Efficacy of Laser-assisted Periodontal Therapy vs. Conventional Scaling and Root Planing.

Background: This study aimed to compare the effectiveness of laser-assisted periodontal therapy (LAPT) with conventional scaling and root planing (CSRP) in the treatment of periodontal disease. The objective was to assess the outcomes of these two treatments on a sample of 30 patients in each group. Materials and Methods: In this study, a total of 60 patients diagnosed with periodontal disease were divided into two groups: the LAPT group and the CSRP group, with 30 patients in each group. The LAPT group received periodontal treatment using laser therapy, while the SRP group underwent traditional SRP. The patients were evaluated for periodontal parameters, including probing depth and clinical attachment level before and after the treatments. Results: After the treatment interventions, both the LAPT group and the CSRP group showed significant improvements in periodontal health. The mean reduction in probing depth was 2.5 mm in the LAPT group and 2.2 mm in the SRP group. In addition, the clinical attachment level increased by 2.8 mm in the LAPT group and 2.5 mm in the SRP group. Statistical analysis using the paired t-test demonstrated a P-value of less than 0.05, indicating the significance of these improvements in both groups. Conclusion: This study suggests that both LAP and CSRP are effective in improving periodontal health in patients with periodontal disease.

Pt(II)-bis(quinolinyl) complexes for photocatalytic hydrogen production.

Three Pt(II)-bis(quinolinyl) complexes with varying electron densities were synthesized, structurally characterized and used for photocatalytic hydrogen production under different conditions. All the complexes were found to be active for hydrogen production giving a maximum turnover number (TON) of 1230 surpassing the conventionally used Pt-terpyridyl complexes.

Efficient Obstacle Detection and Tracking Using RGB-D Sensor Data in Dynamic Environments for Robotic Applications.

Obstacle detection is an essential task for the autonomous navigation by robots. The task becomes more complex in a dynamic and cluttered environment. In this context, the RGB-D camera sensor is one of the most common devices that provides a quick and reasonable estimation of the environment in the form of RGB and depth images. This work proposes an efficient obstacle detection and tracking method using depth images to facilitate quick dynamic obstacle detection. To achieve early detection of dynamic obstacles and stable estimation of their states, as in previous methods, we applied a u-depth map for obstacle detection. Unlike existing methods, the present method provides dynamic thresholding facilities on the u-depth map to detect obstacles more accurately. Here, we propose a restricted v-depth map technique, using post-processing after the u-depth map processing to obtain a better prediction of the obstacle dimension. We also propose a new algorithm to track obstacles until they are within the field of view (FOV). We evaluate the performance of the proposed system on different kinds of data sets. The proposed method outperformed the vision-based state-of-the-art (SoA) methods in terms of state estimation of dynamic obstacles and execution time.

Comparative Evaluation of Gingival Crevicular Fluid Interleukin-17, 18 and 21 in Different Stages of Periodontal Health and Disease.

Background and Objectives: The elicitation of a host's immune−inflammatory responses to overcome oral bacterial biofilm challenges is mediated by numerous cytokines. We explored the role of three such cytokines, viz. interleukin (IL)-17, 18 and 21, by measuring their levels in the gingival crevicular fluid (GCF) of Indian individuals with healthy gingiva, chronic gingivitis, or chronic periodontitis. Materials and Method: Ninety systemically healthy individuals were enrolled in the study on the basis of predefined criteria and were categorized into three groups of 30 participants each. Groups A, B and C were composed of a control group with healthy gingiva, subjects with chronic gingivitis and subjects with chronic periodontitis, respectively. The periodontal disease status was assessed on the basis of a subject's gingival index, probing pocket depth, clinical attachment loss and radiographic evidence of bone loss. After the complete history-taking and identification of gingival sulcus/pocket depth areas for GCF collection, a sample was collected from each subject in all groups for an estimation of the cytokine levels using ELISA. Statistical analysis was performed using SPSS v 21.0. Intergroup comparisons were conducted using a post hoc Tukey's test. A value of p < 0.05 was considered to be statistically significant. Results: The mean IL-17, 18 and 21 concentrations in pg/mL was the greatest for Group C (99.67 ± 18.85, 144.61 ± 20.83 and 69.67 ± 12.46, respectively), followed by Group B (19.27 ± 2.78, 22.27 ± 2.43 and 22.74 ± 1.43, respectively) and finally by Group A (healthy control; 11.56 ± 0.99, 17.94 ± 1.24 and 12.83 ± 1.21 respectively). A statistically significant difference in the mean concentrations of two interleukins (IL-17 and IL-18) was observed between Groups A and C and also between Groups B and C. A statistically significant difference in the mean concentrations of IL-21 was observed between Groups B and C. Conclusions: Within the limitations of the present study, the findings revealed that the GCF levels of IL-17, IL-18 and IL-21 rose and correlated well with the severity of the disease. Thus, these cytokines present in GCF have the potential to be considered as biomarkers for periodontal tissue destruction. IL-21 in particular appears to be a promising biomarker for differentiating between gingivitis and periodontitis.

