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1.  Targeted Therapy Resistance Mediated by Dynamic Regulation of Extrachromosomal Mutant EGFR DNA 
Science (New York, N.Y.)  2013;343(6166):72-76.
Intratumoral heterogeneity contributes to cancer drug resistance, but the underlying mechanisms are not understood. Single-cell analyses of patient-derived models and clinical samples from glioblastoma patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) demonstrate that tumor cells reversibly up-regulate or suppress mutant EGFR expression, conferring distinct cellular phenotypes to reach an optimal equilibrium for growth. Resistance to EGFR TKIs is shown to occur by elimination of mutant EGFR from extrachromosomal DNA. After drug withdrawal, reemergence of clonal EGFR mutations on extrachromosomal DNA follows. These results indicate a highly specific, dynamic, and adaptive route by which cancers can evade therapies that target oncogenes maintained on extrachromosomal DNA.
PMCID: PMC4049335  PMID: 24310612
2.  Current clinical practice: differential management of uveal melanoma in the era of molecular tumor analyses 
Assess current clinical practices for uveal melanoma (UM) and the impact of molecular prognostic testing on treatment decisions.
Cross-sectional survey and sequential medical records review.
Ophthalmologists who treat UM.
(A) Medical records review of all Medicare beneficiaries tested by UM gene expression profile in 2012, conducted under an institutional review board-approved protocol. (B) 109 ophthalmologists specializing in the treatment of UM were invited to participate in 24-question survey in 2012; 72 were invited to participate in a 23-question survey in 2014.
Main outcome measures
Responses analyzed by descriptive statistics, frequency analyses (percentages, Tukey, histograms), and Fisher’s exact test. Descriptive presentation of essay answers.
The review of Medicare medical records included 191 evaluable patients, 88 (46%) with documented medical treatment actions or institutional policies related to surveillance plans. Of these 88, all gene expression profiling (GEP) Class 1 UM patients were treated with low-intensity surveillance. All GEP Class 2 UM patients were treated with high-intensity surveillance (P<0.0001 versus Class 1). There were 36 (19%) with information concerning referrals after initial diagnosis. Of these 36, all 23 Class 2 patients were referred to medical oncology; however, none of the 13 Class 1 patients were referred (P<0.0001 versus Class 1). Only Class 2 patients were recommended for adjunctive treatment regimens. 2012 survey: 50 respondents with an annual median of 35 new UM patients. The majority of respondents (82%) performed molecular analysis of UM tumors after fine needle biopsy (FNAB); median: 15 FNAB per year; 2014 survey: 35 respondents with an annual median of 30 new UM patients. The majority offered molecular analyses of UM tumor samples to most patients. Patients with low metastatic risk (disomy 3 or GEP Class 1) were generally assigned to less frequent (every 6 or 12 months) and less intensive clinical visits. Patients with high metastatic risk (monosomy 3 or GEP Class 2) were assigned to more frequent surveillance with hepatic imaging and liver function testing every 3–6 months. High-risk patients were considered more suitable for adjuvant treatment protocols.
The majority of ophthalmologists treating UM have adopted molecular diagnostic tests for the purpose of designing risk-appropriate treatment strategies.
PMCID: PMC4262218  PMID: 25587217
uveal melanoma; gene expression profiling (GEP); Medicare; molecular diagnostic test
3.  Full Mouth Rehabilitation of a Patient with Extracoronal Attachments and Telescopic Prosthesis - A Case Report 
The management of tooth wear is complex and challenging as it involves multidisciplinary approach. Proper diagnosis and elaborative treatment protocol is necessary to obtain successful and predictable outcome. The objective of full mouth rehabilitation includes identification of the cause, prevention and preservation of the remaining tooth structure. This case report presents the management of the remaining teeth by endodontic and periodontic intervention which was followed by porcelain fused to metal fixed prosthesis, telescopic denture for the upper missing teeth and extra-coronal attachments for the lower missing teeth. Segmental arch technique was utilized for the rehabilitation where anterior teeth were restored first followed by the posterior teeth. Patient had a satisfactory functional and aesthetic results.
PMCID: PMC4253277  PMID: 25478459
Broadrick occlusal plane analyzer;  Extracoronal attachment; Full mouth rehabilitation; Semi-precision attachment; Telescopic denture
4.  Default Mode Network Interference in Mild Traumatic Brain Injury – A Pilot Resting State Study 
Brain research  2013;1537:10.1016/j.brainres.2013.08.034.
