Compromised base excision repair pathway in Mycobacterium tuberculosis imparts superior adaptability in the host.

Tuberculosis caused by Mycobacterium tuberculosis (Mtb) is a significant public health concern, exacerbated by the emergence of drug-resistant TB. To combat the host's dynamic environment, Mtb encodes multiple DNA repair enzymes that play a critical role in maintaining genomic integrity. Mtb possesses a GC-rich genome, rendering it highly susceptible to cytosine deaminations, resulting in the occurrence of uracils in the DNA. UDGs encoded by ung and udgB initiate the repair; hence we investigated the biological impact of deleting UDGs in the adaptation of pathogen. We generated gene replacement mutants of uracil DNA glycosylases, individually (RvΔung, RvΔudgB) or together (RvΔdKO). The double KO mutant, RvΔdKO exhibited remarkably higher spontaneous mutation rate, in the presence of antibiotics. Interestingly, RvΔdKO showed higher survival rates in guinea pigs and accumulated large number of SNPs as revealed by whole-genome sequence analysis. Competition assays revealed the superior fitness of RvΔdKO over Rv, both in ex vivo and in vivo conditions. We propose that compromised DNA repair results in the accumulation of mutations, and a subset of these drives adaptation in the host. Importantly, this property allowed us to utilize RvΔdKO for the facile identification of drug targets.

A multicentric clinical and epidemiological study of chronic and recurrent dermatophytosis in India.

BACKGROUND: There has been an alarming increase in the prevalence of chronic, recurrent and steroid modified dermatophytosis of the glabrous skin in the recent years in India. There is paucity of literature on the magnitude of this major public health problem. OBJECTIVE: To estimate the prevalence of dermatophytosis and clinico-epidemiological features of chronic and recurrent dermatophytosis (CRD) across India and to evaluate the associated risk factors. METHODS: This is a multicentric descriptive cross-sectional study conducted in 13 centres situated across India in two phases during dry and rainy seasons. All consecutive patients presenting with dermatophytosis were screened during the study period of 14 consecutive working days. Patients with CRD of the glabrous skin as per the case definition were included after exclusion of isolated hair and nail infections. Demography, clinical findings and results of potassium hydroxide wet mount were recorded. RESULTS AND CONCLUSION: A total of 41,421 patients were screened, out of which 7174 (17.31%) patients had glabrous dermatophytosis. CRD was observed in 1999 (27.86%) patients with 78.08% and 21.95% of chronic and recurrent dermatophytosis, respectively. Family history was present in 50.03% of patients. History of sharing of fomites was present in 50.37% of them. Synthetic tight clothes were worn by 43.47%, while 50.9% gave history of misuse of topical corticosteroid creams. Multiple site involvement was common (69.58%) with tinea cruris (79.99%) and tinea corporis (75.69%) being the most common clinical types. CRD is associated with sharing of fomites, topical corticosteroid misuse and involvement of multiple sites.

Functioning of Mycobacterial Heat Shock Repressors Requires the Master Virulence Regulator PhoP.

A hallmark feature of Mycobacterium tuberculosis pathogenesis lies in the ability of the pathogen to survive within macrophages under a stressful environment. Thus, coordinated regulation of stress proteins is critically important for an effective adaptive response of M. tuberculosis, the failure of which results in elevated immune recognition of the tubercle bacilli with reduced survival during chronic infections. Here, we show that virulence regulator PhoP impacts the global regulation of heat shock proteins, which protect M. tuberculosis against stress generated by macrophages during infection. Our results identify that in addition to classical DNA-protein interactions, newly discovered protein-protein interactions control complex mechanisms of expression of heat shock proteins, an essential pathogenic determinant of M. tuberculosis While the C-terminal domain of PhoP binds to its target promoters, the N-terminal domain of the regulator interacts with the C-terminal end of the heat shock repressors. Remarkably, our findings delineate a regulatory pathway which involves three major transcription factors, PhoP, HspR, and HrcA, that control in vivo recruitment of the regulators within the target genes and regulate stress-specific expression of heat shock proteins via protein-protein interactions. The results have implications on the mechanism of regulation of PhoP-dependent stress response in M. tuberculosisIMPORTANCE The regulation of heat shock proteins which protect M. tuberculosis against stress generated by macrophages during infection is poorly understood. In this study, we show that PhoP, a virulence regulator of the tubercle bacilli, controls heat shock-responsive genes, an essential pathogenic determinant of M. tuberculosis Our results unravel that in addition to classical DNA-protein interactions, complex mechanisms of regulation of heat shock-responsive genes occur through multiple protein-protein interactions. Together, these findings delineate a fundamental regulatory pathway where transcription factors PhoP, HspR, and HrcA interact with each other to control stress-specific expression of heat shock proteins.

