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1.
J Proteome Res ; 21(10): 2293-2310, 2022 Oct 07.
Article in English | MEDLINE | ID: mdl-36039803

ABSTRACT

Background: Distinct hippocampal subfields are known to get affected during aging, psychiatric disorders, and various neurological and neurodegenerative conditions. To understand the biological processes associated with each subfield, it is important to understand its heterogeneity at the molecular level. To address this lacuna, we investigated the proteomic analysis of hippocampal subfields─the cornu ammonis sectors (CA1, CA2, CA3, CA4) and dentate gyrus (DG) from healthy adult human cohorts. Findings: Microdissection of hippocampal subfields from archived formalin-fixed paraffin-embedded tissue sections followed by TMT-based multiplexed proteomic analysis resulted in the identification of 5,593 proteins. Out of these, 890 proteins were found to be differentially abundant among the subfields. Further bioinformatics analysis suggested proteins related to gene splicing, transportation, myelination, structural activity, and learning processes to be differentially abundant in DG, CA4, CA3, CA2, and CA1, respectively. A subset of proteins was selected for immunohistochemistry-based validation in an independent set of hippocampal samples. Conclusions: We believe that our findings will effectively pave the way for further analysis of the hippocampal subdivisions and provide awareness of its subfield-specific association to various neurofunctional anomalies in the future. The current mass spectrometry data is deposited and publicly made available through ProteomeXchange Consortium via the PRIDE partner repository with the data set identifier PXD029697.


Subject(s)
Magnetic Resonance Imaging , Proteomics , Adult , Aging , Formaldehyde , Hippocampus , Humans , Magnetic Resonance Imaging/methods
2.
J Am Med Inform Assoc ; 28(6): 1308-1317, 2021 06 12.
Article in English | MEDLINE | ID: mdl-33682009

ABSTRACT

OBJECTIVE: Modern health care requires patients, staff, and equipment to navigate complex environments to deliver quality care efficiently. Real-time locating systems (RTLS) are local tracking systems that identify the physical locations of personnel and equipment in real time. Applications and analytic strategies to utilize RTLS-produced data are still under development. The objectives of this systematic review were to describe and analyze the key features of RTLS applications and demonstrate their potential to improve care delivery. MATERIALS AND METHODS: We searched MEDLINE, SCOPUS, and IEEE following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Inclusion criteria were articles that utilize RTLS to evaluate or influence workflow in a healthcare setting. We summarized aspects of relevant articles, identified key themes in the challenges of applying RTLS to workflow improvement, and thematically reviewed the state of quantitative analytic methodologies. RESULTS: We included 42 articles in the final qualitative synthesis. The most frequent study design was observational (n = 24), followed by descriptive (n = 12) and experimental (n = 6). The most common clinical environment for study was the emergency department (n = 12), followed by entire hospital (n = 7) and surgical ward (n = 6). DISCUSSION: The focus of studies changed over time from early experience to optimization to evaluation of an established system. Common narrative themes highlighted lessons learned regarding evaluation, implementation, and information visibility. Few studies have developed quantitative techniques to effectively analyze RTLS data. CONCLUSIONS: RTLS is a useful and effective adjunct methodology in process and quality improvement, workflow analysis, and patient safety. Future directions should focus on developing enhanced analysis to meaningfully interpret RTLS data.


Subject(s)
Computer Systems , Delivery of Health Care , Health Facilities , Hospitals , Humans , Workflow
3.
Neurol India ; 68(4): 832-837, 2020.
Article in English | MEDLINE | ID: mdl-32859823

ABSTRACT

BACKGROUND: The WHO 2016 classification of diffuse gliomas has incorporated molecular markers isocitrate dehydrogenase (IDH) gene mutations (IDHmut) and codeletion of chromosomal arms 1p and 19q (1p/19q codeletion) as tumor defining entities. The diagnosis of diffuse oligodendrogliomas (ODG) and anaplastic oligodendroglioma (AO) mandatorily requires the demonstration of IDH1 and/or IDH2 mutations along with 1p/19q codeletion, whereas the 1p/19q noncodeleted diffuse gliomas are labeled as astrocytomas. The current methodologies for assessing 1p/19q codeletion status are expensive and not widely available. Studies have proposed alpha internexin (INA) expression on immunohistochemistry (IHC) as a surrogate marker for 1p/19q codeletion and a good prognostic marker in gliomas. MATERIALS AND METHODS: In this study, we performed IHC for INA expression on the retrospective cohort of anaplastic gliomas (AGs) from our previously published study. RESULTS: INA positivity on IHC showed a significant positive correlation with 1p/19q codeletion (P < 0.001) with a Spearman's rank correlation coefficient (Rho) of 0.804, sensitivity of 87.5%, specificity of 93.0%, and a diagnostic odds ratio of 93:1 in AGs. Similar to the 1p/19q codeletion status, INA positivity showed a positive correlation with IDHmut (P = 0.002) and a negative correlation with α-thalassemia mental retardation X-linked protein (ATRX) loss of expression (P < 0.001). On univariate survival analysis, INA positivity was associated with significantly prolonged overall survival (OS) and recurrent free survival (RFS) in AGs (P < 0.001). Furthermore, within AO, INA positivity significantly improved RFS (P = 0.022) with OS trending towards significance (P = 0.094). CONCLUSIONS: INA expression on IHC could serve as a potential surrogate marker for 1p/19q, and highlights its prognostic value in AO and AGs.


