Publications by authors named "Satish Kumar Singh"

17 Publications

  • Page 1 of 1

MiR-592 activates the mTOR kinase, ERK1/ERK2 kinase signaling and imparts neuronal differentiation signature characteristic of group 4 medulloblastoma.

Hum Mol Genet 2021 Jul 19. Epub 2021 Jul 19.

Advanced Centre for Treatment, Research & Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, India.

Medulloblastoma, a common malignant brain tumor in children, consists of four molecular subgroups WNT, SHH, Group 3 and Group 4. Group 3, Group 4 tumors have an overlap in their expression profiles and genetic alterations but differ significantly in their clinical characteristics, with Group 3 having the worst five-year overall survival of less than 60%. MiR-592 is overexpressed predominantly in Group 4 tumors. MiR-592 expression reduced the anchorage-independent growth, invasion potential, and tumorigenicity of Group 3 medulloblastoma cells. DEPTOR, an endogenous inhibitor of the mTOR kinase, and EML1 were identified as novel targets of miR-592. The miR-592 mediated decrease in the DEPTOR expression levels activated both mTORC1 and mTORC2 complex in medulloblastoma cells. However, the miR-592 expression also decreased the AKT kinase activity, likely to be due to the activation of the inhibitory feedback of the mTOR signaling. MiR-592 expression upregulated several neuronal differentiation-related genes, a characteristic of Group 4 medulloblastoma in Group 3 cell lines. The expression of miR-592 also upregulated the activity of ERK1/ERK2 kinases indicating activation of the MAPK signaling pathway. The inhibition of MAPK signaling by the ERK1/ERK2 inhibitor and mTOR signaling by rapamycin abrogated the miR-592-mediated upregulation of neuronal differentiation-related genes. Group 4 medulloblastomas showed higher activity of the mTOR and MAPK signaling compared to Group 3 tumors. Thus, miR-592 overexpression appears to be a driver event and a determining factor of Group 4 biology, which activates the mTOR and MAPK signaling pathways and thereby imparts its characteristic expression profile of neuronal differentiation-related genes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/hmg/ddab201DOI Listing
July 2021

Interaction of zinc oxide nanoparticles with soil: Insights into the chemical and biological properties.

Environ Geochem Health 2021 Apr 17. Epub 2021 Apr 17.

Southern Federal University, Rostov-on-Don, Russia, 344090.

Widespread use of zinc oxide nanoparticles (ZnO-NPs) threatens soil, plants, terrestrial and aquatic animals. Thus, it is essential to explore the fate and behavior of NPs in soil and also its mechanism of interaction with soil microbial biodiversity to maintain soil health and quality to accomplish essential ecosystem services. With this background, the model experiment was conducted in the greenhouse to study the impact of ZnO-NPs on soil taking maize as a test crop. The X-ray diffraction, Fourier transform infrared spectroscopy, Scanning electron microscopy and Particles size analysis of engineered NPs confirmed that the material was ZnO-NPs (particle size--65.82 nm). The application of ZnO-NPs resulted in a significant decrease in soil pH. Significantly high EC (0.13 dS m) was recorded where ZnO-NPs were applied at the rate of 2.5 mg Zn kg soil over control (0.12 dS m). A significant increase in soil available phosphorus was observed on applying ZnO-NPs (15.29 mg kg of soil) as compared to control (11.84 mg kg of soil). Maximum soil available Zn (2.09 mg kg) was recorded in ZnO-NPs-amended soil (T) which was significantly higher than control (0.33 mg kg) as well as treatments containing conventional zincatic fertilizers. The inhibition rates of dehydrogenase enzyme activity in the presence of 0.5 mg, 1.25 mg and 2.5 mg ZnO-NPs per kg soil were 31.3, 46.2 and 49.7%, respectively. Soil microbial biomass carbon was significantly reduced (103.33 µg g soil) in soils treated with ZnO-NPs over control (111.33 µg g soil). Soil bacterial count was also significantly lesser (12.33 × 10 CFU) in the case where 2.5 mg kg ZnO-NPs were applied as compared to control (21.33 × 10 CFU). The corresponding decrease in fungal and actinomycetes colony count was 24.16, 37.35, 46.15% and 14.59, 17.97, 22.45% with the application of 0.5 mg, 1.25 mg and 2.5 mg ZnO-NPs per kg soil, respectively, as compared to control. Thus, the use of ZnO-NPs resulted in an increase in soil available Zn but inhibited soil microbial activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10653-021-00929-8DOI Listing
April 2021

An end-to-end breast tumour classification model using context-based patch modelling - A BiLSTM approach for image classification.

