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1.
Appl Acoust ; 188: 108582, 2022 Jan.
Article in English | MEDLINE | ID: mdl-36530553

ABSTRACT

The paper analyzed the impact of lockdown on the ambient noise levels in the seventy sites in the seven major cities of India and ascertained the noise scenario in lockdown period, and on the Janta Curfew day in comparison to the pre-lock down period and year 2019 annual average values. It was observed that the majority of the noise monitoring sites exhibited a decrement in ambient day and night equivalent noise levels on the national Janta Curfew day and Lockdown period as compared with the normal working days attributed to the restricted social, economical, industrial, urbanization activity and reduced human mobility. A mixed pattern was observed at a few sites, wherein the ambient day and night equivalent noise levels during Janta curfew day and Lockdown period had been reported to be higher than that on the normal working days. The study depicts the noise scenario during the lockdown and pre-lockdown period for seventy sites in India and shall be instrumental in analyzing the consequences and implications of imposing lockdowns in future on the environmental noise pollution in Indian cities.

2.
J Acoust Soc Am ; 152(3): 1317, 2022 09.
Article in English | MEDLINE | ID: mdl-36182312

ABSTRACT

This paper analyzes the impact of second wave of COVID-19 lockdown on environmental noise levels of 25 sites in Delhi city and compares the noise scenario during pre-lockdown, lockdown, and post-lockdown periods. The study utilized the noise monitoring data acquired from 25 real-time ambient noise monitoring stations, installed by the Delhi Pollution Control Committee, Delhi, at various sites throughout Delhi city. A significant reduction of up to 10 and 3 dB(A) in day and night equivalent noise levels, respectively, had been observed during the lockdown period as compared to the pre-lockdown and post-lockdown periods. The study also revealed that only nine sites, including four industrial and five commercial zone sites, complied with the ambient noise standards during lockdown period, and no silence or residential zone sites complied with the ambient noise standards even during the lockdown period. A roadmap for environmental noise management and control is suggested. The study also reports the community's perception toward the change in acoustic environment of Delhi city during the lockdown period by conducting an environmental noise perception survey. The present study should be helpful in devising noise control action plans and policy interventions for environmental noise management and control in the metropolitan city Delhi, India.


Subject(s)
COVID-19 , COVID-19/epidemiology , COVID-19/prevention & control , Cities , Communicable Disease Control , Environmental Monitoring , Humans , Noise/adverse effects
3.
J Laryngol Otol ; 135(7): 652-655, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33998420

ABSTRACT

BACKGROUND: Arrhinia is defined as the partial or complete absence of the nasal structures. It is a defect of embryonal origin and can be seen in association with other craniofacial anomalies, central nervous system anomalies, absence of paranasal sinuses, and other palatal and ocular abnormalities. Very few patients with arrhinia have been reported so far in the history of modern medicine. CASE REPORT: This study reports an adult patient with congenital partial arrhinia and reviews the literature along with the embryological basis of such a rare disease. CONCLUSION: Arrhinia is a medical condition with scarce documentation in the literature. This article presents the clinical as well as radiological features of this rare entity.


Subject(s)
Congenital Abnormalities/diagnostic imaging , Craniofacial Abnormalities/diagnostic imaging , Lacrimal Apparatus Diseases/diagnostic imaging , Nose/abnormalities , Congenital Abnormalities/embryology , Craniofacial Abnormalities/embryology , Humans , Lacrimal Apparatus/diagnostic imaging , Lacrimal Apparatus/embryology , Male , Maxillary Sinus/abnormalities , Maxillary Sinus/diagnostic imaging , Maxillary Sinus/embryology , Multidetector Computed Tomography , Nasolacrimal Duct/diagnostic imaging , Nasolacrimal Duct/embryology , Nose/diagnostic imaging , Nose/embryology , Young Adult
4.
Lab Chip ; 20(10): 1815-1826, 2020 05 19.
Article in English | MEDLINE | ID: mdl-32322845

