SARS-CoV-2 infection and seropositivity among household contacts of laboratory confirmed cases of COVID-19 in residents of Delhi, India.

The transmission of respiratory pathogens, including SARS-CoV-2, is often facilitated through household contact. To better understand the transmission rate of COVID-19 among households and factors that affect viral clearance and seroconversion, a case-ascertained community-based prospective study was conducted between December 2020 and June 2021 on the urban population of the national capital region of India. The study collected nasopharyngeal swabs for SARS-CoV-2 RT-PCR on the 1st, 7th, 14th, and 28th day, and blood samples for antibody detection on the 1st, 14th, and 28th day from household contacts (HCs) of laboratory-confirmed COVID-19 cases. The study monitored the demographic data, symptoms, and outcomes of 417 participants, including 99 index cases and 318 contacts, for a period of 28 days. The results of the study showed that SARS-CoV-2 was easily spread within households, with a secondary infection rate of 44.3 %. In fact, almost 70 % of the contacts got infected within 1-2 days of identification of the index case, while 34 % remained asymptomatic. Sero-conversion was found in 35.6 % of the participants while 22.9 % did not produce antibodies after 28 days of infection. The study also revealed that females, spouses, older members, and primary care providers were at higher risk of getting infected in a home setting. However, approximately one-third of individuals in the younger age group managed to avoid infection. The study demonstrated that most infected individuals became RT-PCR negative within two weeks, although viral clearance was delayed in older patients and those with lower cycle threshold values in RT-PCR.

Phenotyping of lymphocyte subsets, Th-1/Th-2 cytokines and other parameters in high-risk contacts of SARS-CoV-2.

Background: The information on the pathophysiology of infection in high-risk contacts of SARS-CoV-2 is limited. Aims: The aim of the present study was to assess the various factors and their elucidation in the protection of SARS- CoV-2 infection in high-risk contacts. Settings and Design: Cross-sectional descriptive clinical study. Materials and Methods: A total of 136 subjects were recruited in the present study including 100 high-risk subjects and 36 control subjects. Out of 100 high-risk subjects, 44 subjects were found positive for SARS-CoV-2 RNA. Further, absolute blood counts of total T-cells (CD3+), T-helper cells (CD4+), T-cytotoxic cells (CD8+), B lymphocytes (CD19+) Natural Killer (NK) Cells (CD16+, CD56+), cytokines, and other parameters were measured in the samples of study subjects. Statistical Analysis Used: The continuous variables were analyzed by unpaired 't' test, analysis of variance and 'Tukey test' for multiple comparisons. Results: A significant reduction of total leukocyte counts and absolute lymphocyte count was found in the acute SARS-CoV-2 positive group as compared to control group (<0.05). Interestingly, IL-4 level was significantly elevated in SARS-CoV-2 negative high-risk subjects as compared to control and acute SARS-CoV-2 positive group (p < 0.05). A significant decrease of T-cytotoxic, B-cells, and NK cells were found in acute SARS-CoV-2 positive subjects as compared to control groups. Conclusion: The findings of this study may augment our knowledge about the pathogenesis of SARS-CoV-2 infection that could help in making future strategies to control its infection.

Household transmission dynamics of COVID-19 among residents of Delhi, India: a prospective case-ascertained study.

Objective: The aim of this study was to observe the secondary infection rate and transmission dynamics of COVID-19 among household contacts, and their associations with various factors across four dimensions of interaction. Methods: This was a case-ascertained study among unvaccinated household contacts of a laboratory-confirmed COVID-19 case in New Delhi between December 2020 and July 2021. For this study, 99 index cases and their 316 household contacts were interviewed and sampled (blood and oro-nasal swab) on days 1, 7, 14, and 28. Results: The secondary infection rate among unvaccinated household contacts was 44.6% (95% confidence interval (CI) 39.1-50.1). The predictors of secondary infection among individual contact levels were: being female (odds ratio (OR) 2.13), increasing age (OR 1.01), symptoms at baseline (OR 3.39), and symptoms during follow-up (OR 3.18). Among index cases, age of the primary case (OR 1.03) and symptoms during follow-up (OR 6.29) were significantly associated with secondary infection. Among household-level and contact patterns, having more rooms (OR 4.44) and taking care of the index case (OR 2.02) were significantly associated with secondary infection. Conclusion: A high secondary infection rate highlights the need to adopt strict measures and advocate COVID-19-appropriate behaviors. A targeted approach for higher-risk household contacts would efficiently limit infections among susceptible contacts.