The transpeptidase PbpA and noncanonical transglycosylase RodA of Mycobacterium tuberculosis play important roles in regulating bacterial cell lengths.

The cell wall of Mycobacterium tuberculosis (Mtb) is a complex structure that protects the pathogen in hostile environments. Peptidoglycan (PG), which helps determine the morphology of the cell envelope, undergoes substantial remodeling under stress. This meshwork of linear chains of sugars, cross-linked through attached peptides, is generated through the sequential action of enzymes termed transglycosylases and transpeptidases. The Mtb genome encodes two classical transglycosylases and four transpeptidases, the functions of which are not fully elucidated. Here, we present work on the yet uncharacterized transpeptidase PbpA and a nonclassical transglycosylase RodA. We elucidate their roles in regulating in vitro growth and in vivo survival of pathogenic mycobacteria. We find that RodA and PbpA are required for regulating cell length, but do not affect mycobacterial growth. Biochemical analyses show PbpA to be a classical transpeptidase, whereas RodA is identified to be a member of an emerging class of noncanonical transglycosylases. Phosphorylation of RodA at Thr-463 modulates its biological function. In a guinea pig infection model, RodA and PbpA are found to be required for both bacterial survival and formation of granuloma structures, thus underscoring the importance of these proteins in mediating mycobacterial virulence in the host. Our results emphasize the fact that whereas redundant enzymes probably compensate for the absence of RodA or PbpA during in vitro growth, the two proteins play critical roles for the survival of the pathogen inside its host.

Intraoperative right coronary artery obstruction due to aortic root prosthesis mismatch after aortic valve replacement-A case report.

Iatrogenic intraoperative coronary artery ostial occlusion is quite rare and a dangerous complication of aortic valve replacement. Intraoperative vigilance and prompt intervention are required to manage this fatal complication. A case report of a 48-year-old female with normal coronaries who underwent aortic valve replacement and had right ventricle distension is described here. It seemed that the cause which led to right coronary ostial obstruction was due to prosthesis aortic root mismatch and it required bypass with a vein graft. Computed tomographic angiography of aortic root showed abutting of right coronary ostium by the aortic valve prosthesis.

Characterization of a secretory hydrolase from Mycobacterium tuberculosis sheds critical insight into host lipid utilization by M. tuberculosis.

Mycobacterium tuberculosis causes tuberculosis in humans and predominantly infects alveolar macrophages. To survive inside host lesions and to evade immune surveillance, this pathogen has developed many strategies. For example, M. tuberculosis uses host-derived lipids/fatty acids as nutrients for prolonged persistence within hypoxic host microenvironments. M. tuberculosis imports these metabolites through its respective transporters, and in the case of host fatty acids, a pertinent question arises: does M. tuberculosis have the enzyme(s) for cleavage of fatty acids from host lipids? We show herein that a previously uncharacterized membrane-associated M. tuberculosis protein encoded by Rv2672 is conserved exclusively in actinomycetes, exhibits both lipase and protease activities, is secreted into macrophages, and catalyzes host lipid hydrolysis. In light of these functions, we annotated Rv2672 as mycobacterial secreted hydrolase 1 (Msh1). Furthermore, we found that this enzyme is up-regulated both in an in vitro model of hypoxic stress and in a mouse model of M. tuberculosis infection, suggesting that the pathogen requires Msh1 under hypoxic conditions. Silencing Msh1 expression compromised the ability of M. tuberculosis to proliferate inside lipid-rich foamy macrophages but not under regular culture conditions in vitro, underscoring Msh1's importance for M. tuberculosis persistence in lipid-rich microenvironments. Of note, this is the first report providing insight into the mechanism of host lipid catabolism by an M. tuberculosis enzyme, augmenting our current understanding of how M. tuberculosis meets its nutrient requirements under hypoxic conditions.