ABSTRACT

A microfluidic approach to seeded crystallization has been demonstrated using abacavir hemisulfate, a nucleoside analog reverse transcriptase inhibitor, in droplet reactors to control polymorphism and produce particles with a low particle size distribution. Two techniques are introduced: (1) the first technique involves an emulsion system consisting of a dispersed phase solvent and a continuous phase, which holds slight solubility of the dispersed phase solvent. The dispersed phase contains both a dissolved active pharmaceutical ingredient (API) and seeds of the desired polymorph. While the continuous phase enables solvent extraction, the negligible solubility of the API allows for growth of seeds inside droplets via extraction and subsequent API saturation. This technique demonstrates the ability to crystallize the API in spherical agglomerates via slow extraction of droplets. (2) The second technique utilizes a combined dispersed phase by joining in-flow a seed suspension stream with a supersaturated active pharmaceutical ingredient (API) stream. The combined dispersed phase is emulsified in a continuous phase for which the dispersed phase solvent and the API are both insoluble - droplets are incubated at temperatures below their saturation limit to induce crystal growth. Decreasing the concentration of seeds in its input stream resulted in a decreased number of crystals per droplet, increase in crystal size, and decrease in PSD. Temperature cycling was utilized as a proof of concept to demonstrate the ability to reduce the number of seeds per droplet where the optimal goal is to obtain a single seed per droplet for all droplets. Utilizing this approach in conjunction with the ability to produce monodispersed droplet reactors allows for enhanced control of particle size distribution (PSD) by precisely controlling the available mass for each individual seed crystal. The development of this technique as a proof-of-concept for crystallization can be expanded to manufacturing scales in a continuous manner using parallelized droplet generators and flow reactors to precisely control the temperature and crystal growth kinetics of individual droplets.


Subject(s)
Microfluidics , Crystallization , Emulsions , Particle Size , Solubility
5.
Arch Pediatr ; 27(1): 39-44, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31780096

ABSTRACT

BACKGROUND: It is unclear whether multiple respiratory viral infections are associated with more severe bronchiolitis requiring pediatric intensive care unit (PICU) admission. We aimed to identify the association between multiple respiratory viral infections and PICU admission among infants with bronchiolitis. METHODS: We performed a 1:1 case-control study enrolling previously healthy full-term infants (≤12 months) with bronchiolitis admitted to the PICU as cases and those to the general pediatric ward as controls from 2015 to 2017. Multiplex polymerase chain reaction (PCR) was used for detection of the respiratory viruses. We summarized the characteristics of infants admitted to the PICU and the general pediatric unit. Multivariable logistic regression analysis was used to fit the association between multiple respiratory viral infections (≥2 strains) and PICU admission. RESULTS: A total of 135 infants admitted to the PICU were compared with 135 randomly selected control infants admitted to the general pediatric unit. The PICU patients were younger (median: 2.2 months, interquartile range: 1.3-4.2) than the general ward patients (median: 3.2 months, interquartile range: 1.6-6.4). Respiratory syncytial virus (74.1%), rhinovirus (28.9%), and coronavirus (5.9%) were the most common viruses for bronchiolitis requiring PICU admission. Patients with bronchiolitis admitted to the PICU tended to have multiple viral infections compared with patients on the general ward (23.0% vs. 10.4%, P<0.001). In the multivariable logistic regression analysis, bronchiolitis with multiple viral infections was associated with higher odds of PICU admission (adjusted odds ratio: 2.56, 95% confidence interval: 1.17-5.57, P=0.02). CONCLUSION: Infants with multiviral bronchiolitis have higher odds of PICU admission compared with those with a single or nondetectable viral infection.


Subject(s)
Bronchiolitis, Viral/virology , Coinfection/virology , Intensive Care Units, Pediatric/statistics & numerical data , Patient Admission/statistics & numerical data , Bronchiolitis, Viral/diagnosis , Bronchiolitis, Viral/therapy , Case-Control Studies , Coinfection/diagnosis , Coinfection/therapy , Female , Humans , Infant , Infant, Newborn , Logistic Models , Male , Multivariate Analysis , Retrospective Studies , Risk Factors , Severity of Illness Index
6.
Eur J Neurol ; 26(8): 1121-1129, 2019 Aug.
Article in English | MEDLINE | ID: mdl-30882969

