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1.  Contamination of water resources by pathogenic bacteria 
AMB Express  2014;4:51.
Water-borne pathogen contamination in water resources and related diseases are a major water quality concern throughout the world. Increasing interest in controlling water-borne pathogens in water resources evidenced by a large number of recent publications clearly attests to the need for studies that synthesize knowledge from multiple fields covering comparative aspects of pathogen contamination, and unify them in a single place in order to present and address the problem as a whole. Providing a broader perceptive of pathogen contamination in freshwater (rivers, lakes, reservoirs, groundwater) and saline water (estuaries and coastal waters) resources, this review paper attempts to develop the first comprehensive single source of existing information on pathogen contamination in multiple types of water resources. In addition, a comprehensive discussion describes the challenges associated with using indicator organisms. Potential impacts of water resources development on pathogen contamination as well as challenges that lie ahead for addressing pathogen contamination are also discussed.
PMCID: PMC4077002
Pathogens; Contamination; Water resources; Watershed; Pathogens transport
2.  Rosa26-GFP Direct Repeat (RaDR-GFP) Mice Reveal Tissue- and Age-Dependence of Homologous Recombination in Mammals In Vivo 
PLoS Genetics  2014;10(6):e1004299.
Homologous recombination (HR) is critical for the repair of double strand breaks and broken replication forks. Although HR is mostly error free, inherent or environmental conditions that either suppress or induce HR cause genomic instability. Despite its importance in carcinogenesis, due to limitations in our ability to detect HR in vivo, little is known about HR in mammalian tissues. Here, we describe a mouse model in which a direct repeat HR substrate is targeted to the ubiquitously expressed Rosa26 locus. In the Rosa26 Direct Repeat-GFP (RaDR-GFP) mice, HR between two truncated EGFP expression cassettes can yield a fluorescent signal. In-house image analysis software provides a rapid method for quantifying recombination events within intact tissues, and the frequency of recombinant cells can be evaluated by flow cytometry. A comparison among 11 tissues shows that the frequency of recombinant cells varies by more than two orders of magnitude among tissues, wherein HR in the brain is the lowest. Additionally, de novo recombination events accumulate with age in the colon, showing that this mouse model can be used to study the impact of chronic exposures on genomic stability. Exposure to N-methyl-N-nitrosourea, an alkylating agent similar to the cancer chemotherapeutic temozolomide, shows that the colon, liver and pancreas are susceptible to DNA damage-induced HR. Finally, histological analysis of the underlying cell types reveals that pancreatic acinar cells and liver hepatocytes undergo HR and also that HR can be specifically detected in colonic somatic stem cells. Taken together, the RaDR-GFP mouse model provides new understanding of how tissue and age impact susceptibility to HR, and enables future studies of genetic, environmental and physiological factors that modulate HR in mammals.
Author Summary
Cancer is a disease of the genome, caused by accumulated genetic changes, such as point mutations and large-scale sequence rearrangements. Homologous recombination (HR) is a critical DNA repair pathway. While generally accurate, HR between misaligned sequences or between homologous chromosomes can lead to insertions, deletions, and loss of heterozygosity, all of which are known to promote cancer. Indeed, most cancers harbor sequence changes caused by HR, and genetic and environmental conditions that induce or suppress HR are often carcinogenic. To enable studies of HR in vivo, we created the Rosa26 Direct Repeat-Green Fluorescent Protein (RaDR-GFP) mice that carry an integrated transgenic recombination reporter targeted to the ubiquitously expressed Rosa26 locus. Being able to detect recombinant cells by fluorescence reveals that the frequency of recombination is highly variable among tissues. Furthermore, new recombination events accumulate over time, which contributes to our understanding of why our risk for cancer increases with age. This mouse model provides new understanding of this important DNA repair pathway in vivo, and also enables future studies of genetic, environmental and physiological factors that impact the risk of HR-induced sequence rearrangements in vivo.
PMCID: PMC4046920  PMID: 24901438
3.  Reassignment of Scattered Emission Photons in Multifocal Multiphoton Microscopy 
Scientific Reports  2014;4:5153.
Multifocal multiphoton microscopy (MMM) achieves fast imaging by simultaneously scanning multiple foci across different regions of specimen. The use of imaging detectors in MMM, such as CCD or CMOS, results in degradation of image signal-to-noise-ratio (SNR) due to the scattering of emitted photons. SNR can be partly recovered using multianode photomultiplier tubes (MAPMT). In this design, however, emission photons scattered to neighbor anodes are encoded by the foci scan location resulting in ghost images. The crosstalk between different anodes is currently measured a priori, which is cumbersome as it depends specimen properties. Here, we present the photon reassignment method for MMM, established based on the maximum likelihood (ML) estimation, for quantification of crosstalk between the anodes of MAPMT without a priori measurement. The method provides the reassignment of the photons generated by the ghost images to the original spatial location thus increases the SNR of the final reconstructed image.