Comput Med Imaging Graph 2021 01 4;87:101838. Epub 2020 Dec 4.

School of Computing, National University of Singapore, 13 Computing Drive, 117417 Singapore, Singapore; Bioinformatics Institute, A*STAR, 30 Biopolis Street, 138671 Singapore, Singapore; Image and Pervasive Access Lab (IPAL), CNRS UMI 2955, 1 Fusionopolis Way, 138632 Singapore, Singapore; Singapore Eye Research Institute, 20 College Road, 169856 Singapore, Singapore.

Researchers working on computational analysis of Whole Slide Images (WSIs) in histopathology have primarily resorted to patch-based modelling due to large resolution of each WSI. The large resolution makes WSIs infeasible to be fed directly into the machine learning models due to computational constraints. However, due to patch-based analysis, most of the current methods fail to exploit the underlying spatial relationship among the patches. In our work, we have tried to integrate this relationship along with feature-based correlation among the extracted patches from the particular tumorous region. The tumour regions extracted from WSI have arbitrary dimensions having the range 20,570 to 195 pixels across width and 17,290 to 226 pixels across height. For the given task of classification, we have used BiLSTMs to model both forward and backward contextual relationship. Also, using RNN based model, the limitation of sequence size is eliminated which allows the modelling of variable size images within a deep learning model. We have also incorporated the effect of spatial continuity by exploring different scanning techniques used to sample patches. To establish the efficiency of our approach, we trained and tested our model on two datasets, microscopy images and WSI tumour regions. Both datasets were published by ICIAR BACH Challenge 2018. Finally, we compared our results with top 5 teams who participated in the BACH challenge and achieved the top accuracy of 90% for microscopy image dataset. For WSI tumour region dataset, we compared the classification results with state of the art deep learning networks such as ResNet, DenseNet, and InceptionV3 using maximum voting technique. We achieved the highest performance accuracy of 84%. We found out that BiLSTMs with CNN features have performed much better in modelling patches into an end-to-end Image classification network. Additionally, the variable dimensions of WSI tumour regions were used for classification without the need for resizing. This suggests that our method is independent of tumour image size and can process large dimensional images without losing the resolution details.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.compmedimag.2020.101838DOI Listing
January 2021

Ibrutinib Resistance Mechanisms and Treatment Strategies for B-Cell lymphomas.

Cancers (Basel) 2020 May 22;12(5). Epub 2020 May 22.

Department of Medical Oncology & Hematology, All India Institute of Medical Sciences, Rishikesh 249203, India.

Chronic activation of B-cell receptor (BCR) signaling via Bruton tyrosine kinase (BTK) is largely considered to be one of the primary mechanisms driving disease progression in B-Cell lymphomas. Although the BTK-targeting agent ibrutinib has shown promising clinical responses, the presence of primary or acquired resistance is common and often leads to dismal clinical outcomes. Resistance to ibrutinib therapy can be mediated through genetic mutations, up-regulation of alternative survival pathways, or other unknown factors that are not targeted by ibrutinib therapy. Understanding the key determinants, including tumor heterogeneity and rewiring of the molecular networks during disease progression and therapy, will assist exploration of alternative therapeutic strategies. Towards the goal of overcoming ibrutinib resistance, multiple alternative therapeutic agents, including second- and third-generation BTK inhibitors and immunomodulatory drugs, have been discovered and tested in both pre-clinical and clinical settings. Although these agents have shown high response rates alone or in combination with ibrutinib in ibrutinib-treated relapsed/refractory(R/R) lymphoma patients, overall clinical outcomes have not been satisfactory due to drug-associated toxicities and incomplete remission. In this review, we discuss the mechanisms of ibrutinib resistance development in B-cell lymphoma including complexities associated with genomic alterations, non-genetic acquired resistance, cancer stem cells, and the tumor microenvironment. Furthermore, we focus our discussion on more comprehensive views of recent developments in therapeutic strategies to overcome ibrutinib resistance, including novel BTK inhibitors, clinical therapeutic agents, proteolysis-targeting chimeras and immunotherapy regimens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12051328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281539PMC
May 2020

diffGrad: An Optimization Method for Convolutional Neural Networks.

IEEE Trans Neural Netw Learn Syst 2020 11 29;31(11):4500-4511. Epub 2020 Oct 29.