In this study we investigated the functional connectivity in 23 Mild TBI (mTBI) patients with and without memory complaints using resting state fMRI in the sub-acute stage of injury as well as a group of control participants. Results indicate that mTBI patients with memory complaints performed significantly worse than patients without memory complaints on tests assessing memory from the Automated Neuropsychological Assessment Metrics (ANAM). Altered functional connectivity was observed between the three groups between the default mode network (DMN) and the nodes of the task positive network (TPN). Altered functional connectivity was also observed between both the TPN and DMN and nodes associated with the Salience Network (SN). Following mTBI there is a reduction in anti-correlated networks for both those with and without memory complaints for the DMN, but only a reduction in the anti-correlated network in mTBI patients with memory complaints for the TPN. Furthermore, an increased functional connectivity between the TPN and SN appears to be associated with reduced performance on memory assessments. Overall the results suggest that a disruption in the segregation of the DMN and the TPN at rest may be mediated through both a direct pathway of increased FC between various nodes of the TPN and DMN, and through an indirect pathway that links the TPN and DMN through nodes of the SN. This disruption between networks may cause a detrimental impact on memory functioning following mTBI, supporting the Default Mode Interference Hypothesis in the context of mTBI related memory deficits.
PMCID: PMC3835746  PMID: 23994210
resting state fMRI; mild traumatic brain injury; working memory; default mode network
5.  Composite alginate hydrogel microparticulate delivery system of zidovudine hydrochloride based on counter ion induced aggregation 
The present study deals with preparation of zidovudine loaded microparticle by counter ion induced aggregation method. During this study effect of polyacrylates and hypromellose polymers on release study were investigated.
Materials and Methods:
The ion induced aggregated alginate based microparticles were characterized for surface morphology, particle size analysis, drug entrapment study, in-vitro study, Fourier-transform infrared (FTIR) spectroscopy, and differential scanning calorimetry (DSC) study.
Results and Discussion:
The result showed Eudragit RL-100 (ERL) based formulations had smoother surface as well as their mean particle sizes were found greater compared with Eudragit RS-100 (ERS) microparticles. Furthermore, drug entrapments were found to be more in ERL formulae as compared with ERS. RL3 released 101.05% drug over a period of 8th h and followed Higuchi profile and Fickian diffusion. Moreover, data obtained illustrated that, higher amount of quaternary ammonium group, alkali value, and glass transition temperature may be possible reason for improving permeability of ERL based formulations. It was also noticed, hyroxypropyl methylcellulose (HPMC) K4M premium grade polymer sustained drug release more than HPMC K15M. In addition, drug-excipient interaction study was carried out by FTIR and DSC study.
PMCID: PMC4181129  PMID: 25298940
Eudragit RL-100; Higuchi profile; hypromellose; hyroxypropyl methylcellulose K4M premium; microparticle; zidovudine
6.  Subclinical atherosclerosis in patients with rheumatoid arthritis by utilizing carotid intima-media thickness as a surrogate marker 
Background & objectives:
Patients with rheumatoid arthritis (RA) are more prone for accelerated atherosclerosis and Asian Indians as an ethnic group are predisposed to a high risk of premature atherosclerosis. However, sparse data are available regarding the burden of atherosclerosis among asymptomatic adult patients with RA in south India. We studied the burden of asymptomatic atherosclerosis in adult south Indian patients with RA at Tirupati, Andhra Pradesh, India, utilizing carotid intima-media thickness (CIMT) as a surrogate marker.
Ultrasound examination of the carotids and CIMT measurement (mm) were carried out in 32 patients with RA, 32 age- and gender-matched normal controls, and 32 patients with atherosclerosis and angiographically proven coronary artery disease. The CIMT values in patients with CAD and normal controls were used to derive the appropriate cut-off value of CIMT for defining atherosclerosis that would be applicable for the ethnic population studied.
Patients with RA had a higher mean CIMT (mm) compared with normal control subjects (0.598 ± 0.131 vs 0.501 ± 0.081; P = 0.001). Carotid plaque was found more frequently among the cases compared with normal controls [5/32 (15.6%) vs 0/32 (0%), P=0.020]. Using this cut-off value derived by the receiver operator characteristic curve method (≥ 0.57 mm; sensitivity 84.4; specificity 90.6%) and the 75th percentile value among normal controls (≥ 0.55 mm) as surrogate markers, the presence of subclinical atherosclerosis was significantly more among asymptomatic patients with RA compared with normal controls [(59.3 vs 12.5%; P<0.001) and (62.5 vs 25%; P<0.001) respectively].
Interpretation & conclusions:
Based on the present findings CIMT appears to be a useful surrogate marker for detecting subclinical atherosclerosis in adult Indian patients with RA.