PMCID: PMC4046171  PMID: 24898470
4.  Determinants of Prelacteal Feeding in Rural Northern India 
Prelacteal feeding is an underestimated problem in a developing country like India, where infant mortality rate is quite high. The present study tried to find out the factors determining prelacteal feeding in rural areas of north India.
A crosssectional study was conducted among recently delivered women of rural Uttar Pradesh, India. Multistage random sampling was used for selecting villages. From them, 352 recently delivered women were selected as the subjects, following systematic random sampling. Chi-square test and logistic regression were used to find out the predictors for prelacteal feeding.
Overall, 40.1% of mothers gave prelacteal feeding to their newborn. Factors significantly associated with such practice, after simple logistic regression, were age, caste, socioeconomic status, and place of delivery. At multivariate level, age (odds ratio (OR) = 1.76, 95% confidence interval (CI) = 1.13-2.74), caste and place of delivery (OR = 2.23, 95% CI = 1.21-4.10) were found to determine prelacteal feeding significantly, indicating that young age, high caste, and home deliveries could affect the practice positively.
The problem of prelacteal feeding is still prevalent in rural India. Age, caste, and place of delivery were associated with the problem. For ensuring neonatal health, the problem should be addressed with due gravity, with emphasis on exclusive breast feeding.
PMCID: PMC4050689  PMID: 24932400
Breast feeding; colostrum; infant feeding; prelacteal feeding; rural India
5.  Genetically Encoded Multispectral Labeling of Proteins with Polyfluorophores on a DNA Backbone 
Genetically-encoded methods for protein conjugation are of high importance as biological tools. Here we describe the development of a new class of dyes for genetically encoded tagging that add new capabilities for protein reporting and detection via HaloTag methodology. Oligodeoxyfluoroside (ODFs) are short DNA-like oligomers in which the natural nucleic acid bases are replaced by interacting fluorescent chromophores, yielding a broad range of emission colors using a single excitation wavelength. We describe the development of an alkyl halide dehalogenase-compatible chloroalkane linker phosphoramidite derivative that enables the rapid automated synthesis of many possible dyes for protein conjugation. Experiments in vitro test enzymatic self-conjugation of nine different DNA-like dyes to proteins with HaloTag domains, and the data confirm rapid and efficient covalent labeling of proteins. Notably, a number of the ODF dyes are found to increase in brightness or change color upon protein conjugation. Tests in mammalian cellular settings reveal that the dyes are functional in multiple cellular contexts, both on the cell surface and within the cytoplasm, allowing protein localization to be imaged in live cells by epifluorescence and laser confocal microscopy.
PMCID: PMC3646636  PMID: 23590213
6.  Degradation of 4-chloro-3-nitrophenol via a novel intermediate, 4-chlororesorcinol by Pseudomonas sp. JHN 
Scientific Reports  2014;4:4475.
A 4-chloro-3-nitrophenol (4C3NP)-mineralizing bacterium, Pseudomonas sp. JHN was isolated from a waste water sample collected from a chemically-contaminated area, India by an enrichment method. Pseudomonas sp. JHN utilized 4C3NP as a sole carbon and energy source and degraded it with the release of stoichiometric amounts of chloride and nitrite ions. Gas chromatography and gas chromatography-mass spectrometry detected 4-chlororesorcinol as a major metabolite of the 4C3NP degradation pathway. Inhibition studies using 2,2′-dipyridyl showed that 4-chlororesorcinol is a terminal aromatic compound in the degradation pathway of 4C3NP. The activity for 4C3NP-monooxygenase was detected in the crude extracts of the 4C3NP-induced JHN cells that confirmed the formation of 4-chlororesorcinol from 4C3NP. The capillary assay showed that Pseudomonas sp. JHN exhibited chemotaxis toward 4C3NP. The bioremediation capability of Pseudomonas sp. JHN was monitored to carry out the microcosm experiments using sterile and non-sterile soils spiked with 4C3NP. Strain JHN degraded 4C3NP in sterile and non-sterile soil with same degradation rates. This is the first report of (i) bacterial degradation and bioremediation of 4C3NP, (ii) formation of 4-chlororesorcinol in the degradation pathway of 4C3NP, (iii) bacterial chemotaxis toward 4C3NP.
PMCID: PMC3966030  PMID: 24667329
7.  Posterior Interosseous Nerve Syndrome from Thermal Injury 
Case Reports in Surgery  2014;2014:891393.
