Titanium Particles Modulate Lymphocyte and Macrophage Polarization in Peri-Implant Gingival Tissues

Titanium dental implants are one of the modalities to replace missing teeth. The release of titanium particles from the implant’s surface may modulate the immune cells, resulting in implant failure. However, little is known about the immune microenvironment that plays a role in peri-implant inflammation as a consequence of titanium particles. In this study, the peri-implant gingival tissues were collected from patients with failed implants, successful implants and no implants, and then a whole transcriptome analysis was performed. The gene set enrichment analysis confirmed that macrophage M1/M2 polarization and lymphocyte proliferation were differentially expressed between the study groups. The functional clustering and pathway analysis of the differentially expressed genes between the failed implants and successful implants versus no implants revealed that the immune response pathways were the most common in both comparisons, implying the critical role of infiltrating immune cells in the peri-implant tissues. The H&E and IHC staining confirmed the presence of titanium particles and immune cells in the tissue samples, with an increase in the infiltration of lymphocytes and macrophages in the failed implant samples. The in vitro validation showed a significant increase in the level of IL-1β, IL-8 and IL-18 expression by macrophages. Our findings showed evidence that titanium particles modulate lymphocyte and macrophage polarization in peri-implant gingival tissues, which can help in the understanding of the imbalance in osteoblast–osteoclast activity and failure of dental implant osseointegration

Remdesivir and three other drugs for hospitalised patients with COVID-19: final results of the WHO Solidarity randomised trial and updated meta-analyses.

BACKGROUND World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with coronavirus disease 2019 (Covid-19). METHODS We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. RESULTS At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan-Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P = 0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P = 0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P = 0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. CONCLUSIONS These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.)

Synthesis and Biocompatibility Evaluation of PCL Electrospun Membranes Coated with MTA/HA for Potential Application in Dental Pulp Capping

This study aimed to develop polycaprolactone (PCL) electrospun membranes coated with mineral trioxide aggregate/hydroxyapatite (MTA/HA) as a potential material for dental pulp capping. Initially, the PCL membrane was prepared by an electrospinning process, which was further surface coated with MTA (labeled as PCLMTA) and HA (labeled as PCLHA). The physico-chemical characterization of the fabricated membranes was carried out using field emission scanning electron microscopy (FE-SEM)/Energy dispersive X-ray (EDX), X-ray diffraction (XRD), Raman spectroscopy, and contact angle analysis. The biocompatibility of the human dental pulp stem cells (hDPSCs) on the fabricated membranes was checked by XTT assay, and the hDPSCs adhesion and spreading were assessed by FE-SEM and confocal microscopy. The wound healing ability of hDPSCs in response to different electrospun membrane extracts was examined by scratch assay. The surface morphology analysis of the membranes by FE-SEM demonstrated a uniform nanofibrous texture with an average fiber diameter of 594 ± 124 nm for PCL, 517 ± 159 nm for PCLHA, and 490 ± 162 nm for PCLMTA. The elemental analysis of the PCLHA membrane indicated the presence of calcium and phosphorous elements related to HA, whereas the PCLMTA membrane showed the presence of calcium and silicate, related to MTA. The presence of MTA and HA in the PCL membranes was also confirmed by Raman spectroscopy. The water contact analysis demonstrated the hydrophobic nature of the membranes. The results indicated that PCL, PCLHA, and PCLMTA membranes were biocompatible, while PCLMTA exhibited better cell adhesion, spreading, and migration

In vitro immunomodulatory effect of solid versus porous phosphate-based glass microspheres using macrophages

