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1.
Chaos ; 29(11): 113112, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31779354

ABSTRACT

Close binary stars are binary stars where the component stars are close enough such that they can exchange mass and/or energy. They are subdivided into semidetached, overcontact, or ellipsoidal binary stars. A challenging problem in the context of close binary stars is their classification into these subclasses based solely on their light curves. Conventionally, this is done by observing subtle features in the light curves like the depths of adjacent minima, which is tedious when dealing with large datasets. In this work, we suggest the use of machine learning algorithms applied to quantifiers derived from recurrence networks to differentiate between classes of close binary stars. We show that overcontact binary stars occupy a region different from semidetached and ellipsoidal binary stars in a plane of characteristic path length and average clustering coefficient, computed from their recurrence networks. We use standard clustering algorithms and report that the clusters formed correspond to the standard classes with a high degree of accuracy.

2.
Lupus ; 27(11): 1867-1875, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30071768

ABSTRACT

Introduction About 10-20% of systemic lupus erythematosus (SLE) patients have onset in childhood and have more severe organ involvement. Survival of juvenile SLE patients is improving worldwide. Long-term data of childhood onset SLE from developing countries is scarce. Methods Clinical and laboratory data at initial presentation and follow-up visits were retrieved from clinic files, hospital information system and personal interviews. Treatment received, complications, flares, outcomes and death were recorded. Survival was calculated using Kaplan-Meier survival curves and regression analysis was done for predictors of mortality. Results Children with SLE ( n = 273, 250 girls) had a median age at onset of 14 years and duration of illness prior to diagnosis at our hospital of 1 year. Fever and arthritis were the most common presenting manifestations. Renal disease was seen in 60.5% and central nervous system (CNS) disease in 29%. The median follow-up period in 248 patients was 3.5 years. Fourteen children died, and 10 of these had active disease at the time of death. The mean actuarial survival was 24.5 years and survival rates at 1, 5 and 10 years were 97.9%, 95% and 89% respectively. Fever, CNS disease, anti-dsDNA levels and serious infections predicted death on univariate and multivariate analysis. Infections were seen in 72 children (26.3%), and 38 of these infections were serious. One-third of the patients had damage on the last follow-up. Flares were seen in 120 children, the majority being major flares. Conclusion Outcomes of pediatric SLE in North Indian children are similar to those seen in developed countries. Infections pose a major challenge in these patients.


Subject(s)
Lupus Erythematosus, Systemic/mortality , Lupus Erythematosus, Systemic/physiopathology , Adolescent , Age of Onset , Cause of Death , Child , Child, Preschool , Developing Countries , Female , Humans , India/epidemiology , Infant , Male , Multivariate Analysis , Prognosis , Retrospective Studies , Survival Analysis , Time Factors
3.
Lupus ; 27(12): 1973-1979, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30041578

ABSTRACT

Several susceptibility genes have been associated with systemic lupus erythematosus (SLE) across different populations worldwide. However, data on association between genetic polymorphisms and SLE from Indian population is scarce. We aimed to replicate the association of single nucleotide polymorphisms (SNPs) in ITGAM, TNFSF4, TNFAIP3 and STAT4 genes with susceptibility to SLE in a North Indian population. Three hundred and ninety-four SLE patients and 583 unrelated healthy controls of the same ethnic background were enrolled. All samples were genotyped for SNPs in ITGAM (rs1143679), TNFSF4 (rs2205960), TNFAIP3 (rs5029939) and STAT4 (rs7574865) using TaqMan genotyping assay. At allele level, significant association with susceptibility to SLE was detected with polymorphisms in ITGAM (A vs. G, odds ratio (OR) = 1.73, 95% confidence interval (CI) = 1.30-2.30, p < 0.001), TNFSF4 (T vs. G, OR = 1.33, 95% CI = 1.08-1.64, p < 0.01), TNFAIP3 (G vs. C, OR = 1.91, 95% CI = 1.27-2.85, p < 0.01) and STAT4 (T vs. G, OR = 1.38, 95% CI = 1.13-1.69, p < 0.01). All four SNPs were associated with SLE under a dominant model with an OR of 1.47 (95% CI = 1.07-2.04, p < 0.05) for ITGAM, 1.30 (95% CI = 1.01-1.69, p < 0.05) for TNFSF4, 1.90 (95% CI = 1.25-2.90, p < 0.01) for TNFAIP3 and 1.38 (95% CI = 1.06-1.78, p < 0.05) for STAT4. Under a recessive model, significant association was found with ITGAM (OR = 4.87, 95% CI = 2.17-10.91, p < 0.001), TNFSF4 (OR = 1.84, 95% CI = 1.13-3.00, p < 0.05) and STAT4 (OR = 1.82, 95% CI = 1.19-2.77, p < 0.01). In conclusion, single nucleotide polymorphisms in ITGAM, TNFSF4, TNFAIP3 and STAT4 genes are associated with susceptibility to SLE in a North Indian population.