Assessment of potential risk factors for COVID-19 among health care workers in a health care setting in Delhi, India -a cohort study.

INTRODUCTION: Healthcare workers (HCW) are most vulnerable to contracting COVID-19 infection. Understanding the extent of human-to-human transmission of the COVID-19 infection among HCWs is critical in managing this infection and for policy making. We did this study to estimate new infection by seroconversion among HCWs in recent contact with COVID-19 and predict the risk factors for infection. METHODS: A cohort study was conducted at a tertiary care COVID-19 hospital in New Delhi during the first and second waves of the COVID-19 pandemic. All HCWs working in the hospital during the study period who came in recent contact with the patients were our study population. The data was collected by a detailed face-to-face interview, serological assessment for anti- COVID-19 antibodies at baseline and end line, and daily symptoms. Potential risk factors for seroprevalence and seroconversion were analyzed by logistic regression keeping the significance at p<0.05. RESULTS: A total of 192 HCWs were recruited in this study, out of which 119 (62.0%) were seropositive. Almost all were wearing Personal protective equipment (PPE) and following Infection prevention and control (IPC) measures during their recent contact with a COVID-19 patient. Seroconversion was observed among 36.7% of HCWs, while 64.0% had a serial rise in the titer of antibodies during the follow-up period. Seropositivity was negatively associated with being a doctor (odds ratio [OR] 0.35, 95% Confidence Interval [CI] 0.18-0.71), having COVID-19 symptoms (OR 0.21, 95% CI 0.05-0.82), having comorbidities (OR 0.14, 95% CI 0.03-0.67), and received IPC training (OR 0.25, 95% CI 0.07-0.86), while positively associated with partial (OR 3.30, 95% CI 1.26-8.69), as well as complete vaccination for COVID-19 (OR 2.43, 95% CI 1.12-5.27). Seroconversion was positively associated with doctor as a profession (OR 13.04, 95% CI 3.39-50.25) and with partially (OR 4.35, 95% CI 1.07-17.65), as well as fully vaccinated for COVID-19 (OR 6.08, 95% CI 1.73-21.4). No significant association was observed between adherence to any IPC measures and PPE adopted by the HCW during the recent contact with COVID-19 patients and seroconversion. CONCLUSION: Almost all the HCW practiced IPC measures in these settings. High seropositivity and seroconversion are most likely due to concurrent vaccination against COVID-19 rather than recent exposure to COVID-19 patients. Further studies using anti-N antibodies serology may help us find the reason for the seropositivity and seroconversion among HCWs.

Exploration of a W/O Nanoemulsion for Antibiofilm Activity against Cariogenic Enterococcus faecalis.

A ciprofloxacin-loaded water-in-oil nanoemulsion (CPX-NE) was prepared and evaluated for the antimicrobial effect against oral biofilms produced by Enterococcus faecalis. CPX-NE was prepared by ultrasonication using functional excipients oleic acid (oil phase), Span 80 (surfactant), and Transcutol P (cosurfactant). Rheological parameters (viscosity = 20 ± 1.24 cp) confirmed optimum values for CPX-NE, a pH of 6.5 ± 0.23 suggested the simulation of CPX-NE with the pH of the mouth cavity, refractive index (1.46 ± 0.22), and % transmittance (92.34 ± 0.02) indicated the isotropic nature of the NE. The droplet size (72.19 ± 1.68 nm), polydispersity index (0.142 ± 0.02), and ζ potential (-28 mV) demonstrated a narrow size distribution and electrostatically stabilized NE. The morphology of the optimized formulation showed uniform spherical nanodroplets, as seen in fluorescence microscopy. In vitro drug release showed an initial burst effect followed by sustained release for 48 h, following Fick's diffusion. The minimum biofilm inhibitory and eradication concentration (MBIC/MBEC) was determined to compare CPX-NE with ciprofloxacin plain drug solution (CPX-PS) for their efficacy. CPX-NE demonstrated a significant inhibitory and eradication effect compared to CPX-PS. It was concluded that the developed CPX-NE has effective antibiofilm activity against E. faecalis and may be useful in the prevention and treatment of dental caries.