ABSTRACT

BACKGROUND AND PURPOSE: Conduction block is a pathognomonic feature of immune-mediated neuropathies. The aim of this study was to advance understanding of pathophysiology and conduction block in chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). METHODS: A multimodal approach was used, incorporating clinical phenotyping, neurophysiology, immunohistochemistry and structural assessments. RESULTS: Of 49 CIDP and 14 MMN patients, 25% and 79% had median nerve forearm block, respectively. Clinical scores were similar in CIDP patients with and without block. CIDP patients with median nerve block demonstrated markedly elevated thresholds and greater threshold changes in threshold electrotonus, whilst those without did not differ from healthy controls in electrotonus parameters. In contrast, MMN patients exhibited marked increases in superexcitability. Nerve size was similar in both CIDP groups at the site of axonal excitability. However, CIDP patients with block demonstrated more frequent paranodal serum binding to teased rat nerve fibres. In keeping with these findings, mathematical modelling of nerve excitability recordings in CIDP patients with block support the role of paranodal dysfunction and enhanced leakage of current between the node and internode. In contrast, changes in MMN probably resulted from a reduction in ion channel density along axons. CONCLUSIONS: The underlying pathologies in CIDP and MMN are distinct. Conduction block in CIDP is associated with paranodal dysfunction which may be antibody-mediated in a subset of patients. In contrast, MMN is characterized by channel dysfunction downstream from the site of block.


Subject(s)
Neural Conduction/physiology , Peripheral Nerves/physiopathology , Polyneuropathies/physiopathology , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/physiopathology , Adult , Animals , Axons/physiology , Female , Humans , Male , Middle Aged , Rats
7.
AJNR Am J Neuroradiol ; 40(3): 543-550, 2019 03.
Article in English | MEDLINE | ID: mdl-30792253

ABSTRACT

BACKGROUND AND PURPOSE: Differentiating nodal metastases from reactive adenopathy in HIV-infected patients with [18F] FDG-PET/CT can be challenging because lymph nodes in HIV-positive patients often show increased [18F] FDG uptake. The purpose of this study was to assess CT textural analysis characteristics of HIV-positive and HIV-negative lymph nodes on [18F] FDG-PET/CT to differentiate nodal metastases from disease-specific nodal reactivity. MATERIALS AND METHODS: Nine HIV-positive patients with head and neck squamous cell carcinoma (7 men, 2 women; 29-62 years of age; median age, 48 years) with 22 lymph nodes (≥1 cm) who underwent contrast-enhanced CT with [18F] FDG-PET followed by pathologic evaluation of cervical lymph nodes were retrospectively reviewed. Twenty-six HIV-negative patients with head and neck squamous cell carcinoma with 61 lymph nodes were evaluated as a control group. Each lymph node was manually segmented, and an in-house-developed Matlab-based texture analysis program extracted 41 texture features from each segmented volume. A mixed linear regression model was used to compare the pathologically proved malignant lymph nodes with benign nodes in the 2 enrolled groups. RESULTS: Thirteen (59%) lymph nodes in the HIV-positive group and 22 (36%) lymph nodes in the HIV-negative control group were confirmed as positive for metastases. There were 7 histogram features (P = .017-0.032), 3 gray-level co-occurrence features (P = .009-.025), and 9 gray-level run-length features (P < .001-.033) that demonstrated a significant difference in HIV-positive patients with either benign or malignant lymph nodes. CONCLUSIONS: CT texture analysis may be useful as a noninvasive method of obtaining additional quantitative information to differentiate nodal metastases from disease-specific nodal reactivity in HIV-positive patients with head and neck squamous cell carcinoma.


Subject(s)
Image Interpretation, Computer-Assisted/methods , Lymphadenopathy/diagnostic imaging , Lymphatic Metastasis/diagnostic imaging , Positron Emission Tomography Computed Tomography/methods , Squamous Cell Carcinoma of Head and Neck/diagnostic imaging , Adult , Diagnosis, Differential , Female , Fluorodeoxyglucose F18 , HIV Infections/complications , HIV Infections/pathology , Humans , Lymphadenopathy/etiology , Lymphadenopathy/virology , Lymphatic Metastasis/pathology , Male , Middle Aged , Retrospective Studies , Sensitivity and Specificity , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/virology
8.
Ann Oncol ; 30(2): 243-249, 2019 02 01.
Article in English | MEDLINE | ID: mdl-30462160