CALMS: Modelling the long-term health and economic impact of Covid-19 using agent-based simulation.

We present our agent-based CoronAvirus Lifelong Modelling and Simulation (CALMS) model that aspires to predict the lifelong impacts of Covid-19 on the health and economy of a population. CALMS considers individual characteristics as well as comorbidities in calculating the risk of infection and severe disease. We conduct two sets of experiments aiming at demonstrating the validity and capabilities of CALMS. We run simulations retrospectively and validate the model outputs against hospitalisations, ICU admissions and fatalities in a UK population for the period between March and September 2020. We then run simulations for the lifetime of the cohort applying a variety of targeted intervention strategies and compare their effectiveness against the baseline scenario where no intervention is applied. Four scenarios are simulated with targeted vaccination programmes and periodic lockdowns. Vaccinations are targeted first at individuals based on their age and second at vulnerable individuals based on their health status. Periodic lockdowns, triggered by hospitalisations, are tested with and without vaccination programme in place. Our results demonstrate that periodic lockdowns achieve reductions in hospitalisations, ICU admissions and fatalities of 6-8% compared to the baseline scenario, with an associated intervention cost of £173 million per 1,000 people and targeted vaccination programmes achieve reductions in hospitalisations, ICU admissions and fatalities of 89-90%, compared to the baseline scenario, with an associated intervention cost of £51,924 per 1,000 people. We conclude that periodic lockdowns alone are ineffective at reducing health-related outputs over the long-term and that vaccination programmes which target only the clinically vulnerable are sufficient in providing healthcare protection for the population as a whole.

Uncommon Ectopic Pregnancies-Challenges in the Management.

Background: The risk factors for ectopic pregnancy are on the rise. Despite the progress (availability of serum ßhCG, USG and MRI), there are diagnostic and therapeutic challenges in the management. Up to 50% of ectopic pregnancies go undetected. Furthermore, cases seen as emergency with hemodynamic instability need urgent intervention with simultaneous arrangement of transport, blood transfusion and at times multidisciplinary team involvement. This is more challenging in a setting where resources are limited. Objective: To evaluate the outcome of women presenting with uncommon ectopic pregnancies as life-threatening emergency. Challenges encountered in diagnosis, pre-operative evaluation, decision for surgery and the procedure are presented. Patients and Methods: This is a series of twelve cases of uncommon ectopic pregnancies belonging to eight different types. These were managed under the first author during the period 2001 to 2019. Subjects were analyzed retrospectively. Results: Diagnostic dilemma was faced in majority of the cases even with the use of ultrasonography. All the conceptions were spontaneous. Emergency surgical interventions were made on the basis of clinical evaluation. Five cases presented with massive hemoperitoneum. Blood transfusion was needed in nine cases. There was no mortality. One woman (case 4), with abdominal pregnancy, went home with a live baby, after the second laparotomy. Conclusion: Uncommon ectopic pregnancies are life-threatening conditions. Clinical acumen and an alert mind are of superior value in diagnosis. Investigations are supportive. Early diagnosis and intervention are lifesaving.

Memory and communication efficient algorithm for decentralized counting of nodes in networks.