Stochastic gradient descent (SGD) is one of the core techniques behind the success of deep neural networks. The gradient provides information on the direction in which a function has the steepest rate of change. The main problem with basic SGD is to change by equal-sized steps for all parameters, irrespective of the gradient behavior. Hence, an efficient way of deep network optimization is to have adaptive step sizes for each parameter. Recently, several attempts have been made to improve gradient descent methods such as AdaGrad, AdaDelta, RMSProp, and adaptive moment estimation (Adam). These methods rely on the square roots of exponential moving averages of squared past gradients. Thus, these methods do not take advantage of local change in gradients. In this article, a novel optimizer is proposed based on the difference between the present and the immediate past gradient (i.e., diffGrad). In the proposed diffGrad optimization technique, the step size is adjusted for each parameter in such a way that it should have a larger step size for faster gradient changing parameters and a lower step size for lower gradient changing parameters. The convergence analysis is done using the regret bound approach of the online learning framework. In this article, thorough analysis is made over three synthetic complex nonconvex functions. The image categorization experiments are also conducted over the CIFAR10 and CIFAR100 data sets to observe the performance of diffGrad with respect to the state-of-the-art optimizers such as SGDM, AdaGrad, AdaDelta, RMSProp, AMSGrad, and Adam. The residual unit (ResNet)-based convolutional neural network (CNN) architecture is used in the experiments. The experiments show that diffGrad outperforms other optimizers. Also, we show that diffGrad performs uniformly well for training CNN using different activation functions. The source code is made publicly available at https://github.com/shivram1987/diffGrad.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TNNLS.2019.2955777DOI Listing
November 2020

Spatial variability of arsenic in Indo-Gangetic basin of Varanasi and its cancer risk assessment.

Chemosphere 2020 Jan 19;238:124623. Epub 2019 Aug 19.

Division of Agricultural Physics, Indian Agricultural Research Institute, New Delhi, 110012, India.

The Indo-Gangetic alluvium is prime region for intensive agricultural. In some areas of this region, groundwater is now becoming progressively polluted by contamination with poisonous substances like arsenic. Intensive irrigation with arsenic contaminated ground water in dry spell results in the formation of As(III) which is more toxic. Thus groundwater quality assessment of Gangetic basin has become essential for its safer use. Therefore we under took study on the spatial variability of arsenic by collecting georeferred groundwater samples on grid basis from various water sources like dug well, bore and hand pumps covering the river bank region of Ganga basin. Water quality was investigated through determination pH, EC, TDS, salinity, Na, K, Ca, Mg, SAR, SSP, CO, HCO, RSC, Cl, As, Fe, Zn, Mn and Cu, etc. Results pointed severe As contamination in ground water of three sites of the study area. ARC GIS software is now able to process maps along with tabular data and compare them well, to provide the spatial visualization of information and using this tool, the Geographical Information System (GIS) of arsenic was developed. It was noticed from spatial maps that concentration of arsenic was more near the meandering points of Ganga.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2019.124623DOI Listing
January 2020

An Intriguing Family with Type 2 Diabetes Mellitus and Complete Heart Block.

Indian J Endocrinol Metab 2017 Sep-Oct;21(5):784-786

Department of Medicine, Nalanda Medical College Hospital, Patna, Bihar, India.

Chronic hyperglycaemia of Type 2 Diabetes Mellitus (T2DM) causes long term damage to heart resulting in coronary artery disease (CAD), myocardial infarction (MI), congestive heart failure (CHF), and sudden death from arrhythmias. A 62 year old male presented to our emergency with complaint of sudden onset giddiness from last 2 hours. This was followed by loss of consciousness. Patient was a known case of T2DM since last 1 year. Family history- patient has two brothers who also have T2DM and both of them also developed Complete Heart Block (CHB) spontaneously. The patient's mother also had T2DM and she also developed CHB. On examination of the cardiovascular system, pulse rate was 36 per minute and a variable intensity of first heart sound was present. Rest of the cardiovascular examination and other system examination was within normal limits. Routine investigations were within normal limits and ECG showed CHB. Echocardiography revealed normal ventricular function with no evidence of ischemic heart disease. This was a case of Type 2 DM and spontaneous onset CHB with a strong family history. This case underscores the fact that CHB can occur spontaneously in Type 2 diabetics without ischemic heart disease. The cause of CHB was most likely Cardiac Autonomic Neuropathy (CAN), which is determined not only by poor glycaemic control, metabolic derangements and duration of diabetes but also by genetic factors (likely maternal).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/ijem.IJEM_449_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5628555PMC
October 2017

Arrhythmias in Type 2 Diabetes Mellitus.