Subject(s)
Brain Neoplasms , Glioma , Oligodendroglioma , Biomarkers , Brain Neoplasms/genetics , Chromosomes, Human, Pair 1/genetics , Chromosomes, Human, Pair 19/genetics , Glioma/diagnosis , Glioma/genetics , Humans , Mutation , Prognosis , Retrospective Studies , World Health Organization
5.
Oncogene ; 36(1): 71-83, 2017 01 05.
Article in English | MEDLINE | ID: mdl-27212030

ABSTRACT

An integrative functional genomics study of multiple forms of data are vital for discovering molecular drivers of cancer development and progression. Here, we present an integrated genomic strategy utilizing DNA methylation and transcriptome profile data to discover epigenetically regulated genes implicated in cancer development and invasive progression. More specifically, this analysis identified fibromodulin (FMOD) as a glioblastoma (GBM) upregulated gene because of the loss of promoter methylation. Secreted FMOD promotes glioma cell migration through its ability to induce filamentous actin stress fiber formation. Treatment with cytochalasin D, an actin polymerization inhibitor, significantly reduced the FMOD-induced glioma cell migration. Small interfering RNA and small molecule inhibitor-based studies identified that FMOD-induced glioma cell migration is dependent on integrin-FAK-Src-Rho-ROCK signaling pathway. FMOD lacking C-terminus LRR11 domain (ΔFMOD), which does not bind collagen type I, failed to induce integrin and promote glioma cell migration. Further, FMOD-induced integrin activation and migration was abrogated by a 9-mer wild-type peptide from the FMOD C-terminus. However, the same peptide with mutation in two residues essential for FMOD interaction with collagen type I failed to compete with FMOD, thus signifying the importance of collagen type I-FMOD interaction in integrin activation. Chromatin immunoprecipitation-PCR experiments revealed that transforming growth factor beta-1 (TGF-ß1) regulates FMOD expression through epigenetic remodeling of FMOD promoter that involved demethylation and gain of active histone marks with a simultaneous loss of DNMT3A and EZH2 occupancy, but enrichment of Sma- and Mad-related protein-2 (SMAD2) and CBP. FMOD silencing inhibited the TGF-ß1-mediated glioma cell migration significantly. In univariate and multivariate Cox regression analysis, both FMOD promoter methylation and transcript levels predicted prognosis in GBM. Thus, this study identified several epigenetically regulated alterations responsible for cancer development and progression. Specifically, we found that secreted FMOD as an important regulator of glioma cell migration downstream of TGF-ß1 pathway and forms a potential basis for therapeutic intervention in GBM.


Subject(s)
Epigenesis, Genetic , Epigenomics , Fibromodulin/genetics , Gene Expression Regulation, Neoplastic , Genes, Essential , Glioma/genetics , Cell Line, Tumor , Cell Movement/drug effects , Chromatin Assembly and Disassembly , Collagen Type I/metabolism , Cytoskeleton/metabolism , DNA Methylation , Epigenomics/methods , Focal Adhesion Protein-Tyrosine Kinases/metabolism , Gene Expression Profiling , Genome-Wide Association Study , Glioma/metabolism , Glioma/mortality , Humans , Kaplan-Meier Estimate , Models, Biological , Prognosis , Promoter Regions, Genetic , Signal Transduction/drug effects , Transcription, Genetic , Transcriptome , Transforming Growth Factor beta1/metabolism , rho-Associated Kinases/metabolism , src-Family Kinases/metabolism
7.
J Clin Pathol ; 69(8): 686-94, 2016 Aug.
Article in English | MEDLINE | ID: mdl-26743027