Genotypic characterization of vancomycin-resistant Enterococcus causing urinary tract infection in northern India.

Background & objectives: Infections caused by vancomycin-resistant Enterococci are difficult to treat given the limited therapeutic alternatives. Different gene clusters are known to confer vancomycin resistance. vanA and vanB genes are transferable and are clinically relevant. This cross-sectional study aimed to identify the vancomycin-resistant genotypes in the strains causing urinary tract infection and also to test the in vitro efficacy of linezolid and pristinamycin against the vancomycin-resistant isolates. Methods: Antimicrobial resistance profile of 118 enterococcal isolates was evaluated. Minimum inhibitory concentration of vancomycin, teicoplanin and high-level gentamicin (HLG) was determined by micro broth dilution. The vancomycin-resistant isolates were tested against linezolid and pristinamycin by micro-broth dilution and E strip method. The presence of vancomycin-resistant genes was detected by multiplex polymerase chain reaction and was sequenced and analyzed. Results: Most commonly isolated species were Enterococcus faecalis (76.9%) and Enterococcus faecium (16.9%). It was found that 43 per cent of the isolates were resistant to HLG and 16.9 per cent to vancomycin. Higher resistance was seen against fluoroquinolones, erythromycin, tetracycline and ß-lactam drugs. However, 5.08 per cent strains were resistant to tigecycline. All vancomycin-resistant strains were sensitive to pristinamycin and one was resistant to linezolid. vanA and vanB gene were found in 15 and five isolates, respectively. The gene sequences were submitted to NCBI gene bank and accession numbers were obtained. Interpretation & conclusions: The present study showed prevalence of vanA and vanB genes carrying Enterococcus in a tertiary care centre in north India. The emergence of resistance against drugs such as tigecycline and linezolid is a topic of concern as it will be a therapeutic challenge for physicians.

High-level gentamicin resistance mediated by Aac(6')-Ie-aph(2")-Ia gene in Enterococcus species isolated from clinical samples in Northern India.

CONTEXT: Enterococci are known to cause life-threatening infections which are difficult to treat as the organism harbors innate resistance to many antibiotics and can amass resistance toward many others through plasmid-mediated genetic exchange. AIMS: The study evaluates the drug susceptibility profile of various Enterococcus species isolated from various patient specimens submitted for bacteriological analysis and check the incidence of aac(6') Ie-aph(2") Ia gene. SETTING AND DESIGN: This in vitro cross-sectional study was executed at bacteriology laboratory of a 470 bedded hospital in New Delhi. MATERIALS AND METHODS: Drug susceptibility testing was carried out on enterococcal isolates. High-level gentamicin-resistant (HLGR) isolates detected by micro broth dilution assay were then subjected to molecular detection of aac(6') Ie-aph(2") Ia gene. STATISTICAL ANALYSIS USED: The level of significance was established by Chi-square test. RESULTS: Among the 182 enterococcal stains detected, 76.9% were Enterococcus faecalis and 20.3% were Enterococcus faecium. 12.08% strains were vancomycin resistant. 39% expressed resistance toward high-level gentamicin (HLG) and this finding was significantly higher in E. faecium than E. faecalis. HLGR strains expressed a higher degree of resistance to other drugs in contrast to non-HLGR isolates. In 67 out of 71 HLGR isolates the bifunctional gene was detected. CONCLUSION: Considerable presence of HLG and vancomycin resistance in the clinical isolates is alarming and should be taken seriously. The study shows high dissemination of aac(6')-Ie-aph(2")-Ia gene among Enterococci isolated from the region.