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) has been shown to acquire RAS and EGFR ectodomain mutations as mechanisms of resistance to epidermal growth factor receptor (EGFR) inhibition (anti-EGFR). After anti-EGFR withdrawal, RAS and EGFR mutant clones lack a growth advantage relative to other clones and decay; however, the kinetics of decay remain unclear. We sought to determine the kinetics of acquired RAS/EGFR mutations after discontinuation of anti-EGFR therapy. PATIENTS AND METHODS: We present the post-progression circulating tumor DNA (ctDNA) profiles of 135 patients with RAS/BRAF wild-type metastatic CRC treated with anti-EGFR who acquired RAS and/or EGFR mutations during therapy. Our validation cohort consisted of an external dataset of 73 patients with a ctDNA profile suggestive of prior anti-EGFR exposure and serial sampling. A separate retrospective cohort of 80 patients was used to evaluate overall response rate and progression free survival during re-challenge therapies. RESULTS: Our analysis showed that RAS and EGFR relative mutant allele frequency decays exponentially (r2=0.93 for RAS; r2=0.94 for EGFR) with a cumulative half-life of 4.4 months. We validated our findings using an external dataset of 73 patients with a ctDNA profile suggestive of prior anti-EGFR exposure and serial sampling, confirming exponential decay with an estimated half-life of 4.3 months. A separate retrospective cohort of 80 patients showed that patients had a higher overall response rate during re-challenge therapies after increasing time intervals, as predicted by our model. CONCLUSION: These results provide scientific support for anti-EGFR re-challenge and guide the optimal timing of re-challenge initiation.


Subject(s)
Colorectal Neoplasms/drug therapy , Drug Resistance, Neoplasm , Neoplastic Cells, Circulating/pathology , Protein Kinase Inhibitors/therapeutic use , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Disease Progression , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , Follow-Up Studies , Humans , Mutation , Neoplasm Metastasis , Prognosis , Retrospective Studies , Survival Rate , ras Proteins/genetics
9.
Br J Biomed Sci ; 75(1): 13-18, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28945174

ABSTRACT

BACKGROUND AND AIM: The emergence of resistance against antimicrobial agents has led to the development of more efficient agents and new techniques for treatment of various microbial infections. The aim of the present study is to determine the antibacterial and antifungal activity of bare and chitosan coated Fe3O4 nanoparticles (NPs) against five organisms, Escherichia coli (E. coli), Bacillus subtilis (B. subtilis), Candida albicans (C. albicans), Aspergillus niger (A. niger) and Fusarium solani (F. solani). METHODS: Fe3O4 NPs were synthesised by coprecipitation and surface coating was done by chitosan polymer to avoid agglomeration. The antimicrobial property of NPs was tested by agar well diffusion and analysed by measuring the diameter of the inhibition zone. RESULTS: Average particle size of Fe3O4 and chitosan coated Fe3O4 NPs was 10.4 ± 4.9 and 11.4 ± 5.2 nm, respectively. Mean diameter of inhibition zone of synthesised chitosan coated Fe3O4 NPs was in the range 14.5 to 18.5 mm. The effect of chitosan coated Iron oxide nanoparticles was F. solani/A. niger < C. albicans < E. coli/B. subtilis (p < 0.001). CONCLUSIONS: Chitosan coated Fe3O4 NPs are effective antimicrobial agents and so may be developed as a microbial resistant coating for biomedical devices.


Subject(s)
Chitosan/chemistry , Coated Materials, Biocompatible/pharmacology , Ferrosoferric Oxide/pharmacology , Magnetite Nanoparticles/chemistry , Aspergillus niger/drug effects , Aspergillus niger/growth & development , Bacillus subtilis/drug effects , Bacillus subtilis/growth & development , Candida albicans/drug effects , Candida albicans/growth & development , Disk Diffusion Antimicrobial Tests , Escherichia coli/drug effects , Escherichia coli/growth & development , Fusarium/drug effects , Fusarium/growth & development , Microbial Viability/drug effects , Particle Size
10.
J Neuroimmunol ; 309: 41-46, 2017 08 15.
Article in English | MEDLINE | ID: mdl-28601286

ABSTRACT

Autoantibodies to nodal/paranodal proteins have been reported in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). To determine the frequency of anti-paranodal antibodies in our cohort of CIDP patients and to validate the presence anti-nodal antibodies in MMN, sera were screened for IgG against human neurofascin 155, contactin-1, neurofascin 186 and gliomedin using ELISA. In CIDP patients, 7% were anti-NF155 IgG4 positive and 7% were anti-CNTN1 IgG4 positive. Positive results were confirmed using cell based assays and indirect immunofluorescence on teased nerve fibres. We did not detect IgG autoantibodies against these nodal/paranodal antigens in MMN patients.


