The implantable left ventricular assist device (LVAD) is a major therapeutic development for end-stage heart failure in selected patients. As their use is expanding, infectious complications are ...emerging, with limited data available to guide their management. We aimed to better characterize LVAD-related infections.
We enrolled all consecutive patients diagnosed with LVAD-related infections in three referral centres in France, using a standardized definition of infections in patients with LVAD. Data were collected from medical charts using a standardized questionnaire.
Between 2007 and 2012, 159 patients received LVAD for end-stage heart failure. Among them, 36 (22.6%; 5 women, 31 men) presented at least one infectious complication, after a median time of 2.9 months from LVAD implantation (interquartile range, 1.8–7.5), with a median follow up of 12 months (interquartile range 8–17). Main co-morbidities were alcoholism (33%), diabetes (11%) and immunosuppression (11%). Mean age at implantation was 51 (±11) years. LVAD were implanted as bridge-to-transplantation (n=22), bridge-to-recovery (n=8), destination therapy (n=4), or unspecified (n=2). LVAD-related infections were restricted to the driveline exit site (n=17), had loco-regional extension (n=13), or reached the internal pump (n=3). The main bacteria isolated were Staphylococcus aureus (n=20), coagulase-negative staphylococci (n=7), Enterobacteriaceae (n=14), Pseudomonas aeruginosa (n=10) and Corynebacterium sp. (n=7), with polymicrobial infections in 19 cases. LVAD could be retained in all patients, with the use of prolonged antibacterial treatment in 34 (94%), and debridement in 17 (47%). One patient died due to LVAD-associated infection.
LVAD-related infections are common after LVAD implantation, and may be controlled by prolonged antibiotic treatment.
Levels of prostaglandin E2 and the prostaglandin-endoperoxide synthase-2 (PTGS2, or COX-2) increase in actively progressing periodontal lesions, but decrease in chronic disease. We hypothesized that ...chronic inflammation is associated with altered DNA methylation levels within the PTGS2 promoter, with effects on COX-2 mRNA expression. PTGS2 promoter methylation levels from periodontally inflamed gingival biopsies showed a 5.06-fold increase as compared with non-inflamed samples (p = 0.03), and the odds of methylation in a CpG site in the inflamed gingival group is 4.46 times higher than in the same site in the non-inflamed group (p = 0.016). The level of methylation at −458 bp was inversely associated with transcriptional levels of PTGS2 (RT-PCR) (p = 0.01). Analysis of the data suggests that, in chronically inflamed tissues, there is a hypermethylation pattern of the PTGS2 promoter in association with a lower level of PTGS2 transcription, consistent with a dampening of COX-2 expression in chronic periodontitis. These findings suggest that the chronic persistence of the biofilm and inflammation may be associated with epigenetic changes in local tissues at the biofilm-gingival interface.
The luminous Type IIn SN 2010jl shows strong signs of interaction between the SN ejecta and dense circumstellar material. Dust may be present in the unshocked ejecta; the cool, dense shell (CDS) ...between the shocks in the interaction region; or in the circumstellar medium (CSM). We present and model new optical and infrared photometry and spectroscopy of SN 2010jl from 82 to 1367 days since explosion. We evaluate the photometric and spectroscopic evolution using the radiative transfer codes mocassin and damocles, respectively. We propose an interaction scenario and investigate the resulting dust formation scenarios and dust masses. We find that SN 2010jl has been continuously forming dust based on the evolution of its infrared emission and optical spectra. There is evidence for preexisting dust in the CSM as well as new dust formation in the CDS and/or ejecta. We estimate that 0.005-0.01 M of predominantly carbon dust grains has formed in SN 2010jl by ∼1400 days post-outburst.
Background and Objectives: Periapical cystic lesions are a pathology frequently addressed to endodontic specialists. Although their therapy is still not standardized, the treatment should be as ...conservative as possible and by endodontic means, as they are lesions of endodontic origin. The present case report describes two cases of upper central incisors with large cyst-like periapical lesions, and their one-year follow up. Materials and Methods: Endodontic orthograde treatment was performed under copious irrigation with sodium hypochlorite, in association with calcium hydroxide as an intra-canal medication for both teeth. Root canal filling was achieved in a separate appointment using the continuous wave of condensation technique. A decompression procedure was used in association with endodontic therapy in the second case to reduce the pressure inside the cystic lesion and to allow its drainage, and only because the root canal could not be dried three weeks after medication. Initial cone beam computed tomography (CBCT) investigations, as well as at the one-year follow up, were used to compare the evolution of the lesion. Results: Both cases had a favorable outcome. New bone formation in the periapical region and complete resolution of the lesion was observed at the one-year control in the first case. In the second case, although the lesion was still not completely healed at 12 months, a significant reduction in its size could be observed, showing active signs of healing. Conclusions: Endodontic treatment is the first choice option in the management of teeth with pulpal necrosis and large periapical cystic-like lesions. Decompression is the only surgical procedure recommended when the canals cannot be dried and obturated. Large surgical interventions are unnecessary in cases where endodontic treatment can be performed.
