A hypothesis: Bitter taste receptors as a therapeutic target for the clinical symptoms of SARS-CoV-2.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has paralysed the livelihood of the global population by inflicting higher mortality among the affected patients. Nearly the entire human physiological system can get disrupted by the virulence of SARS-CoV-2, which exemplifies the significance of discovering a potential drug target. Similar to angiotensin-converting enzyme 2 (ACE2), bitter taste receptors (T2Rs) unequivocally expressed on all vital human organs, particularly on nasal/oral respiratory tract, gastrointestinal organs, innate immune cells, heart, brain and urogenital cells are susceptible to SARS-CoV-2 virulence. Activation of T2Rs by bitter agonists restores vital functions to these organs via activation of large conductance, Ca2+-dependent potassium (K+) channels (BKca), and inducible nitric oxide synthase. T2R activation in the gustatory system can act as the first defence mechanism, primarily preventing or mitigating SARS-CoV-2 entry to the respiratory tract. Moreover, T2R activation is crucial for the improved vasodilation accompanied by the attenuation of systemic inflammation; hyper-innate immune responses; gastrointestinal disorders; defective neurological functions; acute kidney injury; and impotency witnessed in severe SARS-CoV-2 cases. This review discusses the potential for bitter taste receptors to act as drug targets for SARS-CoV-2 symptoms and the use of existing bitter agonists to restore T2R function.

Isolated truncal contrapulsion as a rare presentation of acute thalamic infarct.

Infarcts involving the thalamus can yield many deficits, including sensory syndromes, altered consciousness, and cognitive disturbances, depending on the thalamic vascular territory involved. Isolated truncal contrapulsion due to pure thalamic infarct has been rarely reported. Truncal lateropulsion is a compelling sensation of being pulled toward one side that cannot be explained by weakness or limb ataxia. It is commonly reported in lateral medullary infarcts. It may occur with lesions that involve the peripheral vestibular system, brainstem, cerebellum, basal ganglia, ponto-mesencephalic, and thalamic lesions. We hereby report a 64-year-old woman who presented with truncal contrapulsion as the sole manifestation of an acute right lateral thalamic infarct.

Disruption of fatty acid amide hydrolase activity prevents the effects of chronic stress on anxiety and amygdalar microstructure.

Hyperactivation of the amygdala following chronic stress is believed to be one of the primary mechanisms underlying the increased propensity for anxiety-like behaviors and pathological states; however, the mechanisms by which chronic stress modulates amygdalar function are not well characterized. The aim of the current study was to determine the extent to which the endocannabinoid (eCB) system, which is known to regulate emotional behavior and neuroplasticity, contributes to changes in amygdalar structure and function following chronic stress. To examine the hypothesis, we have exposed C57/Bl6 mice to chronic restraint stress, which results in an increase in fatty acid amide hydrolase (FAAH) activity and a reduction in the concentration of the eCB N-arachidonylethanolamine (AEA) within the amygdala. Chronic restraint stress also increased dendritic arborization, complexity and spine density of pyramidal neurons in the basolateral nucleus of the amygdala (BLA) and increased anxiety-like behavior in wild-type mice. All of the stress-induced changes in amygdalar structure and function were absent in mice deficient in FAAH. Further, the anti-anxiety effect of FAAH deletion was recapitulated in rats treated orally with a novel pharmacological inhibitor of FAAH, JNJ5003 (50 mg per kg per day), during exposure to chronic stress. These studies suggest that FAAH is required for chronic stress to induce hyperactivity and structural remodeling of the amygdala. Collectively, these studies indicate that FAAH-mediated decreases in AEA occur following chronic stress and that this loss of AEA signaling is functionally relevant to the effects of chronic stress. These data support the hypothesis that inhibition of FAAH has therapeutic potential in the treatment of anxiety disorders, possibly by maintaining normal amygdalar function in the face of chronic stress.

It's all relative: A multi-generational study using ForenSeq™ Kintelligence.

