Mycobacterial biofilms: Understanding the genetic factors playing significant role in pathogenesis, resistance and diagnosis.

Even though the genus Mycobacterium is a diverse group consisting of a majority of environmental bacteria known as non-tuberculous mycobacteria (NTM), it also contains some of the deadliest pathogens (Mycobacterium tuberculosis) in history associated with chronic disease called tuberculosis (TB). Formation of biofilm is one of the unique strategies employed by mycobacteria to enhance their ability to survive in hostile conditions. Biofilm formation by Mycobacterium species is an emerging area of research with significant implications for understanding its pathogenesis and treatment of related infections, specifically TB. This review provides an overview of the biofilm-forming abilities of different species of Mycobacterium and the genetic factors influencing biofilm formation with a detailed focus on M. tuberculosis. Biofilm-mediated resistance is a significant challenge as it can limit antibiotic penetration and promote the survival of dormant mycobacterial cells. Key genetic factors promoting biofilm formation have been explored such as the mmpL genes involved in lipid transport and cell wall integrity as well as the groEL gene essential for mature biofilm formation. Additionally, biofilm-mediated antibiotic resistance and pathogenesis highlighting the specific niches, sites of infection along with the possible mechanisms of biofilm dissemination have been discussed. Furthermore, drug targets within mycobacterial biofilm and their role as potential biomarkers in the development of rapid diagnostic tools have been highlighted. The review summarises the current understanding of the complex nature of Mycobacterium biofilm and its clinical implications, paving the way for advancements in the field of disease diagnosis, management and treatment against its multi-drug resistant species.

Facile green synthesis of silver nanoparticles derived from the medicinal plant Clerodendrum serratum and its biological activity against Mycobacterium species.

The emergence of multidrug-resistant mycobacterial strains is a significant crisis that has led to higher treatment failure rates and more toxic and expensive medications for tuberculosis (TB). The urgent need to develop novel therapeutics has galvanized research interest towards developing alternative antimicrobials such as silver nanoparticles (AgNPs). The current study focused on the anti-mycobacterial activity of green-synthesized AgNPs and its polyethylene glycol encapsulated derivative (PEG-AgNPs) with improved stability using the leaves extract of Clerodendrum serratum. Different characterization methods were used to analyze them. DLS analysis revealed a lower polydispersity index of PEG-AgNPs, suggesting a more uniform size distribution than that of AgNPs. The HR-TEM results revealed that the AgNPs and PEG-AgNPs have predominantly spherical shapes in the size range of 9-35 nm and 15-60 nm, respectively, while positive values of Zeta potential indicate their stability. FTIR-ATR analysis confirmed the presence of functional groups responsible for reducing and capping the bio-reduced AgNPs, whereas the XRD data established its crystalline nature. Impressively, the PEG-AgNPs exhibited maximum inhibitory activity against different Tubercular and Non-Tuberculous Mycobacterium species i.e., Mycobacterium smegmatis, Mycobacterium fortuitum and Mycobacterium marinum, relative to those of AgNPs and Linezolid. The flow cytometry assay showed that the anti-mycobacterial action was mediated by an increase in cell wall permeability. Notably, the results of AFM confirm their ability to inhibit mycobacterial biofilm significantly. We demonstrated the nontoxic nature of these AgNPs, explicated by the absence of hemolytic activity against human RBCs. Overall, the results suggest that PEG-AgNPs could offer a novel therapeutic approach with potential anti-mycobacterial activity and can overcome the limitations of existing TB therapies.

Clinical Course of Children 1 to 24 Months Old With Positive Urine Cultures Without Pyuria.