•S-doped TiO2 nanoparticles were synthesized by the single step laser pyrolysis.•TiCl4, (CH3)2S2 and O2 from air were the precursors and C2H4 was the sensitizer.•Different S (1.35–1.54at%) and C ...(13.49–17.34at%) concentrations were found.•Doped samples have a lower bandgap energy (Eg=2.7eV) than the P25 Degussa.
We report the synthesis of carbon coated and sulfur doped titania nanoparticles using a continuous, single-step laser pyrolysis technique. We employed air as oxidant and C2H4 as laser energy transfer agent (sensitizer)/carbon donor, both carrying the TiCl4 vapors as a titania precursor. The volatile (CH3)2S2 was used to introduce sulfur as dopant in the nanopowders. The incorporation of C and S atoms in nanopowders with anatase dominant phase and with average particle diameter between 18 and 25nm was performed through the addition of S2(CH3)2 and C2H4 to the reactive precursor mixtures. The samples were characterized by: EDX, XRD, TEM, XPS and UV–Vis spectroscopy. By the introduction of the sulfur precursor, the anatase-to-rutile ratio within the resulted TiO2-based nanoparticles decreased, as well as their bandgap energy values which are also lower than those of commercial TiO2 Degussa P25.
•Metallic tin-based nanoparticles were synthesized using laser pyrolysis technique.•Tetramethyltin was used as precursors whereas ethylene was the sensitizer.•The nanoparticles where covered with a ...tin oxidized/carbonaceous shell.•Their size where decreased by diminishing the laser beam residence time.
Due to their characteristic to allow a continuous, one-step nanosize particles production, the laser pyrolysis technique was employed to synthesize metallic Sn-based nanoparticles using tetramethyltin vapors as precursors and ethylene as laser energy transfer agent (sensitizer). Small size of tin particles is a requirement for their use as anodes in lithium ion batteries. In order to decrease the particle size, some experimental parameters were varied, allowing the control of the crystallite size down to 30nm. The diminishing diameter of the reactive flow injection nozzle as well as the increasing of the tin precursor vapor flow enhance the gas velocity and the decrease the reactive species residence time in the laser beam, resulting smaller tin nanodroplets which forms solid nanoparticles after rapid cooling. XRD, TEM, EDX and SAED analysis point to the formation of nanosize β-Sn particles accompanied by various amount of disordered carbon as coating provided by ethylene decomposition (associated with their polymerization/dehydrogenation) in the presence of methyl radicals from Sn(CH3)4.
Worldwide, one person dies every 40 seconds by suicide, a potentially preventable tragedy. A limiting step in our ability to intervene is the lack of objective, reliable predictors. We have ...previously provided proof of principle for the use of blood gene expression biomarkers to predict future hospitalizations due to suicidality, in male bipolar disorder participants. We now generalize the discovery, prioritization, validation, and testing of such markers across major psychiatric disorders (bipolar disorder, major depressive disorder, schizoaffective disorder, and schizophrenia) in male participants, to understand commonalities and differences. We used a powerful within-participant discovery approach to identify genes that change in expression between no suicidal ideation and high suicidal ideation states (n=37 participants out of a cohort of 217 psychiatric participants followed longitudinally). We then used a convergent functional genomics (CFG) approach with existing prior evidence in the field to prioritize the candidate biomarkers identified in the discovery step. Next, we validated the top biomarkers from the prioritization step for relevance to suicidal behavior, in a demographically matched cohort of suicide completers from the coroner's office (n=26). The biomarkers for suicidal ideation only are enriched for genes involved in neuronal connectivity and schizophrenia, the biomarkers also validated for suicidal behavior are enriched for genes involved in neuronal activity and mood. The 76 biomarkers that survived Bonferroni correction after validation for suicidal behavior map to biological pathways involved in immune and inflammatory response, mTOR signaling and growth factor regulation. mTOR signaling is necessary for the effects of the rapid-acting antidepressant agent ketamine, providing a novel biological rationale for its possible use in treating acute suicidality. Similarly, MAOB, a target of antidepressant inhibitors, was one of the increased biomarkers for suicidality. We also identified other potential therapeutic targets or biomarkers for drugs known to mitigate suicidality, such as omega-3 fatty acids, lithium