Subject(s)
CD11b Antigen/genetics , Lupus Erythematosus, Systemic/genetics , OX40 Ligand/genetics , STAT4 Transcription Factor/genetics , Tumor Necrosis Factor alpha-Induced Protein 3/genetics , Adult , Alleles , Asian People/genetics , Case-Control Studies , Female , Genetic Predisposition to Disease , Genome-Wide Association Study , Haplotypes , Humans , India , Linkage Disequilibrium , Male , Polymorphism, Single Nucleotide
4.
Clin Exp Immunol ; 187(2): 234-241, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27706807

ABSTRACT

Microarray of peripheral blood (PB) and synovial fluid mononuclear cells (PBMC, SFMC) of patients with juvenile idiopathic arthritis-enthesitis-related arthritis (JIA-ERA) has shown the involvement of monocytes. On the basis of CD14 and CD16 expression, monocytes are classified as classical, intermediate and non-classical. In response to Toll-like receptor (TLR) stimulation, intermediate monocytes produce proinflammatory cytokines and play a role in inflammatory diseases. Therefore, we have studied the microarray profile of monocytes, the frequency of their subsets and cytokine production. Monocyte-specific microarray analysis was performed in six healthy controls' PBMC and six patients' PBMC and SFMC using Illumina chips WG12. Monocyte subsets were assessed in 46 patients with JIA-ERA and 17 healthy controls and 17 disease controls by flow cytometry. Interleukin (IL)-23 and tumour necrosis factor (TNF) levels were measured in culture supernatants of eight controls and seven patients' PBMC/SFMC with/without lipopolysaccharide (LPS) stimulation. Cytokine-producing intermediate monocytes were assessed by flow cytometry. Genes related to antigen presentation, cytokine signalling and TLR pathway were regulated differentially in PB and synovial monocytes of patients with JIA-ERA. Key genes of intermediate monocytes, such as CLEC10A and MARCO, were expressed three- to fourfold more in JIA-ERA. In PB, the frequency of intermediate monocytes was significantly higher in JIA-ERA (4·90% ± 3·5) compared to controls (1·8% ± 1·06; P < 0·001). Patients' synovial cells also had more intermediate monocytes compared to PB (11·25% ± 11·32, 5·9% ± 4·8; P = 0.004). Intermediate monocytes are the major producers of IL-23. Thus, intermediate monocytes may play an important role in JIA-ERA, possibly by producing cytokines, and contribute to joint inflammation.


Subject(s)
Arthritis, Juvenile/immunology , Lectins, C-Type/genetics , Monocytes/physiology , Receptors, Immunologic/genetics , Synovial Membrane/immunology , Adolescent , Adult , Cell Differentiation , Cells, Cultured , Child , Female , Humans , Interleukin-23/metabolism , Lipopolysaccharide Receptors/metabolism , Lipopolysaccharides/immunology , Male , Receptors, IgG/metabolism , Tissue Array Analysis , Tumor Necrosis Factor-alpha/metabolism , Young Adult
5.
Clin Exp Immunol ; 188(2): 254-262, 2017 05.
Article in English | MEDLINE | ID: mdl-28120479

ABSTRACT

The study was aimed at identification by proteomics and validation by enzyme-linked immunosorbent assay (ELISA) of potential urinary biomarkers for lupus nephritis. Study subjects comprised 88 systemic lupus erythematosus (SLE) patients and 60 controls (rheumatoid arthritis, diabetes mellitus and healthy individuals). Based on the SLE disease activity index (SLEDAI), patients were classified as active renal (AR), active non-renal (ANR) or inactive disease (ID). Urinary proteins from a group of patients with AR or ID were resolved by two-dimensional gel electrophoresis and identified by matrix-assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS/MS). The selected biomarkers were validated by ELISA using samples from all patients and controls. AR patients were followed-up for 12 months after start of therapy. Three urinary proteins, alpha-1 anti-chymotrypsin (ACT), haptoglobin (HAP) and retinol binding protein (RBP), were detected in patients with AR and not ID. Upon validation, ACT levels were higher in AR patients than the other groups (P < 0·001) and showed good correlation with renal SLEDAI (r = 0·577, P < 0·001) as well as SLEDAI (r = 0·461, P < 0·001). Similarly, HAP levels were > 10-fold higher in AR than other groups (P < 0·001) and correlated well with renal SLEDAI (r = 0·594, P < 0·001) and SLEDAI (r = 0·371, P < 0·01). RBP levels were also higher in AR patients than in other groups (P < 0·05), except diabetes, and showed moderate correlation with renal SLEDAI (r = 0·284, P < 0·008) and SLEDAI (r = 0·316, P < 0·003). Upon follow-up with treatment, levels of all three proteins declined at 6 and 12 months (P < 0·01). Multiple logistic regression identified ACT as the best marker to differentiate AR from ANR. Urinary HAP, ACT and RBP are potential biomarkers for lupus nephritis activity.


Subject(s)
Haptoglobins/urine , Lupus Nephritis/diagnosis , Retinol-Binding Proteins/urine , alpha 1-Antichymotrypsin/urine , Adult , Arthritis, Rheumatoid/urine , Biomarkers/urine , Diabetes Mellitus/urine , Enzyme-Linked Immunosorbent Assay , Female , Humans , Logistic Models , Lupus Erythematosus, Systemic/urine , Lupus Nephritis/drug therapy , Lupus Nephritis/urine , Male , Proteomics/methods , Severity of Illness Index , Tandem Mass Spectrometry , Young Adult
6.
Clin Exp Immunol ; 187(3): 376-382, 2017 03.
Article in English | MEDLINE | ID: mdl-27804111