Indian J Endocrinol Metab 2017 Sep-Oct;21(5):715-718

Department of Medicine, Nalanda Medical College Hospital, Patna, Bihar, India.

Chronic hyperglycaemia of Type 2 diabetes mellitus causes long term damage to heart resulting in coronary artery disease (CAD), myocardial infarction (MI), congestive heart failure (CHF), and sudden death from arrhythmias.

Aims: To study the prevalence of different types of arrhythmias in T2DM, particularly in association with Cardiac Autonomic Neuropathy (CAN).

Methods: A cross-sectional study including 100 patients of Type 2 Diabetes Mellitus (T2DM) presenting with cardiac arrhythmias, was done at our hospital over 2 years. Detailed history along with physical examination and tests for CAN were done. Routine investigations along with echocardiography, stress test, Holter monitoring were done.

Results: Sinus Tachycardia (ST) was the commonest arrhythmia, found in 32% of patients. 20% had Complete Heart Block (CHB), 15% had Sinus Bradycardia (SB), and 15% had Atrial Fibrillation (AF). Ventricular Premature Complex (VPC) was found in 10% and 3% had Atrial Premature Complex (APC). 3% had first degree AV block, whereas 1% had Paroxysmal Supra Ventricular Tachycardia (PSVT), and another 1% had Ventricular Tachycardia (VT). Poorly controlled diabetes and co-morbidities was associated with higher incidence of arrhythmias. 62% of patients had prolonged QTc, majority of which had CAN. Most of the patients responded to standard therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/ijem.IJEM_448_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5628542PMC
October 2017

Quantifying the Risks of Asparagine Deamidation and Aspartate Isomerization in Biopharmaceuticals by Computing Reaction Free-Energy Surfaces.

J Phys Chem B 2017 02 19;121(4):719-730. Epub 2017 Jan 19.

Pharmaceutical Research and Development, Biotherapeutics Pharmaceutical Sciences, Pfizer Inc. , 700 Chesterfield Pkwy West, Chesterfield, Missouri 63017, United States.

Early identification of asparagine deamidation and aspartate isomerization degradation sites can facilitate the successful development of biopharmaceuticals. Several knowledge-based models have been proposed to assess these degradation risks. In this study, we propose a physics-based approach to identify the degradation sites on the basis of the free-energy barriers along the prechemical conformational step and the chemical reaction pathway. These contributions are estimated from classical and quantum mechanics/molecular mechanics molecular dynamics simulations. The computed barriers are compared to those for reference reactions in water within GNG and GDG sequence motifs in peptides (which demonstrate the highest degradation rates). Two major factors decreasing the degradation rates relative to the reference reactions are steric hindrance toward accessing reactive conformations and replacement of water by less polar side chains in the solvation shell of transition states. Among the potential degradation sites in the complementarity-determining region of trastuzumab and between two DK sites in glial cell-derived neurotropic factor, this method identified NT, NG, DG, and DK, respectively, in agreement with experiments. This approach can be incorporated in early computational screening of chemical degradation sites in biopharmaceuticals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jpcb.6b11614DOI Listing
February 2017

Multichannel Decoded Local Binary Patterns for Content-Based Image Retrieval.

IEEE Trans Image Process 2016 09 7;25(9):4018-32. Epub 2016 Jun 7.

Local binary pattern (LBP) is widely adopted for efficient image feature description and simplicity. To describe the color images, it is required to combine the LBPs from each channel of the image. The traditional way of binary combination is to simply concatenate the LBPs from each channel, but it increases the dimensionality of the pattern. In order to cope with this problem, this paper proposes a novel method for image description with multichannel decoded LBPs. We introduce adder- and decoder-based two schemas for the combination of the LBPs from more than one channel. Image retrieval experiments are performed to observe the effectiveness of the proposed approaches and compared with the existing ways of multichannel techniques. The experiments are performed over 12 benchmark natural scene and color texture image databases, such as Corel-1k, MIT-VisTex, USPTex, Colored Brodatz, and so on. It is observed that the introduced multichannel adder- and decoder-based LBPs significantly improve the retrieval performance over each database and outperform the other multichannel-based approaches in terms of the average retrieval precision and average retrieval rate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TIP.2016.2577887DOI Listing
September 2016

Local Wavelet Pattern: A New Feature Descriptor for Image Retrieval in Medical CT Databases.

