Proprotein convertase subtilisin/Kexin type-9 (PCSK-9) inhibitors induced liver injury - a retrospective analysis.

Background: Proprotein convertase subtilisin/Kexin type 9 (PCSK-9) inhibitors induced liver dysfunction in patients with or without previous liver injury, and this is not well discussed in the previous literature. Methods: A total sample of 202 patients were retrospectively reviewed at the University of Missouri, Kansas City, from the year 2015 to 2018 based on predefined selection criteria. Inclusion criteria involved patients with dyslipidemia, with or without PCSK-9 inhibitors, liver function tests and lipid profile at baseline and at a mean of 6-month follow-up. The variables, including age, gender, and confounding factors like other medications (statin, oral antidiabetic, and antihypertensive) induced, or chronic secondary liver diseases causing liver injury were taken into consideration. Exclusion criteria included patients without dyslipidemia. Results: The mean age of the study population was 64 ± 11 years (63% males and 37% females). The lipid profile including triglyceride and cholesterol levels during 6-month followup visit showed a mean of 184 ± 260 and 163 ± 50 mg/dL as compared to that at baseline of 227 ± 603 and 181 ± 70 mg/dL, respectively. In terms of clinical efficacy, a 6-month follows-up showed a drop in triglyceride and cholesterol levels by 38 and 15 mg/dL, respectively. A liver function test at 6 months in patients taking PCSK-9 inhibitors showed an increase in alanine transaminase (ALT) and aspartate transaminase (AST) by 5.8 mg/dL (p = 0.037) and 6.2 mg/dL (p = 0.008), respectively, from baseline values. Conclusion: PCSK-9 inhibitors should be used cautiously with a follow-up liver function test

Synthesis and characterization of manganese containing mesoporous bioactive glass nanoparticles for biomedical applications

Mesoporous bioactive glass (BG) nanoparticles based in the system: SiO2–P2O5–CaO–MnO were synthesized via a modified Stöber process at various concentrations of Mn (0–7 mol %). The synthesized manganese-doped BG nanoparticles were characterized in terms of morphology, composition, in vitro bioactivity and antibacterial activity. Scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Brunauer–Emmett–Teller (BET) analysis confirmed that the particles had spherical morphology (mean particle size: 110 nm) with disordered mesoporous structure. Energy dispersive X-ray spectroscopy (EDX) confirmed the presence of Mn, Ca, Si and P in the synthesized Mn-doped BG particles. Moreover, X-ray diffraction (XRD) analysis showed that Mn has been incorporated in the amorphous silica network (bioactive glass). Moreover, it was found that manganese-doped BG particles form apatite crystals upon immersion in simulated body fluid (SBF). Inductively coupled plasma atomic emission spectroscopy (ICP-OES) measurements confirmed that Mn is released in a sustained manner, which provided antibacterial effect against Bacillus subtilis, Pseudomonas aeruginosa and Staphylococcus aureus. The results indicate that the incorporation of Mn in the bioactive glass network is an effective strategy to develop novel multifunctional BG nanoparticles for bone tissue engineering.University of Seville (Spain) Grant P2017/83

Primary Pulmonary Lymphoma Presenting with Superior Vena Cava Syndrome in a Young Female

Primary Pulmonary Diffuse Large B Cell Lymphoma (PPDLBCL) is an extremely rare entity, which exhibits an aggressive behavior by compressing local blood vessels. It represents only 0.04% of all lymphoma cases and is extremely rare in young age. We present a case of a primary pulmonary lymphoma with superior vena cava syndrome (SVCS) in a young female. 27-year-old African American female presented with fever, cough, and facial puffiness for 2 weeks and unintentional weight loss. Chest examination showed decreased breath sounds and dullness on percussion on right side. Labs were normal except for mild leukocytosis, high lactate, and lactate dehydrogenase. Chest X-ray showed a large right side infiltrate with pleural effusion but chest CT showed 10 × 14 × 16 cm mass in the right lung without hilar and mediastinal lymphadenopathy. CT guided biopsy of the right lung mass was done and large B cell lymphoma was diagnosed. She received “involved field radiation” because of the bulky tumor size and superior vena cava involvement prior to R-CHOP to which she responded well. PPDLBCL should be considered as one of the differentials in a young patient with a large lung mass, which needs timely diagnosis and management