OBJECTIVE: To describe the clinical course of children with positive urine cultures without pyuria who were not given antibiotics initially, identify predictors of subsequent antibiotic treatment, and evaluate the association between subsequent treatment and urinary tract infection (UTI) within 30 days. METHODS: We conducted a multicenter retrospective cohort study of children 1 to 24 months old who had positive urine cultures without pyuria and who were not started on antibiotics upon presentation to 3 health care systems from 2010 to 2021. Outcomes included clinical status at the time urine cultures resulted, escalation of care (emergency department visit or hospitalization) and subsequent antibiotic treatment within 7 days, and subsequent UTI within 30 days of presentation. RESULTS: Of 202 included children, 61% were female and median age was 9 months. Of 151 patients with clinical status information when cultures resulted, 107 (70.8%, 95% confidence interval [CI] 62.9-77.9%) were improved. Two of 202 children (1.0%, 95% CI 0.2-4.0%) experienced care escalation. Antibiotics were started in 142 (82.2%) children, and treatment was associated with prior UTI (risk ratio [RR] 1.20, 95% CI 1.15-1.26) and lack of improvement (RR 1.22, 95% CI 1.13-1.33). Subsequent UTI was diagnosed in 2 of 164 (1.2%, 95% CI 0.1-4.3%) treated and 0 of 36 (0%, 95% CI 0-9.7%) untreated children. CONCLUSIONS: Seventy percent of children with positive urine cultures without pyuria improved before starting antibiotics; however, >80% were ultimately treated. Future research should study the impact of diagnostic stewardship interventions and various urine testing strategies to optimize the management of children evaluated for UTI.retain-->.

An Analysis of the COVID-19 Situation in India in Terms of Testing, Treatment, Vaccine Acceptance and National Economic Performance.

Objectives: This study aims to provide a comprehensive review on the analysis of COVID-19 pandemic in India and address economic impact, diagnosis approaches, and vaccine acceptance and hesitation. Method: We retrieved articles published in 2020 and 2021 and current data from official websites that narrate the strategy for COVID-19 testing, issues, and challenges, healthcare system insufficiency, statistics of cases, deaths, vaccination, and vaccine acceptance barriers, and beliefs. Results: India being the 2nd largest populated country with a population of 1.4 billion faced massive difficulty in controlling the transmission of SARS-CoV-2. This crisis dramatically impeded the economy of the nation. India witnessed 2nd highest number (43,019,453) of confirmed cases and 3rd highest number of deaths (521,004) across the world. Conclusion: The major cause of the collapse of COVID-19 is the high population of India, pre-existing weak healthcare system, and the lack of awareness among the people. The fall, rise, and statistics provided in the review will help in comparing the current status with other countries and in making strong strategies to combat future calamities.

Influence of Smoking on Gingival Crevicular Fluid Interleukin 1ß and Interleukin-8 in Patients with Severe Chronic Periodontitis among a Rural Population in India.

BACKGROUND AND OBJECTIVE: Smoking is widely prevalent among rural Indian populations. Smoking is considered a significant risk factor for periodontal diseases. The aim of the present study was to evaluate the influence of smoking on the inflammatory cytokines interleukin (IL) IL-1ß and IL-8 in gingival crevicular fluid (GCF) and compare these between smokers and nonsmokers with periodontitis in diseased and healthy sites. MATERIALS AND METHODS: A total of thirty patients with severe chronic periodontitis (15 smokers and 15 nonsmokers) participated in this study. Clinical parameters assessed were gingival index, bleeding on probing, probing depth (PD), and clinical attachment level. One diseased and one healthy site from each of the periodontitis patients were selected for GCF collection and assigned to the following four groups: healthy sites in smoker (SH), diseased sites in smoker (SD), healthy sites in nonsmoker (NH), and diseased sites in nonsmoker (ND) and were analyzed by enzyme-linked immunosorbent assay test (Quantikine®). RESULTS: Intragroup comparisons revealed statistically significant levels of IL-1ß in ND sites compared to NH sites (P < 0.005) and SD sites showed statistically significantly higher levels of IL-1ß compared to SH sites (P < 0.0001). However, there was no significant difference in IL-8 levels between NH and ND sites as well as between SH and SD sites. Intergroup comparisons revealed that SH sites exhibited significantly lower amounts of IL-8 (P < 0.01) compared to NH sites and SD sites showed significantly lower levels of IL-8 compared to ND sites (P < 0.001). However, the comparison of NH and SH sites as well as ND and SD sites showed no significant difference in the levels of IL-1ß. CONCLUSIONS: Cytokine levels were significantly elevated in periodontitis patients. Smokers exhibited a decrease in IL-8 and increase in IL-1ß levels. Hence, this reflects the influence of smoking on immunosuppression and its role in the pathogenesis of periodontal disease.