ABSTRACT

B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) help in B cell activation, maintenance and plasma cell survival. B cell infiltration has been demonstrated in kidneys of patients with lupus nephritis (LN). Serum levels of BAFF and APRIL have shown inconsistent relationships with lupus disease activity. We evaluated urinary levels of BAFF and APRIL as biomarker for LN. Thirty-six patients with proliferative lupus nephritis (AN), 10 with active lupus without nephritis (AL) and 15 healthy controls (HC) were studied. APRIL and BAFF levels were measured in both serum and urine using enzyme-linked immunosorbent assay (ELISA). Urine levels were normalized for urinary creatinine excretion. Urine levels were correlated with conventional disease activity markers and histology. Levels were reassessed in 20 AN patients at 6 months after treatment with cyclophosphamide. Urinary APRIL (uAPRIL) and BAFF (uBAFF) levels were raised significantly in AN. uAPRIL, but not uBAFF, correlated moderately with renal Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in AN (r = 0·36, P < 0·05). On receiver operator curve (ROC) analysis, uBAFF and uAPRIL showed an area under the curve (AUC) of 0·825 and 0·781, respectively, in differentiating between nephritis and non-nephritis, which performed better than low C3, C4 and raised anti-dsDNA antibodies. There was no correlation of serum levels with uBAFF (r = 0·187, P = 0·261) and uAPRIL (r = 0·114, P = 0·494). uAPRIL levels reduced after treatment (mean 125 pg/mg to 36 pg/mg, P < 0·05). uBAFF levels reduced in 16 responders while two of four non-responders had increase in levels. Thus, uBAFF and uAPRIL are potential biomarkers of proliferative lupus nephritis.


Subject(s)
B-Cell Activating Factor/urine , Biomarkers/urine , Lupus Erythematosus, Systemic/urine , Tumor Necrosis Factor Ligand Superfamily Member 13/urine , Adult , B-Lymphocytes/drug effects , Cyclophosphamide/therapeutic use , Female , Humans , Lupus Erythematosus, Systemic/drug therapy , Lupus Nephritis/urine , Male , Middle Aged , Prospective Studies , Severity of Illness Index , Young Adult
7.
Int J Qual Health Care ; 29(1): 63-67, 2017 Feb 01.
Article in English | MEDLINE | ID: mdl-27940521

ABSTRACT

OBJECTIVE: To evaluate the incidence, risk factors and associated mortality of central line-associated bloodstream infection (CLABSI) in an adult intensive care unit (ICU) in India. DESIGN: This prospective observational study was conducted over a period of 16 months at a tertiary care referral medical center. SETTING: We conducted this study over a period of 16 months at a tertiary care referral medical center. PARTICIPANTS: All patients with a central venous catheter (CVC) for >48 h admitted to the ICU were enrolled. INTERVENTION AND MAIN OUTCOME MEASURES: Patient characteristics included were underlying disease, sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation (APACHE II) scores and outcome. Statistical analysis of risk factors for their association with mortality was also done. RESULTS: There were 3235 inpatient-days and 2698 catheter-days. About 46 cases of CLABSI were diagnosed during the study period. The overall rate of CLABSI was 17.04 per 1000 catheter-days and 14.21 per 1000 inpatient-days. The median duration of hospitalization was 23.5 days while the median number of days that a CVC was in place was 17.5. The median APACHE II and SOFA scores were 17 and 10, respectively. Klebsiella pneumoniae was the most common organism (n = 22/55, 40%). Immunosuppressed state and duration of central line more than 10 days were significant factors for developing CLABSI. SOFA and APACHE II scores showed a tendency towards significance for mortality. CONCLUSIONS: Our results underscore the need for strict institutional infection control measures. Regular training module for doctors and nurses for catheter insertion and maintenance with a checklist on nurses' chart for site inspection and alerts in all shifts are some measures planned at our center.


Subject(s)
Bacteremia/epidemiology , Central Venous Catheters/adverse effects , Central Venous Catheters/microbiology , APACHE , Adult , Bacteremia/mortality , Female , Humans , Immunosuppression Therapy , Incidence , India , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Organ Dysfunction Scores , Prospective Studies , Risk Factors , Tertiary Care Centers
8.
Clin Exp Immunol ; 185(2): 210-8, 2016 08.
Article in English | MEDLINE | ID: mdl-27060348

ABSTRACT

In developing countries, one-third of patients with reactive arthritis (ReA) and undifferentiated spondyloarthropathy (uSpA) are triggered by Salmonella typhimurium. Synovial fluid mononuclear cells (SFMCs) of patients with ReA and uSpA proliferate to low molecular weight fractions (lmwf) of outer membrane proteins (Omp) of S. typhimurium. To characterize further the immunity of Omp of Salmonella, cellular immune response to two recombinant proteins of lmwf, OmpA and OmpD of S. typhimurium (rOmpA/D-sal) was assessed in 30 patients with ReA/uSpA. Using flow cytometry, 17 of 30 patients' SF CD8(+) T cells showed significant intracellular interferon (IFN)-γ to Omp crude lysate of S. typhimurium. Of these 17, 11 showed significantly more CD8(+) CD69(+) IFN-γ T cells to rOmpA-sal, whereas only four showed reactivity to rOmpD-sal. The mean stimulation index was significantly greater in rOmpA-sal than rOmpD-sal [3·0 (1·5-6·5) versus 1·5 (1·0-2·75), P < 0·005]. Similarly, using enzyme-linked immunospot (ELISPOT) in these 17 patients, the mean spots of IFN-γ-producing SFMCs were significantly greater in rOmpA-sal than rOmpD-sal [44·9 (3·5-130·7) versus 19·25 (6-41), P < 0·05]. SFMCs stimulated by rOmpA-sal produced significantly more proinflammatory cytokines than rOmpD-sal: IFN-γ [1·44 (0·39-20·42) versus 0·72 (0·048-9·15) ng/ml, P < 0·05], interleukin (IL)-17 [28·60 (6·15-510·86) versus 11·84 (6·83-252·62) pg/ml, P < 0·05], IL-23 [70·19 (15-1161·16) versus 28·25 (> 15-241·52) pg/ml, P < 0·05] and IL-6 [59·78 (2·03-273·36) versus 10·17 (0·004-190·19) ng/ml, P < 0·05]. The rOmpA-sal-specific CD8(+) T cell response correlated with duration of current synovitis (r = 0·53, P < 0·05). Thus, OmpA of S. typhimurium is a target of SF CD8(+) T cells and drives SFMC to produce increased cytokines of the IL-17/IL-23 axis which contribute to the pathogenesis of Salmonella-triggered ReA.


