Evidence linking the association of periodontal viruses and pentraxins in periodontitis patients with coronary artery disease.

BACKGROUND: Although there is ample evidence in the literature supporting a significant positive association between key periodontal pathogens and established inflammatory markers of periodontitis and coronary artery disease (CAD), their exact role remain unclear. Especially, the role of viruses in the etiology and specific biomarkers have not been validated. Thus, the current study aims to evaluate the role of periodontal viruses such as Epstein-Barr virus (EBV), cytomegalovirus (CMV), and herpes simplex virus (HSV), as well as the inflammatory marker pentraxin-3 (PTX3), and to analyze their association with CAD. METHODS: The study included 240 patients divided into four groups of 60 patients each: nonperiodontitis + noncardiac (NP+NC) group, periodontitis + noncardiac patients (P+NC) group, nonperiodontitis + cardiac patients (NP+C) group, and periodontitis + cardiac (P+C) group. The cardiac surgery group (C-S) was a subgroup of NP+C and P+C. It consisted of 60 patients from the abovementioned two cardiac groups in whom coronary artery bypass graft (CABG) was indicated. Demographic variables, cardiac parameters, and periodontal parameters were recorded. The viruses (EBV, CMV, and HSV) and the inflammatory marker PTX3 were evaluated in the subgingival plaque samples of all the four groups and atheromatous plaque samples of the C-S using reverse transcriptase-polymerase chain reaction (RT-PCR) and quantitative polymerase chain reaction (qPCR), respectively, and were compared between the groups. The results were obtained and statistically analyzed. RESULTS: The demographic variables did not differ significantly between the groups, except for age. Systolic blood pressure, diastolic blood pressure, low-density lipoprotein, and random blood sugar were significantly higher in NP+C and P+C, whereas high-density lipoprotein was significantly lower (p ≤ 0.05) in the same. Plaque index (PI), probing pocket depth (PPD), and clinical attachment level (CAL) were significantly higher (p ≤ 0.05) in P+NC and P+C. PTX were significantly elevated in P+C among the four groups. On evaluating the subgingival plaque samples, EBV and CMV were significantly higher in the two periodontitis groups P+NC and P+C (p = 0.000). HSV was significantly higher in the two cardiac groups (NP+C and P+C) (p ≤ 0.05). Cardiac EBV and CMV were significantly elevated in the P+C group with a p value of 0.004 and 0.033, respectively. Cardiac HSV was found in the NP+C group with statistical insignificance (p = 0.410) between the groups. On correlation, oral PTX were significantly associated with bleeding index (BI), PPD, and CAL (p = 0.000). Similarly, cardiac PTX showed significant association with PI, BI, PPD, and CAL (p = 0.000). Oral and cardiac PTX also showed significant correlation with each other. Multiple logistic regression analysis revealed a significant association between CAL and oral EBV (p ≤ 0.05). Similarly, cardiac EBV showed a significant association with CAL and oral EBV (p ≤ 0.05). Multiple logistic regression analysis also revealed that both cardiac and oral PTX showed a significant association only with oral EBV, CMV, and HSV. CONCLUSION: The results of the current study suggest that the clinical severity of periodontitis (CAL), etiology of periodontitis (EBV and CMV), and inflammatory marker of periodontitis (PTX3) were found to be significantly elevated in CAD. These findings suggests that periodontal diseases may be a risk factor that could influence the progression of CAD.

Intra-femoral tunnel graft lengths less than 20 mm do not predispose to early graft failure, inferior outcomes or poor function. A prospective clinico-radiological comparative study.