Node counting on a graph is subject to some fundamental theoretical limitations, yet a solution to such problems is necessary in many applications of graph theory to real-world systems, such as collective robotics and distributed sensor networks. Thus several stochastic and naïve deterministic algorithms for distributed graph size estimation or calculation have been provided. Here we present a deterministic and distributed algorithm that allows every node of a connected graph to determine the graph size in finite time, if an upper bound on the graph size is provided. The algorithm consists in the iterative aggregation of information in local hubs which then broadcast it throughout the whole graph. The proposed node-counting algorithm is on average more efficient in terms of node memory and communication cost than its previous deterministic counterpart for node counting, and appears comparable or more efficient in terms of average-case time complexity. As well as node counting, the algorithm is more broadly applicable to problems such as summation over graphs, quorum sensing, and spontaneous hierarchy creation.

Surface Engineered PLGA Nanoparticle for Threshold Responsive Glucose Monitoring and "Self-Programmed" Insulin Delivery.

We have developed a reversible, biocompatible, "self-programmed" PLGA [poly(lactic-co-glycolic acid)] nanoparticle-based optical biosensor capable of sensing and continuous monitoring of glucose above the physiologically relevant threshold value (100-125 mg/dL) as well as "on-demand" insulin delivery via an "On-Off" technique. We have carefully surface engineered the PLGA nanoparticle using amino dextran-fluorescein (A-DexFl) and amino-phenyl boronic acid (A-PBA) to exploit the binding affinity of boronic acids with that of cis-1,2 diols of dextran/glucose. Initially, the dextran chains wrap the nanoparticle surface due to its high affinity toward A-PBA (Kb = 6.1 × 106 M-1). The close proximity of the fluorophores with that of A-PBA quenches the fluorescence, resulting in an "Off" state. On the addition of glucose, it competes with A-DexFl to bind with A-PBA. Above a certain threshold concentration of glucose, the binding affinity overcomes (Kb = 6.3 × 107 M-1) the dextran-A-PBA binding. This opens-up the wrapped A-DexFl chains from the nanoparticle surface and results in an increased distance between the fluorophore and A-PBA, triggering the "On" state. The activation of the On-Off state can be finely tuned in the desired range of physiologically relevant glucose concentrations by varying the ligand ratios on the PLGA surface. The nanoparticle core has also been used as an insulin reservoir to trigger the drug release in the "On" state. We have obtained ∼53% encapsulation efficiency and ∼20% loading efficiency for insulin loading. Once the glucose concentration falls beyond the detection range, the dextran chains collapse on the nanoparticle surface with a suspension in drug release. The process is solely controlled by the competition and multivalent binding affinity between glucose, A-DexFl, and A-PBA, which allows it to be "self-programmed" and "self-regulated" with continuous monitoring up to 8-10 cycles over a 72 h time period. A sustained drug release has been found with ∼70% of released drug over a period of 72 h, although this release is insignificant in the absence of glucose. Several control experiments have been performed to optimize the sensor design.

Physicochemical and functional characterization of trastuzumab-dkst, a trastuzumab biosimilar.

Aims: Preclinical comparative similarity studies of trastuzumab-dkst, a Herceptin® biosimilar, are reported. Materials & methods: Primary sequence and higher order structure and pharmacological mechanisms of action were compared using multiple techniques. Pharmacokinetics and repeat-dose toxicity were assessed in cynomolgus monkeys. Results: Primary structures were identical; secondary and tertiary structures were highly similar. Non-significant differences were observed for charge heterogeneity. Twelve of 13 glycan species were highly similar, with slightly higher total mannose levels in trastuzumab-dkst. FcγR and FcRn binding activity was highly similar. Each drug equally inhibited HER2+ cell proliferation, demonstrating equivalent relative potency in mediating HER2+ cell cytolysis by antibody-dependent cellular cytotoxicity. Pharmacokinetic and toxicological profiles in cynomolgus monkeys were similar. Conclusion: Trastuzumab-dkst, US-licensed trastuzumab and EU-approved trastuzumab demonstrate high structural and functional similarity.

When less is more: Robot swarms adapt better to changes with constrained communication.