The successful application of Forensic Investigative Genetic Genealogy (FIGG) to the identification of unidentified human remains and perpetrators of serious crime has led to a growing interest in its use internationally, including Australia. Routinely, FIGG has relied on the generation of high-density single nucleotide polymorphism (SNP) profiles from forensic samples using whole genome array (WGA) (∼650,000 or more SNPs) or whole genome sequencing (WGS) (millions of SNPs) for DNA segment-based comparisons in commercially available genealogy databases. To date, this approach has required DNA of a quality and quantity that is often not compatible with forensic samples. Furthermore, it requires the management of large data sets that include SNPs of medical relevance. The ForenSeq™ Kintelligence kit, comprising of 10,230 SNPs including 9867 for kinship association, was designed to overcome these challenges using a targeted amplicon sequencing-based method developed for low DNA inputs, inhibited and/or degraded forensic samples. To assess the ability of the ForenSeq™ Kintelligence workflow to correctly predict biological relationships, a comparative study comprising of 12 individuals from a family (with varying degrees of relatedness from 1st to 6th degree relatives) was undertaken using ForenSeq™ Kintelligence and a WGA approach using the Illumina Global Screening Array-24 version 3.0 Beadchip. All expected 1st, 2nd, 3rd, 4th and 5th degree relationships were correctly predicted using ForenSeq™ Kintelligence, while the expected 6th degree relationships were not detected. Given the (often) limited availability of forensic samples, findings from this study will assist Australian Law enforcement and other agencies considering the use of FIGG, to determine if the ForenSeq™ Kintelligence is suitable for existing workflows and casework sample types considered for FIGG.

A study on conventional IMRT and RapidArc treatment planning techniques for head and neck cancers.

AIM: To evaluate the performance of volumetric arc modulation with RapidArc against conventional IMRT for head and neck cancers. BACKGROUND: RapidArc is a novel technique that has recently been made available for clinical use. Planning study was done for volumetric arc modulation with RapidArc against conventional IMRT for head and neck cancers. MATERIALS AND METHODS: Ten patients with advanced tumors of the nasopharynx, oropharynx, and hypopharynx were selected for the planning comparison study. PTV was delineated for two different dose levels and planning was done by means of simultaneously integrated boost technique. A total dose of 70 Gy was delivered to the boost volume (PTV boost) and 57.7 Gy to the elective PTV (PTV elective) in 35 equal treatment fractions. PTV boost consisted of the gross tumor volume and lymph nodes containing visible macroscopic tumor or biopsy-proven positive lymph nodes, whereas the PTV elective consisted of elective nodal regions. Planning was done for IMRT using 9 fields and RapidArc with single arc, double arc. Beam was equally placed for IMRT plans. Single arc RapidArc plan utilizes full 360° gantry rotation and double arc consists of 2 co-planar arcs of 360° in clockwise and counter clockwise direction. Collimator was rotated from 35 to 45° to cover the entire tumor, which reduced the tongue and groove effect during gantry rotation. All plans were generated with 6 MV X-rays for CLINAC 2100 Linear Accelerator. Calculations were done in the Eclipse treatment planning system (version 8.6) using the AAA algorithm. RESULTS: Double arc plans show superior dose homogeneity in PTV compared to a single arc and IMRT 9 field technique. Target coverage was almost similar in all the techniques. The sparing of spinal cord in terms of the maximum dose was better in the double arc technique by 4.5% when compared to the IMRT 9 field and single arc techniques. For healthy tissue, no significant changes were observed between the plans in terms of the mean dose and integral dose. But RapidArc plans showed a reduction in the volume of the healthy tissue irradiated at V 15 Gy (5.81% for single arc and 4.69% for double arc) and V 20 Gy (7.55% for single arc and 5.89% for double arc) dose levels when compared to the 9-Field IMRT technique. For brain stem, maximum dose was similar in all the techniques. The average MU (±SD) needed to deliver the dose of 200 cGy per fraction was 474 ± 80 MU and 447 ± 45 MU for double arc and single arc as against 948 ± 162 MU for the 9-Field IMRT plan. A considerable reduction in maximum dose to the mandible by 6.05% was observed with double arc plan. Double arc shows a reduction in the parotid mean dose when compared with single arc and IMRT plans. CONCLUSION: RapidArc using double arc provided a significant sparing of OARs and healthy tissue without compromising target coverage compared to IMRT. The main disadvantage with IMRT observed was higher monitor units and longer treatment time.

Treatment planning and dosimetric comparison study on two different volumetric modulated arc therapy delivery techniques.

