Application of Platelet Rich Fibrin and Osseomold Bone Graft in Different Intrabony Defects – 2 Case Reports

ABSTRACT:    Aims & objectives: The motto behind any periodontal treatment is arrest of periodontal disease and regeneration of lost periodontium. Various treatment strategies have been employed in treatment of intrabony defects, but the best way to obtain regeneration is probably by mimicking the actual occurring events that takes place in the formation of the periodontal tissues at embryonic stage. Conventional open flap debridement falls short of regenerating tissues destroyed by the disease and current regenerative procedures offer a limited potential towards attaining complete periodontal regeneration.Platelet rich fibrin (PRF), a second generation platelet concentrate is widely used in osseous regeneration.Case description: The present study aimed to explore the clinical and radiographical effectiveness of autologous PRF along with the osseomold bone graft in treatment of 2 different cases of intrabony defects in chronic periodontics subjects.Conclusion: Among the 2 subjects, case-1 had 2-wall defect and case-2 patient had 3-wall defect. Both the subjects reported to the department with a complaint of food impaction and with clinically accessible >7-8mm pocket.  Pocket depth was assessed at 1st week, 6months and 9months respectively and radio graphically bone gain was accessed at 3 month and 6 months

The causes of bacterial bloodstream infections and antimicrobial resistance patterns in children attending a secondary care hospital in Bhaktapur, Nepal, 2017–2022: a retrospective study

Objectives: Data on antimicrobial resistance (AMR) among children in Nepal are limited. Here we have characterized the causes of bacterial bloodstream infections (BSIs), antimicrobial resistance patterns and the mechanisms of β-lactamase production in Enterobacterales among children attending outpatient and inpatient departments of a secondary care paediatric hospital in Nepal. Methods: We retrospectively collected demographic and clinical data of culture-proven bacterial BSIs between January 2017 and December 2022 among children <18 years attending a 50-bedded paediatric hospital. Stored isolates were subcultured for antimicrobial susceptibility testing against commonly used antimicrobials. Enterobacterales displaying non-susceptibility to β-lactams were phenotypically and genotypically investigated for ESBLs, plasmid-mediated AmpC (pAmpC) β-lactamases and carbapenemases. Results: A total of 377 significant bacteria were isolated from 27 366 blood cultures. Among 91 neonates with a BSI, Klebsiella pneumoniae (n = 39, 42.4%), Pseudomonas aeruginosa (n = 15, 16.3%) and Acinetobacter baumannii complex (n = 13, 14.1%) were most common. In the non-neonates, 275/285 (96.5%) infections were community-acquired including Staphylococcus aureus (n = 89, 32.4%), Salmonella Typhi (n = 54, 19.6%) and Streptococcus pneumoniae (n = 32, 11.6%). Among the 98 S. aureus, 29 (29.6%) were methicillin-resistant Staphylococcus aureus. K. pneumoniae and Escherichia coli demonstrated non-susceptibility to extended-spectrum cephalosporins and carbapenems in both community and hospital-acquired cases. For E. coli and K. pneumoniae, blaCTX-M (45/46), blaEBC (7/10) and blaOXA-48 (5/6) were common among their respective groups. Conclusions: We determined significant levels of AMR among children attending a secondary care paediatric hospital with BSI in Nepal. Nationwide surveillance and implementation of antimicrobial stewardship policies are needed to combat the challenge imposed by AMR

Induced pluripotent stem cells and promises of neuroregenerative medicine

First created in 2006 from adult somatic cells by a simple molecular genetic trick, induced pluripotent stem cells (iPS) system is the latest platform in stem cell research. Induced pluripotent stem cells are produced by nuclear reprogramming technology and they resemble embryonic stem cells (ES) in key elements; they possess the potentiality to differentiate into any type of cell in the body. More importantly, the iPS platform has distinct advantage over ES system in the sense that iPS-derived cells are autologous and therefore the iPS-derived transplantation does not require immunosuppressive therapy. In addition, iPS research obviates the political and ethical quandary associated with embryo destruction and ES research. This remarkable discovery of cellular plasticity has important medical implications. This brief review summarizes currently available stem cell platforms, with emphasis on cellular reprogramming and iPS technology and its application in disease modeling and cell replacement therapy in neurodegenerative diseases