ABSTRACT

AIMS: Anaplastic gliomas (AGs; WHO Grade III) include anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) and are known to have variable prognosis. Since biomarkers have a major impact on prognosis of gliomas, we compared the prognostic significance of the established biomarkers of AGs and the 'histomolecular' subgroups based on the proposed International Society of Neuropathology-Haarlem ('ISN-Haarlem') guidelines, with the current WHO 2007 classification. METHODS: The study was carried out on formalin-fixed paraffin-embedded (FFPE) tissues from 91 adult patients with AG. Clinical, histological and molecular parameters, including 1p/19q codeletion, isocitrate dehydrogenase gene (IDH1)-R132H positivity, α thalassemia/mental retardation syndrome X-linked gene (ATRX) expression and O(6)-methylguanine-DNA-methyltransferase gene (MGMT) promoter methylation (mMGMT), were correlated with overall survival (OS) and recurrence-free survival (RFS). Subsequently, following sequencing for rare IDH mutations, we derived three 'histomolecular' subgroups based on the 'integrated' diagnosis approach proposed by 'ISN-Haarlem' guidelines and correlated this with clinical outcome. RESULTS: Gross tumour resection, administration of radiochemotherapy, 1p/19q codeletion, IDH1-R132H positivity and mMGMT were associated with favourable OS and RFS (p≤0.001), while the WHO histological subgroups were prognostically not significant. The ISN 'histomolecular' subgroups prognosticated best with AOs (IDHmut, 1p/19q codeleted, ATRX predominantly retained) having the best survival, followed by the AAs (IDHmut, ATRX loss or retained, 1p19q non-codeleted) and AA IDH wild type group having the worst OS and RFS (p=<0.001 for OS). CONCLUSIONS: Our study reiterates the prognostic significance of biomarkers, 1p/19q codeletion, IDH1-R132H positivity and mMGMT in AGs. Importantly, we show that the 'histomolecular' subgroups of AGs based on the 'integrated' diagnosis has a prognostic value, superior to the WHO histological classification.


Subject(s)
Astrocytoma/diagnosis , Brain Neoplasms/diagnosis , Oligodendroglioma/diagnosis , Adult , Astrocytoma/metabolism , Astrocytoma/mortality , Astrocytoma/pathology , Brain Neoplasms/metabolism , Brain Neoplasms/mortality , Brain Neoplasms/pathology , DNA Helicases/metabolism , DNA Modification Methylases/metabolism , DNA Repair Enzymes/metabolism , Female , Humans , Isocitrate Dehydrogenase/metabolism , Male , Middle Aged , Nuclear Proteins/metabolism , Oligodendroglioma/metabolism , Oligodendroglioma/mortality , Oligodendroglioma/pathology , Prognosis , Promoter Regions, Genetic , Survival Rate , Tumor Suppressor Proteins/metabolism , X-linked Nuclear Protein , Young Adult
8.
J Clin Diagn Res ; 9(9): XD04-XD05, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26500998

ABSTRACT

Exstrophy of the urinary bladder is a rare congenital anomaly which if untreated causes bladder carcinoma and intestinal tumours noted if urinary diversion is performed. It is seen that 50% of all persons afflicted with exstrophy are dead by their tenth year and 66-67% are dead by their twentieth year. It is thus a great rarity to see a case of ectopia vesicae in adulthood. Still more uncommon is to see a case of exstrophy complicated by carcinoma. Here, we report a case of papillary adenocarcinoma of ectopic urinary bladder in a 42-year-old male patient. In view of locally advanced disease, patient was given neoadjuvant chemotherapy. The case is being reported on account of its rarity to sensitise clinicians about rising incidence of carcinoma if mismanaged due to lack of protocol in oncological screening.

10.
Pathol Res Pract ; 210(7): 407-11, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24690322

ABSTRACT

BACKGROUND: Very little literature exists on frequency of MGMT methylation status in pituitary adenoma. We assessed the frequency of MGMT methylation and protein expression in pituitary adenoma and correlated with patients' age group and prognosis. METHODS: Tumor tissues from 30 patients with pituitary adenoma were evaluated for MGMT promoter methylation status by methylation specific PCR method. All tumors were also immunostained with MIB-1, anti-p53 and anti-MGMT antibodies. RESULTS: MGMT methylation status was noted in 40% of cases (7/20 non-functioning adenomas and 5/10 functioning adenomas). MGMT protein expression on IHC was noted in 72.2% of unmethylated tumors, while only 41.6% of methylated tumors demonstrated protein expression. The mean labeling index of MGMT protein was higher in unmethylated tumors as compared to the methylated group, though the difference was not statistically significant (18.6% vs 8.8%; p=0.131). Tumor regrowth occurred in four unmethylated tumors as compared to none in methylated group. Even though there was no correlation between patient age and MGMT methylation status (p=0.823), we noted that the frequency of methylation in middle age patients (between 30 and 59 yrs) was 64.7%, which was higher compared to other age groups. CONCLUSION: This is the first study from India showing MGMT promoter methylation status with protein expression in pituitary adenoma. We noted that tumor regrowth was higher in unmethylated tumors.