Valproic acid induces three novel cytotoxic secondary metabolites in Diaporthe sp., an endophytic fungus from Datura inoxia Mill.

Addition of the valproic acid (histone deacetylases inhibitor) to a culture of an endophytic fungus Diaporthe sp. harbored from Datura inoxia significantly altered its secondary metabolic profile and resulted in the isolation of three novel compounds, identified as xylarolide A (1), diportharine A (2) and xylarolide B (3) along with one known compound xylarolide (4). The structures of all the compounds (1-4) were determined by detailed analysis of 1D and 2D NMR spectroscopic data. The relative configurations of compounds 1-3 were determined with the help of NOESY data and comparison of optical rotations with similar compounds with established stereochemistry. All the isolated compounds were screened for antibacterial, antioxidant and cytotoxic activities. Xylarolide A (1) and xylarolide (4) displayed significant growth inhibition of MIAPaCa-2 with an IC50 of 20 and 32 µM respectively and against PC-3 with an IC50 of 14 and 18 µM respectively. Moreover, compound 1 displayed significant DPPH scavenging activity with EC50 of 10.3 µM using ascorbic acid as a positive control.

Post-cholecystectomy syndrome: A new look at an old problem.

BACKGROUND: Despite being the most commonly performed operations, sometimes cholecystectomy fails to relieve symptoms; this is now a well-recognised clinical entity termed 'post-cholecystectomy syndrome' (PCS). Very few studies from India deal with PCS, and the present study was carried out to find the incidence and risk factors for PCS in patients undergoing elective laparoscopic cholecystectomy (LC). MATERIALS AND METHODS: The records of 207 patients undergoing elective LC were prospectively maintained for 6 months after surgery. Persistence or appearance of new symptoms after surgery was documented and investigated only when they persisted beyond 30 days of surgery. RESULTS: There were 185 (89.4%) female patients and 22 (10.6%) male patients with a mean age of 44.4 years (age range: 12-79 years). Conversion to open cholecystectomy was done in 18 patients (8.69%), mainly due to adhesions and unclear anatomy. The incidence of symptoms was found to be 13% at 6 months follow-up, showing a reducing trend from 58% in the 1st week after LC; the most common symptom in symptomatic patients was dyspepsia (55.56%). On investigation, a cause for symptoms could be detected in only 0.97%. CONCLUSION: Symptoms are common after LC, but they settle over time. Very few patients have a detectable cause for symptoms after LC, and it is difficult to predict which patients will become symptomatic after LC; in the present series, previous attacks of cholecystitis and presence of co-morbid conditions were the only consistent risk factors for symptoms after LC.

Serine/Threonine Protein Phosphatase PstP of Mycobacterium tuberculosis Is Necessary for Accurate Cell Division and Survival of Pathogen.

