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There is uncertainty regarding the effect of the SARS-CoV-2 infection on patients with autoimmune rheumatic diseases (AIRD) who are on immunosuppressive drugs. We did a multicity cross-sectional seroprevalence study conducted in five different cities in India before COVID-19 immunization. Patients with a diagnosis of AIRD and DMARDs were included. Relatives of the patients, preferably staying in the same household with no known rheumatic diseases served as controls. Serum IgG antibodies to SARS-CoV-2 Receptor Binding Domain (RBD) of the spike protein and nucleoprotein (NP) were assayed in eight hundred and eighty nine sera (subjects with disease = 379 and in subjects without disease = 510). IgG antibodies to either RBD and/or NP were positive in 135 (36%) subjects with AIRD as compared to 196 (38%) controls. The seroprevalence of anti-RBD and anti-NP varied between different cities but was not significantly different between subjects with and without disease in Mumbai, Ahmedabad, Bengaluru and Bhubaneswar. However, the occurrence of IgG antibodies to RBD was significantly (p < 0.05) lower in subjects with disease (28/65;43%) as compared to subjects without disease (42/65;65%) in Kolkata, where the positivity rate was lower in connective tissue disease group than in inflammatory arthritis group. Overall, patients with rheumatic diseases on DMARDs have IgG antibodies to RBD and NP of SARSCoV-2 at a comparable level with that of subjects without disease, but the level of antibodies to RBD is lower in patients with connective tissue disease on immunosuppressive drugs in one centre.
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Antirreumáticos , Enfermedades Autoinmunes , COVID-19 , Enfermedades Reumáticas , Humanos , SARS-CoV-2 , COVID-19/epidemiología , Ciudades , Estudios Transversales , Estudios Seroepidemiológicos , Antirreumáticos/uso terapéutico , Enfermedades Autoinmunes/epidemiología , Inmunoglobulina G , Inmunosupresores/uso terapéutico , Enfermedades Reumáticas/epidemiología , Anticuerpos AntiviralesRESUMEN
MIS-C is a rare, highly inflammatory state resembling incomplete Kawasaki disease, temporarily associated with COVID-19. The pathogenesis is not completely known. RNAseq was carried out on whole blood of six treatment-naïve MIS-C patients. This was compared against RNAseq transcriptomics data of five healthy controls (HC), four Kawasaki Disease (KD) and seven systemic Juvenile Idiopathic Arthritis (sJIA). Using PCA, MIS-C clustered separately from HC, KD and sJIA. Amongst the top 50 significant genes in the three comparisons with HC, KD, and sJIA, common genes were: TMCC2, ITGA2B, DMTN, GFI1B, PF4, QSER1, GRAP2, TUBB1. DSEA revealed that maximum number of hits for overexpressed pathways was for NABA matrisome activation when MIS-C was compared against HC. Cytokine stimulated cellular activation pathways, specifically IL-10 were downregulated. MIS-C had more activated pathways of neutrophil degranulation and acquired immune activation but less of coagulation system or heat-shock system involvement as compared to KD. As compared to sJIA, humoral immune response and complements were activated. Matrisome activation was higher, with increased cell-cell interaction and ECM signalling. This analysis revealed novel insights into the pathogenesis of MIS-C, including the potential role of matrisomes, humoral immune system and down-regulated interleukin-10 pathways.
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BACKGROUND: Expanded-spectrum quinolones (ciprofloxacin) are highly effective against gram-negative bacteria, but significant resistance to quinolones has been increasingly reported. We sought to evaluate the prevalence of gram-negative ciprofloxacin-resistant isolates (CRIs) from our hospital and their mechanism of action. METHODS: Gram-negative CRIs were identified as per standard procedures and confirmed using the Ezy MICTM Strip (HiMedia). DNA from 67 CRIs was amplified for the quinolone resistance-determining region (QRDR) and plasmid-mediated quinolone resistance genes. Thirty isolates positive for QRDR DNA were sequenced by Sanger's method to detect mutation. RESULTS: Of the isolates, 42.5% were found to be CRIs, the majority (74.42%) from inpatient departments, and E scherichia coli (64.19%) was the predominant isolate. Among the CRIs, 24.55% were ESBL producers and 35.29% were multidrug resistant. The polymerase chain reaction results showed the majority were amplified by QRDR target regions of gyrA (35.4%) while 4.61% were amplified for the plasmid-mediated fluoroquinolone resistance region of the qnrB gene. Further sequencing of QRDR-positive genes showed point mutations with amino acid changes at codons Ser83 and Asp87 in the gyrA gene and Ser80, Glu84, and Leu88 positions in the parC gene. CONCLUSION: Ciprofloxacin resistance observed in our study was mostly due to point mutations. Hence, strategies for rational use of ciprofloxacin and adherence to the dose and duration of treatment could be helpful to prevent selection and spread of mutant CRIs/strains.