PURPOSE: Increasing demands on skills with mounting pressures from expectations from arthroscopic anterior cruciate ligament (ACL) reconstructions requires precise knowledge of technical details by surgeons. One such element is the minimum length of graft in femoral tunnel to allow for adequate tendon-to-bone healing and early return to activities and sports. This has, however, remained an unanswered question. PURPOSE: To study and compare clinico-radiological outcomes of ACL reconstructions in patients with < 20 mm of intra-femoral tunnel graft length with those measuring ≥ 20 mm. METHODS: All eligible patients undergoing arthroscopic ACL reconstruction were sequentially divided into two groups based on the intra-femoral tunnel graft lengths (A: < 20 mm, n = 27; and B: ≥ 20 mm, n = 25). Exclusions were made for those > 45 years of age, with chondral and/or multi-ligamentous injuries and with systemic pathologies. All patients were postoperatively evaluated in clinics by physical examination and functional scoring (Lysholm and modified Cincinnati scores) at 3, 6 and 12-month intervals. Graft vascularity was assessed by signal-to-noise quotient ratio (SNQR) using magnetic resonance imaging (MRI) at 3 and 12 months. RESULTS: No significant differences were noted in mean Lysholm and modified Cincinnati scores between the two groups at the end of 1 year. There were also no significant differences in graft maturation over time and SNQR at 3 and 12 months in the region of interest (ROI). CONCLUSIONS: Intra-femoral tunnel graft length of less than 20 mm does not compromise early clinical and functional outcomes of ACL reconstructions.

Association of pentraxin in periodontitis patients with coronary artery disease.

Objectives: Pentraxin 3 (PTX3) is a biomarker, associated with the pathogenesis of Periodontitis and coronary artery disease (CAD) individually, but their role in patients with both diseases remains unclear. The current study aims to evaluate the association of PTX in patients with concomitant periodontitis and CAD. Materials and Methods: In a case-control study, 240 participants were selected and divided into four groups. Nonperiodontitis + noncardiac = 60 patients, periodontitis + noncardiac (P + NC) = 60 patients, nonperiodontitis + cardiac (NP + C) = 60 patients, periodontitis + cardiac (P + C) = 60 patients. Demographic variables, cardiac and periodontal parameters were recorded. PTX was evaluated in the subgingival plaque and atheromatous plaque samples using real-time quantitative polymerase chain reaction and compared between the groups. The results were statistically analyzed. Results: Among the demographic variables, age showed a significant difference between the groups. Systolic and diastolic blood pressure, low-density lipoprotein, and random blood sugar were significantly higher in NP + C and P + C groups (P ≤ 0.05). The plaque index, probing pocket depth, and clinical attachment loss were significantly higher in P + NC and P + C groups (P ≤ 0.05). PTX was significantly elevated in P + C group (P = 0.000). Pearson's correlation revealed a significant correlation between the periodontal parameters and PTX in both the cardiac and oral samples. Conclusion: PTX3 levels were elevated in CAD patients with periodontitis suggesting the influence of periodontal inflammation in the progression of CAD. PTX3 may serve as a diagnostic and prognostic tool for both periodontitis and CAD. This study could provide an understanding and awareness about the potential role of PTX3 in both periodontitis and CAD.

Insights of Extracellular Vesicles of Mesenchymal Stem Cells: a Prospective Cell-Free Regenerative Medicine for Neurodegenerative Disorders.

Mesenchymal stem cells (MSCs) are multipotent, adult stem cells which are found in numerous tissues like the umbilical cord, Wharton's jelly, bone marrow, and adipose tissue. They possess the capacity of self-renewal by dividing and differentiating into various cellular lineages. Their characteristic therapeutic potential exploited so far has made them a desirable candidate in regenerative medicine. Neurodegenerative diseases (NDs) like Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and ischemic stroke have been treated with MSCs and MSC-derived products. Over the past few decades, we have witnessed significant contributions in discovering the etiology of various NDs and their possible therapeutic solutions. One of the MSC-based therapeutics is extracellular vesicles (EVs), which contain multiple biologically active molecules like nucleic acids and proteins. The contents of EVs are ferried between cells for intercellular communication which then leads to regulation of the homeostasis of recipient cells. EVs serve as a considerable means of cell-free therapies like for tissue repair or regeneration as EVs can maintain therapeutically effective cargo of parent cells and are free of various ethical issues in cell-based therapies. Due to paucity of standard protocols in extraction procedures of EVs and their pharmacological properties and mechanisms, the development of new EV dependent therapies is challenging. With this review, an attempt has been made to annotate these mechanisms, which can help advance the novel therapeutic approaches towards the treat and define a more narrowed down approach for each ND to devise effective MSC-based therapies to cure and avert these diseases.