Subject(s)
Arthritis, Reactive/immunology , Bacterial Outer Membrane Proteins/immunology , CD8-Positive T-Lymphocytes/immunology , Interleukin-17/biosynthesis , Interleukin-23/biosynthesis , Salmonella typhimurium/immunology , Spondylarthropathies/immunology , Synovial Fluid/immunology , Adolescent , Adult , Aged , Arthritis, Reactive/microbiology , Arthritis, Reactive/physiopathology , Bacterial Outer Membrane Proteins/chemistry , Bacterial Outer Membrane Proteins/genetics , Bacterial Outer Membrane Proteins/pharmacology , Cytokines/biosynthesis , Female , Humans , Interferon-gamma/immunology , Interleukin-17/immunology , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/immunology , Male , Middle Aged , Prohibitins , Salmonella Infections/immunology , Salmonella typhimurium/chemistry , Salmonella typhimurium/genetics , Synovial Fluid/cytology , Young Adult
9.
Clin Exp Immunol ; 186(3): 313-320, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27568583

ABSTRACT

An increased expansion of T helper type 17 (Th17) cells in the synovium has been shown to play a key role in cartilage and bone destruction in rheumatoid arthritis (RA). Because the correlation of the peripheral blood helper T cell subsets and various inflammatory cytokines with the magnetic resonance imaging (MRI)-based parameters have not been studied adequately to date, we sought to look for the same in this study. RA patients with disease duration less than 36 months, disease-modifying anti-rheumatic drugs (DMARDs) and steroid-naive, were recruited. MRI of the dominant hand and wrist was performed using a 0·2 Tesla MRI machine. Peripheral blood Th1 and Th17 were enumerated by flow cytometry and serum interleukin (IL)-6 and IL-17 by enzyme-linked immunosorbent assay (ELISA). Forty consecutive seropositive RA patients [33 females, mean disease duration 12·2 months, mean disease activity score (DAS)28 = 4·4] were included. MRI revealed erosions in 80% of these subjects. On subgroup analysis, prevalence of erosions (94 versus 68%) as well as mean erosion score (11·5 ± 18·9 versus 3·5 ± 6·0) were significantly higher in established RA (13-36 months' duration) compared to early RA (0-12 months). The median peripheral blood Th17 frequencies were significantly higher in patients (1·4%) compared to healthy controls (0·7%) and had a strong negative correlation with MRI parameters of erosion and osteitis as well as with DAS28 in the established RA subgroup. The frequency of peripheral blood Th17 subset was significantly expanded in established RA which correlated inversely with disease activity as well as MRI based erosions and osteitis.


Subject(s)
Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/diagnosis , Lymphocyte Count , Magnetic Resonance Imaging , Osteitis/pathology , Th17 Cells/immunology , Adult , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Biomarkers , Case-Control Studies , Cytokines/blood , Cytokines/metabolism , Female , Humans , Male , Middle Aged , Severity of Illness Index , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Th17 Cells/metabolism
10.
Lupus ; 25(5): 547-57, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26637291

ABSTRACT

INTRODUCTION: Childhood SLE (cSLE) has a higher prevalence of lupus nephritis (LN), and there are ethnic variations in response to treatment as well as outcome of LN. There are limited data on long-term outcome of LN in cSLE from the Indian subcontinent. METHODS: Retrospective analysis of case records of patients with cSLE (satisfying revised American College of Rheumatology (ACR) 1997 criteria for diagnosis) and age of onset <18 years was conducted from 1989 to 2013. Data on clinical features, renal involvement and biopsy findings, treatment, renal outcome, damage accrual and mortality were collected. End-stage renal disease (ESRD) was defined as the need for renal replacement therapy. Actuarial ESRD-free survival was studied as the primary outcome measure using Kaplan-Meier analysis. RESULTS: Among 205 children with cSLE, 134 (121 girls) had evidence of LN. The mean age at disease onset was 13.7 ± 3.5 years and the mean disease duration at presentation was 1.9 ± 2.5 years. Kidney biopsy was available for 92 patients, and histology included: 13 (14.2%) Class II, 24 (26%) Class III, 43 (46.7%) Class IV and 12 (13.1%) Class V LN. The mean follow-up period was 6.75 ± 5.7 years. At last visit, 81 (60.4%) children were in complete remission, 28 (20.9%) were in partial remission, 15 (11.2%) still had active nephritis and 10 (7.4%) had progressed to ESRD. Almost two-thirds (62.9%) of patients experienced lupus flares, and mean flare rate was 0.09 flares/patient follow-up year. Fifty-six (43.8%) children accrued damage and the mean Systemic Lupus International Collaborating Clinics (SLICC)/ACR damage score was 0.79 ± 1.13. Actuarial ESRD-free survival at five, 10 and 15 years was 91.1%, 79% and 76.2%, and five-, 10- and 15-year renal survival was 93.8%, 87.1% and 84%, respectively. Although multiple factors individually predicted poor outcome (death/ESRD), only raised serum creatinine at onset (R square = 0.65, p ≤ 0.0001) and damage accrual (R square = 0.62, p ≤ 0.0001) remained significant on multivariate analysis. Eleven (8.2%) children died during the follow-up period, and infections were the leading cause of mortality. CONCLUSIONS: Long-term outcome of LN in cSLE in our cohort was better than previous reports from India. However, a high rate of major infection still remains the leading cause of mortality.