PMCID: PMC4248384  PMID: 25366205
Atherosclerosis; carotid intima-media thickness; India; rheumatoid arthritis
7.  Shelf-life and colour change kinetics of Aloe vera gel powder under accelerated storage in three different packaging materials 
Aloe vera gel powder was produced through dehumidified air drying of Aloe vere gel at optimized conditions of temperature, relative humidity and air velocity of 64 °C, 18% and 0.8 m.s−1, respectively. The powder was packed in three different packaging materials viz., laminated aluminum foil (AF), biaxially oriented polypropylene (BOPP) and polypropylene (PP). The shelf-life of the powder was predicted on the basis of free flowness of product under accelerated storage condition (38 ± 1 °C, 90 ± 1% relative humidity) and was calculated to be 33.87, 42.58 and 51.05 days in BOPP, PP and AF, respectively. The storage stability of powder in terms of colour change was studied. The magnitude of colour change of Aloe vera gel powder during storage suggests that AF was better than BOPP and PP. The colour change of powder during storage followed first order reaction kinetics with a rate constant of 0.0444 per day for AF, 0.075 per day for BOPP and 0.0498 per day for PP.
PMCID: PMC3671063  PMID: 24425977
Accelerated storage; Aloe vera gel powder; Dehumidified air drying; Shelf-life
8.  Intersession reliability of fMRI activation for heat pain and motor tasks 
NeuroImage : Clinical  2014;5:309-321.
As the practice of conducting longitudinal fMRI studies to assess mechanisms of pain-reducing interventions becomes more common, there is a great need to assess the test–retest reliability of the pain-related BOLD fMRI signal across repeated sessions. This study quantitatively evaluated the reliability of heat pain-related BOLD fMRI brain responses in healthy volunteers across 3 sessions conducted on separate days using two measures: (1) intraclass correlation coefficients (ICC) calculated based on signal amplitude and (2) spatial overlap. The ICC analysis of pain-related BOLD fMRI responses showed fair-to-moderate intersession reliability in brain areas regarded as part of the cortical pain network. Areas with the highest intersession reliability based on the ICC analysis included the anterior midcingulate cortex, anterior insula, and second somatosensory cortex. Areas with the lowest intersession reliability based on the ICC analysis also showed low spatial reliability; these regions included pregenual anterior cingulate cortex, primary somatosensory cortex, and posterior insula. Thus, this study found regional differences in pain-related BOLD fMRI response reliability, which may provide useful information to guide longitudinal pain studies. A simple motor task (finger-thumb opposition) was performed by the same subjects in the same sessions as the painful heat stimuli were delivered. Intersession reliability of fMRI activation in cortical motor areas was comparable to previously published findings for both spatial overlap and ICC measures, providing support for the validity of the analytical approach used to assess intersession reliability of pain-related fMRI activation. A secondary finding of this study is that the use of standard ICC alone as a measure of reliability may not be sufficient, as the underlying variance structure of an fMRI dataset can result in inappropriately high ICC values; a method to eliminate these false positive results was used in this study and is recommended for future studies of test–retest reliability.
•Intersession reliability of pain-related fMRI responses was fair-to-moderate•Intersession reliability of pain-related fMRI responses varied by brain region•Intersession reliability is comparable for fixed temperature and fixed perception stimuli•Standard methods of assessing intersession reliability can lead to false positives
PMCID: PMC4141974  PMID: 25161897
Intraclass correlation coefficient; Reliability coefficient; Reproducibility; Repeatability; Anterior insula; Cingulate cortex
9.  Efficacy of orally disintegrating film of ondansetron versus intravenous ondansetron in prophylaxis of postoperative nausea and vomiting in patients undergoing elective gynaecological laparoscopic procedures: A prospective randomised, double-blind placebo-controlled study 
Indian Journal of Anaesthesia  2014;58(4):423-429.
Background and Aims:
Ondansetron is one of the most widely used drugs for postoperative nausea and vomiting (PONV) prophylaxis. Orally disintegrating film (ODF) formulations are relatively recent innovations. We evaluated the efficacy of ODF of ondansetron for the prophylaxis of PONV.
One hundred and eighty American Society of Anaesthesiologists-I or II women, in the age group 18-65 years, scheduled for elective gynaecological laparoscopic procedures were studied in a prospective randomised, double-blind, placebo-controlled trial. The patients were randomised into four groups: Placebo, intravenous (IV) ondansetron 4 mg, ODF of ondansetron 4 mg (ODF4) and 8 mg (ODF8) groups. PONV was assessed in two epochs of 0-6 and 7-24 h. Primary outcome measure was the incidence of PONV and secondary outcome measures were severity of nausea, need for rescue anti-emetic, analgesic consumption, time to oral intake, overall patient satisfaction and side effects such as headache and dizziness. PONV was compared using analysis of variance or Mann–Whitney U-test as applicable.