IEEE Trans Image Process 2015 Dec 26;24(12):5892-903. Epub 2015 Oct 26.

A new image feature description based on the local wavelet pattern (LWP) is proposed in this paper to characterize the medical computer tomography (CT) images for content-based CT image retrieval. In the proposed work, the LWP is derived for each pixel of the CT image by utilizing the relationship of center pixel with the local neighboring information. In contrast to the local binary pattern that only considers the relationship between a center pixel and its neighboring pixels, the presented approach first utilizes the relationship among the neighboring pixels using local wavelet decomposition, and finally considers its relationship with the center pixel. A center pixel transformation scheme is introduced to match the range of center value with the range of local wavelet decomposed values. Moreover, the introduced local wavelet decomposition scheme is centrally symmetric and suitable for CT images. The novelty of this paper lies in the following two ways: 1) encoding local neighboring information with local wavelet decomposition and 2) computing LWP using local wavelet decomposed values and transformed center pixel values. We tested the performance of our method over three CT image databases in terms of the precision and recall. We also compared the proposed LWP descriptor with the other state-of-the-art local image descriptors, and the experimental results suggest that the proposed method outperforms other methods for CT image retrieval.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TIP.2015.2493446DOI Listing
December 2015

A Direct Metal-Free Decarboxylative Sulfono Functionalization (DSF) of Cinnamic Acids to α,β-Unsaturated Phenyl Sulfones.

Org Lett 2015 Jun 8;17(11):2656-9. Epub 2015 May 8.

Department of Chemistry (Centre of Advanced Study), Banaras Hindu University, Varanasi 221005, India.

A metal-free room temperature decarboxylative cross-coupling between cinnamic acids and arylsulfonyl hydrazides has been realized for the first time for the synthesis of (E)-vinyl sulfones. The scope and versatility of the reaction has been demonstrated by the regio- and stereoselective synthesis of 22 derivatives with diverse structural features.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.5b01037DOI Listing
June 2015

Polychlorinated Biphenyls in Residential Soils and their Health Risk and Hazard in an Industrial City in India.

J Public Health Res 2014 Jul 1;3(2):252. Epub 2014 Jul 1.

National Reference Trace Organics Laboratory, Central Pollution Control Board , Delhi, India.

Background: Polychlorinated biphenyls (PCBs) have never been produced in India, but were used in industrial applications. PCBs have been detected in environmental samples since 1966, and their sources in soils come from depositions of industrial applications, incinerators and biomass combustions. PCBs adsorb to soil particles and persist for long time due to their properties. Their close proximity may also lead to human exposure through ingestion, inhalation, dermal contact, and may exert neurotoxic, mutagenic and carcinogenic health effects.

Background: Residential soil from Korba, India, was extracted using pressurized liquid extraction procedure, cleaned on modified silica and quantified for PCBs. Soil ingestion was considered as the main exposure pathways of life-long intake of PCBs. Human health risk in terms of life time average daily dose, incremental lifetime cancer risk (ILCR) and non-cancer hazard quotient (HQ) were estimated using established guidelines.

Background: The estimated average ILCR from non dioxin like PCBs for human adults and children was 3.1×10(-8) and 1.1×10(-7), respectively. ILCR from dioxin like PCBs for human adults and children was 3.1×10(-6) and 1.1×10(-5), respectively. The HQ for PCBs was 6.3×10(-4) and 2.2×10(-3), respectively for human adults and children. Study observed that ILCR from non dioxin like PCBs was lower than acceptable guideline range of 10(-6)-10(-4), and ILCR from dioxin like PCBs was within the limit. HQ was lower than safe limit of 1.

Background: Study concluded that human population residing in Korba had low health risk due to PCBs in residential soils. Significance for public healthThe concentrations of polychlorinated biphenyls (PCBs) in soils from an industrial city in India were measured for the assessment of human health risk. PCBs composition profiles were dominated with tri-chlorinated and tetra-chlorinated biphenyls. The possible sources of PCBs contamination can be attributed to local industrial emissions and long range transport depositions. The daily intakes of PCBs, and corresponding incremental lifetime cancer risk and hazard quotient for humans were estimated and found to be lower than acceptable levels. This baseline study may provide database on persistent organic pollutants in tropical countries and may also be useful in risks assessment of the industrial pollutants on human population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4081/jphr.2014.252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207023PMC
July 2014

Rotation and illumination invariant interleaved intensity order-based local descriptor.