Subject(s)
Kidney Failure, Chronic/epidemiology , Lupus Nephritis/epidemiology , Adolescent , Age of Onset , Anti-Infective Agents/therapeutic use , Biopsy , Cause of Death , Chi-Square Distribution , Child , Communicable Diseases/drug therapy , Communicable Diseases/epidemiology , Communicable Diseases/mortality , Disease Progression , Disease-Free Survival , Humans , India/epidemiology , Kaplan-Meier Estimate , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/mortality , Kidney Failure, Chronic/therapy , Logistic Models , Lupus Nephritis/diagnosis , Lupus Nephritis/mortality , Lupus Nephritis/therapy , Male , Multivariate Analysis , Remission Induction , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome
11.
Lupus ; 25(11): 1230-6, 2016 Oct.
Article in English | MEDLINE | ID: mdl-26936893

ABSTRACT

OBJECTIVES: Urinary biomarkers may help in identification, treatment and assessment of response in patients with lupus nephritis (LN). Osteoprotegerin (OPG) is produced by the kidneys and lymphoid cells and may reflect renal disease activity better. The data on its utility are sparse. METHODS: Fifty-eight patients with active LN (AN), 24 with active non-renal disease (ANR) and 39 with inactive disease (ID) were included. Median disease duration was 32 (1-204) months and median age was 27 (12-50) years. AN patients were followed up every three months for one year. Urine and serum samples were collected for OPG measurement by ELISA (pg/ml) and urinary values were normalised for creatinine excretion (pg/mg). Urine samples from 24 healthy individuals (HCs) and 20 patients each of rheumatoid arthritis (RA) and diabetic nephropathy (DM) served as controls. Variables were expressed as median (range). RESULTS: At baseline, normalised urinary OPG (uOPG) was significantly higher (p < 0.001) in AN (1229 (0-8577)) than ANR (236 (0-14713)), ID (463 (7-4253)), HCs (366 (120-2849)) and DM (350 (127-1577)) but it was not different from RA (1511 (122-8849)). uOPG correlated modestly with rSLEDAI (r = 0.4, p < 0.001) and SLEDAI (r = 0.31, p < 0.001) but not with serum OPG (sOPG). uOPG but not sOPG could differentiate between AN and ANR groups. In the longitudinal study, uOPG and sOPG decreased significantly with treatment at all follow-up visits but the trend of fall in sOPG was erratic. uOPG values at baseline, 3, 6, 9 and 12 months were 1229 (0-8577), 466 (3-4874), 104 (0-1598), 325 (0-4025) and 555 (6-6771) pg/mg, respectively. uOPG but not sOPG rose before conventional markers in three patients who had a relapse of LN. In two patients who developed chronic kidney disease, uOPG remained persistently high. For differentiating AN from ANR patients, uOPG performed the best on receiver operator characteristics analysis (AUC = 0.72) when compared with anti-dsDNA antibodies, C3, C4 and sOPG. CONCLUSION: uOPG is derived from kidneys and helps differentiate active SLE patients with and without LN. It shows modest correlation with disease activity and has a potential to predict poor response to therapy and relapse of LN.


Subject(s)
Biomarkers/blood , Biomarkers/urine , Lupus Nephritis/urine , Osteoprotegerin/urine , Adolescent , Adult , Child , Female , Humans , Longitudinal Studies , Lupus Nephritis/blood , Male , Middle Aged , Osteoprotegerin/blood , ROC Curve , Young Adult
12.
Lupus ; 24(3): 273-9, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25305215