Thrombotic thrombocytopenic purpura in a postoperative patient taking cephalexin responding to plasmapheresis: A case report and review of cephalosporin-induced TTP.

The clinical presentation of thrombotic thrombocytopenic purpura (TTP) is often atypical delaying diagnosis and treatment. A number of drugs have been implicated in the development of TTP, including cyclosporine, tacrolimus, clopidogrel, and quinine. To our knowledge, only three cases of cephalosporin-induced TTP have been described, with two of these cases occurring with these use of cephalexin. We herein describe a case of TTP occurring in a postoperative patient taking cephalexin, requiring plasmapheresis. Following plasmapheresis, the patient's mental status and platelet count significantly improved. J. Clin. Apheresis 31:473-475, 2016. © 2015 Wiley Periodicals, Inc.

Interleukin 1ß (+3954, -511 and -31) polymorphism in chronic periodontitis patients from North India.

OBJECTIVE: Several studies have implicated the role of interleukin-1 in various chronic diseases including periodontitis. The present study was carried out with an aim to evaluate the role of interleukin 1ß polymorphisms, namely +3954C/T, -511C/T and -31T/C, in the development of chronic periodontitis. MATERIALS AND METHODS: Twenty-nine chronic periodontitis patients and 31 healthy controls of North Indian origin from Chhattisgarh were recruited for the study. The genotypes for the three variants were determined using the PCR-RFLP technique and the strength of association between genotypes and periodontitis was determined by odds ratio with 95% confidence interval (CI) and chi-square analysis. RESULTS: Analysis for the +3954 allelic and genotypic frequencies of the polymorphism revealed a significant difference in the CT genotype between periodontitits patients and controls (p = 0.03). A significant difference was also observed in the allelic frequencies between the two groups (p = 0.02). For the -511 site, TT genotype revealed a significant association with the disease (p = 0.01). A significant association was also found following the co-dominant model (p = 0.007). However, the -31 polymorphism revealed no significant difference between patients and controls. CONCLUSIONS: In conclusion, the present study suggests a strong association of the TT genotype of -511 and CT genotype of +3954 variant of interleukin 1ß with chronic periodontitis. However, the -31 variant did not show a significant association with the disease.

Evaluation of interleukin-1ß and 8 in gutka chewers with periodontitis among a rural Indian population.

PURPOSE: Smokeless tobacco-based oral-use products like gutka are popular in India. Gutka usage leads to increased periodontal destruction and inflammation; however, the relevant mechanism remains unknown. This study aimed to elucidate the role of gutka in periodontitis by examining its effect on the levels of interleukin (IL) 1ß and IL-8 from the gingival crevicular fluid (GCF). METHODS: A total of 45 patients were enrolled in this study. Thirty patients with periodontitis (15 gutka chewers [GCP] and 15 nongutka chewers [NGC]) and 15 periodontally healthy controls (HC) were selected. The full-mouth plaque index (PI), gingival index (GI), probing depth (PD), clinical attachment level (CAL), and recession (RC) were recorded. The IL-1ß and IL-8 levels in the GCF of all subjects were assessed through an enzyme-linked immunosorbent assay (Quantikine). RESULTS: The IL-1ß and IL-8 levels were not significantly higher in the GCP group (IL-1ß, 369.01±273.44 µL; IL-8, 205.97±196.78 µL) as compared to those in the NGC group (IL-1ß, 195.57±96.85 µL; IL-8, 178.61±149.35 µL). More gingival RC and loss of attachment was seen among the GCP group (RC: 2.02±0.31, P=0.013; CAL: 4.60±0.56, P<0.001) than among the NGC group (RC, 1.21±1.15; CAL, 3.70±0.32); however, PD was deeper among the NGC subjects (P=0.002). PI and GI were significantly higher for the periodontitis group (P<0.001) when compared to the HC, but there was no difference among gutka chewers and non-chewers (P=0.22 and P=0.89). A positive correlation was found between the IL-8 levels and the duration of gutka chewing (r=-0.64, P<0.01). CONCLUSIONS: Gutka chewing leads to increased gingival RC and clinical loss of attachment. There was no effect seen in the proinflammatory cytokine levels in the GCF of gutka users.