Recurrence and progression of periodontitis and methods of management in long-term care: A systematic review and meta-analysis

Aim: To systematically review the literature to evaluate the recurrence of disease of people in long-term supportive periodontal care (SPC), previously treated for periodontitis, and determine the effect of different methods of managing recurrence. The review focused on stage IV periodontitis. Materials and methods: An electronic search was conducted (until May 2020) for prospective clinical trials. Tooth loss was the primary outcome. Results: Twenty-four publications were retrieved to address recurrence of disease in long-term SPC. Eight studies were included in the meta-analyses for tooth loss, and three studies for disease progression/recurrence (clinical attachment level [CAL] loss ≥2 mm). For patients in SPC of 5–20 years, prevalence of losing more than one tooth was 9.6% (95% confidence interval [CI] 5%–14%), while experiencing more than one site of CAL loss ≥2 mm was 24.8% (95% CI 11%–38%). Six studies informed on the effect of different methods of managing recurrence, with no clear evidence of superiority between methods. No data was found specifically for stage IV periodontitis. Conclusions: A small proportion of patients with stage III/IV periodontitis will experience tooth loss in long-term SPC (tendency for greater prevalence with time). Regular SPC appears to be important for reduction of tooth loss. No superior method to manage disease recurrence was found

Quantification of vaporized targeted nanodroplets using high-frame-rate ultrasound and optics

Owing to their ability to efficiently deliver biological cargo and sense the intracellular milieu, vertical arrays of high aspect ratio nanostructures, known as nanoneedles,are being developed as minimally invasive tools for cell manipulation. However, little is known of the mechanisms of cargo transfer across the cell membrane-nanoneedle interface. Particularly,the contributions of membrane piercing, modulation of membrane permeability and endocytosis to cargo transfer remain largelyunexplored. Here, combining state-of-the-art electron and scanning ion conductance microscopy with molecular biology techniques, we show that porous silicon nanoneedle arrays concurrently stimulate independent endocytic pathways which contribute to enhanced biomolecule delivery into human mesenchymal stem cells. Electron microscopy of the cell membrane at nanoneedle sites shows an intact lipid bilayer, accompanied by an accumulation of clathrin-coated pits and caveolae. Nanoneedles enhance the internalisation of biomolecular markers of endocytosis, highlighting the concurrent activation of caveolae-and clathrin-mediated endocytosis, alongside macropinocytosis. These events contribute to the nanoneedle-mediated delivery (nanoinjection) of nucleic acids into human stem cells, which distribute across the cytosol and the endolysosomal system. This data extends the understanding of how nanoneedles modulate biological processes to mediate interaction with the intracellular space, providing indications for the rational design of improved cell-manipulation technologies

Robust beamforming and user clustering for guaranteed fairness in downlink NOMA with partial feedback

In this paper, a downlink multiuser non-orthogonal multiple access (NOMA) with full and partial channel state information (CSI) feedback is considered. We investigate beam design and user clustering from the throughput-fairness trade-off perspective. To enhance this trade-off, two proportional fairness (PF) based scheduling algorithms are proposed, each has two stages. The first algorithm is based on integrating the maximum product of effective channel gains and the maximum signal to interference ratio with the PF principle (PF-MPECG-SIR), to select the strong users in the first stage and the weak users in the second stage. This algorithm is designed to maximize the throughput with moderate fairness enhancement. Whereas, in the second algorithm, the MPECG and the maximum correlation are combined within the PF selection criterion (PF-MPECG-CORR) in order to maximize the fairness with a slight degradation in the total throughput. In addition, we present an optimal power allocation that can achieve a high data rate for the overall system without sacrificing the sum-rate of weak users under full and partial CSI. Simulation results show that the proposed PF-MPECG-CORR can significantly improve the fairness up to 50.82% and 44.90% with only 0.42% and 1.13% degradation in the total throughput, for full and partial CSI, respectively. All these performance gains are achieved without increasing the computational complexity

Safety and efficacy of human Wharton's Jelly-derived mesenchymal stem cells therapy for retinal degeneration

Purpose To investigate the safety and efficacy of subretinal injection of human Wharton’s Jelly-derived mesenchymal stem cells (hWJ-MSCs) on retinal structure and function in Royal College of Surgeons (RCS) rats. Methods RCS rats were divided into 2 groups: hWJ-MSCs treated group (n = 8) and placebo control group (n = 8). In the treatment group, hWJ-MSCs from healthy donors were injected into the subretinal space in one eye of each rat at day 21. Control group received saline injection of the same volume. Additional 3 animals were injected with nanogold-labelled stem cells for in vivo tracking of cells localisation using a micro-computed tomography (microCT). Retinal function was assessed by electroretinography (ERG) 3 days before the injection and repeated at days 15, 30 and 70 after the injection. Eyes were collected at day 70 for histology, cellular and molecular studies. Results No retinal tumor formation was detected by histology during the study period. MicroCT scans showed that hWJ-MSCs stayed localised in the eye with no systemic migration. Transmission electron microscopy showed that nanogold-labelled cells were located within the subretinal space. Histology showed preservation of the outer nuclear layer (ONL) in the treated group but not in the control group. However, there were no significant differences in the ERG responses between the groups. Confocal microscopy showed evidence of hWJ-MSCs expressing markers for photoreceptor, Müller cells and bipolar cells. Conclusions Subretinal injection of hWJ-MSCs delay the loss of the ONL in RCS rats. hWJ-MSCs appears to be safe and has potential to differentiate into retinal-like cells. The potential of this cell-based therapy for the treatment of retinal dystrophies warrants further studies