ABSTRACT

OBJECTIVES: T cells play an important role in the pathogenesis of lupus nephritis (LN). We studied the role of urinary soluble CD25 (sCD25) as a biomarker of LN disease activity in a cross-sectional and longitudinal study. METHODS: Patients with systemic lupus erythematosus were classified as active LN (AN), inactive disease (ID) and active non-renal (ANR) based on disease activity and renal involvement at the time of enrolment. Urine and serum samples were collected at baseline from all patients and at 3-monthly follow-up from patients with AN. SLE disease activity index (SLEDAI) was used for disease activity assessment at all visits. sCD25 was measured by ELISA and normalized to urinary creatinine excretion and is expressed as pg/mg. Urine samples from 10 healthy individuals (HC) served as controls. RESULTS: There were 119 patients (111 females, median age 27 years, 57 AN, 43 ID, 19 ANR). Median SLEDAI was 18, 2 and 8 in AN, ID and ANR groups, respectively. Median renal SLEDAI in AN was 8. Mean (±SD) urinary sCD25 in the AN, ID, ANR and HC groups at baseline was 741.1 (±794.9), 407.8 (±511.1), 735.4 (±667.7) and 250.9 (±122.2) pg/mg respectively (p = 0.019). Mean (±SD) serum sCD25 in AN, ID and ANR was 8285.25 (±5922.2), 6044 (±3501.92) and 6568.72 (±4333.62) pg/ml, respectively. Urinary sCD25 correlated with SLEDAI (r = 0.22; p = 0.015) but did not correlate with serum sCD25 or proteinuria. Urinary sCD25 compares well with traditional markers of disease activity in differentiating active from inactive renal disease. On follow-up mean urinary sCD25 decreased to 470.0 (±449.6; p < 0.05) at 3 months, 496.7 (±465.8; p = 0.006) at 6 months, 471.9 (±303.2; p = 0.041) at 9 months and 358.6 (±496.9; p = 0.007) at 12 months from baseline value of 741.1 (±794.9). In four patients who either had relapse, persistent disease activity or developed chronic kidney disease, urinary sCD25 showed rise preceding traditional abnormalities on urine examination. CONCLUSIONS: Urinary sCD25 is a good biomarker for follow-up of LN. It may also have the potential to predict poor response and relapse.


Subject(s)
Interleukin-2 Receptor alpha Subunit/analysis , Lupus Nephritis/urine , Adolescent , Adult , Biomarkers/urine , Case-Control Studies , Child , Female , Humans , Male , Middle Aged , Prospective Studies , Young Adult
13.
Phys Chem Chem Phys ; 16(36): 19122-9, 2014 Sep 28.
Article in English | MEDLINE | ID: mdl-25101805

ABSTRACT

Semiconducting conjugated polymers such as (3-hexylthiophene) (P3HT) and carbon nanotubes are attractive for applications that include field-effect transistors and photovoltaic devices. In these applications, the control of structure, morphology, and alignment of polymer chains is important from the perspective of charge transport and optical properties. In this regard, a novel solution-based nucleation approach involving direct epitaxial nucleation of nanofibers of the poly(3-hexylthiophene) (P3HT) polymer on carbon nanotubes (CNTs) leading to supramolecular structure is demonstrated. The supramolecular structure of P3HT on CNTs is characterized by nucleation of oriented precursors of P3HT on CNTs by an epitaxial mechanism, onto which high density transcrystalline ∼800-1000 nm long nanofibrils of P3HT with a thickness of ∼2-3 nm are nucleated in a periodic manner. The nanoscale structure of epitaxially grown P3HT nanofibrils exhibits optical and photoluminescence characteristics. The UV-vis spectroscopy study of the fabricated structure suggests a combination of π-π electronic transition and a strong lattice vibration in the conjugated polymer chains. Furthermore, the supramolecular structure is envisaged to comprise an accumulating thread for charge transport, onto which nanometer thick long fibrils are assembled in a periodic configuration with strong potential for organic-inorganic optoelectronic devices. In conclusion, the described approach enables fabrication of supramolecular structure on carbon nanotube-based electrodes, making it attractive for functional devices.

14.
Nano Lett ; 13(10): 4857-61, 2013 Oct 09.
Article in English | MEDLINE | ID: mdl-24000961

ABSTRACT

We have combined hard X-ray photoelectron spectroscopy with angular dependent O K-edge and V L-edge X-ray absorption spectroscopy to study the electronic structure of metallic and insulating end point phases in 4.1 nm thick (14 units cells along the c-axis of VO2) films on TiO2(001) substrates, each displaying an abrupt MIT centered at ~300 K with width <20 K and a resistance change of ΔR/R > 10(3). The dimensions, quality of the films, and stoichiometry were confirmed by a combination of scanning transmission electron microscopy with electron energy loss spectroscopy, X-ray spectroscopy, and resistivity measurements. The measured end point phases agree with their bulk counterparts. This clearly shows that, apart from the strain induced change in transition temperature, the underlying mechanism of the MIT for technologically relevant dimensions must be the same as the bulk for this orientation.


Subject(s)
Electric Conductivity , Metals/chemistry , Oxides/chemistry , Vanadium Compounds/chemistry , Phase Transition , Photoelectron Spectroscopy , Surface Properties , X-Ray Absorption Spectroscopy
15.
Indian J Physiol Pharmacol ; 58(3): 284-9, 2014.
Article in English | MEDLINE | ID: mdl-25906613

ABSTRACT

The aim of present study was to assess fetomaternal blood flows in normal and abnormal pregnancies using color Doppler indices. Subjects were divided into two groups as: Group A of 25 subjects of normal pregnancy as controls and group B of 25 subjects of pregnancy induced hypertension. All the subjects were lying in the age-group of 25-35 years and having 28 to 34 weeks of gestation; the patients were evaluated by detailed history and were subjected to complete general examination. Blood pressure was taken on two occasions at least 6 hours apart. Systemic examination and obstetrical examination was done in all subjects. All cases were subjected to pathological tests- Haemogram, Test for proteins in urine. Ultrasound assessment of fetal growth was done by measuring BPD (Biparietal diameter), HC (Head circumference), FL (Femur length) and AC (Abdominal circumference): Average gestational age and effective fetal weight was then calculated by ultrasound machine. Color Doppler was used to assess the various Doppler indices indices: Pulsatility index (PI), Resistive index (RI) and Systolic diastolic ratio (S/D ratio) in bilateral uterine, umbilical and middle cerebral arteries and compared to the standard normograms. Percentage of subjects having abnormal Doppler indices were calculated. Assessment of percentage of SGA (small for gestational age) fetuses was done in all the three groups. Decline in mean values of all Doppler indices was found with advancing gestational age in normal pregnancy suggesting decreased vascular resistance and increased blood flow in fetomaternal circulation. In pregnancy induced hypertensives, the mean values of Doppler indices showed a decline as in normal pregnancy but showed an increase (more than 2 S.D. of the mean) for that gestational age in comparison to the control group suggesting increased impedance to blood flow in uteroplacental and fetomaternal circulation. Umbilical artery Doppler indices were found to be the most sensitive indicator of uteroplacental and fetoplacental insufficiency in pregnancy induced hypertensives (P = 0.001). Thus we concluded that color Doppler can detect changes in fetomaternal circulation which correlate strongly with the fetal growth and therefore associated with pregnancy outcome.