Protein phosphatases play vital roles in phosphorylation-mediated cellular signaling. Although there are 11 serine/threonine protein kinases in Mycobacterium tuberculosis, only one serine/threonine phosphatase, PstP, has been identified. Although PstP has been biochemically characterized and multiple in vitro substrates have been identified, its physiological role has not yet been elucidated. In this study, we have investigated the impact of PstP on cell growth and survival of the pathogen in the host. Overexpression of PstP led to elongated cells and partially compromised survival. We find that depletion of PstP is detrimental to cell survival, eventually leading to cell death. PstP depletion results in elongated multiseptate cells, suggesting a role for PstP in regulating cell division events. Complementation experiments performed with PstP deletion mutants revealed marginally compromised survival, suggesting that all of the domains, including the extracellular domain, are necessary for complete rescue. On the other hand, the catalytic activity of PstP is absolutely essential for the in vitro growth. Mice infection experiments establish a definitive role for PstP in pathogen survival within the host. Depletion of PstP from established infections causes pathogen clearance, indicating that the continued presence of PstP is necessary for pathogen survival. Taken together, our data suggest an important role for PstP in establishing and maintaining infection, possibly via the modulation of cell division events.

Comparative Proteomic Analyses of Avirulent, Virulent, and Clinical Strains of Mycobacterium tuberculosis Identify Strain-specific Patterns.

Mycobacterium tuberculosis is an adaptable intracellular pathogen, existing in both dormant as well as active disease-causing states. Here, we report systematic proteomic analyses of four strains, H37Ra, H37Rv, and clinical isolates BND and JAL, to determine the differences in protein expression patterns that contribute to their virulence and drug resistance. Resolution of lysates of the four strains by liquid chromatography, coupled to mass spectrometry analysis, identified a total of 2161 protein groups covering ∼54% of the predicted M. tuberculosis proteome. Label-free quantification analysis of the data revealed 257 differentially expressed protein groups. The differentially expressed protein groups could be classified into seven K-means cluster bins, which broadly delineated strain-specific variations. Analysis of the data for possible mechanisms responsible for drug resistance phenotype of JAL suggested that it could be due to a combination of overexpression of proteins implicated in drug resistance and the other factors. Expression pattern analyses of transcription factors and their downstream targets demonstrated substantial differential modulation in JAL, suggesting a complex regulatory mechanism. Results showed distinct variations in the protein expression patterns of Esx and mce1 operon proteins in JAL and BND strains, respectively. Abrogating higher levels of ESAT6, an important Esx protein known to be critical for virulence, in the JAL strain diminished its virulence, although it had marginal impact on the other strains. Taken together, this study reveals that strain-specific variations in protein expression patterns have a meaningful impact on the biology of the pathogen.

Clathrin-Independent Killing of Intracellular Mycobacteria and Biofilm Disruptions Using Synthetic Antimicrobial Polymers.

Current membrane targeting antimicrobials fail to target mycobacteria due to their hydrophobic membrane structure, ability to form drug-resistant biofilms, and their natural intracellular habitat within the confines of macrophages. In this work, we describe engineering of synthetic antimicrobial polymers (SAMPs) derived from biocompatible polyamides that can target drug-sensitive and drug-resistant mycobacteria with high selectivity. Structure-activity relationship studies revealed that reduced hydrophobicity of cationic pendants induces enhanced and selective permeabilization of mycobacterial membranes. The least hydrophobic SAMP (TAC1) was found to be the most active with maximum specificity toward mycobacteria over E. coli, S. aureus, and mammalian cells. Membrane perturbation studies, scanning electron microscopy, and colony PCR confirmed the ability of TAC1 to induce membrane lysis and to bind to the genomic material of mycobacteria, thereby inducing mycobacterial cell death. TAC1 was most effective in perfusing and disrupting the mycobacterial biofilms and was also able to kill the intracellular mycobacteria effectively without inducing any toxicity to mammalian cells. Cellular uptake studies revealed clathrin independent uptake of TAC1, thereby allowing it to escape hydrolytic lysosomal degradation and effectively kill the intracellular bacteria. Therefore, this manuscript presents the design and selective antimycobacterial nature of polyamide polymers with charged hydrophobic pendants that have ability to disrupt the biofilms and kill intracellular mycobacteria.