Data of 173 patients were analysed. The incidence of postoperative nausea was significantly lower (P = 0.04) only during the 0-6 h in the ODF8 group when compared with the placebo group. During the 0-6 h interval postoperatively, the ODF8 group had a significantly lower incidence of vomiting when compared with the placebo (P = 0.002) and the IV group (P = 0.044). During the 0-24 h interval postoperatively, ODF4 (P = 0.01) and ODF8 (P = 0.002) groups had a significantly lower incidence of vomiting compared to the placebo group.
Orally disintegrating film of ondansetron is an efficacious, novel, convenient and may be a cost-effective option for the prophylaxis of PONV.
PMCID: PMC4155287  PMID: 25197110
Laparoscopic surgical procedures; ondansetron; postoperative nausea and vomiting; randomized controlled trial
10.  Effects of ceftriaxone on the acquisition and maintenance of ethanol drinking in peri-adolescent and adult female alcohol-preferring (P) rats 
Neuroscience  2013;241:229-238.
Increased glutamatergic neurotransmission appears to mediate the reinforcing properties of drugs of abuse, including ethanol (EtOH). We recently reported that the administration of ceftriaxone (CEF), a β-lactam antibiotic known to upregulate glutamate transporter 1 (GLT1) levels/activity, decreased the maintenance of EtOH intake in adult male alcohol-preferring (P) rats. In the present study, we tested whether CEF administration would reduce the acquisition and maintenance of EtOH drinking in adolescent and adult female P rats. The rats were treated with saline or 200 mg/kg ceftriaxone for 7 days (starting at 35 or 75 days old, respectively) followed by the EtOH acquisition test. Five weeks later the effects of CEF were examined regarding the maintenance of EtOH intake. For the maintenance test, half of the animals that received CEF during acquisition received CEF for 7 days and the other half received saline for 7 days. Saline-treated acquisition animals were treated similarly. The results indicated that pretreatment with ceftriaxone reduced the maintenance of EtOH intake in both animals that started as adolescents and those that started as adults. However, the beneficial effect of CEF was more pronounced in rats pretreated with CEF as adults compared with rats pretreated as adolescents. Reductions in EtOH intake by ceftriaxone were paralleled by an upregulation of GLT1 protein levels in both the nucleus accumbens (µ25% in rats starting at both ages) and prefrontal cortex (µ50% in rats starting as peri-adolescents and µ65% in those starting as adults). These findings provide further support for GLT1-associated mechanisms in high alcohol consuming behavior, and hold promise for the development of effective treatments targeting alcohol abuse and dependence.
PMCID: PMC3657748  PMID: 23537837
Ceftriaxone; EAAT2; acquisition; maintenance
11.  Chemical composition and functional properties of mrigal (Cirrhinus mrigala) egg protein concentrates and their application in pasta 
Protein concentrates were prepared from underutilized mrigal (Cirrhinus mrigala) roe to produce value added by-products for food applications. Chemical composition and physicochemical properties of protein concentrates prepared from mrigal (Cirrhinus mrigala) roes were determined. The effects of pH and salt concentration on protein solubility were investigated. The protein content of the concentrates was found to be 75, and 91%, respectively for dehydrated and defatted powders. The maximum protein solubility was observed at pH 12, while minimum protein solubility was observed at pH 5, for both dehydrated and defatted protein concentrates. Salt concentration (0.1 to 1 M Nacl) significantly affected the solubility of protein concentrates. The mineral analysis revealed substantial amounts of iron and phosphorus. The emulsifying capacities of dehydrated and defatted protein concentrates were noted as 5.9, and 7.1 ml/g protein, respectively. SDS-PAGE analysis of fresh, dehydrated and defatted roe proteins has revealed the presence of major protein with a molecular weight (MW) of 97 kDa. Addition of defatted fish egg protein concentrate to pasta preparations had improved taste and texture. The results indicated that protein concentrates from underutilized mrigal fish egg may be useful for preparing protein rich food supplements.
PMCID: PMC3602574  PMID: 24425946
Mrigal; Cirrhinus mrigala; Fish egg; Protein concentrates; Protein solubility; SDS-PAGE; Sensory analysis
12.  Delayed Hippocampal Effects From a Single Exposure of Prepubertal Guinea Pigs to sub-lethal dose of Chlorpyrifos: A Magnetic Resonance Imaging and Spectroscopy Study 
Neurotoxicology  2013;36:42-48.