This study aimed to investigate the immunomodulatory effect of two different forms of phosphate-based glass microspheres (solid and porous), on human macrophages. Human THP-1 monocytes were converted to M0 macrophages after being treated with 100 ng/mL phorbol 12-myristate 13-acetate for 48 h. The differentiated cells were analysed for the CD14 marker using flow cytometry. The adhesion, spreading, and viability of M0 macrophages grown directly or indirectly (extracts) at varying concentrations of solid and porous glass microspheres (GMs) were analysed via phase contrast microscopy, confocal microscopy, and XTT assay. The expression of IL-8, IL-1β, IL-6, IL-10, TNF-α, and IL-12p70 cytokines was investigated using flow cytometry. The conversion to M0 macrophages was confirmed by their adherent nature, increased granularity, and CD14 expression. The results showed that both solid and porous GMs or extracts favored the attachment, spreading, and proliferation of macrophages in a comparable manner to cells grown in a normal tissue culture medium. Only the higher concentration of porous GMs (10 mg/mL) changed the morphology of M0 macrophages and increased the expression of IL-1β and IL-8 pro-inflammatory cytokines; this could be related to the fast degradation nature of porous GMs. Of the six cytokines analysed, M0 macrophages grown directly or indirectly with GMs only expressed IL-1β, IL-10, and IL-8. Accordingly, solid microspheres may have advantages as regenerative agents due to their controlled degradation

15-LOX metabolites and angiogenesis: angiostatic effect of 15(S)-HPETE involves induction of apoptosis in adipose endothelial cells

Inflammation is critical in the dysregulated growth of adipose tissue and associated vascular dysfunctions. 15-Lipoxygenase metabolites, important mediators of inflammation in adipose tissue during obese conditions, may contribute to codependence of inflammation and angiogenesis in adipose tissue. We have already reported the pro-angiogenic effect of 15(S)-HETE in adipose tissue. The present study was designed to understand the effect of 15(S)-HPETE, precursor of 15(S)-HETE, on angiogenesis in adipose tissue. Results showed that 15(S)-HPETE exerts an anti-angiogenic effect in adipose tissue. This was evidenced from decreased endothelial sprouting in adipose tissue explants, inhibition of angiogenic phenotype in adipose endothelial cells, decreased production of CD31 and VEGF in endothelial cells treated with 15(S)-HPETE. Further studies to examine the molecular mechanism of anti-angiogenic effect of 15(S)-HPETE showed that it inhibited cell survival signaling molecule Akt and anti-apoptotic Bcl-2 and also activated caspase-3 in adipose endothelial cells. These observations indicate that 15(S)-HPETE exerts its angiostatic effect in adipose tissue by inducing apoptosis of endothelial cells

Adhesive luting to hybrid ceramic and resin composite CAD/CAM Blocks:Er:YAG Laser versus chemical etching and micro-abrasion pretreatment.

PURPOSE: To evaluate the effect of Er:YAG laser on the roughness, surface topography, and bond strength to resin luting cement based on chemical and micro-abrasion pretreatments of different computer-aided design/computer-aided manufacturing materials. METHODS: A polymer-infiltrated-ceramic-network (PICN) material (Vita Enamic, VE), three indirect resin composite (Cerasmart, CS; Shofu HC, SH; Lava Ultimate, LU), and one lithium disilicate ceramic (IPS e.max CAD, EM) blocks were subjected to one of the following pretreatments: no treatment (NC ), Er:YAG etching with one of two powers (either 3 or 6 W), hydrofluoric acid (HF) etching, self-etching ceramic primer (ME), or micro-abrasion (MA). The shear bond strength (SBS) of resin luting cement to pretreated materials was tested. Surface roughness was measured via atomic force microscopy, and surface topography was analyzed via scanning electron microscopy. Two-way analysis of variance, Tukey post-hoc test, and Pearson correlation were applied. RESULTS: Etching EM and VE with HF or the ME resulted in the highest SBS values in their groups (P < 0.05). LU, SH, VE, and CS indicated similar SBS values when treated with 3 W, 6 W, and MA. The highest surface roughness (Sa ) values were obtained for the LU, CS, and VE groups when treated with 6 W, whereas the lowest Sa values were obtained for CS when treated with the ME and EM when treated with the ME or 3 W. Only SH and CS indicated a significant correlation between surface rough ness and bond strength. CONCLUSIONS: Er:YAG laser etching is comparable to micro-abrasion when treating resin composite blocks and may induce fewer surface cracks. HF etching remains the gold standard for the treatment of glass-based ceramics and PICNs