A perspective on the role of uncertainty in sustainability science and engineering.

The Trans-Atlantic Research and Development Interchange on Sustainability Workshop (TARDIS) is a meeting on scientific topics related to sustainability. The 2019 workshop theme was "On the Role of Uncertainty in Managing the Earth for Global Sustainability." This paper presents the perspectives on this topic derived from talks and discussions at the 2019 TARDIS workshop. There are four kinds of uncertainties encountered in sustainability ranging from clear enough futures to true surprises. The current state-of-the-art in assessing and mitigating these uncertainties is discussed.

PRP versus steroids in a deadlock for efficacy: long-term stability versus short-term intensity-results from a randomised trial.

PURPOSE: A popular choice for lateral epicondylitis (LE), corticosteroid injections have been associated with prominent side effects, which has led to the conception of modalities like platelet-rich plasma (PRP). This randomised trial aimed to evaluate and compare the 6-week, 3-month and 1-year outcomes with PRP and corticosteroid injections in LE. We hypothesised that PRP would prove more effective in relieving pain and improving function. METHODS: At the sports medicine unit of our tertiary care teaching centre, 80 patients with LE were randomised into either receiving PRP (group A) or corticosteroids (group B) injections. Pre-injection visual analogue scale (VAS), disabilities of the arm, shoulder and hand (DASH) score, Mayo elbow performance score (MEPS) and grip strength score (GSS) were recorded. Common extensor origins were identified and infiltrated with 3 ml of either PRP or corticosteroid (triamcinolone in 2% xylocaine) using a peppering technique. Follow-up scores and extent of pain relief were recorded and compared. RESULTS: At 6 weeks, there were greater improvements in group B versus A in mean VAS (13.8 vs. 44.5; p < 0.001), DASH (64.2 vs. 53.3; p < 0.001), MEPS (88.0 vs. 74.5; p = 0.004) and GSS (89.3 vs. 73.4; p = 0.039). These scores showed a reversed pattern at 3 months when group A outcomes superseded group B (VAS p = 0.002; DASH p < 0.001; MEPS p = 0.002; GSS p = 0.045). At 1-year follow-up, group A continued to enjoy better pain relief and function (VAS p = 0.024; DASH p < 0.001; MEPS p = 0.009; GSS p = 0.028). CONCLUSIONS: Albeit corticosteroid injections show good short-term results at 6 weeks, patients receiving PRP injections fare better at 3 and 12 months.

Secretome of Differentiated PC12 Cells Restores the Monocrotophos-Induced Damages in Human Mesenchymal Stem Cells and SHSY-5Y Cells: Role of Autophagy and Mitochondrial Dynamics.

A perturbed cellular homeostasis is a key factor associated with xenobiotic exposure resulting in various ailments. The local cellular microenvironment enriched with secretory components aids in cell-cell communication that restores this homeostasis. Deciphering the underlying mechanism behind this restorative potential of secretome could serve as a possible solution to many health hazards. We, therefore, explored the protective efficacy of the secretome of differentiated PC12 cells with emphasis on induction of autophagy and mitochondrial biogenesis. Monocrotophos (MCP), a widely used neurotoxic organophosphate, was used as the test compound at sublethal concentration. The conditioned medium (CM) of differentiated PC12 cells comprising of their secretome restored the cell viability, oxidative stress and apoptotic cell death in MCP-challenged human mesenchymal stem cells and SHSY-5Y, a human neuroblastoma cell line. Delving further to identify the underlying mechanism of this restorative effect we observed a marked increase in the expression of autophagy markers LC3, Beclin-1, Atg5 and Atg7. Exposure to autophagy inhibitor, 3-methyladenine, led to a reduced expression of these markers with a concomitant increase in the expression of pro-apoptotic caspase-3. Besides that, the increased mitochondrial fission in MCP-exposed cells was balanced with increased fusion in the presence of CM facilitated by AMPK/SIRT1/PGC-1α signaling cascade. Mitochondrial dysfunctions are strongly associated with autophagy activation and as per our findings, cellular secretome too induces autophagy. Therefore, connecting these three potential apices can be a major breakthrough in repair and rescue of xenobiotic-damaged tissues and cells.