This study was designed to test the hypothesis that in vivo Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) can detect in adulthood the neurotoxic effects of a single exposure of prepubertal guinea pigs to the organophosphorus pesticide chlorpyrifos. Twelve female guinea pigs were given either a single dose of chlorpyrifos (0.6xLD50 or 300 mg/kg, sc) or peanut oil (vehicle; 0.5 ml/kg, sc) at 35–40 days of age. One year after the exposure, the animals were tested in the Morris water maze. Three days after the end of the behavioral testing, the metabolic and structural integrity of the brain of the animals was examined by means of MRI/MRS. In the Morris water maze, the chlorpyrifos-exposed guinea pigs showed significant memory deficit. Although no significant anatomical differences were found between the chlorpyrifos-exposed guinea pigs and the control animals by in vivo MRI, the chlorpyrifos-exposed animals showed significant decreases in hippocampal myo-inositol concentration using MRS. The present results indicate that a single sub-lethal exposure of prepubertal guinea pigs to the organophosphorus pesticide chlorpyrifos can lead to long-term memory deficits that are accompanied by significant reductions in the levels of hippocampal myo-inositol.
PMCID: PMC3669662  PMID: 23411083
Chlorpyrifos; Magnetic resonance imaging; 1H magnetic resonance spectroscopy; Myo-inositol; Hippocampus
13.  Current status of management, control, complications and psychosocial aspects of patients with diabetes in India: Results from the DiabCare India 2011 Study 
DiabCare India 2011 was a cross-sectional study in patients with diabetes mellitus, undertaken to investigate the relationship between diabetes control, management and complications in a subset of urban Indian diabetes patients treated at referral diabetes care centres in India.
Materials and Methods:
This was a cross-sectional, multicentre (330 centres) survey in 6168 diabetes patients treated at general hospitals, diabetes clinics and referral clinics across India. Patient data, including medical and clinical examination reports during the past year were collected during their routine visit. The patients’ and physicians’ perceptions about diabetes management were recorded using a questionnaire.
A total of 6168 subjects with diabetes (95.8% type 2), mean age 51.9 ± 12.4 years and mean duration of diabetes, 6.9 ± 6.4 years were included. Mean HbA1c was 8.9 ± 2.1% and the mean fasting (FPG), post prandial (PPG) and random (RBG) plasma glucose levels were 148 ± 50 mg/dl 205 ± 66 mg/dl and 193 ± 68mg/dl respectively. Neuropathy was the most common complication (41.4%); other complications were: Foot (32.7%), eye (19.7%), cardiovascular (6.8%) and nephropathy (6.2%). The number of diabetic complications increased with mean duration of diabetes. Most (93.2%) of the patients were on oral anti-diabetic drugs (OADs) and 35.2% were on insulin (±OADs). More than 15% physicians felt that the greatest barrier to insulin therapy from patient's perspective were pain and fear of using injectable modality; 5.2% felt that the greatest barrier to insulin therapy from physician's perspective was the treatment cost; 4.8% felt that the major barriers to achieve optimum diabetic care in practice was loss to follow-up followed by lack of counselling (3.9%) and treatment compliance (3.6%).
DiabCare India 2011 has shown that type 2 diabetes sets in early in Indians and glycaemic control is often sub-optimal in these patients. These results indicate a need for more structured intervention at an early stage of the disease and need for increased awareness on benefits of good glycaemic control. It cannot be overemphasized that the status of diabetes care in India needs to be further improved. ( identifier: NCT01351922)
PMCID: PMC4056138  PMID: 24944934
Control and complications; current status of diabetes care; DiabCare India
14.  Knowledge and awareness of diabetes in urban and rural India: The Indian Council of Medical Research India Diabetes Study (Phase I): Indian Council of Medical Research India Diabetes 4 
Representative data on knowledge and awareness about diabetes is scarce in India and is extremely important to plan public health policies aimed at preventing and controlling diabetes.
The aim of the following study is to assess awareness and knowledge about diabetes in the general population, as well as in individuals with diabetes in four selected regions of India.
Materials and Methods:
The study subjects were drawn from a representative sample of four geographical regions of India, Chandigarh, Tamil Nadu, Jharkhand and Maharashtra representing North, South, East and West and covering a population of 213 million. A total of 16,607 individuals (5112 urban and 11,495 rural) aged ≥20 years were selected from 188 urban and 175 rural areas. Awareness of diabetes and knowledge of causative factors and complications of diabetes were assessed using an interviewer administered structured questionnaire in 14,274 individuals (response rate, 86.0%), which included 480 self-reported diabetic subjects.
Only 43.2% (6160/14,274) of the overall study population had heard about a condition called diabetes. Overall urban residents had higher awareness rates (58.4%) compared to rural residents (36.8%) (P < 0.001). About 46.7% of males and 39.6% of females reported that they knew about a condition called diabetes (P < 0.001). Of the general population, 41.5% (5726/13,794) knew about a condition called diabetes. Among them, 80.7% (4620/5726) knew that the prevalence of diabetes was increasing, whereas among diabetic subjects, it was 93.0% (448/480). Among the general and diabetic population, 56.3% and 63.4% respectively, were aware that diabetes could be prevented. Regarding complications, 51.5% of the general population and 72.7% diabetic population knew that diabetes could affect other organs. Based on a composite knowledge score to assess knowledge among the general population, Tamil Nadu had the highest (31.7) and Jharkhand the lowest score (16.3). However among self-reported diabetic subjects, Maharashtra had the highest (70.1) and Tamil Nadu, the lowest score (56.5).