Background. Due to anatomical proximity to bone, the radial nerve is the most frequently injured major nerve of the upper extremity, frequently secondary to fractures (Li et al. (2013)). We describe an incidence when a branch of the radial nerve is injured as a result of a thermal injury. Observation. Radial nerve injury can occur anywhere along the anatomical course with varied etiologies, but commonly related to trauma. The most frequent site is in the proximal forearm involving the posterior interosseous branch. However, problems can occur at the junction of the middle and proximal thirds of the humerus and wrist radially. When the radial nerve is injured by a burn, a new rehabilitation dynamic arises. Not only does one agonize about the return of nerve function but also fret about the skin grafts that replaced the devitalized tissue housing that compartment. Discussion. Although posterior interosseous nerve syndrome has been described in the context of many different etiologies, it has not previously been discussed in relation to burn injuries. In this case, not only did the patient's rehabilitation involve aggressive therapy for return of sensation and function of the arm, but also prevention of contracture normally seen in replacement of full thickness burns.
PMCID: PMC3965921  PMID: 24707432
8.  Three dimensional HiLo-based structured illumination for a digital scanned laser sheet microscopy (DSLM) in thick tissue imaging 
Optics Express  2012;20(25):27337-27347.
Laser sheet based microscopy has become widely accepted as an effective active illumination method for real time three-dimensional (3D) imaging of biological tissue samples. The light sheet geometry, where the camera is oriented perpendicular to the sheet itself, provides an effective method of eliminating some of the scattered light and minimizing the sample exposure to radiation. However, residual background noise still remains, limiting the contrast and visibility of potentially interesting features in the samples. In this article, we investigate additional structuring of the illumination for improved background rejection, and propose a new technique, “3D HiLo” where we combine two HiLo images processed from orthogonal directions to improve the condition of the 3D reconstruction. We present a comparative study of conventional structured illumination based demodulation methods, namely 3Phase and HiLo with a newly implemented 3D HiLo approach and demonstrate that the latter yields superior signal-to-background ratio in both lateral and axial dimensions, while simultaneously suppressing image processing artifacts.
PMCID: PMC3601593  PMID: 23262684
(180.6900) Three-dimensional microscopy; (180.2520) Fluorescence microscopy; (110.6880) Three-dimensional image acquisition; (100.3020) Image reconstruction-restoration
9.  5-AED enhances survival of irradiated mice in a G-CSF-dependent manner, stimulates innate immune cell function, reduces radiation-induced DNA damage and induces genes that modulate cell cycle progression and apoptosis 
Journal of Radiation Research  2012;53(6):840-853.
The steroid androst-5-ene-3ß,17ß-diol (5-androstenediol, 5-AED) elevates circulating granulocytes and platelets in animals and humans, and enhances survival during the acute radiation syndrome (ARS) in mice and non-human primates. 5-AED promotes survival of irradiated human hematopoietic progenitors in vitro through induction of Nuclear Factor-κB (NFκB)-dependent Granulocyte Colony-Stimulating Factor (G-CSF) expression, and causes elevations of circulating G-CSF and interleukin-6 (IL-6). However, the in vivo cellular and molecular effects of 5-AED are not well understood. The aim of this study was to investigate the mechanisms of action of 5-AED administered subcutaneously (s.c.) to mice 24 h before total body γ- or X-irradiation (TBI). We used neutralizing antibodies, flow cytometric functional assays of circulating innate immune cells, analysis of expression of genes related to cell cycle progression, DNA repair and apoptosis, and assessment of DNA strand breaks with halo-comet assays. Neutralization experiments indicated endogenous G-CSF but not IL-6 was involved in survival enhancement by 5-AED. In keeping with known effects of G-CSF on the innate immune system, s.c. 5-AED stimulated phagocytosis in circulating granulocytes and oxidative burst in monocytes. 5-AED induced expression of both bax and bcl-2 in irradiated animals. Cdkn1a and ddb1, but not gadd45a expression, were upregulated by 5-AED in irradiated mice. S.c. 5-AED administration caused decreased DNA strand breaks in splenocytes from irradiated mice. Our results suggest 5-AED survival enhancement is G-CSF-dependent, and that it stimulates innate immune cell function and reduces radiation-induced DNA damage via induction of genes that modulate cell cycle progression and apoptosis.
PMCID: PMC3483857  PMID: 22843381
10.  Ultrastructural Changes of Airway in Murine Models of Allergy and Diet-Induced Metabolic Syndrome 
ISRN Allergy  2013;2013:261297.
Studying ultrastructural changes could reveal novel pathophysiology of obese-asthmatic condition as existing concepts in asthma pathogenesis are based on the histological changes of the diseased airway. While asthma is defined in functional terms, the potential of electron microscopy (EM) in providing cellular and subcellular detail is underutilized. With this view, we have performed transmission EM in the lungs from allergic mice that show key features of asthma and high-fat- or high-fructose-fed mice that mimicked metabolic syndrome to illustrate the ultrastructural changes. The primary focus was epithelial injury and metaplasia, which are cardinal features of asthma and initiate airway remodeling. EM findings of the allergically inflamed mouse lungs correlate with known features of human asthma such as increased mitochondria in airway smooth muscle, platelet activation and subepithelial myofibroblasts. Interestingly, we found a clear and unambiguous evidence to suggest that ciliated cells can become goblet cells using immunoelectron microscopy. Additionally, we show for the first time the stressed mitochondria in the bronchial epithelia of high-fat- or high-fructose-fed mice even without allergen exposure. These results may stimulate interest in using EM in understanding novel pathological mechanisms for different subtypes of asthma including obese asthma.
