions are used to constrain the energy content of the CME plasma and to determine the heating rate. We find that the heating is larger than the kinetic energy, and compare it to theoretical predictions from models of CME plasma heating and acceleration.
Although gephyrin is an important postsynaptic scaffolding protein at GABAergic synapses, the role of gephyrin for GABAergic synapse formation and/or maintenance is still under debate. We report here ...that knocking down gephyrin expression with small hairpin RNAs (shRNAs) in cultured hippocampal pyramidal cells decreased both the number of gephyrin and GABA(A) receptor clusters. Similar results were obtained by disrupting the clustering of endogenous gephyrin by overexpressing a gephyrin-EGFP fusion protein that formed aggregates with the endogenous gephyrin. Disrupting postsynaptic gephyrin clusters also had transsynaptic effects leading to a significant reduction of GABAergic presynaptic boutons contacting the transfected pyramidal cells. Consistent with the morphological decrease of GABAergic synapses, electrophysiological analysis revealed a significant reduction in both the amplitude and frequency of the spontaneous inhibitory postsynaptic currents (sIPSCs). However, no change in the whole-cell GABA currents was detected, suggesting a selective effect of gephyrin on GABA(A) receptor clustering at postsynaptic sites. It is concluded that gephyrin plays a critical role for the stability of GABAergic synapses.
Spinal muscular atrophy (SMA) is a neuromuscular genetic disease caused by reduced survival motor neuron (SMN) protein. SMN is ubiquitous and deficient levels cause spinal cord motoneurons (MNs) ...degeneration and muscle atrophy. Nevertheless, the mechanism by which SMN reduction in muscle contributes to SMA disease is not fully understood. Therefore, studies evaluating atrophy mechanisms in SMA muscles will contribute to strengthening current knowledge of the pathology. Here we propose to evaluate autophagy in SMA muscle, a pathway altered in myotube atrophy. We analized autophagy proteins and mTOR in muscle biopsies, fibroblasts, and lymphoblast cell lines from SMA patients and in gastrocnemius muscles from a severe SMA mouse model. Human MNs differentiated from SMA and unaffected control iPSCs were also included in the analysis of the autophagy. Muscle biopsies, fibroblasts, and lymphoblast cell lines from SMA patients showed reduction of the autophagy marker LC3-II. In SMA mouse gastrocnemius, we observed lower levels of LC3-II, Beclin 1, and p62/SQSTM1 proteins at pre-symptomatic stage. mTOR phosphorylation at Ser2448 was decreased in SMA muscle cells. However, in mouse and human cultured SMA MNs mTOR phosphorylation and LC3-II levels were increased. These results suggest a differential regulation in SMA of the autophagy process in muscle cells and MNs. Opposite changes in autophagy proteins and mTOR phosphorylation between muscle cells and neurons were observed. These differences may reflect a specific response to SMN reduction, which could imply diverse tissue-dependent reactions to therapies that should be taken into account when treating SMA patients. Keywords: Spinal muscular atrophy, Survival motor neuron, Autophagy, Neuromuscular disease, Human iPSCs, Neurodegeneration, Motoneuron
Eighty‐four HCV/HIV‐coinfected and 252‐matched HCV‐monoinfected liver transplant recipients were included in a prospective multicenter study. Thirty‐six (43%) HCV/HIV‐coinfected and 75 (30%) ...HCV‐monoinfected patients died, with a survival rate at 5 years of 54% (95% CI, 42–64) and 71% (95% CI, 66 to 77; p = 0.008), respectively. When both groups were considered together, HIV infection was an independent predictor of mortality (HR, 2.202; 95% CI, 1.420–3.413 p < 0.001). Multivariate analysis of only the HCV/HIV‐coinfected recipients, revealed HCV genotype 1 (HR, 2.98; 95% CI, 1.32–6.76), donor risk index (HR, 9.48; 95% CI, 2.75–32.73) and negative plasma HCV RNA (HR, 0.14; 95% CI, 0.03–0.62) to be associated with mortality. When this analysis was restricted to pretransplant variables, we identified three independent factors (HCV genotype 1, pretransplant MELD score and centers with <1 liver transplantation/year in HIV‐infected patients) that allowed us to identify a subset of 60 (71%) patients with a similar 5‐year prognosis (69%95% CI, 54–80) to that of HCV‐monoinfected recipients. In conclusion, 5‐year survival in HCV/HIV‐coinfected liver recipients was lower than in HCV‐monoinfected recipients, although an important subset with a favorable prognosis was identified in the former.
Taken as a whole, HCV/HIV‐coinfected liver transplant recipients have lower posttransplant survival than matched HCV‐monoinfected liver transplant recipients, although an important subset of coinfected patients with survival similar to that of HCV‐monoinfected patients can be identified retrospectively.
Spinal Muscular Atrophy (SMA) is a severe genetic neuromuscular disorder that occurs in childhood and is caused by misexpression of the survival motor neuron (SMN) protein. SMN reduction induces ...spinal cord motoneuron (MN) degeneration, which leads to progressive muscular atrophy and weakness. The link between SMN deficiency and the molecular mechanisms altered in SMA cells remains unclear. Autophagy, deregulation of intracellular survival pathways and ERK hyperphosphorylation may contribute to SMN-reduced MNs collapse, offering a useful strategy to develop new therapies to prevent neurodegeneration in SMA. Using SMA MN in vitro models, the effect of pharmacological inhibition of PI3K/Akt and ERK MAPK pathways on SMN and autophagy markers modulation was studied by western blot analysis and RT-qPCR. Experiments involved primary cultures of mouse SMA spinal cord MNs and differentiated SMA human MNs derived from induced pluripotent stem cells (iPSCs). Inhibition of the PI3K/Akt and the ERK MAPK pathways reduced SMN protein and mRNA levels. Importantly, mTOR phosphorylation, p62, and LC3-II autophagy markers protein level were decreased after ERK MAPK pharmacological inhibition. Furthermore, the intracellular calcium chelator BAPTA prevented ERK hyperphosphorylation in SMA cells. Our results propose a link between intracellular calcium, signaling pathways, and autophagy in SMA MNs, suggesting that ERK hyperphosphorylation may contribute to autophagy deregulation in SMN-reduced MNs.
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