Knowledge and awareness about diabetes in India, particularly in rural areas, is poor. This underscores the need for conducting large scale diabetes awareness and education programs.
PMCID: PMC4056139  PMID: 24944935
Asian Indians; awareness; diabetes; Indian Council of Medical Research India Diabetes; India; knowledge; rural; South Asians; urban
16.  Extranodal Marginal Zone Lymphoma Presenting within the Meckel Diverticulum as Diverticulitis: A Case Report 
Case Reports in Pathology  2014;2014:374814.
Meckel diverticulum is the most common congenital defect of the gastrointestinal tract. It can be asymptomatic or mimic appendicitis and may be complicated by bleeding, diverticulitis, obstruction, and, rarely, neoplasia. We report the first case of extranodal marginal zone lymphoma occupying a Meckel diverticulum. A 44-year-old man with history of colonic diverticulitis presented to the emergency department for evaluation of acute abdominal pain. Radiography showed enteric obstruction, prompting diagnostic laparoscopy. Above the level of mid-ileum an intact Meckel diverticulum was identified. Microscopy showed extensive infiltration of sheets of small lymphocytes with abundant cytoplasm (monocytoid B-cells) prominently in submucosa and focally transmural involving serosal adipose tissue with multiple reactive germinal centers. The immunostains showed positivity for CD20, BCL-2, and CD43 (weak) and negativity for CD3, CD5, BCL-1, CD10, and BCL-6 in monocytoid B-cells. Fluorescence in situ hybridization studies revealed API2-MALT1 fusion signals consistent with t(11;18)(q21;q21), which confirmed the diagnosis of extranodal marginal zone lymphoma, also known as mucosa associated lymphoid tissue lymphoma.
PMCID: PMC4020529  PMID: 24868477
17.  Motor Cortex Stimulation Suppresses Cortical Responses to Noxious Hindpaw Stimulation after Spinal Cord Lesion in Rats 
Brain stimulation  2013;7(2):182-189.
Motor cortex stimulation (MCS) is a potentially effective treatment for chronic neuropathic pain. The neural mechanisms underlying the reduction of hyperalgesia and allodynia after MCS are not completely understood.
To investigate the neural mechanisms responsible for analgesic effects after MCS. We test the hypothesis that MCS attenuates evoked blood oxygen-level dependent signals in cortical areas involved in nociceptive processing in an animal model of chronic neuropathic pain.
We used adult female Sprague-Dawley rats (n = 10) that received unilateral electrolytic lesions of the right spinal cord at the level of C6 (SCL animals). In these animals, we performed magnetic resonance imaging (fMRI) experiments to study the analgesic effects of MCS. On the day of fMRI experiment, 14 days after spinal cord lesion, the animals were anesthetized and epidural bipolar platinum electrodes were placed above the left primary motor cortex. Two 10-minute sessions of fMRI were performed before and after a session of MCS (50 μA, 50 Hz, 300 μs, for 30 min.). During each fMRI session, the right hindpaw was electrically stimulated (noxious stimulation: 5 mA, 5 Hz, 3 ms) using a block design of 20 s stimulation off and 20 s stimulation on. A general linear model-based statistical parametric analysis was used to analyze whole brain activation maps. Region of interest (ROI) analysis and paired t-test were used to compare changes in activation before and after MCS in these ROI.
MCS suppressed evoked blood oxygen dependent signals significantly (Family-wise error corrected p < 0.05) and bilaterally in 2 areas heavily implicated in nociceptive processing. These areas consisted of the primary somatosensory cortex and the prefrontal cortex.
These findings suggest that, in animals with SCL, MCS attenuates hypersensitivity by suppressing activity in the primary somatosensory cortex and prefrontal cortex.
PMCID: PMC4000711  PMID: 24468093
Functional magnetic resonance imaging (fMRI); neuropathic pain; central pain; motor cortex stimulation; noxious electrical stimulation
18.  Concurrent multiscale imaging with magnetic resonance imaging and optical coherence tomography 
Journal of Biomedical Optics  2013;18(4):040506.
We develop a novel platform based on a tele-operated robot to perform high-resolution optical coherence tomography (OCT) imaging under continuous large field-of-view magnetic resonance imaging (MRI) guidance. Intra-operative MRI (iMRI) is a promising guidance tool for high-precision surgery, but it may not have sufficient resolution or contrast to visualize certain small targets. To address these limitations, we develop an MRI-compatible OCT needle probe, which is capable of providing microscale tissue architecture in conjunction with macroscale MRI tissue morphology in real time. Coregistered MRI/OCT images on ex vivo chicken breast and human brain tissues demonstrate that the complementary imaging scales and contrast mechanisms have great potential to improve the efficiency and the accuracy of iMRI procedure.