The (2j-1) rule with other interactions

We recently formulated a rule for isomeric states for a system of 4 nucleons with isospin T=1, namely that if the nucleons are in a single j shell then states with angular momenta J=2 and J=(2j-1) are either isomeric or ground states [ze12]. To show that this is a robust result, we here consider a new interaction from the literature that was used to discuss even-even and odd-even nuclei. We here apply it to an odd-odd nucleus.Comment: arXiv admin note: substantial text overlap with arXiv:1107.4068, arXiv:1112.480

Ceramic Stereolithography of Bioactive Glasses: Influence of Resin Composition on Curing Behavior and Green Body Properties

Herein we report on the preparation of a bioactive glass (BAG)-based photocurable resin for the additive manufacturing of BAG scaffolds with high filler loadings. The preparation of glass/ceramics resins for stereolithography with high filler loading is always a challenge, especially for fillers with a high refractive index variance. Various photocurable resin compositions with and without bioactive glass fillers have been investigated to see the influence of bioactive glass on physical properties of the resin and resulting green body. The effect of concentration of monomers, reactive diluent, light absorber (Sudan orange G dye), photoinitiator (PI), non-reactive diluent, and fillers (BAG) on rheology and photocuring behavior of the resin and tomography of the resulting 3D structures have been investigated. The BAG contents affect the rheology of resin and influence the rate of the polymerization reaction. The resin compositions with 55–60% BAG, 10% PEG-200 (diluent), 1% of PI and 0.015% of the dye were found to be suitable compositions for the stereolithographic fabrication. A higher percentage of PI caused over-curing, while a higher amount of dye decreased the cure depth of the resin. The micro-computed tomography (µ-CT) and scanning electron microscopic (SEM) images of the resulting green bodies display a relatively dense glass scaffold without any visible cracks and good interlayer connection and surface finishing. These properties play an important role in the mechanical behavior of 3D scaffolds. This study will be helpful to prepare high density glass/ceramic slurries and optimize their printing properties

Effects of Cholecystokinin in the Supraoptic Nucleus and Paraventricular Nucleus are Negatively Modulated by Leptin in 24-h Fasted Lean Male Rats

Cholecystokinin (CCK) and leptin are two important satiety factors that are considered to act in synergy to reduce meal size. Peripheral injection of CCK activates neurones in several hypothalamic nuclei, including the supraoptic (SON) and paraventricular (PVN) nuclei and neurones in the brainstem of fed rats. We investigated whether peripheral leptin would modulate the effects of CCK on neuronal activity in the hypothalamus and brainstem of fasted rats by investigating Fos expression in the PVN, SON, arcuate nucleus, ventromedial hypothalamus (VMH), dorsomedial hypothalamus (DMH), area postrema (AP) and the nucleus tractus solitarii (NTS). Male rats, fasted for 24 h, received either one i.p. injection of vehicle, leptin or CCK-8 alone, or received one injection of vehicle or leptin before an i.p. injection of CCK-8. We found that CCK increased Fos expression in the PVN and SON as well as in the NTS and AP, but had no effect on Fos expression in the arcuate nucleus, VMH or DMH compared to vehicle. Leptin injected alone significantly increased Fos expression in the arcuate nucleus but had no effect on Fos expression in the VMH, DMH, SON, PVN, AP or NTS compared to vehicle. Fos expression was significantly increased in the AP in rats injected with both leptin and CCK compared to rats injected with vehicle and CCK. Unexpectedly, there was significantly less Fos expression in the PVN and SON of fasted rats injected with leptin and CCK than in rats injected with vehicle and CCK, suggesting that leptin attenuated CCK-induced Fos expression in the SON and PVN. However, Fos expression in the NTS was similar in fasted rats injected with vehicle and CCK or with leptin and CCK. Taken together, these results suggest that leptin dampens the effects of CCK on Fos expression in the SON and PVN, independently from NTS pathways, and this may reflect a direct action on magnocellular neurones

Effects of written feedback and revision on learners' accuracy in using two English grammatical structures