IEEE Trans Image Process 2014 Dec;23(12):5323-33

The region descriptors using local intensity ordering patterns have become more popular recent years for image matching due to its enhanced discriminative ability. However, the dimension of these descriptors increases rapidly with the slight increase in the number of local neighbors under consideration and becomes unreasonable for image matching due to time constraint. In this paper, we reduce the dimension of the descriptor and matching time significantly while keeping up the comparable performance by considering the number of neighboring sample points in an interleaved manner. The proposed interleaved order based local descriptor (IOLD) considers the local neighbors of a pixel as a set of interleaved neighbors and constructs the descriptor over each set separately and finally combines them to produce a single pattern. We extract the local ordering pattern to cope up with the illumination effect in an inherent rotation invariant manner. The novelty lies with using multiple neighboring sets in an interleaved fashion. We also explored the local intensity order pattern in a multisupport-region scenario. Results are compared over three challenging and widely adopted image matching data sets with other prominent descriptors under various image transformations. Results based on experiments suggest that the proposed IOLD descriptor outperforms in terms of both improved matching performance and reduced matching time. We also found that the amount of improvement is significant under complex illumination difference while showing more robustness toward noise.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TIP.2014.2358879DOI Listing
December 2014

Epidemiology of diabetes mellitus in young population in rural districts of northern Bihar.

J Indian Med Assoc 2013 Feb;111(2):103-6

Department of Medicine, SK Medical College, Muzzafarpur 842004.

Diabetes mellitus is a major public health problem worldwide, and it is a known risk factor for coronary artery disease. Younger population, a group which lacks epidemiological data on diabetes mellitus, the prevalence of diabetes in them was investigated in the rural districts of north Bihar (India). Furthermore, the risk factors associated with diabetes mellitus in this younger population were also assessed. A total of 3957 subjects in the age group of 12-30 years from northern Bihar participated in the study. Data were obtained from history, random capillary blood glucose levels detected by glucometer and body mass index. Of the available 3955 results, glucometer identified 103 subjects (2.6%) as positives with the cut-off value of 150 mg/dl. Out of these, 12 (0.3%) were diabetic while 35 (0.88%) had impaired glycaemic control by intravenous blood sugar method. The random blood glucose levels varied from 53-391 mg/dl (mean and SD: 105.3 and 21.2). Amongst these subjects; only 103 (2.6%) were declared to be diabetic. The fasting and postprandial blood glucose levels for diabetic subjectes were 148.5 and 227.1 mg/dl respectively. The logistic regression evidenced that positive glucometer results was associated with age (> 25 years), sex (male), high BMI (> 18.5), high BP (> 120/80) and occupation. The increasing prevalence of diabetes in young may have adverse effects on nation's health and economy. Data from this study highlights the importance of early screening, diagnosis and management of diabetes mellitus.
View Article and Find Full Text PDF

Download full-text PDF

Source
February 2013

Impact of product-related factors on immunogenicity of biotherapeutics.

J Pharm Sci 2011 Feb 25;100(2):354-87. Epub 2010 Aug 25.

Pfizer, Inc., BioTherapeutics Pharmaceutical Sciences, Pharmaceutical Research and Development, Chesterfield, Missouri 63017, USA.

All protein therapeutics have the potential to be immunogenic. Several factors, including patient characteristics, disease state, and the therapy itself, influence the generation of an immune response. Product-related factors such as the molecule design, the expression system, post-translational modifications, impurities, contaminants, formulation and excipients, container, closure, as well as degradation products are all implicated. However, a critical examination of the available data shows that clear unequivocal evidence for the impact of these latter factors on clinical immunogenicity is lacking. No report could be found that clearly deconvolutes the clinical impact of the product attributes on patient susceptibility. Aggregation carries the greatest concern as a risk factor for immunogenicity, but the impact of aggregates is likely to depend on their structure as well as on the functionality (e.g., immunostimulatory or immunomodulatory) of the therapeutic. Preclinical studies are not yet capable of assessing the clinically relevant immunogenicity potential of these product-related factors. Simply addressing these risk factors as part of product development will not eliminate immunogenicity. Minimization of immunogenicity has to begin at the molecule design stage by reducing or eliminating antigenic epitopes and building in favorable physical and chemical properties.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jps.22276DOI Listing
February 2011

Giant left anterior descending artery aneurysm.

Ann Card Anaesth 2006 Jul;9(2):155

Rabindranath Tagore International Institute of Cardiac Science, Kolkata, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
July 2006
-->