Resveratrol Prevents the Cellular Damages Induced by Monocrotophos via PI3K Signaling Pathway in Human Cord Blood Mesenchymal Stem Cells.

The role of resveratrol (RV) as a neuroprotectant is well recognized, and cellular molecules involved in imparting the physiological effect have been well illustrated. However, some ambiguity still prevails as the specific receptor, and downstream signaling molecules are not yet clearly stated. So, we investigated the signaling pathway(s) involved in its cellular protection in the human umbilical cord blood mesenchymal stem cell (hUCB-MSC) derived neuronal cells. The mesenchymal stem cells were exposed to various concentrations (10, 100, 1000 µM) of monocrotophos (MCP), a known developmental neurotoxic organophosphate pesticide, for a period of 24 h. The MAPK signaling pathways (JNK, p38, and ERK) known to be associated with MCP-induced damages were also taken into consideration to identify the potential connection. The biological safe dose of RV (10 µM) shows a significant restoration in the MCP-induced alterations. Under the specific growth conditions, RV exposure was found to promote neuronal differentiation in the hUCB-MSCs. The exposure of cells to a specific pharmacological inhibitor (LY294002) of PI3K confirms the significant involvement of PI3K-mediated pathway in the ameliorative responses of RV against MCP exposure. Our data identifies the substantial role of RV in the restoration of MCP-induced cellular damages, thus proving to have a therapeutic potential against organophosphate pesticide-induced neurodegeneration.

Secretome of Differentiated PC12 Cells Enhances Neuronal Differentiation in Human Mesenchymal Stem Cells Via NGF-Like Mechanism.

The secretome-mediated responses over cellular physiology are well documented. Stem cells have been ruling the field of secretomics and its role in regenerative medicine since the past few years. However, the mechanistic aspects of secretome-mediated responses and the role of other cells in this area remain somewhat elusive. Here, we investigate the effects of secretome-enriched conditioned medium (CM) of neuronally differentiated PC12 cells on the neuronal differentiation of human mesenchymal stem cells (hMSCs). The exposure to CM at a ratio of 1:1 (CM: conditioned medium of PC12 cells) led to neuronal induction in hMSCs. This neuronal induction was compared with a parallel group of cells exposed to nerve growth factor (NGF). There was a marked increase in neurite length and expression of neuronal markers (ß-III tubulin, neurofilament-M (NF-M), synaptophysin, NeuN in exposed hMSCs). Experimental group co-exposed to NGF and CM showed an additive response via MAPK signaling and directed the cells particularly towards cholinergic lineage. The ability of CM to enhance the neuronal properties of stem cells could aid in their rapid differentiation into neuronal subtypes in case of stem cell transplantation for neuronal injuries, thus broadening the scope of non-stem cell-based applications in the area of secretomics.

PKA-GSK3ß and ß-Catenin Signaling Play a Critical Role in Trans-Resveratrol Mediated Neuronal Differentiation in Human Cord Blood Stem Cells.

The role of resveratrol (RV), a natural polyphenol, is well documented, although its role on neurogenesis is still controversial and poorly understood. Therefore, to decipher the cellular insights of RV on neurogenesis, we investigated the potential effects of the compound on the survival, proliferation, and neuronal differentiation of human cord blood-derived mesenchymal stem cells (hCBMSCs). For neuronal differentiation, purified and characterized hCBMSCs were exposed to biological safe doses of RV (10 µM) alone and in combination with nerve growth factor (NGF-50 ng). The cells exposed only to NGF (50 ng/mL) served as positive control for neuronal differentiation. The genes showing significant involvement in the process of neuronal differentiation were further funneled down at transcriptional and translational level. It was observed that RV promotes PKA-mediated neuronal differentiation in hCBMSCs by inducing canonical pathway. The studies with pharmacological inhibitors also confirmed that PKA significantly induces ß-catenin expression via GSK3ß induction and stimulates CREB phosphorylation and pERK1/2 induction. Besides that, the studies also revealed that RV additionally possesses the binding sites for molecules other than PKA and GSK3ß, with which it interacts. The present study therefore highlights the positive impact of RV over the survival, proliferation, and neuronal differentiation in hCBMSCs via PKA-mediated induction of GSK3ß, ß catenin, CREB, and ERK1/2.