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The vaso-occlusive crisis (VOCs) in sickle cell disease (SCD) is often associated with stress. Epinephrine released during stress acts via beta 2-adrenergic receptors (ß2-AR or ADRB2) to stimulate the synthesis of cyclic adenosine monophosphate (cAMP) in the red blood cells (RBCs). Higher cAMP levels promote adhesion of sickled RBCs to vascular endothelium, a major contributor for VOCs. Several single-nucleotide polymorphisms (SNPs) of the ß2-AR gene have been reported; two of them at codon 16 (rs1042713) and codon 27 (rs1042714) have been extensively studied for their clinical relevance. Therefore, we assessed the influence of polymorphism at these two sites of the ß2-AR gene on the RBC cAMP concentrations with and without epinephrine stimulation in SCD subjects. We determined the frequency distribution of different genotypes of codon 16 and codon 27 of the ß2-AR gene using the Sanger sequencing method in the SCD subjects. We measured the RBC-cAMP levels at baseline and after stimulation with epinephrine, to ascertain the influence of different genotypes in determining cAMP levels. There was no difference in the socio-demographic and hematological indicators in different genotypes of both codon 16 and 27. In the sham-treated erythrocytes, the cAMP levels were significantly different with three genotypes of codon 16 (F = 3.39, P = 0.036; one way ANOVA) but not with different genotypes of codon 27. A significant increase in cAMP levels was noticed with epinephrine treatment in all genotypes of codons 16 and 27 (P = 0.001; Wilcoxon signed-rank test). However, the extent of increase in the epinephrine-treated cAMP values from the sham-treated (baseline) cAMP values was significantly different between the three genotypes of codon 16 (H = 8.74; P = 0.012; Kruskal-Wallis test) but not in codon 27 genotypes. Polymorphism in codon 16 (rs1042713) of the ß2-AR gene influences cAMP concentrations in the RBC both before and after epinephrine treatment. Higher cAMP levels may lead to increased adhesion of sickle cell RBCs to vascular endothelium and may increase the frequency of VOCs.
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Anemia de Células Falciformes/genética , AMP Cíclico/genética , Eritrocitos/fisiología , Polimorfismo de Nucleótido Simple/genética , Receptores Adrenérgicos beta 2/genética , Adolescente , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/epidemiología , Niño , AMP Cíclico/sangre , Femenino , Humanos , India/epidemiología , Masculino , Receptores Adrenérgicos beta 2/sangre , Adulto JovenRESUMEN
INTRODUCTION: The rising incidence of carbapenem resistance in Enterobacterales and Pseudomonas aeruginosa is a concern. Since carbapenemase production is the primary resistance mechanism, detecting and identifying the genes responsible for it is crucial to effectively monitor its spread. OBJECTIVE: This study aims to detect positivity for the modified carbapenem inactivation method (mCIM) and ethylenediaminetetraacetic acid (EDTA)-carbapenem inactivation method (eCIM) for the detection of carbapenemase-producing Enterobacterales and Pseudomonas aeruginosa. METHODS: Methods: A cross-sectional study was carried out at a tertiary care hospital, including 250 clinical isolates of Enterobacterales and Pseudomonas aeruginosa. These isolates exhibited resistance to at least one of the carbapenems as determined by the VITEK AST 2 System (bioMérieux, USA). The isolates were subjected to mCIM testing, and those that tested positive were further tested using eCIM. The results were interpreted in accordance with the guidelines provided by the Clinical and Laboratory Standards Institute (CLSI) 2023. RESULTS: Out of the total 250 carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa isolates, 151 (60.4%) were Klebsiella pneumonia, 44 (17.6%) were Escherichia coli, 10 (4.0%) were Enterobacter cloacae, 6 (2.4%) were Providencia spp., 4 (1.6%) were Serratia marcescens, 4 (1.6%) were Proteus mirabilis and 31 (12.4%) were Pseudomonas aeruginosa. Positivity for the mCIM was observed in 96% (240 out of 250) of the isolates. Of the mCIM-positive isolates, 234 (97.5%) also tested positive for eCIM, indicating metallo-ß-Lactamase (MLB) production. A statistically significant association was found between both mCIM and eCIM positivity and the degree of resistance to carbapenem (p<0.05). Conclusion: This study shows that the inexpensive method, a combination of mCIM and eCIM assists in differentiating between serine carbapenemase producers and MLB producers, thereby guiding the selection of appropriate therapy and useful in infection control in resource-limited settings.