Gingival Vitiligo: Report of a Case and Review of the Literature

Rarely cases have been reported regarding depigmented lesions of the oral cavity. On reviewing the literature, only few cases of gingival vitiligo or similar lesions have been reported till date. These lesions pose a cosmetic challenge. We present here a case of vitiligo affecting gingiva. Vitiligo has been defined as an acquired, slowly progressive loss of cutaneous pigment which occurs as irregular, sharply defined patches which may or may not be surrounded by macroscopic hyperpigmentation. Differential diagnosis, detailed clinical history, histopathology, immunohistochemistry, and pathogenesis of this condition are discussed

Association of Interleukin-17 polymorphism (-197G/A) in chronic and localized aggressive periodontitis

Abstract Interleukin 17(IL-17) is a pro-inflammatory cytokine produced mainly by Th17 cells. The present study was undertaken to investigate a possible association between IL-17 A genetic polymorphism at (-197A/G) and susceptibility to chronic and localized aggressive periodontitis (LAgP) in an Indian population. The study was carried out on 105 subjects, which included 35 LAgP patients, 35 chronic periodontitis patients and 35 healthy controls. Blood samples were drawn from the subjects and analyzed for IL-17 genetic polymorphism at (-197A/G), by using the polymerase chain reaction-restriction fragment length polymorphism method. A statistically significant difference was seen in the genotype distribution among chronic periodontitis patients, LAgP patients and healthy subjects. There was a significant difference in the distribution of alleles among chronic periodontitis patients, LAgP patients and healthy subjects. The odds ratio for A allele versus G allele was 5.1 between chronic periodontitis patients and healthy controls, and 5.1 between LAgp patients and healthy controls. Our study concluded that IL-17 A gene polymorphism at (-197A/G) is linked to chronic periodontitis and LAgP in Indian population. The presence of allele A in the IL-17 gene polymorphism (-197A/G) can be considered a risk factor for chronic periodontitis and LAgP

Prevalence of archaea in chronic periodontitis patients in an Indian population

Aim: The aim of this study was to investigate the prevalence of archaea in the subgingival crevices of patients with chronic periodontitis in an Indian population. Materials and Methods: Thirty four chronic periodontitis patients and 16 healthy subjects were included in the study. Thirty four subgingival plaque samples were collected from chronic periodontitis patients, of which 17 samples were from deep pockets and 17 were from shallow pockets. Sixteen subgingival plaque samples were collected from healthy subjects. The presence of archaea in plaque samples was detected by polymerase chain reaction. Results: Prevalence of archaea in chronic periodontitis patients was 29.4% and in healthy subjects was 11.8%, which was not a statistically significant difference. However, prevalence of archaea, in deep periodontal pockets was 47.1%, in shallow periodontal pockets was 11.8% and in healthy sulcus was 12.5%, respectively. Thus, showing a statistically significant difference between prevalence of archaea in deep periodontal pockets (47.1%) and healthy sulcus (12.5%) and also between deep periodontal pockets (47.1%) and shallow pockets (11.8%), respectively. Conclusion: Archaea were detected commonly in severe periodontitis suggesting that these microorganisms might be involved in the pathogenesis of periodontal diseases

Evaluation of efficacy of oral administration of pro-drug of triptolide against pancreatic cancer

296 Background: Pancreatic cancer is an aggressive disease. The current chemotherapy only marginally increases the survival of patients with PDAC. Hence there is an urgent need for novel therapies. We have shown that minnelide, a pro-drug of triptolide which is currently in phase I trials, when administered intra-peritoneally is very effective against pancreatic cancer in multiple animal models. In the current study we evaluated the efficacy of oral minnelide against pancreatic cancer, alone or in combination with standard therapy in PDAC. Methods: Xenograft, subcutaneous and orthotopic models were established using S2-VP10 and MIA PaCa-2 cell lines. Minnelide was used in doses ranging from 0.15-0.6 mg/kg/day either oral or i.p. and standard chemotherapy was gemcitabine 250 mg/kg/week + nab-paclitaxel 25 mg/kg/week. The tumor burden was compared between various treatment groups. Results: Minnelide i.p significantly decreased tumor mass in MIA PaCa-2 derived tumors and oral administration had equipotent effects. In the S2-VP10 model, combination of low doses of orally administered minnelide with gemcitabine + nab-paclitaxel was significantly more effective in decreasing the tumor burden leading to an increased survival of tumor bearing mice when compared with either therapy alone (p < 0.05). Combination therapy significantly reduced cancer-related morbidity by decreasing ascites and metastasis. Conclusions: Oral administration of minnelide is effective against pancreatic cancer at doses which have been shown to be safe in phase I clinical trial. Oral minnelide has great potential to emerge as novel therapy for pancreatic cancer