A Case of Non-Traumatic Avascular Necrosis of Femur in Case of Transfusion-Dependent Thalassemia.

INTRODUCTION: Avascular necrosis of the head of femur (AVNF) has frequently been reported with sickle cell anemia but is not commonly associated with beta thalassemia. CASE REPORT: We report a case of 14-year-old male with transfusion-dependent thalassemia (TDT) and hepatitis C, who developed bilateral atraumatic AVNF requiring surgical correction. The likely etiopathogenesis and the review of literature for this uncommon finding are discussed. CONCLUSION: AVNF should be considered as a possibility in a patient with TDT presenting with hip pain. Multiple disease and treatment related factors are likely to play a key role in its causation.

An immunological approach of sperm sexing and different methods for identification of X- and Y-chromosome bearing sperm.

Separation of X- and Y-chromosome bearing sperm has been practiced for selection of desired sex of offspring to increase the profit in livestock industries. At present, fluorescence-activated cell sorter is the only successful method for separation of X- and Y-chromosome bearing sperm. This technology is based on the differences in DNA content between these two types of sperm and has been commercialized for bovine sperm. However, this technology still has problems in terms of high economic cost, sperm damage, and lower pregnancy rates compared to unsorted semen. Therefore, an inexpensive, convenient, and non-invasive approach for sperm sexing would be of benefit to agricultural sector. Within this perspective, immunological sperm sexing method is one of the attractive choices to separate X- and Y-chromosome bearing sperm. This article reviews the current knowledge about immunological approaches, viz., H-Y antigen, sex-specific antigens, and differentially expressed proteins for sperm sexing. Moreover, this review also highlighted the different methods for identification of X- and Y-sperm.

Adoptive Autophagy Activation: a Much-Needed Remedy Against Chemical Induced Neurotoxicity/Developmental Neurotoxicity.

The profound significance of autophagy as a cell survival mechanism under conditions of metabolic stress is a well-proven fact. Nearly a decade-long research in this area has led scientists to unearth various roles played by autophagy other than just being an auto cell death mechanism. It is implicated as a vital cell survival pathway for clearance of all the aberrant cellular materials in case of cellular injury, metastasis, disease states, cellular stress, neurodegeneration and so on. In this review, we emphasise the critical role of autophagy in the environmental stressors-induced neurotoxicity and its therapeutic implications for the same. We also attempt to shed some light on the possible protective role of autophagy in developmental neurotoxicity (DNT) which is a rapidly growing health issue of the human population at large and hence a point of rising concern amongst researchers. The intimate association between DNT and neurodegenerative disorders strongly indicates towards adopting autophagy activation as a much-needed remedy for DNT.

Pre-discharge postoperative radiographs after primary total knee replacement : tradition or science?

Consistent evidence exists on the inutility of immediate postoperative radiographs after a total knee replacement (TKR). We hypothesized that eliminating the pre-discharge film would not have any effect on the postoperative patient outcomes. Retrospective analysis of prospectively collected data was performed on 220 knees. Patients undergoing a simple primary TKR operated by 2 surgeons (Surgeon A and B) from January 2013 to July 2015 were divided into 2 groups (Groups 1 and 2 having 112 and 108 knees respectively). While Surgeon A routinely asked for the second postoperative day pre-discharge radiograph, Surgeon B directly performed weight bearing radiographs 6 weeks postoperatively. Greater knee pain was seen in Group 1 (p = 0.01). No changes in rehabilitation protocols based on pre-discharge radiographs, complications, medico-legal issues or revision surgery could be identified in any patient. The quality of the pre-discharge radiographs was adequate in 65 of the 112 knees (58%). A cost reduction of approximately $220 per patient was observed with the exclusion of the pre-discharge film. Eliminating routine inpatient pre-discharge radio-graphs after simple primary TKR does not alter the rehabilitation protocol, identify any of the standard complication or have any medico-legal implications. On the contrary, these films seem to increase postoperative pain and costs.