Efficacy of polyherbal formulations for prevention of COVID-19 infection in high-risk subjects: A randomized open-label controlled clinical trial.

COVID-19 is arguably the biggest health crisis the world has faced in the 21st century. Therefore, two of the polyherbal formulations, Infuza and Kulzam were assessed for the prevention of COVID-19 infection as a repurposed medication. Four hundred seven high-risk subjects were recruited in the present open-label randomized controlled clinical trial for eligibility. After assessment for eligibility, remaining 251 subjects were randomized to the test and control groups. Further, 52 high-risk subjects in Infuza, 51 in Kulzam, 51 in Infuza & Kulzam and 53 in control group completed the 14 days of intervention/assessment. The phenotyping of lymphocytes at baseline (0 day) and after 14 days of treatment was carried out by flow cytometry assays. A total of 15.09% high-risk subjects in control group turned positive as compared to only 7.69% in Infuza, 3.92% in Kulzam and 1.96% in Infuza & Kulzam groups. The rate of conversion to COVID-19 infection in Infuza & Kulzam group was minimal and statistically significant as compared to control group (p0.017). No significant changes in phenotype of lymphocytes (T, B, NK cells), absolute lymphocyte count and cytokine levels were found in study groups. However, there was a decreasing trend of hs-CRP level in high-risk subjects after intervention of polyherbal formulations for 14 days. The combination of Infuza and Kulzam may synergistically prevent COVID-19 infection in high-risk subjects of COVID-19.

Effectiveness of BBV152/Covaxin and AZD1222/Covishield vaccines against severe COVID-19 and B.1.617.2/Delta variant in India, 2021: a multi-centric hospital-based case-control study.

OBJECTIVES: India introduced BBV152/Covaxin and AZD1222/Covishield vaccines in January 2021. We estimated the effectiveness of these vaccines against severe COVID-19 among individuals aged ≥45 years. METHODS: We did a multi-centric, hospital-based, case-control study between May and July 2021. Cases were severe COVID-19 patients, and controls were COVID-19 negative individuals from 11 hospitals. Vaccine effectiveness (VE) was estimated for complete (2 doses ≥ 14 days) and partial (1 dose ≥ 21 days) vaccination; interval between two vaccine doses and vaccination against the Delta variant. We used the random effects logistic regression model to calculate the adjusted odds ratios (aOR) with a 95% confidence interval (CI) after adjusting for relevant known confounders. RESULTS: We enrolled 1143 cases and 2541 control patients. The VE of complete vaccination was 85% (95% CI: 79-89%) with AZD1222/Covishield and 71% (95% CI: 57-81%) with BBV152/Covaxin. The VE was highest for 6-8 weeks between two doses of AZD1222/Covishield (94%, 95% CI: 86-97%) and BBV152/Covaxin (93%, 95% CI: 34-99%). The VE estimates were similar against the Delta strain and sub-lineages. CONCLUSION: BBV152/Covaxin and AZD1222/Covishield were effective against severe COVID-19 among the Indian population during the period of dominance of the highly transmissible Delta variant in the second wave of the pandemic. An escalation of two-dose coverage with COVID-19 vaccines is critical to reduce severe COVID-19 and further mitigate the pandemic in the country.

Asymptomatic SARS-COV-2 carriage and sero-positivity in high risk contacts of COVID-19 cases'.