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Burkholderia pseudomallei causes melioidosis in both humans as well as animals and is classified as a tier 1 pathogen by the US CDC. Melioidosis is a disease that occurs predominantly in subtropical and tropical regions. It is endemic to northern Australia and parts of Southeast Asia, as well as the Indian subcontinent. Diagnosis can be made through history, clinical examination, imaging, and microbiological studies. We report a case where Burkholderia pseudomallei was isolated froma 41-year-old man who complained of pain in the left hip and the left shoulder and swelling in both lower limbs. Chest X-ray showed bilateral consolidation. USG of the left shoulder and bilateral hips showed a mass in the anterior region of the left upper arm and the lateral region of the left thigh. Pus aspirated from left shoulder grew Burkholderia pseudomallei on culture and was carbapenem-resistant. The isolate harbored two carbapenemase genes, blaNDM and blaOXA-48, which is a novel finding.
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Methicillin-resistant Staphylococcus aureus (MRSA) is one of the major causes of hospital and community-acquired infections. Fewer drugs, such as vancomycin, teicoplanin, and daptomycin, are effective against it, but they come with high toxicity. Fifth-generation cephalosporins like ceftaroline and second-generation cefuroxime are effective against MRSA. Limited studies are available on ceftaroline resistance in the literature. This study was undertaken to determine ceftaroline resistance in MRSA in a tertiary care hospital in Eastern India. A cross-sectional, hospital-based study was carried out with MRSA isolates obtained from various clinical samples of patients. Identification of the isolates to the species level was performed by an automated Vitek system, and selected samples were genotypically confirmed by detecting the mecA gene via real-time PCR. Out of a total of 334 Staphylococcus aureus isolates examined in this study, the prevalence of MRSA was seen in 59.3% (198/334), and methicillin-sensitive Staphylococcus aureus was in 40.7% (136/334). Of the total 198 MRSA isolates, ceftaroline intermediate MRSA was seen in 8.6% (17/198), and ceftaroline sensitive MRSA was in 91.4% (181/198), respectively. Among the 17 ceftaroline intermediate MRSA isolates, 88.2% (15/17) showed a minimum inhibitory concentration (MIC) of 2 µg/ml, and 11.8% (2/17) showed an MIC of 3 µg/ml. All the remaining 91.4% (181/198) isolates were sensitive to ceftaroline and showed an MIC ≤1 µg/ml. Real-time PCR confirmed the presence of the mecA gene in MRSA isolates. In this present study, not a single isolate was resistant to ceftaroline, suggesting that it, being a safer drug, can be used in place of glycopeptides such as vancomycin or teicoplanin and linezolid, where resistance has already been detected. The rational use of ceftaroline could be useful in clinical settings, and further studies will confirm the findings.
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(1) Background: Lysyl oxidase (LOX) plays a dual role in carcinogenesis and studies show a higher risk of cancer in LOX G473A variants. The present study evaluated the pattern of LOX G473A polymorphism (rs1800449) and serum LOX levels in ovarian cancer patients. (2) Methods: Serum LOX levels were estimated by enzyme linked immunosorbent assay (ELISA). A polymorphism of rs1800449 of LOX gene was detected by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Selected samples were sequenced for external validation. (3) Results: A majority of study participants were from low socio-economic status. Serum LOX level was significantly higher in ovarian cancer patients as compared to control. Serum LOX level in early-stage ovarian cancer was significantly lower as compared to advanced stage (FIGO stage III & IV). Wild type GG genotype was used as reference. Genotypes AA were associated with a significant risk of epithelial ovarian cancer (OR 3.208; p value- 0.033). A allele of rs1800449 polymorphism of LOX gene, the odds ratio was 1.866 (95% Confidence Interval 1.112-3.16) p value = 0.017 (4) Conclusions: A allele of rs1800449 polymorphism of LOX gene presents an increased risk of ovarian cancer in East Indian population. Serum LOX levels could be a potential biomarker for the diagnosis and prognosis of ovarian cancer.
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Human cytomegalovirus (HCMV) is the most common cause of congenital infections and is an important pathogen in immunocompromised individuals. Despite a robust host immune system, HCMV able to replicate, evade host defenses, establish latency for life. A significant portion of HCMV genome dedicated to encode gene products for modulation of host immune response. Growing number of HCMV gene products are being recognized to play role in immune evasion. Information on viral immune evasion mechanisms by which HCMV persists in host will be useful in devising antiviral intervention strategies and development of new vaccines. This minireview provides a brief overview of immune evasion strategy adapted by HCMV by utilizing its gene products in modulation of host immune response.