Subject(s)
Autoantibodies/blood , Polyneuropathies/blood , Polyneuropathies/diagnosis , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/blood , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/diagnosis , Adult , Aged , Animals , Autoantibodies/immunology , Cell Adhesion Molecules/blood , Cell Adhesion Molecules/immunology , Female , HeLa Cells , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Male , Membrane Proteins/blood , Membrane Proteins/immunology , Middle Aged , Nerve Growth Factors/blood , Nerve Growth Factors/immunology , Nerve Tissue Proteins/blood , Nerve Tissue Proteins/immunology , Polyneuropathies/immunology , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/immunology , Rats , Rats, Inbred Lew
11.
Methods Enzymol ; 586: 1-14, 2017.
Article in English | MEDLINE | ID: mdl-28137558

ABSTRACT

The thiol moiety of cysteine residues can undergo a number of biologic modifications including oxidation, sulfenylation, nitrosylation, persulfidation, metalation, and other modifications. These modifications can control biological function, including gain as well as loss of function. Herein, we focus attention on the proteomic analysis of S-nitrosylation in health and disease. We describe a novel quantitative approach that combines accurate, sensitive fluorescence modification of cysteinyl-S-nitrosylation that leaves electrophoretic mobility unaffected (SNOFlo), and introduce unique concepts for measuring changes in S-nitrosylation status relative to protein abundance. We present several studies where suitability of this approach for investigating endogenous S-nitrosylation is addressed.


Subject(s)
Cysteine/analogs & derivatives , Protein Processing, Post-Translational , Proteome/analysis , S-Nitrosothiols/analysis , Animals , Cysteine/analysis , Cysteine/metabolism , Humans , Proteome/metabolism , S-Nitrosothiols/metabolism , Spectrometry, Fluorescence
12.
Oncogene ; 36(5): 606-617, 2017 02 02.
Article in English | MEDLINE | ID: mdl-27775079

ABSTRACT

Medulloblastoma (MB), the most common malignant paediatric brain tumor, is currently treated using a combination of surgery, craniospinal radiotherapy and chemotherapy. Owing to MB stem cells (MBSCs), a subset of MB patients remains untreatable despite standard therapy. CD133 is used to identify MBSCs although its functional role in tumorigenesis has yet to be determined. In this work, we showed enrichment of CD133 in Group 3 MB is associated with increased rate of metastasis and poor clinical outcome. The signal transducers and activators of transcription-3 (STAT3) pathway are selectively activated in CD133+ MBSCs and promote tumorigenesis through regulation of c-MYC, a key genetic driver of Group 3 MB. We screened compound libraries for STAT3 inhibitors and treatment with the selected STAT3 inhibitors resulted in tumor size reduction in vivo. We propose that inhibition of STAT3 signaling in MBSCs may represent a potential therapeutic strategy to treat patients with recurrent MB.


Subject(s)
AC133 Antigen/biosynthesis , Brain Neoplasms/drug therapy , Brain Neoplasms/pathology , Medulloblastoma/drug therapy , Medulloblastoma/pathology , Neoplasm Recurrence, Local/pathology , Neoplastic Stem Cells/pathology , STAT3 Transcription Factor/antagonists & inhibitors , AC133 Antigen/immunology , Animals , Brain Neoplasms/immunology , Cell Line, Tumor , Cell Proliferation/physiology , Female , Heterografts , Humans , Male , Medulloblastoma/immunology , Mice , Neoplasm Recurrence, Local/immunology , Neoplastic Stem Cells/immunology , Neoplastic Stem Cells/metabolism , STAT3 Transcription Factor/metabolism , Signal Transduction , Small Molecule Libraries/pharmacology , Up-Regulation
13.
Ann R Coll Surg Engl ; 99(1): e8-e10, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27502344

ABSTRACT

INTRODUCTION Larsen syndrome is an autosomal-dominant osteochondrodysplasia characterised by large joint dislocations and craniofacial anomalies. CASE HISTORY We present a rare case of Larsen syndrome with bilateral dislocated hips and knees and severe clubfeet at 7-year follow-up. We undertook bilateral open reduction of both hips at age 8 months. This procedure was preceded by open reduction and left-knee V-Y quadricepsplasty at age 4 months following a failed trial of closed reduction of the left knee. Both feet had a severe deformity (Pirani score of 5.5 and 6.0) and were treated using the Ponseti method, but the left foot relapsed at 24 months and required posteromedial release. CONCLUSIONS We tried to address the difficult questions on the timing and sequence of surgical interventions by treating clubfeet and dislocated knees early using Ponseti casts which included the knees. Open reduction of hips was done later, and further interventions were guided by functional needs.