PMCID: PMC3631782
optical coherence tomography; magnetic resonance imaging; multimodal imaging
19.  Concurrent multiscale imaging with magnetic resonance imaging and optical coherence tomography 
Journal of Biomedical Optics  2013;18(4):046015.
We develop a novel platform based on a tele-operated robot to perform high-resolution optical coherence tomography (OCT) imaging under continuous large field-of-view magnetic resonance imaging (MRI) guidance. Intra-operative MRI (iMRI) is a promising guidance tool for high-precision surgery, but it may not have sufficient resolution or contrast to visualize certain small targets. To address these limitations, we develop an MRI-compatible OCT needle probe, which is capable of providing microscale tissue architecture in conjunction with macroscale MRI tissue morphology in real time. Coregistered MRI/OCT images on ex vivo chicken breast and human brain tissues demonstrate that the complementary imaging scales and contrast mechanisms have great potential to improve the efficiency and the accuracy of iMRI procedure.
PMCID: PMC3634554  PMID: 23609326
optical coherence tomography; magnetic resonance imaging; multimodal imaging
20.  A Rare Case of a Synchronous Anaplastic Carcinoma Thyroid with Ductal Carcinoma Breast 
Dual malignancy was first reported by Billroth in 1889. Incidence of second malignancy in cancer patients is as high as 10%, but synchronous anaplastic thyroid cancer along with breast tumor is a rare entity. We present a case of a 61-year-old female with a synchronous anaplastic carcinoma thyroid with ductal carcinoma breast. The plausible association of breast cancers with thyroid carcinomas should thus be evaluated in larger cohort studies. More importantly, this report is to highlight the unusual synchronous occurrence of anaplastic thyroid cancer with ductal breast cancer and the therapeutic challenges involved in such cases.
PMCID: PMC4005064  PMID: 24822141
21.  Evaluation of Partial k-space strategies to speed up Time-domain EPR Imaging 
Narrow-line spin probes derived from the trityl radical have led to the development of fast in vivo time-domain EPR imaging. Pure phase-encoding imaging modalities based on the Single Point Imaging scheme (SPI) have demonstrated the feasibility of 3D oximetric images with functional information in minutes. In this paper, we explore techniques to improve the temporal resolution and circumvent the relatively short biological half-lives of trityl probes using partial k-space strategies. There are two main approaches: one involves the use of the Hermitian character of the k-space by which only part of the k-space is measured and the unmeasured part is generated using the Hermitian symmetry. This approach is limited in success by the accuracy of numerical estimate of the phase roll in the k-space that corrupts the Hermiticy. The other approach is to measure only a judicially chosen reduced region of k-space (a centrosymmetric ellipsoid region) that more or less accounts for >70% of the k-space energy. Both of these aspects were explored in FT-EPR imaging with a doubling of scan speed demonstrated by considering ellipsoid geometry of the k-space. Partial k-space strategies help improve the temporal resolution in studying fast dynamics of functional aspects in vivo with infused spin probes.
PMCID: PMC3548084  PMID: 23045171
MRI; Time-domain EPR imaging; Partial Fourier; partial k-space acquisition; conjugate symmetry; Single Point Imaging; homodyne detection; projection onto convex sets (POCS)
22.  Multiplex PCR assay using SCAR primers to detect Eimeria spp. in chicken 
About 11 faecal samples from various regions of Tamil Nadu and Andhra Pradesh containing mixed spectrum of Eimeria species detected by morphometry viz. 15.4 × 11.2, 28.5 × 20.3, 31.1 × 18.5, 13.2 × 12.4, 20.8 × 17.5 and 22 × 18 μm for E. acervulina, E. brunetti, E. maxima, E. mitis, E. necatrix, E. praecox and E. tenella respectively were taken for the study. The oocysts were concentrated and purified using faecal harvest protocol. The genomic DNA is extracted as per kit protocol. The amplicons of sizes 539 bp (E. tenella) and 460 bp (E. mitis) obtained could be visualised in a single lane for the multiplex PCR assay using sequence characterized amplified region primers.
PMCID: PMC3590386  PMID: 24431550
Mixed spectrum; Eimeria; Morphometry; Faecal harvest; Multiplex PCR; SCAR
23.  Characterizing Long-Term Land Use/Cover Change in the United States from 1850 to 2000 Using a Nonlinear Bi-analytical Model 
Ambio  2012;42(3):285-297.