PURPOSE: Identifying asymptomatic SARS-COV-2 carriage is one of the crucial factors in controlling the COVID 19 pandemic. The relationship between the asymptomatic viral carriage and the rate of seroconversion needs better understanding. The present study was conducted to identify the asymptomatic COVID-19 infection and seropositivity in high-risk contacts in the southern district of Delhi, India. METHODS: Following the screening of 6961 subjects, a total of 407 asymptomatic high-risk subjects were selected. Demographic data, socioeconomic status, and history of COVID-19 related symptoms in the last 4 months were recorded. Blood samples and Nasopharyngeal/oropharyngeal swabs were collected for the detection of SARS-COV-2 RNA and anti-SARS-COV-2 antibodies. RESULTS: 55 asymptomatic high-risk subjects (13.5%) tested positive for SARS-COV-2 infection and among them, 70.9% remained asymptomatic throughout their course of infection. The seropositivity among the subjects was 28.9% (n â€‹= â€‹118) and was found significantly higher among lower-middle socioeconomic strata (p â€‹= â€‹0.01). The antibody levels were significantly higher (p â€‹= â€‹0.033) in individuals with a previous history of COVID-19 like symptoms as compared to the subjects, who had no such history. Asymptomatic healthcare workers showed a significantly increased rate of SARS-COV-2 infection (p â€‹= â€‹0.004) and seropositivity (p â€‹= â€‹0.005) as compared to the non-healthcare workers. Subjects, who were exposed to infection at their workplace (non-hospital setting) had the least RT-PCR positivity rate (p â€‹= â€‹0.03). CONCLUSIONS: A large proportion of SARS-COV-2 infection remains completely asymptomatic. The rate of asymptomatic carriage and seropositivity is significantly higher in healthcare workers as compared to the general population. The level of SARS-COV-2 antibodies is directly related to the appearance of symptoms. These observations may contribute to redefining COVID 19 screening, infection control, and professional health practice strategies.

Development and Validation of Signature Sequence-Based PCR for Improved Molecular Diagnosis of Tuberculosis.

Reliable, fast, and affordable diagnosis for tuberculosis (TB) remains a challenge to reduce disease incidence in resource-poor countries. Tests based on nucleotide sequences that are signature to Mycobacterium tuberculosis have the potential to make a positive impact on case detection rates, which can eventually help control TB. Using extensive comparative bioinformatics approach, we mined the genome for M. tuberculosis-specific genes and identified four genes so-called signature sequence (SS). With <25% homology with other known genes/proteins of mycobacterial/nonmycobacterial origin in various databases, these SS genes are ideal targets for species-specific identification. Sputum from suspected patients was liquefied using novel complete liquefying reagent, and DNA was isolated. Samples from patients (n = 417), reporting to TB clinics at two different hospitals, which met our inclusion criteria, were collected for this study. A small number (n = 143) was used for initial standardization, and the remaining patient samples (n = 274) were evaluated by SS and compared with smear microscopy, GeneXpert, culture, and clinical outcome. An overwhelming sensitivity of 97.0%, significantly higher than GeneXpert (95.0%), was seen. SS could pick all smear-negative, but culture-positive samples, along with other culture-negative samples; some of the latter were declared clinically positive. Our results yielded superior sensitivity and specificity through conventional PCR.

Mutations in two component system (PhoPQ and PmrAB) in colistin resistant Klebsiella pneumoniae from North Indian tertiary care hospital.

Colistin resistance in Gram negative bacteria is mainly attributed to chromosomal mutations in Two Component Systems(TCS) PhoPQ and PmrAB and plasmid-borne genes(mcr and its variants). The aim of this study was to understand the molecular basis of colistin resistance in Klebsiella pneumoniae and determine clonal transmission, in a North Indian tertiary care hospital over a 2.5 year period. Antimicrobial susceptibility was determined by Vitek and colistin resistance was confirmed by broth microdilution. Carbapenemases(blaKPC, blaVIM, blaIMP, blaNDM, blaOXA-48) and mcr-1 screening was done by PCR. Mutations in chromosomal genes mgrB, phoP, phoQ, pmrA, pmrB were analysed. Sequence typing was performed by Multilocus sequence typing(MLST). OXA-48 was detected in thirteen isolates while three isolates co-expressed OXA-48 and NDM. The mcr-1 gene was absent in all 16 isolates. Deleterious mutations in mgrB included insertion sequences IS903 and ISkpn26 and a premature stop codon. A total of 18 point mutations were identified in PhoPQ and PmrAB TCS; of which, novel mutations were reported in phoQ (K46E, L322V, D152N, F373L, R249G), pmrB (P159R) and pmrA (D149L). Six different sequence types ST231, ST147, ST395, ST42, ST14 and ST101 were identified. Phylogenetic analysis showed that sequence types ST14, ST395 and ST147 are closely related to ST101 and all identified sequence types had a common ancestor ST231. Colistin resistance in K. pneumoniae was attributed to mutations in PhoPQ and PmrAB TCS, while location specific distribution of strains indicates clonal transmission. The results of this study will help in formulation of effective infection prevention and antimicrobial development strategies.