PMCID: PMC3782840  PMID: 24106613
11.  Identification of two regions in the p140Cap adaptor protein that retain the ability to suppress tumor cell properties 
p140Cap is an adaptor protein that negatively controls tumor cell properties, by inhibiting in vivo tumor growth and metastasis formation. Our previous data demonstrated that p140Cap interferes with tumor growth and impairs invasive properties of cancer cells inactivating signaling pathways, such as the tyrosine kinase Src or E-cadherin/EGFR cross-talk. In breast cancer p140Cap expression inversely correlates with tumor malignancy. p140Cap is composed of several conserved domains that mediate association with specific partners. Here we focus our attention on two domains of p140Cap, the TER (Tyrosine Enriched Region) which includes several tyrosine residues, and the CT (Carboxy Terminal) which contains a proline rich sequence, involved in binding to SH2 and SH3 domains, respectively. By generating stable cell lines expressing these two proteins, we demonstrate that both TER and CT domains maintain the ability to associate the C-terminal Src kinase (Csk) and Src, to inhibit Src activation and Focal adhesion kinase (Fak) phosphorylation, and to impair in vitro and in vivo tumor cell features. In particular expression of TER and CT proteins in cancer cells inhibits in vitro and in vivo growth and directional migration at a similar extent of the full length p140Cap protein. Moreover, by selective point mutations and deletion we show that the ability of the modules to act as negative regulators of cell migration and proliferation mainly resides on the two tyrosines (Y) inserted in the EPLYA and EGLYA sequences in the TER module and in the second proline-rich stretch contained in the CT protein. Gene signature of cells expressing p140Cap, TER or CT lead to the identification of a common pattern of 105 down-regulated and 128 up-regulated genes, suggesting that the three proteins can act through shared pathways. Overall, this work highlights that the TER and CT regions of p140Cap can efficiently suppress tumor cell properties, opening the perspective that short, defined p140Cap regions can have therapeutic effects.
PMCID: PMC3696535  PMID: 23841028
p140Cap; breast cancer; lung cancer; colon cancer; cell signaling; Csk; Src
12.  Src Dependent Pancreatic Acinar Injury Can Be Initiated Independent of an Increase in Cytosolic Calcium 
PLoS ONE  2013;8(6):e66471.
Several deleterious intra-acinar phenomena are simultaneously triggered on initiating acute pancreatitis. These culminate in acinar injury or inflammatory mediator generation in vitro and parenchymal damage in vivo. Supraphysiologic caerulein is one such initiator which simultaneously activates numerous signaling pathways including non-receptor tyrosine kinases such as of the Src family. It also causes a sustained increase in cytosolic calcium- a player thought to be crucial in regulating deleterious phenomena. We have shown Src to be involved in caerulein induced actin remodeling, and caerulein induced changes in the Golgi and post-Golgi trafficking to be involved in trypsinogen activation, which initiates acinar cell injury. However, it remains unclear whether an increase in cytosolic calcium is necessary to initiate acinar injury or if injury can be initiated at basal cytosolic calcium levels by an alternate pathway. To study the interplay between tyrosine kinase signaling and calcium, we treated mouse pancreatic acinar cells with the tyrosine phosphatase inhibitor pervanadate. We studied the effect of the clinically used Src inhibitor Dasatinib (BMS-354825) on pervanadate or caerulein induced changes in Src activation, trypsinogen activation, cell injury, upstream cytosolic calcium, actin and Golgi morphology. Pervanadate, like supraphysiologic caerulein, induced Src activation, redistribution of the F-actin from its normal location in the sub-apical area to the basolateral areas, and caused antegrade fragmentation of the Golgi. These changes, like those induced by supraphysiologic caerulein, were associated with trypsinogen activation and acinar injury, all of which were prevented by Dasatinib. Interestingly, however, pervanadate did not cause an increase in cytosolic calcium, and the caerulein induced increase in cytosolic calcium was not affected by Dasatinib. These findings suggest that intra-acinar deleterious phenomena may be initiated independent of an increase in cytosolic calcium. Other players resulting in acinar injury along with the Src family of tyrosine kinases remain to be explored.
PMCID: PMC3688910  PMID: 23824669
13.  Spontaneous Collapse of Bilateral Bullae with Conservative Management 
We report a case of bilateral apical lung bullae that collapsed following an episode of community-acquired pneumonia with bilateral air fluid levels. With standard treatment for community-acquired pneumonia, management of a patient that may have qualified for bullectomy, (as in our case) showed complete resolution of all pathology without surgical intervention. Conservative management took precedence in alleviating pathology over surgical intervention.