The study compared the effects of two types of form-focused written feedback-direct corrective feedback (DCF) and metalinguistic explanation (ME) given to the whole class-on Japanese university students' accuracy of use of two grammatical structures: indefinite article and the hypothetical conditional. Both types of feedback were given with and without an opportunity to rewrite. Accuracy of use was measured in new pieces of writing. The feedback led to increased accuracy for the hypothetical conditional but not for the indefinite article. The effectiveness of the DCF proved longer lasting than the ME. Also, providing opportunity for revision enhanced the effect of the feedback. Overall, DCF followed by revision proved the most effective type of feedback. The results suggest that when form-focused written feedback is directed at two features that vary in saliency and complexity, learners are likely to focus on the structure that contributes more to the global meaning of the text. The results also indicate that directly correcting the errors learners make with respect to a complex syntactical structure is more beneficial than giving them a metalinguistic explanation. © 2013 Language Learning Research Club, University of Michigan

The Effects of the Timing of Corrective Feedback on the Acquisition of a New Linguistic Structure

The article reports on a study investigating the comparative effects of immediate and delayed corrective feedback in learning the English past passive construction, a linguistic structure of which the learners had little prior knowledge. A total of 120 learners of English as a foreign language (EFL) from 4 intact classes at a Chinese middle school were randomly assigned to conditions: immediate feedback, delayed feedback, task-only, and control. The 3 experimental groups attended a 2-hour treatment session where they performed 2 dictogloss (narrative) tasks in groups, each followed by a reporting phase in which they took turns telling the narrative to the class. The 2 feedback groups received either immediate or delayed corrective feedback in the form of a prompt, followed by recasts of utterances containing errors in their use of the target structure. No effect for the corrective feedback was found on elicited imitation test scores, but both the immediate and delayed feedback resulted in gains in grammaticality judgment test scores, with immediate feedback showing some advantage over delayed feedback. We interpret these results as showing that the feedback only aided the development of declarative/explicit knowledge and that the advantage found for immediate feedback was due to the learners using the feedback progressively in the production of new past passive sentences, whereas this did not occur in the delayed feedback condition

The background in the neutrinoless double beta decay experiment GERDA

The GERmanium Detector Array (GERDA) experiment at the Gran Sasso underground laboratory (LNGS) of INFN is searching for neutrinoless double beta decay of 76Ge. The signature of the signal is a monoenergetic peak at 2039 keV, the Q-value of the decay, Q_bb. To avoid bias in the signal search, the present analysis does not consider all those events, that fall in a 40 keV wide region centered around Q_bb. The main parameters needed for the neutrinoless double beta decay analysis are described. A background model was developed to describe the observed energy spectrum. The model contains several contributions, that are expected on the basis of material screening or that are established by the observation of characteristic structures in the energy spectrum. The model predicts a flat energy spectrum for the blinding window around Q_bb with a background index ranging from 17.6 to 23.8*10^{-3} counts/(keV kg yr). A part of the data not considered before has been used to test if the predictions of the background model are consistent. The observed number of events in this energy region is consistent with the background model. The background at Q-bb is dominated by close sources, mainly due to 42K, 214Bi, 228Th, 60Co and alpha emitting isotopes from the 226Ra decay chain. The individual fractions depend on the assumed locations of the contaminants. It is shown, that after removal of the known gamma peaks, the energy spectrum can be fitted in an energy range of 200 kev around Q_bb with a constant background. This gives a background index consistent with the full model and uncertainties of the same size

2νββ2\nu\beta\beta decay of 76^{76}Ge into excited states with GERDA Phase I

Two neutrino double beta decay of $^{76}$Ge to excited states of $^{76}$Se has been studied using data from Phase I of the GERDA experiment. An array composed of up to 14 germanium detectors including detectors that have been isotopically enriched in $^{76}$Ge was deployed in liquid argon. The analysis of various possible transitions to excited final states is based on coincidence events between pairs of detectors where a de-excitation $\gamma$ ray is detected in one detector and the two electrons in the other. No signal has been observed and an event counting profile likelihood analysis has been used to determine Frequentist 90\,\% C.L. bounds for three transitions: ${0^+_{\rm g.s.}-2^+_1}$: $T^{2\nu}_{1/2}>$1.6$\cdot10^{23}$ yr, ${0^+_{\rm g.s.}-0^+_1}$: $T^{2\nu}_{1/2}>$3.7$\cdot10^{23}$ yr and ${0^+_{\rm g.s.}-2^+_2}$: $T^{2\nu}_{1/2}>$2.3$\cdot10^{23}$ yr. These bounds are more than two orders of magnitude larger than those reported previously. Bayesian 90\,\% credibility bounds were extracted and used to exclude several models for the ${0^+_{\rm g.s.}-0^+_1}$ transition