Preparation, characterization and cytotoxic evaluation of bovine serum albumin nanoparticles encapsulating 5-methylmellein: A secondary metabolite isolated from Xylaria psidii.

In this study, 5-methylmellein (5-MM) loaded bovine serum albumin nanoparticles (BSA NPs) were developed using desolvation technique. The developed nanoparticles were characterized for their mean particle size, polydispersity, zeta potential, loading efficiency, X-ray diffractometry (XRD), differential scanning calorimetry (DSC) and release profile. The developed nanoparticles were spherical in shape under transmission electron microscopy (TEM) and atomic force microscopy (AFM). The developed 5-MM loaded BSA NPs demonstrated a mean particle size with a diameter of 154.95 ±â€¯4.44 nm. The results from XRD and DSC studies demonstrated that the crystal state of the 5-MM was converted to an amorphous state in polymeric matrix. The encapsulation and loading efficiency was found to be 73.26 ±â€¯4.48% and 7.09 ±â€¯0.43%. The in vitro cytotoxicity in human prostate cancer cell line (PC-3), human colon cancer cells (HCT-116) and human breast adenocarcinoma cell line (MCF-7) cells demonstrated enhanced cytotoxicity of 5-MM BSA NPs as compared to native 5-MM after 72-h treatment. The enhancement in cytotoxicity of 5-MM BSA NPs was also supported by increase in cellular apoptosis, mitochondrial membrane potential loss and generation of high reactive oxygen species (ROS). In conclusion, these findings collectively indicated that BSA nanoparticles may serve as promising drug delivery system for improving the efficacy of 5-methylmellein.

An update on polysaccharide-based nanomaterials for antimicrobial applications.

Scientific community has made a lot of efforts to combat the infectious diseases using antimicrobial agents, but these are associated with problems of development of multi-drug resistance and their adverse side effects. To tackle these challenges, nanocarrier-based drug delivery system using polysaccharides has received enormous attention in the past few years. These antimicrobial agents can become more efficacious when adsorbed, entrapped, or linked to polysaccharides. In addition, these nanocarrier-based systems provide an increase in the surface area of the drug and are able to achieve the targeted drug delivery as well as used for the synthesis of packaging materials with improved mechanical strength, barrier, and antimicrobial properties. This review focuses on potential therapeutic applications of nanocarrier-based drug delivery systems using polysaccharides for antimicrobial applications.

Incidental radiation to uninvolved internal mammary lymph nodes in breast cancer.

Routine treatment of clinically uninvolved internal mammary nodes in breast cancer patients requiring post-mastectomy radiation therapy is controversial. The purpose of this study was to measure the incidental radiation dose to the internal mammary lymph nodes not included in the planning target volume (PTV) in women with breast cancer receiving post-mastectomy radiation therapy. This retrospective protocol utilized CT-based 3D conformal treatment plans. Fifty consecutive patients were included in the analysis: 25 left breast and 25 right breast patients. 3D conformal treatment plans chest wall tangent fields and matched supraclavicular were used. All plans were prescribed to a total dose of 50 Gy in 25 fractions to the chest wall and 46 Gy in 23 fractions to the supraclavicular field. The internal mammary node chain was intentionally not included in the target volume. For purposes of this study, internal mammary vessels were contoured following the Radiation Therapy Oncologist Group atlas with a 7-mm PTV expansion, utilizing original CT simulation images. The internal mammary nodes were contoured in between the first 3 and first 5 intercostal spaces for comparison. Percent volume of internal mammary node PTV receiving 95 % of the prescribed dose (47.5 Gy) with 7-mm expansion and first 5 intercostal spaces for all patients was 25.2 % (range 0.04-97.6 %, standard deviation (SD) 23.5). The mean internal mammary node dose for all patients was 24.98 Gy (range 3.54-55.93 Gy, SD 16). Results of this study suggest the incidental dose to the internal mammary nodes does not achieve clinically significant therapeutic levels in post-mastectomy breast cancer patients treated with standard 3D conformal radiation therapy chest wall irradiation. If risk factors for microscopic involvement are present, internal mammary nodes must be specifically included in target volumes in order to be adequately treated.