AIM: To compare and evaluate the performance of two different volumetric modulated arc therapy delivery techniques. BACKGROUND: Volumetric modulated arc therapy is a novel technique that has recently been made available for clinical use. Planning and dosimetric comparison study was done for Elekta VMAT and Varian RapidArc for different treatment sites. MATERIALS AND METHODS: Ten patients were selected for the planning comparison study. This includes 2 head and neck, 2 oesophagus, 1 bladder, 3 cervix and 2 rectum cases. Total dose of 50 Gy was given for all the plans. All plans were done for RapidArc using Eclipse and for Elekta VMAT with Monaco treatment planning system. All plans were generated with 6 MV X-rays for both RapidArc and Elekta VMAT. Plans were evaluated based on the ability to meet the dose volume histogram, dose homogeneity index, radiation conformity index, estimated radiation delivery time, integral dose and monitor units needed to deliver the prescribed dose. RESULTS: RapidArc plans achieved the best conformity (CI95% = 1.08 ± 0.07) while Elekta VMAT plans were slightly inferior (CI95% = 1.10 ± 0.05). The in-homogeneity in the PTV was highest with Elekta VMAT with HI equal to 0.12 ± 0.02 Gy when compared to RapidArc with 0.08 ± 0.03. Significant changes were observed between the RapidArc and Elekta VMAT plans in terms of the healthy tissue mean dose and integral dose. Elekta VMAT plans show a reduction in the healthy tissue mean dose (6.92 ± 2.90) Gy when compared to RapidArc (7.83 ± 3.31) Gy. The integral dose is found to be inferior with Elekta VMAT (11.50 ± 6.49) × 10(4) Gy cm(3) when compared to RapidArc (13.11 ± 7.52) × 10(4) Gy cm(3). Both Varian RapidArc and Elekta VMAT respected the planning objective for all organs at risk. Gamma analysis result for the pre-treatment quality assurance shows good agreement between the planned and delivered fluence for 3 mm DTA, 3% DD for all the evaluated points inside the PTV, for both VMAT and RapidArc techniques. CONCLUSION: The study concludes that a variable gantry speed with variable dose rate is important for efficient arc therapy delivery. RapidArc presents a slight improvement in the OAR sparing with better target coverage when compared to Elekta VMAT. Trivial differences were noted in all the plans for organ at risk but the two techniques provided satisfactory conformal avoidance and conformation.

A study on dosimetric properties of electronic portal imaging device and its use as a quality assurance tool in Volumetric Modulated Arc Therapy.

AIM: In this study, the dosimetric properties of the electronic portal imaging device were examined and the quality assurance testing of Volumetric Modulated Arc Therapy was performed. BACKGROUND: RapidArc involves the variable dose rate, leaf speed and the gantry rotation. The imager was studied for the effects like dose, dose rate, field size, leaf speed and sag during gantry rotation. MATERIALS AND METHODS: A Varian RapidArc machine equipped with 120 multileaf collimator and amorphous silicon detector was used for the study. The characteristics that are variable in RapidArc treatment were studied for the portal imager. The accuracy of a dynamic multileaf collimator position at different gantry angles and during gantry rotation was examined using the picket fence test. The control of the dose rate and gantry speed was verified using a test field irradiating seven strips of the same dose with different dose rate and gantry speeds. The control over leaf speed during arc was verified by irradiating four strips of different leaf speeds with the same dose in each strip. To verify the results, the RapidArc test procedure was compared with the X-Omat film and verified for a period of 6 weeks using EPID. RESULTS: The effect of gantry rotation on leaf accuracy was minimal. The dose in segments showed good agreement with mean deviation of 0.8% for dose rate control and 1.09% for leaf speed control over different gantry speeds. CONCLUSION: The results provided a precise control of gantry speed, dose rate and leaf speeds during RapidArc delivery and were consistent over 6 weeks.

Analysis of Indian blue ballpoint pen inks tagged with rare-earth thenoyltrifluoroacetonates by inductively coupled plasma-mass spectrometry and instrumental neutron activation analysis.