and clozapine. Overall, 14% of the top candidate biomarkers also had evidence for involvement in psychological stress response, and 19% for involvement in programmed cell death/cellular suicide (apoptosis). It may be that in the face of adversity (stress), death mechanisms are turned on at a cellular (apoptosis) and organismal level. Finally, we tested the top increased and decreased biomarkers from the discovery for suicidal ideation (CADM1, CLIP4, DTNA, KIF2C), prioritization with CFG for prior evidence (SAT1, SKA2, SLC4A4), and validation for behavior in suicide completers (IL6, MBP, JUN, KLHDC3) steps in a completely independent test cohort of psychiatric participants for prediction of suicidal ideation (n=108), and in a future follow-up cohort of psychiatric participants (n=157) for prediction of psychiatric hospitalizations due to suicidality. The best individual biomarker across psychiatric diagnoses for predicting suicidal ideation was SLC4A4, with a receiver operating characteristic (ROC) area under the curve (AUC) of 72%. For bipolar disorder in particular, SLC4A4 predicted suicidal ideation with an AUC of 93%, and future hospitalizations with an AUC of 70%. SLC4A4 is involved in brain extracellular space pH regulation. Brain pH has been implicated in the pathophysiology of acute panic attacks. We also describe two new clinical information apps, one for affective state (simplified affective state scale, SASS) and one for suicide risk factors (Convergent Functional Information for Suicide, CFI-S), and how well they predict suicidal ideation across psychiatric diagnoses (AUC of 85% for SASS, AUC of 89% for CFI-S). We hypothesized a priori, based on our previous work, that the integration of the top biomarkers and the clinical information into a universal predictive measure (UP-Suicide) would show broad-spectrum predictive ability across psychiatric diagnoses. Indeed, the UP-Suicide was able to predict suicidal ideation across psychiatric diagnoses with an AUC of 92%. For bipolar disorder, it predicted suicidal ideation with an AUC of 98%, and future hospitalizations with an AUC of 94%. Of note, both types of tests we developed (blood biomarkers and clinical information apps) do not require asking the individual assessed if they have thoughts of suicide, as individuals who are truly suicidal often do not share that information with clinicians. We propose that the widespread use of such risk prediction tests as part of routine or targeted healthcare assessments will lead to early disease interception followed by preventive lifestyle modifications and proactive treatment.
•Carbon-encapsulated Fe–FexC nanoparticles were synthesized by laser pyrolysis.•Fe–C@PANI was obtained by redox polymerization in aqueous acid suspension.•The composite show low coercivity and 6emu/g ...saturation magnetization.•Electric and redox behavior of Fe–C@PANI is similar with those of pure PANI.
We report the synthesis of novel magnetic nanocomposite based on polyaniline (PANI) matrix and Fe–C nanoparticles. These hydrophobic Fe–FexC@C nanoparticles (having diameters under 20nm) were synthesized by laser pyrolysis from Fe(CO)5 and C2H4/H2 and dispersed in water using sodium carboxymethylcellulose, followed by the PANI coating using ultrasonication-assisted oxidative polymerization of aniline hydrochloride. The structure of the resulted composite was characterized by Transmission Electron Microscopy, X-ray diffraction and also by Raman and Infrared spectroscopy. The composite powder shows ferromagnetic behavior with low coercivity and 6.4emu/g saturation magnetization, having also electric and electrochemical behavior similar with pure PANI reference.
Missing mass spectroscopy with the $(e,e^{\prime}K^{+})$ reaction was performed at JLab Hall C for the neutron rich $\Lambda$ hypernucleus $^{9}_{\Lambda}{\rm Li}$. The ground state energy was ...obtained to be $B_{\Lambda}^{\rm g.s.}=8.84\pm0.17^{\rm stat.}\pm0.15^{\rm sys.}~{\rm MeV}$ by using shell model calculations of a cross section ratio and an energy separation of the spin doublet states ($3/2^{+}_1$ and $5/2^{+}_1$). In addition, peaks that are considered to be states of $^{8}{\rm Li}(3^{+})\otimes s_{\Lambda}=3/2^{+}_{2}, 1/2^{+}$ and $^{8}{\rm Li}(1^{+})\otimes s_{\Lambda}=5/2^{+}_{2}, 7/2^{+}$ were observed at $E_{\Lambda}(\#2)=1.74\pm0.27^{\rm stat.}\pm0.11^{\rm sys.}~{\rm MeV}$ and $E_{\Lambda}(\#3)=3.30\pm0.24^{\rm stat.}\pm0.11^{\rm sys.}~{\rm MeV}$, respectively. The $E_{\Lambda}(\#3)$ is larger than shell model predictions by a few hundred keV, and the difference would indicate that a ${\rm ^{5}He}+t$ structure is more developed for the $3^{+}$ state than those for the $2^{+}$ and $1^{+}$ states in a core nucleus $^{8}{\rm Li}$ as a cluster model calculation suggests.