Subject(s)
Fetus/blood supply , Hypertension, Pregnancy-Induced/physiopathology , Pregnancy/physiology , Ultrasonography, Doppler, Color , Adult , Female , Gestational Age , Humans , Regional Blood Flow , Umbilical Arteries/physiology
16.
Artif Cells Nanomed Biotechnol ; 52(1): 229-237, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38590145

ABSTRACT

The cytological behaviour and functional dynamics (adhesion, spreading, synthesis of proteins) of fibroblasts when interacting with biomedical surfaces are intricately influenced by the inherent nature of surface (nanocrystalline or microcrystalline), where the nanocrystalline (NC) surface is preferred in relation to the microcrystalline (MC) surface. This preference is a direct consequence of the distinct differences in physical and chemical characteristics between NC and MC surfaces, which include crystal boundary bio-physical attributes, electron work function, surface energy, and charge carrier density. The observed variances in cytological behaviour at the interfaces of NC and MC bio-surfaces can be attributed to these fundamental differences, particularly accounting for the percentage and nature of crystal boundaries. Recognising and understanding these physical and chemical characteristics establish the groundwork for formulating precise guidelines crucial in the development of the forthcoming generation of biomedical devices.


The significance of nanoscale surface in favourably modulating the cellular functionality is described with the aim to provide the solution to the current day challenges in the biomedical arena. Furthermore, the perspective presented advances the nano-bio science forward by implying that the nanoscale structure induces chemical and physical changes that can be considered responsible for favourable modulation of cellular activity in the living organism.


Subject(s)
Fibroblasts , Surface Properties
17.
Int J Nanomedicine ; 19: 4515-4531, 2024.
Article in English | MEDLINE | ID: mdl-38803996

ABSTRACT

Introduction: There is an ongoing need for improved healing response and expedited osseointegration on the Ti implants in acetabular fracture sites. To achieve adequate bonding and mechanical stability between the implant surface and the acetabular fracture, a new coating technology must be developed to promote bone integration and prevent bacterial growth. Methods: A cylindrical Ti substrate mounted on a rotating specimen holder was used to implant Ca2+, P2+, and Sr2+ ions at energies of 100 KeV, 75 KeV and 180 KeV, respectively, using a low-energy accelerator to synthesize strontium-substituted hydroxyapatite at varying conditions. Ag2+ ions of energy 100 KeV were subsequently implanted on the as-formed surface at the near-surface region to provide anti-bacterial properties to the as-formed specimen. Results: The properties of the as-formed ion-implanted specimen were compared with the SrHA-Ag synthesized specimens by cathodic deposition and low-temperature high-speed collision technique. The adhesion strength of the ion-implanted specimen was 43 ± 2.3 MPa, which is well above the ASTM standard for Ca-P coating on Ti. Live/dead cell analysis showed higher osteoblast activity on the ion-implanted specimen than the other two. Ag in the SrHA implanted Ti by ion implantation process showed superior antibacterial activity. Discussion: In the ion implantation technique, nano-topography patterned surfaces are not concealed after implantation, and their efficacy in interacting with the osteoblasts is retained. Although all three studies examined the antibacterial effects of Ag2+ ions and the ability to promote bone tissue formation by MC3T3-E1 cells on SrHA-Ag/Ti surfaces, ion implantation techniques demonstrated superior ability. The synthesized specimen can be used as an effective implant in acetabular fracture sites based on their mechanical and biological properties.


Subject(s)
Acetabulum , Anti-Bacterial Agents , Silver , Strontium , Titanium , Titanium/chemistry , Titanium/pharmacology , Silver/chemistry , Silver/pharmacology , Strontium/chemistry , Strontium/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Acetabulum/injuries , Animals , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Osseointegration/drug effects , Mice , Surface Properties , Fractures, Bone/therapy , Durapatite/chemistry , Durapatite/pharmacology , Osteoblasts/drug effects , Hydroxyapatites/chemistry , Hydroxyapatites/pharmacology , Prostheses and Implants , Ions/chemistry , Ions/pharmacology , Humans , Cell Line
18.
Phys Chem Chem Phys ; 15(31): 12988-97, 2013 Aug 21.
Article in English | MEDLINE | ID: mdl-23817610