PMCID: PMC3700969  PMID: 23843717
emphysema/bullae; lung infection; infection; chest
14.  Towards identification of finger flexions using single channel surface electromyography – able bodied and amputee subjects 
This research has established a method for using single channel surface electromyogram (sEMG) recorded from the forearm to identify individual finger flexion. The technique uses the volume conduction properties of the tissues and uses the magnitude and density of the singularities in the signal as a measure of strength of the muscle activity.
SEMG was recorded from the flexor digitorum superficialis muscle during four different finger flexions. Based on the volume conduction properties of the tissues, sEMG was decomposed into wavelet maxima and grouped into four groups based on their magnitude. The mean magnitude and the density of each group were the inputs to the twin support vector machines (TSVM). The algorithm was tested on 11 able-bodied and one trans-radial amputated volunteer to determine the accuracy, sensitivity and specificity. The system was also tested to determine inter-experimental variations and variations due to difference in the electrode location.
Accuracy and sensitivity of identification of finger actions from single channel sEMG signal was 93% and 94% for able-bodied and 81% and 84% for trans-radial amputated respectively, and there was only a small inter-experimental variation.
Volume conduction properties based sEMG analysis provides a suitable basis for identifying finger flexions from single channel sEMG. The reported system requires supervised training and automatic classification.
PMCID: PMC3680228  PMID: 23758881
15.  Purification, crystallization and preliminary X-ray crystallographic analysis of MIL, a glycosylated jacalin-related lectin from mulberry (Morus indica) latex 
The purification, preliminary characterization and crystallization of a lectin purified from M. indica latex are presented. Using synchrotron radiation, a diffraction data set to 2.8 Å resolution was collected.
A quantitatively major protein has been purified from the latex of Morus indica. The purified previously uncharacterized protein, M. indica lectin (MIL), was further shown to be a glycosylated tetramer and belongs to the family of jacalin-related lectins. Crystallization of MIL was also accomplished and the tetragonal crystals diffracted synchrotron X-rays to a resolution of 2.8 Å.
PMCID: PMC3087652  PMID: 21543873
mulberry latex; lectins; tetramers; glycosylation
16.  Mental health, substance use, and intimate partner problems among pregnant and postpartum suicide victims in the National Violent Death Reporting System 
General Hospital Psychiatry  2011;34(2):139-145.
Suicide during pregnancy and the postpartum is a tragic event for the victim and profoundly impacts the baby, the family, and the community. Prior efforts to study risks for pregnancy-associated suicide have been hampered by the lack of data sources which capture pregnancy and delivery status of victims. Introduction of the United States National Violent Death Reporting System (NVDRS) offers new insights into violent deaths by linking multiple data sources and allowing better examination of psychosocial risk factors.
The analysis used data from 17 states reporting to the NVDRS from 2003–2007 to evaluate suicide patterns among pregnant, postpartum, and non-pregnant or postpartum women. Demographic factors, mental health status, substance use, precipitating circumstances, intimate partner problems, and suicide methods were compared among groups.
The 2083 female suicide victims of reproductive age demonstrated high prevalence of existing mental health diagnosis and current depressed mood with depressed mood significantly higher among postpartum women. Substance use and presence of other precipitating factors were high and similar among groups. Intimate partner problems were higher among pregnant and postpartum victims. Postpartum women were more likely die via asphyxia as cause of death compared to poisoning or firearms
These findings describe important mental health, substance use, and intimate partner problems seen with pregnancy-associated suicide. The study highlights mental health risk factors which could potentially be targeted for intervention in this vulnerable population.
PMCID: PMC3275697  PMID: 22055329
Pregnancy; postpartum; suicide; mental health; intimate partner violence
17.  β-Catenin is Essential for Ethanol Metabolism and Protection Against Alcohol-mediated Liver Steatosis in Mice 
Hepatology (Baltimore, Md.)  2012;55(3):931-940.
The liver plays a central role in ethanol metabolism and oxidative stress is implicated in alcohol-mediated liver injury. β-Catenin regulates hepatic metabolic zonation and adaptive response to oxidative stress. We hypothesized that β-catenin regulates the hepatic response to ethanol ingestion. Female liver-specific β-catenin knockout (KO) mice and wild type (WT) littermates were fed the Lieber-Decarli liquid diet (5% ethanol) in a pair-wise fashion. Liver histology, biochemistry, and gene expression studies were performed. Plasma alcohol and ammonia levels were measured using standard assays. Ethanol-fed KO mice exhibited systemic toxicity and early mortality. KO mice exhibited severe macrovesicular steatosis and five to six-fold higher serum ALT and AST levels. KO mice had modest increase in hepatic oxidative stress, lower expression of mitochondrial superoxide dismutase (SOD-2), and lower citrate synthase activity, the first step in the tricarboxylic acid cycle. N-Acetyl cysteine (NAC) did not prevent ethanol-induced mortality in KO mice. In WT livers, β-catenin was found to co-precipitate with FoxO3, the upstream regulator of SOD-2. Hepatic alcohol dehydrogenase and aldehyde dehydrogenase activities and expression were lower in KO mice. Hepatic cytochrome P450 2E1 protein levels were upregulated in ethanol-fed WT mice but were nearly undetectable in KO mice. These changes in ethanol-metabolizing enzymes were associated with 30-fold higher blood alcohol levels in KO mice.