Subject(s)
Clubfoot/surgery , Hip Dislocation, Congenital/surgery , Knee Dislocation/surgery , Osteochondrodysplasias/complications , Child , Female , Humans , Knee Dislocation/congenital , Recurrence , Treatment Outcome
15.
Tuberculosis (Edinb) ; 101S: S35-S44, 2016 12.
Article in English | MEDLINE | ID: mdl-27733245

ABSTRACT

Pathogens frequently exploit or evade inflammasome activation in order to survive and proliferate. Alternatively, inadequate inflammasome activation by attenuated microorganisms or adjuvanted subunit vaccines may contribute to poor longevity of protection. To further understand these pathways, we determined the differential inflammasome transcriptome of human THP monocyte-derived macrophages in response to Mycobacterium bovis BCG, as compared to LPS or Trypanosoma cruzi. The results identify the highly specific innate recognition programs associated with inflammasome activation by human macrophages exposed to these microbial stimuli. BCG, T. cruzi, and LPS strongly induced expression of both unique and overlapping genes downstream of TLR signaling pathways including cytokines and chemokines that mediate inflammation and regulate cell death pathways. Compared to LPS, BCG failed to directly activate anti-apoptotic molecules and multiple NLR and inflammasome complex components including caspase-1, and actively repressed important signaling intermediates in AP-1 and NFκB transcription factor pathways. Both BCG and T. cruzi repressed expression of TXNIP, an anti-oxidant inhibitor that recruits caspase-1 to the NLRP3 inflammasome, while T. cruzi infection uniquely failed to activate TNF-α. These results identify unique pathogen specific strategies to activate inflammation and modulate cell death that may drive inflammatory outcomes and suggest avenues of investigation to optimize host immunity.


Subject(s)
BCG Vaccine/pharmacology , Inflammasomes/metabolism , Macrophage Activation/drug effects , Macrophages/drug effects , Macrophages/parasitology , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Trypanosoma cruzi/pathogenicity , Apoptosis/drug effects , Apoptosis Regulatory Proteins/metabolism , Cell Line , Cytokines/metabolism , Host-Pathogen Interactions , Humans , Immunity, Innate/drug effects , Inflammasomes/drug effects , Inflammasomes/genetics , Inflammasomes/immunology , Lipopolysaccharides/pharmacology , Macrophages/immunology , Macrophages/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/immunology , Signal Transduction/drug effects , Time Factors , Toll-Like Receptors/metabolism , Trypanosoma cruzi/immunology
16.
J Genet ; 95(2): 263-72, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27350668

ABSTRACT

Mutations in sarcomeric genes are common genetic cause of cardiomyopathies. An intronic 25-bp deletion in cardiac myosin binding protein C (MYBPC3) at 3' region is associated with dilated and hypertrophic cardiomyopathies in Southeast Asia. However, the frequency of sarcomeric gene polymorphisms and associated clinical presentation have not been established with left ventricular dysfunction (LVD). Therefore, the aim of the present study was to explore the association of MYBPC3 25-bp deletion, titin (TTN) 18 bp I/D, troponin T type 2 (TNNT2) 5 bp I/D and myospryn K2906N polymorphisms with LVD. This study includes 988 consecutive patients with angiographically confirmed coronary artery disease (CAD) and 300 healthy controls. Among the 988 CAD patients, 253 with reduced left ventricle ejection fraction (LVEF≤45%) were categorized as LVD. MYBPC3 25-bp deletion, TTN 18 bp I/D and TNNT2 5 bp I/D polymorphisms were determined by direct polymerase chain reaction method, while myospryn K2906N polymorphism by TaqMan assay. Our results showed that MYBPC3 25-bp deletion polymorphism was significantly associated with elevated risk of LVD (LVEF <45) (healthy controls versus LVD: OR=3.85, P <0.001; and nonLVD versus LVD: OR=1.65, P = 0.035), while TTN 18 bp I/D, TNNT2 5 bp I/D and myospryn K2906N polymorphisms did not show any significant association with LVD. The results also showed that MYBPC3 25-bp deletion polymorphism was significantly associated with other parameters of LV remodelling, i.e. LV dimensions (LV end diastole dimension, LVEDD: P = 0.037 and LV end systolic dimension, LVESD: P = 0.032). Our data suggests that MYBPC3 25-bp deletion may play significant role in conferring LVD as well as CAD risk in north Indian population.