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Infecciones por Citomegalovirus/inmunología , Citomegalovirus/fisiología , Evasión Inmune , Huésped Inmunocomprometido/inmunología , Replicación Viral/inmunología , Humanos , Latencia del VirusRESUMEN
Dengue is the most rapidly spreading viral disease transmitted by the bite of infected Aedes mosquitos. The pathogenesis of dengue is still unclear; although host immune responses and virus serotypes have been proposed to contribute to disease severity. In this study, we examined the circulating dengue virus (DENV) and measured plasma levels of inflammatory mediators. Ninety-eight patients during a dengue outbreak in eastern India in 2016 were included in the study. The presence of DENV was demonstrated by detecting NS1 antigen; IgM capture ELISA and serotypes were discriminated by type-specific RT-PCR and/or sequencing. Plasma samples were assayed for 41-plex cytokine/chemokines using multiplex Luminex assay. Eighty-five (87%) samples were positive by NS1/IgM capture ELISA/RT-PCR. All four serotypes of DENV were detected in this outbreak, with DENV-2 as the predominant type, seen in 55% of cases. Mixed infections were seen in 39% of subjects. Among the host inflammatory biomarkers, GM-CSF, IFN-γ, IL-10, IL-15, IL-8, MCP-1, IL-6, MIP-1ß, and TNF-α levels were significantly increased in dengue with and without warning signs, in severe dengue patients in comparison to healthy controls. Four cytokines IFN-γ, GM-CSF, IL-10, and MIP-1ß correlated significantly with disease severity and could serve as potential predictor for disease severity. Information on the host biomarkers and the dengue serotype may help guide in optimizing effective intervention strategies.
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Citocinas/sangre , Interacciones Huésped-Patógeno/inmunología , Dengue Grave/inmunología , Transcriptoma , Proteínas Adaptadoras Transductoras de Señales/genética , Adolescente , Adulto , Anciano , Anticuerpos Antivirales/sangre , Biomarcadores/sangre , Quimiocinas/sangre , Quimiocinas/inmunología , Coinfección/inmunología , Coinfección/virología , Citocinas/inmunología , Virus del Dengue , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina M/sangre , India , Interleucina-10/genética , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/inmunología , Adulto JovenRESUMEN
To determine the incidence and natural history of congenital cytomegalovirus (CMV) infection in a population of women with near universal serologic reactivity for CMV, a prospective study of 423 women attending the antenatal clinic of the Comprehensive Rural Health Center in northern India was conducted. All 9 (2.1%) CMV positive infants were born to mothers who were CMV seropositive at the first antenatal visit. One child had hepatosplenomegaly at birth and another child had mild unilateral hearing loss at 4 months of age.
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Infecciones por Citomegalovirus/epidemiología , Citomegalovirus/aislamiento & purificación , Enfermedades del Recién Nacido/epidemiología , Enfermedades del Recién Nacido/virología , Adolescente , Adulto , Anticuerpos Antivirales/sangre , Infecciones por Citomegalovirus/complicaciones , Femenino , Pérdida Auditiva/etiología , Hepatomegalia/etiología , Humanos , Inmunoglobulina M/sangre , Incidencia , India/epidemiología , Recién Nacido , Madres , Estudios Prospectivos , Población Rural , Esplenomegalia/etiología , Orina/virologíaRESUMEN
This hospital-based study in New Delhi, North India was performed to evaluate the prevalence of human papillomavirus (HPV) in cases of invasive cervical carcinoma (ICC). A total of 10 cases presenting with an obvious cervical growth were included in this study. 108 cases that was shown to be ICC on histology (101 squamous cell carcinomas, 4 adenocarcinomas, and one neuroendocrine carcinoma) were included in the analysis. DNA was extracted from tumor tissue and HPV genotype was determined by a consensus PCR assay using a reverse line blot hybridization assay. Of 106 evaluable cases, 104 (98.1%) were positive for HPV infection. Twelve different high-risk HPV types were found. There were 125 infections, 119 of which were high risk. Six cases had associated low risk infections. HPV 16 was the commonest type, seen in 73.6% cases followed by HPV 18 (14.2%) and 45 (11.3%). A vaccine with 100% efficacy in prevention of HPV 16 and 18 infections would theoretically reduce the total cancer burden in New Delhi by more than 75% (assuming 100% coverage). Increasing the genotype spectrum (e.g. valency) if the existing vaccines would be expected to have only a modest impact on the potential for cervical protection.