Suicide remains a clear, present and increasing public health problem, despite being a potentially preventable tragedy. Its incidence is particularly high in people with overt or un(der)diagnosed ...psychiatric disorders. Objective and precise identification of individuals at risk, ways of monitoring response to treatments and novel preventive therapeutics need to be discovered, employed and widely deployed. We sought to investigate whether blood gene expression biomarkers for suicide (that is, a 'liquid biopsy' approach) can be identified that are more universal in nature, working across psychiatric diagnoses and genders, using larger cohorts than in previous studies. Such markers may reflect and/or be a proxy for the core biology of suicide. We were successful in this endeavor, using a comprehensive stepwise approach, leading to a wealth of findings. Steps 1, 2 and 3 were discovery, prioritization and validation for tracking suicidality, resulting in a Top Dozen list of candidate biomarkers comprising the top biomarkers from each step, as well as a larger list of 148 candidate biomarkers that survived Bonferroni correction in the validation step. Step 4 was testing the Top Dozen list and Bonferroni biomarker list for predictive ability for suicidal ideation (SI) and for future hospitalizations for suicidality in independent cohorts, leading to the identification of completely novel predictive biomarkers (such as CLN5 and AK2), as well as reinforcement of ours and others previous findings in the field (such as SLC4A4 and SKA2). Additionally, we examined whether subtypes of suicidality can be identified based on mental state at the time of high SI and identified four potential subtypes: high anxiety, low mood, combined and non-affective (psychotic). Such subtypes may delineate groups of individuals that are more homogenous in terms of suicidality biology and behavior. We also studied a more personalized approach, by psychiatric diagnosis and gender, with a focus on bipolar males, the highest risk group. Such a personalized approach may be more sensitive to gender differences and to the impact of psychiatric co-morbidities and medications. We compared testing the universal biomarkers in everybody versus testing by subtypes versus personalized by gender and diagnosis, and show that the subtype and personalized approaches permit enhanced precision of predictions for different universal biomarkers. In particular, LHFP appears to be a strong predictor for suicidality in males with depression. We also directly examined whether biomarkers discovered using male bipolars only are better predictors in a male bipolar independent cohort than universal biomarkers and show evidence for a possible advantage of personalization. We identified completely novel biomarkers (such as SPTBN1 and C7orf73), and reinforced previously known biomarkers (such as PTEN and SAT1). For diagnostic ability testing purposes, we also examined as predictors phenotypic measures as apps (for suicide risk (CFI-S, Convergent Functional Information for Suicidality) and for anxiety and mood (SASS, Simplified Affective State Scale)) by themselves, as well as in combination with the top biomarkers (the combination being our a priori primary endpoint), to provide context and enhance precision of predictions. We obtained area under the curves of 90% for SI and 77% for future hospitalizations in independent cohorts. Step 5 was to look for mechanistic understanding, starting with examining evidence for the Top Dozen and Bonferroni biomarkers for involvement in other psychiatric and non-psychiatric disorders, as a mechanism for biological predisposition and vulnerability. The biomarkers we identified also provide a window towards understanding the biology of suicide, implicating biological pathways related to neurogenesis, programmed cell death and insulin signaling from the universal biomarkers, as well as mTOR signaling from the male bipolar biomarkers. In particular, HTR2A increase coupled with ARRB1 and GSK3B decreases in expression in suicidality may provide a synergistic mechanistical corrective target, as do SLC4A4 increase coupled with AHCYL1 and AHCYL2 decrease. Step 6 was to move beyond diagnostics and mechanistical risk assessment, towards providing a foundation for personalized therapeutics. Items scored positive in the CFI-S and subtypes identified by SASS in different individuals provide targets for personalized (psycho)therapy. Some individual biomarkers are targets of existing drugs used to treat mood disorders and suicidality (lithium, clozapine and omega-3 fatty acids), providing a means toward pharmacogenomics stratification of patients and monitoring of response to treatment. Such biomarkers merit evaluation in clinical trials. Bioinformatics drug repurposing analyses with the gene expression biosignatures of the Top Dozen and Bonferroni-validated universal biomarkers identified novel potential therapeutics for suicidality, such as ebselen (a lithium mimetic), piracetam (a nootropic), chlorogenic acid (a polyphenol) and metformin (an antidiabetic and possible longevity promoting drug). Finally, based on the totality of our data and of the evidence in the field to date, a convergent functional evidence score prioritizing biomarkers that have all around evidence (track suicidality, predict it, are reflective of biological predisposition and are potential drug targets) brought to the fore APOE and IL6 from among the universal biomarkers, suggesting an inflammatory/accelerated aging component that may be a targetable common denominator.
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