Biofilm synthesis and other virulence factors in multidrug-resistant uropathogenic enterococci isolated in Northern India.

Purpose: Enterococci express high degree of resistance towards wide range of antibiotics. Production of biofilm and many virulence factors along with drug resistance makes it difficult to eradicate the infection from urinary tract. The present study detected the expression of such factors including biofilm production by multidrug-resistant (MDR) enterococci. Materials and Methods: Drug susceptibility of 103 uropathogenic enterococci was performed followed by estimation of minimum inhibitory concentration of high-level gentamicin and vancomycin by microbroth dilution method. Vancomycin-resistant genes were detected by multiplex polymerase chain reaction. Production of virulence factors such as haemagglutination, caseinase, lipase, gelatinase, haemolysin and ß-lactamase was detected by phenotypic methods in MDR strains. Biofilm production was detected by calcofluor-white fluorescence staining and semi-quantitative adherence assay. Results: 45% and 18.4% of the isolates were high-level gentamicin-resistant and vancomycin-resistant enterococci (VRE), respectively. vanA gene was detected in 14 and vanB gene in 5 strains. Biofilm, caseinase and gelatinase were the most expressed virulence factor. Expression of caseinase, gelatinase and lipase was significantly higher in Enterococcus faecalis (P < 0.05). Expression of haemagglutination, gelatinase and haemolysin among the vancomycin-resistant isolates was significantly higher (P < 0.05). Conclusion: VanA and vanB are the prevalent genotypes responsible for vancomycin resistance. The high prevalence of MDR enterococcal strains producing biofilm and virulence determinants raises concern. asa1, hyl, esp, gelE, cyl and other genes are known to express these factors and contribute to biofilm formation. Most uropathogenic enterococci expressed biofilm at moderate level and can be detected effectively by calcofluor-white staining. No correlation was noted between vancomycin resistance and biofilm production.

Design and in vitro/in vivo evaluations of a multiple-drug-containing gingiva disc for periodontotherapy.

In the current work, we set out to develop and evaluate a gingiva disc of cellulose acetate phthalate and poloxamer F-127 for the simultaneous delivery of multiple drugs, namely minocycline, celecoxib, doxycycline hyclate, and simvastatin, to abolish infection, impede inflammation, avert collagen destruction, and promote alveolar bone regeneration, respectively. In vitro release studies revealed the sustained release profiles of the drugs for 12 h and that they were active against Staphylococcus aureus, Escherichia coli and Streptococcus mutans. The in vivo bioactivity levels of these drugs were assessed by comparing the number of colony forming units during different phases of a study on Wistar rats, and the results showed a reduction in the number of bacterial colonies with the applied formulation. A mucosal irritation study conducted on Wistar rat gingiva confirmed the non-irritancy of the optimal gingiva disc. Hence, this customized, non-invasive polymeric gingiva disc displaying a sustained release of drugs can be a useful tool to treat acute to moderate stages of periodontitis.

SeeTB: A novel alternative to sputum smear microscopy to diagnose tuberculosis in high burden countries.

Microscopy-based tuberculosis (TB) diagnosis i.e. Ziehl-Neelsen screening still remains the primary diagnostic method in resource poor and high TB burden countries, however this method has poor sensitivity (~60%). Bringing three million TB patients who are left undiagnosed under the treatment has been a major focus as part of END-TB strategy across the world. We have developed a portable set-up called 'SeeTB' that converts a bright-field microscope into fluorescence microscope (FM) with minimal interventions. SeeTB, a total internal reflection-based fluorescence excitation system allows visualization of auramine-O stained bacilli efficiently with high signal-to-noise ratio. Along with the device, we have developed a sputum-processing reagent called 'CLR' that homogenizes and digests the viscous polymer matrix of sputum. We have compared the performance of SeeTB system in 237 clinical sputum samples along with FM, GeneXpert and liquid culture. In comparison with culture as gold standard, FM has sensitivity of 63.77% and SeeTB has improved sensitivity to 76.06%. In comparison with GeneXpert, FM has sensitivity of 73.91% while SeeTB has improved sensitivity to 85.51%. However, there is no significant change in the specificity between FM and SeeTB system. In short, SeeTB system offers the most realistic option for improved TB case identification in resource-limited settings.