β-catenin is essential for hepatic ethanol metabolism and plays a protective role in alcohol-mediated liver steatosis. Our results strongly suggest that integration of these functions by β-catenin is critical for adaptation to ethanol ingestion in vivo.
PMCID: PMC3288318  PMID: 22031168
Wnt pathway; Alcohol dehydrogenase; Cyp2E1; SOD-2; oxidative stress
18.  Analysis of Relationship between Paraspinal Muscle Fatty Degeneration and Cervical Spine Motion Using Kinetic Magnetic Resonance Imaging 
Global Spine Journal  2012;2(1):33-38.
The alignment and mobility of the cervical spine is influenced by factors related to the vertebral bodies, intervertebral discs, ligaments, facet joints, and muscles. Few reports have described the role played by the paraspinal muscles in cervical spine mobility. In this study, we investigate the relationship between fatty degeneration of the paraspinal muscles and cervical motion as assessed with kinetic magnetic resonance imaging (kMRI). One hundred eighty-eight symptomatic patients underwent cervical kMRI in neutral, flexion, and extension positions. We quantified cervical paraspinal muscle fatty infiltration and measured angular variation and translational motion at each cervical level, and the global Cobb angle. Cervical paraspinal muscle fatty degeneration demonstrated a pattern in which C3 and C7 had significantly more fatty infiltration than C4, C5, and C6. Additionally, when the normal group was compared with the fatty degeneration group with respect to angular variation, translational motion, and Cobb angle, no significant differences were found except in angular variation at the C3–C4 level. In conclusion, we found a significantly larger quantity of fatty degeneration in the paraspinal muscles at C3 and C7 than the middle cervical levels. Also, we demonstrate that fatty degeneration does not significantly affect cervical lordotic alignment or mobility characteristics.
PMCID: PMC3864418  PMID: 24353944
kinematic magnetic resonance imaging; cervical spine; cervical paraspinal muscle; cervical lordosis; fatty degeneration; fatty infiltration; multifidus muscle
19.  Linoleic acid metabolite drives severe asthma by causing airway epithelial injury 
Scientific Reports  2013;3:1349.
Airway epithelial injury is the hallmark of various respiratory diseases, but its mechanisms remain poorly understood. While 13-S-hydroxyoctadecadienoic acid (13-S-HODE) is produced in high concentration during mitochondrial degradation in reticulocytes little is known about its role in asthma pathogenesis. Here, we show that extracellular 13-S-HODE induces mitochondrial dysfunction and airway epithelial apoptosis. This is associated with features of severe airway obstruction, lung remodeling, increase in epithelial stress related proinflammatory cytokines and drastic airway neutrophilia in mouse. Further, 13-S-HODE induced features are attenuated by inhibiting Transient Receptor Potential Cation Channel, Vanilloid-type 1 (TRPV1) both in mouse model and human bronchial epithelial cells. These findings are relevant to human asthma, as 13-S-HODE levels are increased in human asthmatic airways. Blocking of 13-S-HODE activity or disruption of TRPV1 activity attenuated airway injury and asthma mimicking features in murine allergic airway inflammation. These findings indicate that 13-S-HODE induces mitochondrial dysfunction and airway epithelial injury.
PMCID: PMC3583002  PMID: 23443229
20.  CASE REPORT Sternal Chondrosarcoma After Sternotomy for Coronary Artery Bypass Grafting 
Eplasty  2013;13:e7.
Objective: Primary bony tumors of the chest wall are usually benign and most commonly located in the ribs or sternum. Chondrosarcoma is regarded as one of the most frequent primary malignancies of the chest wall and its incidence after a sternotomy for a cardiac procedure is extremely rare. We present a case of sternal chondrosarcoma. Methods: The patient presented with a sternal mass 4 years after undergoing coronary artery bypass grafting for ischemic coronary artery disease. The mass originally emanated from the upper portion of the patients’ sternum and then rapidly enlarged to include the anterior aspects of his neck. Radiologic imaging studies were undertaken: computed tomographic scan and magnetic resonance imaging, with surgical intervention for excision. Results: Computed tomographic scan and magnetic resonance imaging established an 8.4 × 6.2 × 8.6 cm3 complex solid tissue mass within the lower neck arising from the sternal manubrium, with extensive bone destruction. Computed tomography-guided biopsy showed cells of uncertain significance. Surgical excision was performed and the mass was diagnosed as a grade II chondrosarcoma. Discussion: Primary sarcomas of the sternum though uncommon are potentially curable with wide surgical excision. Success depends on tumor histologic type and grade, which dictate recurrence.