Subject(s)
Base Sequence , Carrier Proteins/genetics , Coronary Artery Disease/genetics , Genetic Predisposition to Disease , Sequence Deletion , Ventricular Dysfunction, Left/genetics , Aged , Alleles , Case-Control Studies , Connectin/genetics , Coronary Artery Disease/diagnosis , Coronary Artery Disease/physiopathology , Female , Gene Expression , Heterozygote , Homozygote , Humans , Male , Middle Aged , Muscle Proteins/genetics , Polymerase Chain Reaction , Polymorphism, Genetic , Stroke Volume , Troponin T/genetics , Ventricular Dysfunction, Left/diagnosis , Ventricular Dysfunction, Left/physiopathology
17.
Article in English | MEDLINE | ID: mdl-26622188

ABSTRACT

INNOVATION: What is already known about the topic: psoriasis (PsO) is a common skin disease with major impact on quality of life (QoL). Patient-reported data on QoL from large number of PsO patients with and without psoriatic arthritis (PsA) are limited. WHAT THIS STUDY ADDS: In a large cohort referred to a university psoriasis center, patients with PsO and concomitant PsA (~30% in this group) had greater degrees of skin and nail involvement and experienced greater negative impacts on QoL. Despite large numbers of patients with moderate-to-severe disease, use of systemic therapy by community practitioners was uncommon. BACKGROUND: PsO and PsA are common diseases that have marked adverse impacts on QoL. The disease features and patient-reported QoL data comparing PsO and PsA patients are limited. OBJECTIVE: To identify and compare demographics, clinical disease characteristics, and QoL scores in a large cohort of PsO patients with and without PsA. METHODS: All PsO patients seen in a psoriasis specialty clinic, named the Center of Excellence for Psoriasis and Psoriatic Arthritis, were enrolled in an observational cohort. Demographic, QoL, and clinical data were collected from patient-reported questionnaires and from physical examinations performed by Center of Excellence for Psoriasis and Psoriatic Arthritis dermatologists and a rheumatologists. Cross sectional descriptive data were collected and comparisons between patients with PsO alone and those with concomitant PsA are presented. RESULTS: A total of 568 patients were enrolled in the database. Mean age of PsO onset was 28 years and mean disease duration was 18 years. Those with family history had an earlier onset of PsO by ~7 years. Mean body surface area involvement with PsO was 14%. Mean body mass index was 30.7. Prevalence of PsA was 29.8%. PsA patients had a higher mean body surface area compared to patients with PsO alone (16.7% vs 13.4%, P<0.05), higher prevalence of psoriatic nail changes (54.4% vs 36%, P<0.0002), and worse QoL scores as assessed by the Short Form-12 (67 vs 52, P<0.00001), Psoriasis Quality of Life-12 questionnaire (62 vs 71, P<0.01), and Routine Assessment of Patient Index Data 3 (2.3 vs 4.7, P<0.01). Strikingly, 49% of patients with PsO had never received any systemic therapy. CONCLUSION: These data highlight that PsO has marked negative impacts on QoL, while those patients with concomitant PsA are affected to a much greater degree. Despite large numbers of patients presenting with moderate-to-severe disease, use of systemic therapy for both PsO and PsA was uncommon.

18.
Appl Clin Inform ; 6(1): 185-99, 2015.
Article in English | MEDLINE | ID: mdl-25848422

ABSTRACT

BACKGROUND: Hospital closures are becoming increasingly common in the United States. Patients who received care at the closing hospitals must travel to different, often farther hospitals for care, and nearby remaining hospitals may have difficulty coping with a sudden influx of patients. OBJECTIVES: Our objectives are to analyze the dispersion patterns of patients from a closing hospital and to correlate that with distance from the closing hospital for three specific visit types: emergency, inpatient, and ambulatory. METHODS: In this study, we used data from a health information exchange to track patients from Saint Vincent's Medical Center, a hospital in New York City that closed in 2010, to determine where they received emergency, inpatient, and ambulatory care following the closure. RESULTS: We found that patients went to the next nearest hospital for their emergency and inpatient care, but ambulatory encounters did not correlate with distance. DISCUSSION: It is likely that patients followed their ambulatory providers as they transitioned to another hospital system. Additional work should be done to determine predictors of impact on nearby hospitals when another hospital in the community closes in order to better prepare for patient dispersion.