Binding mode of dihydroquinazolinones with lysozyme and its antifungal activity against Aspergillus species.

Aspergillosis is one of the infectious fungal diseases affecting mainly the immunocompromised patients. The scarcity of the antifungal targets has identified the importance of N-myristoyl transferase (NMT) in the regulation of fungal pathway. The dihydroquinazolinone molecules were designed on the basis of fragments responsible for binding with the target enzyme. The aryl halide, 1(a-g), aryl boronic acid and potassium carbonate were heated together in water and dioxane mixture to yield new CC bond formation in dihydroquinazolinone. The bis(triphenylphosphine)palladium(II) dichloride was used as catalyst for the CC bond formation. The synthesized series were screened for their in vitro antifungal activity against Aspergillus niger and Aspergillus fumigatus. The binding interactions of the active compound with lysozyme were explored using multiple spectroscopic studies. Molecular docking study of dihydroquinazolinones with the enzyme revealed the information regarding various binding forces involved in the interaction.

Effect of surgical mandibular advancement on pharyngeal airway dimensions: a three-dimensional computed tomography study.

The aim of this study was to quantify the changes in pharyngeal airway space (PAS) in patients with a skeletal class II malocclusion managed by bilateral sagittal split ramus osteotomy for mandibular advancement, using three-dimensional (3D) registration. The sample comprised 16 patients (mean age 21.69±2.80 years). Preoperative (T0) and postoperative (T1) computed tomography scans were recorded. Linear, cross-sectional area (CSA), and volumetric parameters of the velopharynx, oropharynx, and hypopharynx were evaluated. Parameters were compared with paired samples t-tests. Highly significant changes in dimension were measured in both sagittal and transverse planes (P<0.001). CSA measurements increased significantly between T0 and T1 (P<0.001). A significant increase in PAS volume was found at T1 compared with T0 (P<0.001). The changes in PAS were quantified using 3D reconstruction. Along the sagittal and transverse planes, the greatest increase was seen in the oropharynx (12.16% and 11.50%, respectively), followed by hypopharynx (11.00% and 9.07%) and velopharynx (8.97% and 6.73%). CSA increased by 41.69%, 34.56%, and 28.81% in the oropharynx, hypopharynx, and velopharynx, respectively. The volumetric increase was greatest in the oropharynx (49.79%) and least in the velopharynx (38.92%). These established quantifications may act as a useful guide for clinicians in the field of dental sleep medicine.

Stem Cells in Neurotoxicology/Developmental Neurotoxicology: Current Scenario and Future Prospects.

Stem cell biology has played a pivotal role in the field of disease modeling, regenerative medicine, and tissue engineering. The scope of stem cell research has been further extended to address the issues associated with toxicity and biosafety. However, its role in the field of neurotoxicity (NT) and the emerging field of developmental neurotoxicity (DNT) is somewhat underrepresented and needs thorough investigation. Several challenges have hindered the progress of NT and DNT studies, and there is a dire need for human-specific high-throughput in vitro system(s) as a tool with better predictivity, reliability, and reproducibility. The unique proliferation and pluripotency of stem cells makes them a tremendous resource for human material, allowing the prediction of drug toxicity and metabolic effects of chemicals. Recognizing the growing importance of NT and DNT and the application of stem cell biology, in this review article, we provide the diversified approaches of stem cell research which can be effectively applied to the NT and DNT studies and provide an update of the recent progress made so far. We further provide a futuristic approach towards novel stem cell-based strategies for NT and DNT testing. We have further discussed the current technologies, role of induced pluripotent stem cells, the application of three-dimensional (3D) cultures and role of stem cell-derived organs in the NT and DNT studies.