PMCID: PMC3556636  PMID: 23372861
21.  CASE REPORT Anomalies Associated With Congenitally Corrected Transposition of Great Arteries: Expect the Unexpected 
Eplasty  2013;13:e6.
Objective: Congenitally corrected transposition of great arteries (CCTGA) is characterized by atrioventricular and ventriculoarterial discordance. Characterizations of these anomalies are important because they may influence surgical approach and management. Methods: We present a case of newly diagnosed CCTGA at the age of 50. He presented with sudden onset of shortness of breath for the first time and was diagnosed with CCTGA. Echocardiogram, magnetic resonance imaging, and cardiac catheterization were utilized to elucidate the pathology. Results: Intraoperatively, patient's CCTGA and ventricularization of the right ventricle were confirmed. The severe systemic atrioventricular valve regurgitation was replaced with a bioprosthetic valve (Medtronic Mosaic No. 29) with placement of epicardial ventricular leads for possible future placement of automatic implantable cardioverter defibrillators. Pathology report confirmed a degeneration of the systemic atrioventricular valve. Conclusions: Significant coronary artery anomalies have also been described in literature with CCTGA. The variances encountered in this case are excellent examples of the intricacies associated in diagnosis and surgical care in patients with CCTGA.
PMCID: PMC3556635  PMID: 23409204
22.  Lentivirus-Induced Dendritic Cells for Immunization Against High-Risk WT1+ Acute Myeloid Leukemia 
Human Gene Therapy  2013;24(2):220-237.
Wilms' tumor 1 antigen (WT1) is overexpressed in acute myeloid leukemia (AML), a high-risk neoplasm warranting development of novel immunotherapeutic approaches. Unfortunately, clinical immunotherapeutic use of WT1 peptides against AML has been inconclusive. With the rationale of stimulating multiantigenic responses against WT1, we genetically programmed long-lasting dendritic cells capable of producing and processing endogenous WT1 epitopes. A tricistronic lentiviral vector co-expressing a truncated form of WT1 (lacking the DNA-binding domain), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-4 (IL-4) was used to transduce human monocytes ex vivo. Overnight transduction induced self-differentiation of monocytes into immunophenotypically stable “SmartDC/tWT1” (GM-CSF+, IL-4+, tWT1+, IL-6+, IL-8+, TNF-α+, MCP-1+, HLA-DR+, CD86+, CCR2+, CCR5+) that were viable for 3 weeks in vitro. SmartDC/tWT1 were produced with peripheral blood mononuclear cells (PBMC) obtained from an FLT3-ITD+ AML patient and surplus material from a donor lymphocyte infusion (DLI) and used to expand CD8+ T cells in vitro. Expanded cytotoxic T lymphocytes (CTLs) showed antigen-specific reactivity against WT1 and against WT1+ leukemia cells. SmartDC/tWT1 injected s.c. into Nod.Rag1−/−.IL2rγc−/− mice were viable in vivo for more than three weeks. Migration of human T cells (huCTLs) to the immunization site was demonstrated following adoptive transfer of huCTLs into mice immunized with SmartDC/tWT1. Furthermore, SmartDC/tWT1 immunization plus adoptive transfer of T cells reactive against WT1 into mice resulted in growth arrest of a WT1+ tumor. Gene array analyses of SmartDC/tWT1 demonstrated upregulation of several genes related to innate immunity. Thus, SmartDC/tWT1 can be produced in a single day of ex vivo gene transfer, are highly viable in vivo, and have great potential for use as immunotherapy against malignant transformation overexpressing WT1.
Sundarasetty and colleagues generate long-lasting, self-differentiated myeloid-derived antigen-presenting cells reactive against tumors (SmartDC) expressing a truncated form of Wilms' tumor 1 antigen (tWT1). SmartDC/tWT1 generated from a patient with acute myeloid leukemia (AML) efficiently stimulated expansion and activation of anti-WT1 cytotoxic responses against primary blasts obtained from the patient. SmartDC/tWT1 injected into a mouse model of adoptive T cell transfer remained viable in vivo for more than 3 weeks, and it was capable of attracting cytotoxic T cells.