Subject(s)
Health Facility Closure , Hospitals , Patients/statistics & numerical data , Humans , New York City , Time Factors
19.
Bone Joint J ; 97-B(3): 412-9, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25737527

ABSTRACT

We undertook a retrospective comparative study of all patients with an unstable slipped capital femoral epiphysis presenting to a single centre between 1998 and 2011. There were 45 patients (46 hips; mean age 12.6 years; 9 to 14); 16 hips underwent intracapsular cuneiform osteotomy and 30 underwent pinning in situ, with varying degrees of serendipitous reduction. No patient in the osteotomy group was lost to follow-up, which was undertaken at a mean of 28 months (11 to 48); four patients in the pinning in situ group were lost to follow-up, which occurred at a mean of 30 months (10 to 50). Avascular necrosis (AVN) occurred in four hips (25%) following osteotomy and in 11 (42%) following pinning in situ. AVN was not seen in five hips for which osteotomy was undertaken > 13 days after presentation. AVN occurred in four of ten (40%) hips undergoing emergency pinning in situ, compared with four of 15 (47%) undergoing non-emergency pinning. The rate of AVN was 67% (four of six) in those undergoing pinning on the second or third day after presentation. Pinning in situ following complete reduction led to AVN in four out of five cases (80%). In comparison, pinning in situ following incomplete reduction led to AVN in 7 of 21 cases (33%). The rate of development of AVN was significantly higher following pinning in situ with complete reduction than following intracapsular osteotomy (p = 0.048). Complete reduction was more frequent in those treated by emergency pinning and was strongly associated with AVN (p = 0.005). Non-emergency intracapsular osteotomy may have a protective effect on the epiphyseal vasculature and should be undertaken with a delay of at least two weeks. The place of emergency pinning in situ in these patients needs to be re-evaluated, possibly in favour of an emergency open procedure or delayed intracapsular osteotomy. Non-emergency pinning in situ should be undertaken after a delay of at least five days, with the greatest risk at two and three days after presentation. Intracapsular osteotomy should be undertaken after a delay of at least 14 days. In our experience, closed epiphyseal reduction is harmful. Cite this article: Bone Joint J 2015;97-B:412-19.


Subject(s)
Bone Nails , Slipped Capital Femoral Epiphyses/surgery , Adolescent , Child , Female , Humans , Joint Capsule/diagnostic imaging , Joint Capsule/surgery , Male , Osteotomy/methods , Postoperative Complications/epidemiology , Radiography , Retrospective Studies , Slipped Capital Femoral Epiphyses/diagnostic imaging , Treatment Outcome
20.
Clin Rheumatol ; 34(10): 1745-51, 2015 Oct.
Article in English | MEDLINE | ID: mdl-24827874

ABSTRACT

Delaying diagnosis of psoriatic arthritis (PsA) can lead to poor quality of life and disability. The purpose of this study is to identify simple questions for dermatologists to screen psoriasis patients for psoriatic arthritis. Data regarding psoriasis and arthritis were prospectively collected by a questionnaire from all psoriasis patients. Patients with joint-related symptoms were assessed by a rheumatologist for the presence of PsA. Retrospectively, the sensitivity and specificity, positive and negative predictive values, likelihood ratios, and posttest probabilities of various screening questions were calculated to identify the best combination of parameters. Of 517 patients seen in dermatology clinic, 117 (22.63 %) were found to have PsA. Four screening questions ("Do you have a history of joint pain or swelling?" "Do you have stiffness in the morning?" "Have you had X-rays taken of your joints?" "Do you have PsA?") with psoriatic nail changes demonstrated high sensitivity and specificity for predicting PsA. A cutoff of three out of these five parameters correctly classified patients with and without PsA with 86.9 % sensitivity, 71.3 % specificity, 53 % positive predictive value (PPV), 93.6 % negative predictive value (NPV), and area under the curve (AUC) of 0.87. Likelihood ratios for individual parameters varied between1.6 and 3.7, and with a combination of certain parameters, the posttest probability of PsA was 76 %. This is a preliminary data on a potential screening questionnaire which can help dermatologists quickly screen for PsA. All patients not having evaluated by a rheumatologist could have led to underdiagnosis of PsA and potential misclassification. Psoriasis patients seen at a specialty clinic may introduce a referral bias.


Subject(s)
Arthritis, Psoriatic/diagnosis , Dermatology/methods , Mass Screening/methods , Surveys and Questionnaires , Aged , Area Under Curve , Cross-Sectional Studies , Female , Humans , Likelihood Functions , Male , Middle Aged , Predictive Value of Tests , Probability , Quality of Life , Regression Analysis , Research Design , Retrospective Studies , Rheumatology/methods , Sensitivity and Specificity
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