Ultrasound guided transrectal catheter drainage of pelvic collections.

The transrectal approach to draining deep-seated pelvic collections may be used to drain The transrectal approach to draining deep-seated pelvic collections may be used to drain intra-abdominal collections not reached by the transabdominal approach. We discuss 6 patients with such pelvic collections treated with transrectal drainage using catheter placement via Seldinger technique. Transrectal drainage helped achieve clinical and radiological resolution of pelvic collections in 6 and 5 of 6 cases, respectively. It simultaneously helped avoid injury to intervening bowel loops and neurovascular structures using real-time visualization of armamentarium used for drainage. Radiation exposure from fluoroscopic/CT guidance was avoided. Morbidity and costs incurred in surgical exploration were reduced using this much less invasive ultrasound guided transrectal catheter drainage of deep-seated pelvic collections.

3D Virtual Bronchoscopy as an Aid to Airway Management in a Patient with Anterior Mediastinal Mass.

ABSTRACT: Mediastinal masses pose one of the great challenges for any anesthesiologist during airway maintenance, underlining the need to devise a well-formulated plan to avoid perioperative complications. As a general rule, such patients are managed with spontaneous ventilation without the use of muscle relaxants and awake intubation. We report a case of a 66-year-old male with severe dyspnea, having a very large invasive anterior mediastinal mass, causing left lung collapse for urgent debulking surgery. The tracheobronchial compromise was ruled out using three-dimensional reconstruction on computed tomography imaging (virtual bronchoscopy) and that helped in using general anesthesia with muscle relaxation for subsequent endotracheal intubation and surgery.

Effect of COVID-19 Pandemic on Knowledge, Attitude and Practices Towards Antenatal Care Among Antenatal Women: A Study From a Tertiary Care Hospital in Delhi, India.

OBJECTIVE:  Effect of the COVID-19 pandemic on knowledge, attitude, and practices toward antenatal care among antenatal women. DESIGN:  Prospective observational study. METHOD: After taking written and informed consent, 3000 term/near-term SARS CoV2-negative antenatal women admitted to the hospital for emergency were enrolled; excluding those in advance labour or critically ill. An interview was conducted and a knowledge, attitude, and practices (KAP) questionnaire was filled out based on verbatim answers. All women were then given individualized antenatal and postnatal care as per hospital protocols and discharged accordingly. The data obtained during the study was recorded on predesigned case proforma and analysed at the end of the study using the SPSS v. 23 software, after the application of appropriate statistical tests. MAIN RESULT: All women knew about the pandemic and its signs and symptoms along with precautions to be taken. Most of the women 2652 (88.4%) thought that they were at increased risk of contracting an infection during pregnancy and 2208 (73.6%) thought that coronavirus can harm the baby and will increase the risk of pregnancy. Awareness of nearby health facilities providing antenatal care was in 71.2% and 94% were aware of functional outpatient department services but only 1.4% were aware of teleconsultation services. About 2094 women have had any ANC visits. All of them knew that taking iron, Ca and vitamin supplements and getting an ultrasound and investigations were necessary but only 1524 (50.8%) took these supplements regularly, 1752 (58.4%) got their ultrasound done and 41.6% got investigations done. Two thousand four hundred thirty-six (81.2%) women had this fear that they would contract COVID-19 infection during their visit to the hospital. All the respondents of our study wanted to have hospital delivery and knew that it was necessary to have ANC registration and none of them wanted to have home delivery. CONCLUSION: Mastering correct knowledge will foster a positive attitude among antenatal women and will not only prevent disease transmission but also improve pregnancy outcomes.

Clinically relevant mutations in the PhoR sensor kinase of host-adapted Mycobacterium abscessus isolates impact response to acidic pH and virulence.