PMCID: PMC3696945  PMID: 23311414
23.  Metabolic engineering of raffinose-family oligosaccharides in the phloem reveals alterations in carbon partitioning and enhances resistance to green peach aphid 
Many plants employ energized loading strategies to accumulate osmotically-active solutes into the phloem of source organs to accentuate the hydrostatic pressure gradients that drive the flow of water, nutrients and signals from source to sinks. Proton-coupled symport of sugars from the apoplasm into the phloem symplasm is the best studied phloem-loading mechanism. As an alternative, numerous species use a polymer trapping mechanism to load through symplasm: sucrose enters the phloem through specialized plasmodesmata and is converted to raffinose-family oligosaccharides (RFOs) which accumulate because of their larger size. In this study, metabolic engineering was used to generate RFOs at the inception of the translocation stream of Arabidopsis thaliana, which loads from the apoplasm and transports predominantly sucrose, and the fate of the sugars throughout the plant determined. Three genes, GALACTINOL SYNTHASE, RAFFINOSE SYNTHASE and STACHYOSE SYNTHASE, were expressed from promoters specific to the companion cells of minor veins. Two transgenic lines homozygous for all three genes (GRS63 and GRS47) were selected for further analysis. Three-week-old plants of both lines had RFO levels approaching 50% of total soluble sugar. RFOs were also identified in exudates from excised leaves of transgenic plants whereas levels were negligible in exudates from wild type (WT) leaves. Differences in starch accumulation between WT and GRS63 and GRS47 lines were not observed. Similarly, there were no differences in vegetative growth between WT and engineered plants, but the latter flowered slightly earlier. Finally, since the sugar composition of the translocation stream appeared altered, we tested for an impact on green peach aphid (Myzus persicae Sulzer) feeding. When given a choice between WT and transgenic plants, green peach aphids preferred settling on the WT plants. Furthermore, green peach aphid fecundity was lower on the transgenic plants compared to the WT plants. When added to an artificial diet, RFOs did not have a negative effect on aphid fecundity, suggesting that although aphid resistance in the transgenic plants is enhanced, it is not due to direct toxicity of RFO toward the insect.
PMCID: PMC3715723  PMID: 23882277
raffinose family oligosaccharides; green peach aphid; phloem transport; sugar transport; metabolic engineering
24.  Determinants of Utilization of Antenatal Care Services in Rural Lucknow, India 
Antenatal care services are the first steps towards ensuring the health of mothers and the newborn. This is the key component for achieving Millennium Development Goals by 2015. But India's performance continues to be poor in providing antenatal care services to its huge population, particularly in the rural areas.
To assess the determinants of utilization of antenatal services by rural beneficiaries in Lucknow, a district of north India.
Materials and Methods:
The study, cross-sectional in design, was conducted from August 2009 to July 2010. Multistage random sampling was used for selecting villages. A total of 352 recently delivered women were selected following systematic random sampling. Logistic regression was used to find out the determinants of three antenatal care services.
Overall, 85.5% of the beneficiaries surveyed were found to receive at least three antenatal care services from any health facility. Community health centre was the most common source for such care. Significant difference was found between beneficiaries who took three antenatal care visits and who did not in terms of age, socio economic status, and timing of registration. On multiple regression, only age (OR = 2.107, 95% CI = 1.132 – 3.923) and timing of registration (OR = 2.817, 95% CI = 1.487 – 5.338) were found to be the predictors for three antenatal care visits.
Intervention should be focused on young and late registered women for ensuring sufficient care during pregnancy.
PMCID: PMC3894022  PMID: 24479045
Antenatal care; determinant; recently delivered women; rural India
25.  Assessment of effectiveness of percutaneous adhesiolysis and caudal epidural injections in managing post lumbar surgery syndrome: 2-year follow-up of a randomized, controlled trial 
Journal of Pain Research  2012;5:597-608.
The literature is replete with evaluations of failed surgery, illustrating a 9.5%–25% reoperation rate. Speculated causes of post lumbar surgery syndrome include epidural fibrosis, acquired stenosis, recurrent disc herniation, sacroiliac joint pain, and facet joint pain among other causes.
Patients (n = 120) were randomly assigned to two groups with a 2-year follow-up. Group I (control group, n = 60) received caudal epidural injections with catheterization up to S3 with local anesthetic (lidocaine 2%, 5 mL), nonparticulate betamethasone (6 mg, 1 mL), and 6 mL of 0.9% sodium chloride solution. Group II (intervention group, n = 60) received percutaneous adhesiolysis of the targeted area, with targeted delivery of lidocaine 2% (5 mL), 10% hypertonic sodium chloride solution (6 mL), and nonparticulate betamethasone (6 mg). The multiple outcome measures included the Numeric Rating Scale, the Oswestry Disability Index 2.0, employment status, and opioid intake with assessments at 3, 6, 12, 18, and 24 months posttreatment. Primary outcome was defined as 50% improvement in pain and Oswestry Disability Index scores.
Significant improvement with at least 50% relief with pain and improvement in functional status was illustrated in 82% of patients at the 2-year follow-up in the intervention group compared to 5% in the control group receiving caudal epidural injections. The average number of procedures over a period of 2 years in Group II was 6.4 ± 2.35 with overall total relief of approximately 78 weeks out of 104 weeks.
The results of this study show significant improvement in 82% of patients over a period of 2 years with an average of six to seven procedures of 1-day percutaneous adhesiolysis in patients with failed back surgery syndrome.
PMCID: PMC3533727  PMID: 23293536
epidural adhesions; epidural steroid injections; epidural fibrosis

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