ABSTRACT

The natural tendency of carbon nanotubes (CNTs) to agglomerate is an underlying reason that prevents the realization of their full potential. On the other hand, covalent functionalization of CNTs to control dispersion leads to disruption of π-conjugation in CNTs and the non-covalent functionalization leads to a weak CNT-polymer interface. To overcome these challenges, we describe the characteristics of fostering of direct nucleation of polymers on nanostructured carbon (CNTs of diameters (~2-200 nm), carbon nanofibers (~200-300 nm), and graphene), which culminates in interfacial adhesion, resulting from electrostatic and van der Waals interaction in the hybrid nanostructured carbon-polymer architecture. Furthermore, the structure is tunable through a change in undercooling. High density polyethylene and polypropylene were selected as two model polymers and two sets of experiments were carried out. The first set of experiments was carried out using CNTs of diameter ~2-5 nm to explore the effect of undercooling and polymer concentration. The second set of experiments was focused on studying the effect of dimensionality on geometrical confinements. The periodic crystallization of polyethylene on small diameter CNTs is demonstrated to be a consequence of the geometrical confinement effect, rather than epitaxy, such that petal-like disks nucleate on large diameter CNTs, carbon nanofibers, and graphene. The application of the process is illustrated in terms of fabricating a system for cellular uptake and bioimaging.


Subject(s)
Nanotubes, Carbon/chemistry , Organometallic Compounds/chemistry , Cells, Cultured , HeLa Cells , Humans , Particle Size , Polymers/chemistry , Surface Properties
19.
J Mater Sci Mater Med ; 24(7): 1789-98, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23529292

ABSTRACT

This article reports the intermittent pulse electric field stimulus mediated in vitro cellular response of L929 mouse fibroblast/SaOS2 osteoblast-like cells on austenitic steel substrates in reference to the field strength dependent behavior. The cellular density and morphometric analyses revealed that the optimal electric (E) fields for the maximum cell density of adhered L929 (~270 % to that of untreated sample) and SaOS2 (~280 % to that of untreated sample) cells are 1 V (0.33 V/cm) and 2 V (0.67 V/cm), respectively. The trend in aspect ratio of elongated SaOS2 cells did not indicate any significant difference among the untreated and treated (up to 3.33 V/cm) cells. The average cell and nucleus areas (for SaOS2 cells) were increased with an increase in the applied voltage up to 8 V (2.67 V/cm) and reduced thereafter. However, the ratio of nucleus to total cell area was increased significantly on the application of higher voltages (2-10 V), indicating the possible influence of E-field on cell growth. Further, the cell density results were compared with earlier results obtained with sintered Hydroxyapatite (HA) and HA-BaTiO3 composites and such comparison revealed that the enhanced cell density on steel sample occurs upon application of much lower field strength and stimulation time. This indicates the possible role of substrate conductivity towards cell growth in pulsed E-field mediated culture conditions.


Subject(s)
Fibroblasts/drug effects , Osteoblasts/drug effects , Stainless Steel/pharmacology , Animals , Cell Proliferation/drug effects , Cells, Cultured , Electric Conductivity , Electric Stimulation/methods , Fibroblasts/cytology , Fibroblasts/physiology , Humans , Mice , Microscopy, Fluorescence , Osteoblasts/cytology , Osteoblasts/physiology , Osteogenesis/drug effects , Osteogenesis/physiology , Stainless Steel/chemistry , Surface Properties , Tissue Scaffolds/chemistry
20.
Acta Cytol ; 57(3): 303-8, 2013.
Article in English | MEDLINE | ID: mdl-23635450

ABSTRACT

UNLABELLED: Spindle epithelial tumor with thymus-like differentiation (SETTLE) is an extremely rare type of thyroid tumor with fewer than 35 reported cases available in the literature so far, most of them having been diagnosed histologically after resection. The tumor is believed to be derived from branchial-pouch or thymic remnants, occurring in young adults, predominantly in males, with a male:female ratio 1.8:1. CASE: A 14-year-old girl presented with a nodular mass in her right thyroid that had been present for 1 year. Ultrasonological study revealed a heterogeneous solid mass (2.5 × 1.5 × 1.5 cm) in the right lobe of the thyroid. Fine-needle aspiration (FNA) smears were highly cellular and comprised of predominantly dissociated uniform spindle cells with naked oval nuclei along with some aggregates and groups. Occasional islands of epithelial cells were also present. Cytologically, the spindle cells had bland nuclear chromatin, with very scanty mitotic figures. Upon examination of the FNA smears, a provisional diagnosis of SETTLE was suggested along with a request for an incisional biopsy to rule out another differential diagnosis of medullary carcinoma thyroid. On the resected tissue specimen, diagnosis was histologically confirmed to be SETTLE. Immunohistochemical study revealed a strong and diffuse positivity for high-molecular-weight keratin and vimentin, and negativity for thyroglobulin, calcitonin, S-100 protein, desmin, chromogranin and synaptophysin. CONCLUSION: Cytologically, SETTLE can safely be considered, especially if spindle elements are observed along with the occasional group of epithelial cells in FNA smears from the thyroid of young adults. It can help in the preoperative recognition of lesions based on distinctive cytomorphological features and immunohistochemical characteristics, allowing a more sound therapeutic approach because these patients can present with delayed metastasis.


Subject(s)
Carcinoma/pathology , Cell Differentiation , Thymus Gland/pathology , Thyroid Neoplasms/pathology , Adolescent , Biomarkers, Tumor/analysis , Biopsy, Fine-Needle , Carcinoma/chemistry , Carcinoma/surgery , Female , Humans , Immunohistochemistry , Predictive Value of Tests , Thyroid Neoplasms/chemistry , Thyroid Neoplasms/surgery , Thyroidectomy
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