Subject(s)
Adenoma/genetics , DNA Methylation/genetics , DNA Modification Methylases/genetics , DNA Repair Enzymes/genetics , Pituitary Neoplasms/genetics , Tumor Suppressor Proteins/genetics , Adolescent , Adult , Aged , Female , Humans , Immunohistochemistry , India , Male , Middle Aged , Prognosis , Reverse Transcriptase Polymerase Chain Reaction , Young Adult
11.
J Environ Sci Eng ; 56(1): 37-40, 2014 Jan.
Article in English | MEDLINE | ID: mdl-26445754

ABSTRACT

Rice variety KMP101 was treated with both organic and inorganic manure. The field and experimental studies were conducted, before applying organic and inorganic manures.The values obtained for available nitrogen, phosphorous and potassium were 360 kg/ha, 12 kg/ha and 166 kg/ha respectively. After treatment and harvest there was a gradual increase in available nitrogen, phosphorus and potassium ranging between 335-415, 14 -23 and 173- 235 kg/ha respectively among the treatments. Applying 15 t of vermicompost /ha and 10 t of vermicompost /ha and recommended dose of fertilizer showed a greater availability of nitrogen and phosphorus. It is revealed that after addition of organics into the soil year-wise, the soil became more stable. Also, the biological activity increased in the soil and was influenced to maintain the available nitrogen in the soil. Therefore, it is evident that vermicompost significantly increases the availability of available nutrients.


Subject(s)
Fertilizers/analysis , Nitrogen/metabolism , Oligochaeta/physiology , Phosphorus/metabolism , Potassium/metabolism , Soil/chemistry , Animals , Crops, Agricultural/growth & development , Crops, Agricultural/metabolism , Manure/analysis , Oryza/growth & development , Oryza/metabolism , Recycling
12.
J Health Commun ; 18 Suppl 1: 143-57, 2013.
Article in English | MEDLINE | ID: mdl-24093352

ABSTRACT

Limited health literacy is associated with worse executive function, but the association between limited health literacy and decline in executive function has not been established because of a lack of longitudinal studies. The authors aimed to examine this association by studying a prospective cohort in the setting of a randomized controlled trial to promote walking in older adults. Participants were community-dwelling older adults (65 years of age or older) who scored 2 or more on the Mini-Cog, without depression (score of less than 15 on the 9-item Patient Health Questionnaire), and who completed baseline and 12-month evaluations (n = 226). Health literacy was measured using the Short Test of Functional Health Literacy in Adults. Executive function measured at baseline and 12 months using the Trail Making Test (TMT), Controlled Oral Word Association Test, and Category Fluency. The associations between health literacy and 12-month decline in each test of executive function were modeled using multivariate linear regression. Health literacy was found to be limited in 37% of participants. Limited health literacy was associated with reduced performance on all 3 executive function tests. In fully adjusted models, limited health literacy was associated with greater 12-month decline in performance on the TMT than higher health literacy (p = .01). In conclusion, older adults with limited health literacy are at risk for more rapid decline in scores on the TMT, a measure of executive function.


Subject(s)
Executive Function/physiology , Health Literacy/statistics & numerical data , Aged , Aged, 80 and over , Female , Humans , Linear Models , Male , Multivariate Analysis , Prospective Studies , Risk Assessment , Trail Making Test
13.
Enzyme Res ; 2011: 805187, 2011.
Article in English | MEDLINE | ID: mdl-21912739

ABSTRACT

A large number of enzymes from bacteria, fungi, and plants have been reported to be involved in the biodegradation of toxic organic pollutants. Bioremediation is a cost effective and nature friendly biotechnology that is powered by microbial enzymes. The research activity in this area would contribute towards developing advanced bioprocess technology to reduce the toxicity of the pollutants and also to obtain novel useful substances. The information on the mechanisms of bioremediation-related enzymes such as oxido-reductases and hydrolases have been extensively studied. This review attempts to provide descriptive information on the enzymes from various microorganisms involved in the biodegradation of wide range of pollutants, applications, and suggestions required to overcome the limitations of their efficient use.

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