Characterization and assessment of inks on sensitive documents for absolute/relative age determination is the challenging forensic problem in spite of practical difficulties. Tagging of ballpoint pen ink with suitable taggant(s) is a unique method to come out with definitive inferences on the detection of forgery in documents written with ballpoint pens. Selection of a proper taggant primarily depends on sensitivity of analytical determination and their absence in normal varieties of ink used for document writing. Rare-earth elements, from all technical considerations can be potential taggant(s) for inks. To ensure more compatibility with ink, 13 rare-earth thenoyltrifluoroacetonate chelates were prepared and characterized. The ballpoint pen inks were tagged with rare-earth thenoyltrifluoroacetonate chelates individually at about 1-100 ppm level depending on sensitivity of element under suitable optimized experimental conditions and instrumental sensitivity. Aliquots of such tagged ink having varying amounts of taggants were analyzed by ICP-MS and INAA. Satisfactory recoveries and a good linear relationship of intensity (signal) against concentrations/amounts were observed. Under the optimized experimental conditions, the detection limits were worked out. This study of tagging metal ions in combination with ICP-MS and NAA as an analytical tool can allow to draw various combination options based on different rare-earth chelates as suitable materials for tagging of ballpoint pen inks for absolute/relative age determination to aid in document related crime examination. The advantages and limitations of proposed analytical techniques are discussed.

Suppression of estrogen-regulated extracellular tissue plasminogen activator activity of MCF-7 cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) suppresses the estrogen enhancement of tissue plasminogen activator (t-PA) by MCF-7 breast cancer cells. 17 beta-estradiol treatment of MCF-7 cells was previously shown to enhance t-PA secretion in a receptor-mediated process dependent on RNA and protein synthesis. The current studies demonstrate that treatment with TCDD, at a concentration as low as 10(-11) M, reduces the 17 beta-estradiol-induced enhancement of t-PA secretion in these cells. Treatment of MCF-7 cells with TCDD alone does not alter t-PA activity nor was inhibition of t-PA activity observed when TCDD was added directly to the enzyme assay. Kinetic studies and the lack of inhibition following in vitro mixing of conditioned media from TCDD-treated and control 17 beta-estradiol stimulated MCF-7 cells argue against TCDD induction of a plasminogen activator inhibitor. The related polychlorinated dibenzofuran, 2,3,7,8,-tetrachlorodibenzofuran, while also active, is less potent that TCDD. Other polychlorinated dibenzodioxins, polychlorinated dibenzofurans, and polychlorinated biphenyls do not suppress 17 beta-estradiol induction of t-PA over the concentrations tested. These results are in agreement with the structure-activity relationships established using these compounds in other assay systems. Treatment with TCDD does not alter the number or affinity of 17 beta-estradiol receptors of MCF-7 cells. TCDD treatment does not suppress constitutive t-PA activity in the estrogen independent breast cancer line MDA-MB-231 nor the t-PA induced by 12-O-tetradecanoylphorbol-13-acetate in HeLa cells. These effects suggest that TCDD is not acting directly on expression of the t-PA genome. Induction of aryl hydrocarbon hydroxylase by TCDD, a cytochrome P-450 regulated metabolic enzyme for which TCDD is the most potent known inducer, was observed in MCF-7 cells but not in MDA-MB-231 or HeLa cells. A plausible mechanism for the antiestrogenic activity of TCDD is based on the metabolic conversion of 17 beta-estradiol to less active derivatives by TCDD induced cytochrome P-450 metabolic enzymes.

Transcriptional regulation of surfactant proteins SP-A and SP-B by phorbol ester.

Phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA) activate protein kinase C and have been previously shown to down-regulate surfactant proteins SP-A and SP-B in H441 adenocarcinoma cells. We used H441 cells and human fetal lung to further study the mechanism of TPA action and to examine physiologic relevance. In H441 cells, TPA (10 nM) treatment for 24 h decreased SP-A mRNA content to approximately 5% of control cells, with half-maximal effect at approximately 0.5 nM, and reduced SP-A gene transcription rate to 28% of control after 8 h exposure. In cells cultured in the presence of dexamethasone, which increases the low basal level of SP-B expression, TPA decreased both SP-B mRNA content (approximately 8% of control) and rate of transcription (7% of control). In cultured human fetal lung explants, TPA decreased SP-A and SP-B protein and mRNA in a time- and dose-dependent fashion, with half-maximal effect on mRNAs at approximately 3 nM and approximately 50% inhibition after 24 h of exposure, and similarly reduced SP-A and SP-B gene transcription (approximately 55% of control at 8-24 h). We conclude that TPA acts primarily at the level of gene transcription to down-regulate both SP-A and SP-B in H441 and fetal lung cells, and we speculate that inflammatory and other agents that act through PKC may modulate expression of the surfactant proteins and alter surfactant function in vivo.