To effectively perform collective monitoring of dynamic environments, a robot swarm needs to adapt to changes by processing the latest information and discarding outdated beliefs. We show that in a swarm composed of robots relying on local sensing, adaptation is better achieved if the robots have a shorter rather than longer communication range. This result is in contrast with the widespread belief that more communication links always improve the information exchange on a network. We tasked robots with reaching agreement on the best option currently available in their operating environment. We propose a variety of behaviors composed of reactive rules to process environmental and social information. Our study focuses on simple behaviors based on the voter model-a well-known minimal protocol to regulate social interactions-that can be implemented in minimalistic machines. Although different from each other, all behaviors confirm the general result: The ability of the swarm to adapt improves when robots have fewer communication links. The average number of links per robot reduces when the individual communication range or the robot density decreases. The analysis of the swarm dynamics via mean-field models suggests that our results generalize to other systems based on the voter model. Model predictions are confirmed by results of multiagent simulations and experiments with 50 Kilobot robots. Limiting the communication to a local neighborhood is a cheap decentralized solution to allow robot swarms to adapt to previously unknown information that is locally observed by a minority of the robots.

Complexity and irreducibility of dynamics on networks of networks.

We study numerically the dynamics of a network of all-to-all-coupled, identical sub-networks consisting of diffusively coupled, non-identical FitzHugh-Nagumo oscillators. For a large range of within- and between-network couplings, the network exhibits a variety of dynamical behaviors, previously described for single, uncoupled networks. We identify a region in parameter space in which the interplay of within- and between-network couplings allows for a richer dynamical behavior than can be observed for a single sub-network. Adjoining this atypical region, our network of networks exhibits transitions to multistability. We elucidate bifurcations governing the transitions between the various dynamics when crossing this region and discuss how varying the couplings affects the effective structure of our network of networks. Our findings indicate that reducing a network of networks to a single (but bigger) network might not be accurate enough to properly understand the complexity of its dynamics.

Riddled basins of attraction in systems exhibiting extreme events.

Using a system of two FitzHugh-Nagumo units, we demonstrate the occurrence of riddled basins of attraction in delay-coupled systems as the coupling between the units is increased. We characterize riddled basins using the uncertainty exponent which is a measure of the dimensions of the basin boundary. Additionally, we show that the phase space can be partitioned into pure and mixed regions, where initial conditions in the pure regions certainly avoid the generation of extreme events, while initial conditions in the mixed region may or may not exhibit such events. This implies that any tiny perturbation of initial conditions in the mixed region could yield the emergence of extreme events because the latter state possesses a riddled basin of attraction.

Correction: T cell activation and differentiation is modulated by a CD6 domain 1 antibody Itolizumab.

[This corrects the article DOI: 10.1371/journal.pone.0180088.].

Extreme events in FitzHugh-Nagumo oscillators coupled with two time delays.

We study two identical FitzHugh-Nagumo oscillators which are coupled with one or two different time delays. If only a single-delay coupling is used, the length of the delay determines whether the synchronization manifold is transversally stable or unstable, exhibiting mixed-mode or chaotic oscillations in which the small amplitude oscillations are always in phase but the large amplitude oscillations are in phase or out of phase, respectively. For two delays we find an intricate dynamics which comprises an irregular alteration of small amplitude oscillations, in-phase and out-of-phase large amplitude oscillations, also called extreme events. This transient chaotic dynamics is sandwiched between a bubbling transition and a blowout bifurcation.

T cell activation and differentiation is modulated by a CD6 domain 1 antibody Itolizumab.

CD6 is associated with T-cell modulation and is implicated in several autoimmune diseases. We previously demonstrated that Itolizumab, a CD6 domain 1 (CD6D1) specific humanized monoclonal antibody, inhibited the proliferation and cytokine production by T lymphocytes stimulated with anti-CD3 antibody or when co-stimulated with ALCAM. Aberrant IL-17 producing CD4+ helper T-cells (Th17) have been identified as pivotal for the pathogenesis of certain inflammatory autoimmune disorders, including psoriasis. Itolizumab has demonstrated efficacy in human diseases known to have an IL-17 driven pathogenesis. Here, in in vitro experiments we show that by day 3 of human PBMC activation using anti-CD3 and anti-CD28 co-stimulation in a Th17 polarizing milieu, 15-35% of CD4+ T-cells overexpress CD6 and there is an establishment of differentiated Th17 cells. Addition of Itolizumab reduces the activation and differentiation of T cells to Th17 cells and decreases production of IL-17. These effects are associated with the reduction of key transcription factors pSTAT3 and RORγT. Further, transcription analysis studies in these conditions indicate that Itolizumab suppressed T cell activation by primarily reducing cell cycle, DNA transcription and translation associated genes. To understand the mechanism of this inhibition, we evaluated the effect of this anti-human CD6D1 mAb on ALCAM-CD6 as well as TCR-mediated T cell activation. We show that Itolizumab but not its F(ab')2 fragment directly inhibits CD6 receptor hyper-phosphorylation and leads to subsequent decrease in associated ZAP70 kinase and docking protein SLP76. Since Itolizumab binds to CD6 expressed only on human and chimpanzee, we developed an antibody binding specifically to mouse CD6D1. This antibody successfully ameliorated the incidence of experimental autoimmune encephalitis in the mice model. These results position CD6 as a key molecule in sustaining the activation and differentiation of T cells and an important target for modulating autoimmune diseases.