IMPORTANCE: Difficult-to-treat pulmonary infections caused by nontuberculous mycobacteria of the Mycobacterium abscessus group have been steadily increasing in the USA and globally. Owing to the relatively recent recognition of M. abscessus as a human pathogen, basic and translational research to address critical gaps in diagnosis, treatment, and prevention of diseases caused by this microorganism has been lagging behind that of the better-known mycobacterial pathogen, Mycobacterium tuberculosis. To begin unraveling the molecular mechanisms of pathogenicity of M. abscessus, we here focus on the study of a two-component regulator known as PhoPR which we found to be under strong evolutionary pressure during human lung infection. We show that PhoPR is activated at acidic pH and serves to regulate a defined set of genes involved in host adaptation. Accordingly, clinical isolates from chronically infected human lungs tend to hyperactivate this regulator enabling M. abscessus to escape macrophage killing.

In vivo evaluation of clinical performance of Cention N and glass ionomer cement in proximal restorations of primary molars.

Introduction: Restoring a proximal lesion in primary tooth has met with many challenges which has led to evolution of many materials. An alternative to Glass Ionomer Cements which has fluoride releasing capacity, offers good bond strength and is esthetic have been long looked for. Aim: This study aimed to compare the clinical performance of GIC and Cention N in proximal restorations of primary molars. Materials and Methodology: A prospective study was conducted on 154 primary molars in patients aged between 5 and 8 years using a split-mouth design. Patients were divided into two groups. Control group restored with GIC and study group received Cention N. Both groups were assessed at baseline 3, 6 and 9 months according to Ryge criteria and data was statistically analysed using Fisher's Exact. Results: Statistically significant difference was found between GIC and Cention N restorations for color match at baseline and color stability at 3 months (P < 0.001), while the other parameters did not show any significant difference among the two restorative materials. Conclusion: Cention N can be used as a suitable alternative to GIC for restoring Class II restorations in primary molars.

A Study of Q-switched Nd:YAG Laser versus Itraconazole in Management of Onychomycosis.

CONTEXT: Onychomycosis (OM) accounts for 20%-40% of all nail disorders. Slow growth of nails, resistance to antifungal drugs, their side effects, and drug interactions limit treatment options. Q-switched neodymium-doped yttrium aluminum garnet (Nd:YAG) laser is approved for nail clearance of OM, however conflicting reports exist in literature about its efficacy. This study was conducted to compare the efficacy of Q-switched Nd:YAG laser. AIM: The aim of this study was to find the efficacy of Q-switched Nd:YAG laser (1064 nm) management of OM as monotherapy in comparison to itraconazole. SETTINGS AND DESIGN: A randomized parallel group, outcome assessor trial was conducted over 18 months from July 1, 2015 to December 31, 2016, at skin center of a tertiary care hospital. SUBJECTS AND METHODS: In the first group, patients of OM were administered 12 weekly sessions of the laser. Second group was administered itraconazole 200 mg twice a day for 1 week per month for the 3 months. Confirmed cases of OM, who had not received treatment 6 months before presentation, were selected and randomly allocated to two groups of 50 each. Onychomycosis severity index (OSI) and visual analog scale (VAS) score were used to assess nail involvement at the start of study, 3 months and 1 year after enrollment. STATISTICAL ANALYSIS: Clinical profile of patients was analyzed by chi-square test for qualitative variables. For comparison of quantitative variables, Student t test was performed. A 5% probability level was considered as statistically significant (P < 0.05). RESULTS: VAS and OSI showed statistically significant improvement at 3 and 12 months in Group I, while resulting in faster clearance with laser; OSI was comparable in both groups at 12 months. Mycological cure was significantly higher in Group I. Both dermatophytes as well as non-dermatophytes responded well to laser treatment, whereas non-dermatophytes responded better to laser. CONCLUSIONS: Q-switched Nd:YAG laser is effective in inducing nail clearance in OM and is better than itraconazole in managing non-dermatophyte OM.