Chrysin inhibits adipogenesis by modulating PPARγ: <i>in silico</i> and <i>in vitro</i> studies

Adipose tissue is the major storage site of lipids and plays a vital role in energy homeostasis. Adipogenesis is a well-regulated process wherein preadipocytes differentiate into adipocytes. It requires the sequential activation of numerous transcription factors, including peroxisome proliferator activated receptor-γ (PPAR-γ). Phytochemicals have been reported to regulate adipogenesis and flavonoids represent the most researched groups of phytochemicals with regard to their effect on adipogenesis. Chrysin is a naturally occurring flavone and is reported to have anti-inflammatory effects in obese conditions. The present study was aimed to examine the effect of chrysin on adipogenesis. In silico Molecular docking, dynamic simulation studies and in vitro cell-based assays showed that chrysin inhibited adipogenesis by modulating key adipogenic transcription factor PPARγ. Enhanced adipogenesis leads to obesity and targeting adipogenesis is potential in regulating adipose tissue development. So, these investigations may provide important information for designing therapeutic interventions to control adiposity. Communicated by Ramaswamy H. Sarma</p

Multi-gene testing in neurological disorders showed an improved diagnostic yield: data from over 1000 Indian patients

Background Neurological disorders are clinically heterogeneous group of disorders and are major causes of disability and death. Several of these disorders are caused due to genetic aberration. A precise and confirmatory diagnosis in the patients in a timely manner is essential for appropriate therapeutic and management strategies. Due to the complexity of the clinical presentations across various neurological disorders, arriving at an accurate diagnosis remains a challenge. Methods We sequenced 1012 unrelated patients from India with suspected neurological disorders, using TruSight One panel. Genetic variations were identified using the Strand NGS software and interpreted using the StrandOmics platform. Results We were able to detect mutations in 197 genes in 405 (40%) cases and 178 mutations were novel. The highest diagnostic rate was observed among patients with muscular dystrophy (64%) followed by leukodystrophy and ataxia (43%, each). In our cohort, 26% of the patients who received definitive diagnosis were primarily referred with complex neurological phenotypes with no suggestive diagnosis. In terms of mutations types, 62.8% were truncating and in addition, 13.4% were structural variants, which are also likely to cause loss of function. Conclusion In our study, we observed an improved performance of multi-gene panel testing, with an overall diagnostic yield of 40%. Furthermore, we show that NGS (next-generation sequencing)-based testing is comprehensive and can detect all types of variants including structural variants. It can be considered as a single-platform genetic test for neurological disorders that can provide a swift and definitive diagnosis in a cost-effective manner

Repurposed Antiviral Drugs for Covid-19 : Interim WHO Solidarity Trial Results

BACKGROUND World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs — remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a — in patients hospitalized with coronavirus disease 2019 (Covid-19). METHODS We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. RESULTS At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan–Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P = 0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P = 0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P = 0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. CONCLUSIONS These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.)Medicine, Faculty ofNon UBCPediatrics, Department ofReviewedFacultyResearche

Abstracts of National Conference on Research and Developments in Material Processing, Modelling and Characterization 2020

This book presents the abstracts of the papers presented to the Online National Conference on Research and Developments in Material Processing, Modelling and Characterization 2020 (RDMPMC-2020) held on 26th and 27th August 2020 organized by the Department of Metallurgical and Materials Science in Association with the Department of Production and Industrial Engineering, National Institute of Technology Jamshedpur, Jharkhand, India. Conference Title: National Conference on Research and Developments in Material Processing, Modelling and Characterization 2020Conference Acronym: RDMPMC-2020Conference Date: 26–27 August 2020Conference Location: Online (Virtual Mode)Conference Organizer: Department of Metallurgical and Materials Engineering, National Institute of Technology JamshedpurCo-organizer: Department of Production and Industrial Engineering, National Institute of Technology Jamshedpur, Jharkhand, IndiaConference Sponsor: TEQIP-