Anti-cancer effects and mechanism of actions of aspirin analogues in the treatment of glioma cancer

INTRODUCTION: In the past 25 years only modest advancements in glioma treatment have been made, with patient prognosis and median survival time following diagnosis only increasing from 3 to 7 months. A substantial body of clinical and preclinical evidence has suggested a role for aspirin in the treatment of cancer with multiple mechanisms of action proposed including COX 2 inhibition, down regulation of EGFR expression, and NF-κB signaling affecting Bcl-2 expression. However, with serious side effects such as stroke and gastrointestinal bleeding, aspirin analogues with improved potency and side effect profiles are being developed. METHOD: Effects on cell viability following 24 hr incubation of four aspirin derivatives (PN508, 517, 526 and 529) were compared to cisplatin, aspirin and di-aspirin in four glioma cell lines (U87 MG, SVG P12, GOS – 3, and 1321N1), using the PrestoBlue assay, establishing IC50 and examining the time course of drug effects. RESULTS: All compounds were found to decrease cell viability in a concentration and time dependant manner. Significantly, the analogue PN517 (IC50 2mM) showed approximately a twofold increase in potency when compared to aspirin (3.7mM) and cisplatin (4.3mM) in U87 cells, with similar increased potency in SVG P12 cells. Other analogues demonstrated similar potency to aspirin and cisplatin. CONCLUSION: These results support the further development and characterization of novel NSAID derivatives for the treatment of glioma

Main structural targets for engineering lipase substrate specificity

Microbial lipases represent one of the most important groups of biotechnological biocatalysts. However, the high-level production of lipases requires an understanding of the molecular mechanisms of gene expression, folding, and secretion processes. Stable, selective, and productive lipase is essential for modern chemical industries, as most lipases cannot work in different process conditions. However, the screening and isolation of a new lipase with desired and specific properties would be time consuming, and costly, so researchers typically modify an available lipase with a certain potential for minimizing cost. Improving enzyme properties is associated with altering the enzymatic structure by changing one or several amino acids in the protein sequence. This review detailed the main sources, classification, structural properties, and mutagenic approaches, such as rational design (site direct mutagenesis, iterative saturation mutagenesis) and direct evolution (error prone PCR, DNA shuffling), for achieving modification goals. Here, both techniques were reviewed, with different results for lipase engineering, with a particular focus on improving or changing lipase specificity. Changing the amino acid sequences of the binding pocket or lid region of the lipase led to remarkable enzyme substrate specificity and enantioselectivity improvement. Site-directed mutagenesis is one of the appropriate methods to alter the enzyme sequence, as compared to random mutagenesis, such as error-prone PCR. This contribution has summarized and evaluated several experimental studies on modifying the substrate specificity of lipase

Distant Voices: Learners' Stories About the Affective Side of Learning a Language at a Distance

Learning a language at a distance has its own special challenges. The remoteness of the learning context can mean isolation for the learner, communication difficulties for the teacher and problems of access for the researcher. Yet distance language learners are likely to be no more skilled in self-regulation than classroom learners, and to require high levels of support. Research tools are needed, therefore, which allow them to talk freely about their learning in order to help distance educators target support appropriately. This paper draws on data from two pilot ethnographic studies of distance language learners using think-aloud protocols to access their thought processes as they tackled two designated language tasks. They were carried out as part of a wider study in each case to investigate aspects of affect including beliefs, motivation and anxiety. The audio-taped voices provided rich insights into the advantages and disadvantages, pleasures and frustrations, comforts and anxieties of learning a language at a distance, and the strategies learners use to manage in a distance environment. The studies underlined the importance of listening to students and using their voices as a basis for discussion on improving aspects of the design and delivery of distance language courses

Lipocalin 2 modulates the cellular response to amyloid beta

The production, accumulation and aggregation of amyloid beta (Aß) peptides in Alzheimer's disease (AD) are influenced by different modulators. Among these are iron and iron-related proteins, given their ability to modulate the expression of the amyloid precursor protein and to drive Aß aggregation. Herein, we describe that lipocalin 2 (LCN2), a mammalian acute-phase protein involved in iron homeostasis, is highly produced in response to Aß1-42 by choroid plexus epithelial cells and astrocytes, but not by microglia or neurons. Although Aß1-42 stimulation decreases the dehydrogenase activity and survival of wild-type astrocytes, astrocytes lacking the expression of Lcn2 are not affected. This protection results from a lower expression of the proapoptotic gene Bim and a decreased inflammatory response. Altogether, these findings show that Aß toxicity to astrocytes requires LCN2, which represents a novel mechanism to target when addressing AD.Cell Death and Differentiation advance online publication, 23 May 2014; doi:10.1038/cdd.2014.68.We thank Dr. Ioannis Sotiropoulos for reagents and comments. Sandro Da Mesquita and Ana Catarina Ferreira are recipients of PhD fellowships and Fernanda Marques is recipient of a postdoctoral fellowship by the Fundacao para a Ciencia e Tecnologia (FCT, Portugal)/FEDER. This work was supported by a grant from FCT/FEDER (EXPL/NEUOSD/2196/2013)

New Measure of Insulin Sensitivity Predicts Cardiovascular Disease Better than HOMA Estimated Insulin Resistance

10.1371/journal.pone.0074410PLoS ONE89-POLN