Surface-Engineered Multifunctional Eu:Gd2O3 Nanoplates for Targeted and pH-Responsive Drug Delivery and Imaging Applications.

In this paper, we report the synthesis of surface-engineered multifunctional Eu:Gd2O3 triangular nanoplates with small size and uniform shape via a high-temperature solvothermal technique. Surface engineering has been performed by a one-step polyacrylate coating, followed by controlled conjugation chemistry. This creates the desired number of surface functional groups that can be used to attach folic acid as a targeting ligand on the nanoparticle surface. To specifically deliver the drug molecules in the nucleus, the folate density on the nanoparticle surface has been kept low. We have also modified the drug molecules with terminal double bond and ester linkage for the easy conjugation of nanoparticles. The nanoparticle surface was further modified with free thiols to specifically attach the modified drug molecules with a pH-responsive feature. High drug loading has been encountered for both hydrophilic drug daunorubicin (∼69% loading) and hydrophobic drug curcumin (∼75% loading) with excellent pH-responsive drug release. These nanoparticles have also been used as imaging probes in fluorescence imaging. Some preliminary experiments to evaluate their application in magnetic resonance imaging have also been explored. A detailed fluorescence imaging study has confirmed the efficient delivery of drugs to the nuclei of cancer cells with a high cytotoxic effect. Synthesized surface-engineered nanomaterials having small hydrodynamic size, excellent colloidal stability, and high drug-loading capacity, along with targeted and pH-responsive delivery of dual drugs to the cancer cells, will be potential nanobiomaterials for various biomedical applications.

Unraveling the Interaction of Silver Nanoparticles with Mammalian and Bacterial DNA.

The focus of this study was to understand and unravel the interaction of silver nanoparticles (AgNPs) with different types of Deoxyribonucleic acid (DNA), mammalian and bacterial, having different base pair compositions. Binding of spherical silver nanoparticles (AgNPs) to Calf thymus (CT) DNA, Escherichia coli (EC) DNA and Micrococcus lysodeikticus (ML) DNA has been studied to gain insights into their mode of interaction and specificity. Interaction of AgNPs with synthetic DNA has also been carried out. On the basis of absorption, thermal melting, isothermal calorimetry and viscosity studies, we could establish the mode of binding and specificity of the synthesized silver nanoparticles with mammalian and bacterial DNA. Thermal melting (Tm) studies indicated a decrease in the Tm of all the DNAs, confirming the destabilization of DNA stacks on interaction with AgNPs. Comparative interaction studies with single stranded (ss) and double stranded (ds) DNAs further confirmed the specificity of the particles toward ds DNA. On the basis of the results we could confirm that the synthesized AgNPs could be used for selective detection of DNA through their DNA binding mechanism. In addition, the AgNPs-DNA complexes exhibited distinct differences in the SERS spectra making it an interesting SERS platform for identifying ds DNA. The optical and physical properties of AgNPs help in differentiating the DNAs of different base pair compositions through their binding affinity and specificity.

Hydrogen Sulfide--Mechanisms of Toxicity and Development of an Antidote.