NFκB-Mediated Invasiveness in CD133 + Pancreatic TICs Is Regulated by Autocrine and Paracrine Activation of IL1 Signaling

Tumor-initiating cells (TIC) have been implicated in pancreatic tumor initiation, progression, and metastasis. Among different markers that define this cell population within the tumor, the CD133 cancer stem cell (CSC) population has reliably been described in these processes. CD133 expression has also been shown to functionally promote metastasis through NF-κB activation in this population, but the mechanism is unclear. In the current study, overexpression of CD133 increased expression and secretion of IL1β (IL1B), which activates an autocrine signaling loop that upregulates NF-κB signaling, epithelial-mesenchymal transition (EMT), and cellular invasion. This signaling pathway also induces CXCR4 expression, which in turn is instrumental in imparting an invasive phenotype to these cells. In addition to the autocrine signaling of the CD133 secreted IL1β, the tumor-associated macrophages (TAM) also produced IL1β, which further activated this pathway in TICs. The functional significance of the TIC marker CD133 has remained elusive for a very long time; the current study takes us one step closer to understanding how the downstream signaling pathways in these cells regulate the functional properties of TICs. This study demonstrates the important role of tumor- and macrophage-derived IL1β stimulation in pancreatic cancer. IL1 signaling is increased in cells with CD133 expression, leading to increased NF-kB activity, EMT induction, and invasion. Increased invasiveness via IL1β stimulation is mediated by the upregulation of CXCR4 expression. The study highlights the importance of IL1-mediated signaling in TICs.

Comparative accuracy of prognostic models for short-term mortality in acute-on-chronic liver failure patients: CAP-ACLF

Background: Multiple predictive models of mortality exist for acute-on-chronic liver failure (ACLF) patients that often create confusion during decision-making. We studied the natural history and evaluated the performance of prognostic models in ACLF patients.Methods: Prospectively collected data of ACLF patients from APASL-ACLF Research Consortium (AARC) was analyzed for 30-day outcomes. The models evaluated at days 0, 4, and 7 of presentation for 30-day mortality were: AARC (model and score), CLIF-C (ACLF score, and OF score), NACSELD-ACLF (model and binary), SOFA, APACHE-II, MELD, MELD-Lactate, and CTP. Evaluation parameters were discrimination (c-indices), calibration [accuracy, sensitivity, specificity, and positive/negative predictive values (PPV/NPV)], Akaike/Bayesian Information Criteria (AIC/BIC), Nagelkerke-R2, relative prediction errors, and odds ratios.Results: Thirty-day survival of the cohort (n = 2864) was 64.9% and was lowest for final-AARC-grade-III (32.8%) ACLF. Performance parameters of all models were best at day 7 than at day 4 or day 0 (p \u3c 0.05 for C-indices of all models except NACSELD-ACLF). On comparison, day-7 AARC model had the numerically highest c-index 0.872, best accuracy 84.0%, PPV 87.8%, R2 0.609 and lower prediction errors by 10-50%. Day-7 NACSELD-ACLF-binary was the simple model (minimum AIC/BIC 12/17) with the highest odds (8.859) and sensitivity (100%) but with a lower PPV (70%) for mortality. Patients with day-7 AARC score \u3e 12 had the lowest 30-day survival (5.7%).Conclusions: APASL-ACLF is often a progressive disease, and models assessed up to day 7 of presentation reliably predict 30-day mortality. Day-7 AARC model is a statistically robust tool for classifying risk of death and accurately predicting 30-day outcomes with relatively lower prediction errors. Day-7 AARC score \u3e 12 may be used as a futility criterion in APASL-ACLF patients