Molecular Docking-Guided Ungual Drug-Delivery Design for Amelioration of Onychomycosis.

The present work envisaged an adherent luliconazole-loaded bilayer nail lacquer (BNL) with significant transungual activity. The locally applied sustained-release BNL formulation was designed for an improved retention, payload, and final dermatokinetic disposition. A primary step in the fabrication of a BNL included overcoming of physical barriers like α-keratin (also α-keratin), a protein present in human nails, and then allowing the drug molecule to permeate at the site of action. Although luliconazole is an established antifungal agent, has limited clinical exploitation for its use in treating onychomycosis. An in silico study elucidating its interaction with lanosterol-14-α demethylase, an enzyme which is the key region of drug action mechanism, was highly supportive of its imminent clinical potential. Optimization of prepared BNL formulations via response surface modeling (Box-Behnken Design-Expert 10.0.6) logically ascertained the effect of selected independent variables and showcased its effect via dependent responses. Surface morphology of the prepared BNL films was well corroborated for the presence of two distinct polymeric layers through scanning electron microscopy imaging. Nail permeation studies revealed a cumulative drug release of 71.25 ± 0.11% through bovine hooves up to 24 h. Luliconazole while exposing antifungal activity against clinical isolates of Trichophyton rubrum in agar cup-plate method disclosed a 38 mm diameter zone of inhibition. Further, the optimized BNL exhibited a bioadhesive force of 1.9 ± 0.11 N, which assured its retention on the nail surface for prolonged duration of time. In Conclusion, it is deduced that the conventional treatment modalities for onychomycosis require circumvention of certain pharmacotechnical caveats. Therefore, in the present study, a multipronged BNL system was proposed, which negates the need of frequent drug application, improvises cosmetic appearance, yields fruitful therapeutic outcomes, and has a clinical supremacy over the available therapeutics.

Cytokine-induced expression of nitric oxide synthases in Chlamydia trachomatis-infected spontaneous aborters.

Purpose: The aim of study was to evaluate expression of inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) in Chlamydia trachomatis (CT)-infected spontaneous aborters (SA). Materials and methods: Endometrial curettage tissue was collected from 140 SA (sporadic SA- 70; recurrent SA- 70) (Group I) and 140 age-matched controls (Group II) from Department of Obstetrics and Gynecology, Safdarjung Hospital, New Delhi, India. Polymerase chain reaction was performed for diagnosis of CT. The expression of iNOS/ eNOS/ IFN-γ/ TNF-α was assessed by real-time polymerase chain reaction (PCR). Results: 15.7% SA were CT-positive (Group I); none in controls. Sporadic spontaneous aborters (SSA) (n = 8/70), recurrent spontaneous aborters (RSA) (n = 14/70) diagnosed as CT-positive (Group-I). Significant upregulation of iNOS/ eNOS was found in CT-positive SSA/RSA compared with CT-negative SSA/RSA and healthy controls. TNF-α and IFN-γ were expressed in CT-positive SSA/RSA compared with negative SSA/controls. iNOS showed a significant strong positive correlation with TNF-α and IFN-γ in CT-infected SA. eNOS showed a significant positive correlation with TNF-α and no correlation with IFN-γ in CT-infected SA. TNF-α was positively correlated with IFN-γ. Conclusions: Significantly high expression of iNOS/ eNOS and proinflammatory cytokines affected pregnancy in CT-infected RSA, thereby implying that there occurs cytokine-induced expression of nitric oxide synthase (NOS).

Antimicrobial Susceptibility Patterns of an Emerging Multidrug Resistant Nosocomial Pathogen: Acinetobacter baumannii.

Multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) bacterium, a nosocomial pathogen associated with a high mortality rate and limited therapeutic options have emerged as a serious problem throughout the world. The present study aimed to assess the current levels of antibiotic susceptibility among the isolates of Acinetobacter species. The sensitivity patterns were analysed from various clinical specimens obtained from both in-patients and outpatients of a teaching hospital. Isolation was performed on 5% sheep blood agar and MacConkey agar. Urine samples were inoculated into CLED agar. Antibiotic susceptibility was performed by the disc diffusion method. A total of 16,452 samples were collected. The total number of samples positive for Acinetobacter species was 67 (0.4%). The highest number of isolates 26 (38.8%) were obtained from urine. Majority 80.3% of the isolates exhibited resistance to three or more classes of antibiotics. All isolates were susceptible to colistin (100%). The susceptibility rate of A. baumannii isolates was 80% for tigecycline and 53.3% for carbapenem. Combination therapies including colistin and tigecycline seem to be the rational treatment for MDR A. baumannii until new alternatives come forward.

Differential expression of circulating Th1/ Th2/ Th17 cytokines in serum of Chlamydia trachomatis-infected women undergoing incomplete spontaneous abortion.

The study aimed to elucidate role of Th1/Th2/Th17 cytokines in the immunopathogenesis of spontaneous abortion in Chlamydia trachomatis (Ct)-positive first-trimester aborters. Endometrial curettage tissue and serum were collected from 145 aborters (spontaneous abortion (SA) group, n = 85; recurrent miscarriage (RM) group, n = 60) and 120 controls attending Department of Obstetrics & Gynecology at Safdarjung hospital, New Delhi (India). Polymerase chain reaction was used to detect Ct plasmid/MOMP, while commercial cytometric bead array kit was utilized to estimate circulating serum cytokines. 13.7% aborters were Ct-positive, however, none was found to be infected among controls. IFN-γ, TNF-α, IL-2, IL-6 and IL-17A cytokines were significantly increased in SA group/RM group (Ct-infected) versus controls. IL-4 showed no difference between groups, while IL-10 was significantly elevated in controls versus Ct-infected subjects in SA group/RM group. Furthermore, IFN-γ, TNF-α, IL-6, IL-17A cytokines were significantly elevated in Ct-positive RM group versus Chlamydia-infected SA group. However, IL-2, IL-4 and IL-10 cytokines showed no significant difference between Ct-positive SA group versus infected RM group. Positive correlation was found between few cytokines (TNF-α and IFN-γ/IL-17A; IL-17A and IFN-γ/IL-6) in Ct-positive aborters. Our study clearly established the role of Th1/Th2/Th17 cytokines in the pathogenesis of spontaneous abortion in Ct-infected subjects and found that Chlamydia-positive recurrent aborters had a predominant Th1/Th17 bias.

A vaginal drug delivery model.

Efficient drug delivery at vaginal cavity is often a challenge owing to its peculiar physiological variations including vast differences in pH. Keeping in view this attribute of the target site, the current work was aimed at developing formulation strategies which could overcome this and successfully deliver molecules like itraconazole through SLNs. Optimized SLNs with the given composition was selected for further development into mucoadhesive and thermosensitive gel. Stearic acid and Compritol 888 (1:1, w/w ratio) as lipid, a mixture of 3% Poloxomer 188 and 0.5% sodium taurocholate as surfactant and organic to aqueous ratio of 10:50 was taken. Carbopol 934 and Pluronic F 127 were taken for the development of gel. Optimized gel exhibited a desired gelling temperature (35 °C); viscosity (0.920 PaS) and appreciable in vitro drug release (62.2% in 20 h). MTT assay did not show any cytotoxic effect of the gel. When evaluated in vivo, it did not exhibit any irritation potential despite appreciable bioadhesion. A remarkable decrease in CFUs was also observed in comparison with control and marketed formulation when evaluated in rat infection model. Thus, the proposed study defines the challenges for developing a suitable formulation system overcoming the delivery barriers of the vaginal site.