We relate the historical (1850–2000) spatial and temporal changes in cropland cover in the conterminous United States to several socio-economic and biophysical determinants using an eco-region based spatial framework. Results show population density as a major determinant during the nineteenth century, and biophysical suitability as the major determinant during the twentieth century. We further examine the role of technological innovations, socio-economic and socio-ecological feedbacks that have either sustained or altered the cropland trajectories in different eco-regions. The cropland trajectories for each of the 84 level-III eco-regions were analyzed using a nonlinear bi-analytical model. In the Eastern United States, low biophysically suitable eco-regions, e.g., New England, have shown continual decline in the cropland after reaching peak levels. The cropland trajectories in high biophysically suitable regions, e.g., Corn Belt, have stabilized after reaching peak levels. In the Western United States, low-intensity crop cover (<10 %) is sustained with irrigation support. A slower rate of land conversion was found in the industrial period. Significant effect of Conservation Reserve Program on planted crop area is found in last two decades (1990–2010).
Electronic supplementary material
The online version of this article (doi:10.1007/s13280-012-0354-6) contains supplementary material, which is available to authorized users.
PMCID: PMC3606703  PMID: 23151939
Land cover change; Cropland change; Spatial determinants; United States
24.  The role of circulating sex hormones in menstrual cycle dependent modulation of pain-related brain activation 
Pain  2013;154(4):548-559.
Sex differences in pain sensitivity have been consistently found but the basis for these differences is incompletely understood. The present study assessed how pain-related neural processing varies across the menstrual cycle in normally cycling, healthy females, and whether menstrual cycle effects are based on fluctuating sex hormone levels. Fifteen subjects participated in four test sessions during their menstrual, mid-follicular, ovulatory, and midluteal phases. Brain activity was measured while nonpainful and painful stimuli were applied with a pressure algometer. Serum hormone levels confirmed that scans were performed at appropriate cycle phases in 14 subjects. No significant cycle phase differences were found for pain intensity or unpleasantness ratings of stimuli applied during fMRI scans. However, lower pressure pain thresholds were found for follicular compared to other phases. Pain-specific brain activation was found in several regions traditionally associated with pain processing, including the medial thalamus, anterior and mid-insula, mid-cingulate, primary and secondary somatosensory cortices, cerebellum, and frontal regions. The inferior parietal lobule, occipital gyrus, cerebellum and several frontal regions demonstrated interaction effects between stimulus level and cycle phase, indicating differential processing of pain-related responses across menstrual cycle phases. Correlational analyses indicated that cycle-related changes in pain sensitivity measures and brain activation were only partly explained by varying sex hormone levels. These results show that pain-related cerebral activation varies significantly across the menstrual cycle, even when perceived pain intensity and unpleasantness remain constant. The involved brain regions suggest that cognitive pain or more general bodily awareness systems are most susceptible to menstrual cycle effects.
PMCID: PMC3608932  PMID: 23528204
circulating hormones; pain sensitivity; pain-related brain activation; menstrual cycle; functional brain imaging
25.  Sustaining a “culture of silence” in the neonatal intensive care unit during nonemergency situations: A grounded theory on ensuring adherence to behavioral modification to reduce noise levels 
The aim of this study was to generate a substantive theory explaining how the staff in a resource-limited neonatal intensive care unit (NICU) of a developing nation manage to ensure adherence to behavioral modification components of a noise reduction protocol (NsRP) during nonemergency situations. The study was conducted after implementation of an NsRP in a level III NICU of south India. The normal routine of the NICU is highly dynamic because of various categories of staff conducting clinical rounds followed by care-giving activities. This is unpredictably interspersed with very noisy emergency management of neonates who suddenly fall sick. In-depth interviews were conducted with 36 staff members of the NICU (20 staff nurses, six nursing aides, and 10 physicians). Group discussions were conducted with 20 staff nurses and six nursing aides. Data analysis was done in line with the reformulated grounded theory approach, which was based on inductive examination of textual information. The results of the analysis showed that the main concern was to ensure adherence to behavioral modification components of the NsRP. This was addressed by using strategies to “sustain a culture of silence in NICU during nonemergency situations” (core category). The main strategies employed were building awareness momentum, causing awareness percolation, developing a sense of ownership, expansion of caring practices, evolution of adherence, and displaying performance indicators. The “culture of silence” reconditions the existing staff and conditions new staff members joining the NICU. During emergency situations, a “noisy culture” prevailed because of pragmatic neglect of behavioral modification when life support overrode all other concerns. In addition to this, the process of operant conditioning should be formally conducted once every 18 months. The results of this study may be adapted to create similar strategies and establish context specific NsRPs in NICUs with resource constraints.
PMCID: PMC3959455  PMID: 24646472
Grounded theory; noise; NICU; operant conditioning

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