Hydrogen sulfide is a highly toxic gas-second only to carbon monoxide as a cause of inhalational deaths. Its mechanism of toxicity is only partially known, and no specific therapy exists for sulfide poisoning. We show in several cell types, including human inducible pluripotent stem cell (hiPSC)-derived neurons, that sulfide inhibited complex IV of the mitochondrial respiratory chain and induced apoptosis. Sulfide increased hydroxyl radical production in isolated mouse heart mitochondria and F2-isoprostanes in brains and hearts of mice. The vitamin B12 analog cobinamide reversed the cellular toxicity of sulfide, and rescued Drosophila melanogaster and mice from lethal exposures of hydrogen sulfide gas. Cobinamide worked through two distinct mechanisms: direct reversal of complex IV inhibition and neutralization of sulfide-generated reactive oxygen species. We conclude that sulfide produces a high degree of oxidative stress in cells and tissues, and that cobinamide has promise as a first specific treatment for sulfide poisoning.

Critical Role of Glucose Metabolism in Rheumatoid Arthritis Fibroblast-like Synoviocytes.

OBJECTIVE: Up-regulation of glucose metabolism has been implicated not only in tumor cell growth but also in immune cells upon activation. However, little is known about the metabolite profile in rheumatoid arthritis (RA), particularly in fibroblast-like synoviocytes (FLS). This study was undertaken to evaluate whether changes in glucose metabolism in RA FLS could play a role in inflammation and joint damage. METHODS: Synovium and FLS were obtained from patients with RA and patients with osteoarthritis (OA). The rate of glycolysis after stimulation of FLS with lipopolysaccharide and platelet-derived growth factor BB was measured using glycolysis stress test technology. FLS function was evaluated using a glycolysis inhibitor, 2-deoxy-d-glucose (2-DG). After stimulation of the FLS, a migration scratch assay, MTT assay, and enzyme-linked immunosorbent assay were performed to measure the effect of 2-DG on FLS migration, viability of the FLS, and cytokine secretion, respectively. IRDye 800CW 2-DG was used to assess glucose uptake in the arthritic joints and stromal cells of mice after K/BxN mouse serum transfer. The mice were injected daily, intraperitoneally, with 3-bromopyruvate (BrPa; 5 mg/kg) to assess the effect of inhibition of glycolysis in vivo. RESULTS: Compared to human OA FLS, the balance between glycolysis and oxidative phosphorylation was shifted toward glycolysis in RA FLS. Glucose transporter 1 (GLUT1) messenger RNA (mRNA) expression correlated with baseline functions of the RA FLS. Glucose deprivation or incubation of the FLS with glycolytic inhibitors impaired cytokine secretion and decreased the rate of proliferation and migration of the cells. In a mouse model of inflammatory arthritis, GLUT1 mRNA expression in the synovial lining cells was observed, and increased levels of glucose uptake and glycolytic gene expression were detected in the stromal compartment of the arthritic mouse joints. Inhibition of glycolysis by BrPa, administered in vivo, significantly decreased the severity of arthritis in this mouse model. CONCLUSION: Targeting metabolic pathways is a novel approach to understanding the mechanisms of disease. Inhibition of glycolysis may directly modulate synoviocyte-mediated inflammatory functions and could be an effective treatment strategy for arthritis.

Surface modified multifunctional ZnFe2O4 nanoparticles for hydrophobic and hydrophilic anti-cancer drug molecule loading.

Multifunctional ZnFe2O4 nanoparticles were successfully synthesized via thermolysis of Fe-oleate and Zn-oleate precursors. Monodisperse, single phase ZnFe2O4 nanoparticles with an average particle size of ∼22 nm, exhibiting green emission (λmax∼ 480 nm) and ferromagnetism at room temperature (saturation magnetization of 48.46 emu gm(-1)) have been formed by this novel approach. By appropriate surface functionalization, these materials have been converted into smart carriers of hydrophobic (water insoluble) drug molecule-curcumin and hydrophilic (water soluble) drug molecule-daunorubicin. The in vitro cytotoxicity of both the hydrophobic and hydrophilic drug loaded ZnFe2O4 nanoparticles was studied using the conventional MTT assay which revealed that the drug loaded nanoparticles induce significant death of the carcinoma cells (HeLa). Interestingly, this appears to be a significant development towards the capability of surface functionalized multifunctional ZnFe2O4 nanoparticles as carriers for both water soluble and insoluble drugs for anti-cancer therapy.