Estrogen regulation of creatine kinase-B in the rat uterus.

Creatine kinase-B (CKB) synthesis is rapidly and specifically induced by estrogen in the uterus of the immature rat. This study indicates that this elevation is due at least in part to increases in the levels of mRNA for CKB. The stimulation of CKB mRNA levels is rapid (a 7- to 10-fold increase is detected 1-3 h after estrogen administration), but transient, as levels return to near control values by 6 h. Analysis of cDNAs to both uterine and brain CKB mRNA indicate that the same sequence is expressed in both tissues despite earlier observations of heterogeneity of the protein isolated from the two tissues. A 1.7-kilobasepair DNA fragment containing the CKB promoter and 5' flanking sequences confers estrogen sensitivity on expression of the bacterial chloramphenicol acetyl transferase gene in HeLa cells on cotransfection with an estrogen-receptor expression vector. However, the CKB promoter sequences lack any motif with convincing similarity to the currently accepted consensus estrogen response element GGTCAnnnTGACC.

Estrogen regulation of human breast cancer cell line MCF-7 tissue plasminogen activator.

The human breast cancer cell line MCF-7 produces a number of estrogen-regulated proteins, among which is tissue plasminogen activator (tPA). Increased medium concentrations of PA activity were observed after the addition of 17 beta-estradiol to cultures of MCF-7 cells. However, in the current study these hormone-regulated increases are limited to cultures near or at confluence, but not in the preconfluent period. MCF-7 cell cultures produce either tPA activity alone or in combination with urokinase activators. At confluence, a single exposure to 17 beta-estradiol stimulates a marked transitory rise in tPA activity in the extracellular and cell-associated compartments; the peak increases were at 48 h for medium activity and 24-48 h for cell-associated activity. Sustained exposure to hormone leads to a persistent increase in activity in both compartments. Examination of the structure-function relationships of estrogen agonists, steroidal and nonsteroidal, as well as nonestrogenic steroids indicated that stimulation of PA activity was restricted to estrogen agonists. The increased activity was reflected in enhancement of tissue PA activity when viewed using sodium dodecyl sulfate-polyacrylamide gel zymography. Those cultures expressing both activators revealed no alteration of urokinase activity due to hormone addition. Antiestrogens added to MCF-7 cells not rigorously limited in exogenous estrogens selectively suppressed tissue PA activity, but not that of urokinase. These data indicate that at the point when MCF-7 cell cultures are no longer growing exponentially, addition of estrogen agonists at physiological concentrations elevates tPA activity while not altering expression of urokinase activity. The discussion suggests a possible role that this regulation may subserve in the function of breast epithelial cells.

Diethylpyrocarbonate inhibition of estradiol receptor binding to oligonucleotides.

Exposure of calf uterine estradiol-receptor complexes to diethylpyrocarbonate (ethoxyformic anhydride) at pH 6.3-6.5 results in a decrease in the ability of the receptor to bind to oligodeoxyribonucleotides. The inhibition of binding to oligodeoxypyrimidines is greater than the inhibition of binding to oligodeoxyguanylate. The inhibition by 6.6 mM diethylpyrocarbonate is complete within 10 min at 4 degrees C. Addition of equimolar quantities of histidine or imidazole prior to exposure to diethylpyrocarbonate prevents subsequent inhibition of oligodeoxyribonucleotide binding. In comparison to histidine, other amino acids tested were deficient in this ability. Diethylpyrocarbonate modification of the receptor causes complete loss of oligodeoxyribonucleotide binding activity at times when there is a loss of less than 20% of bound steroid. Pyridoxal 5'-phosphate treatment of receptor does not prevent subsequent modification by diethylpyrocarbonate, suggesting that the site of reaction is not an essential lysine of the DNA-binding domain. Treatment of the ethoxyformylated receptor with 0.45 M hydroxylamine results in recovery of 70% of the receptor's oligonucleotide-binding ability. The time course of the reaction of diethylpyrocarbonate with the estradiol receptor and the demonstration of hydroxylamine reversal of inhibition suggest that histidine is involved in the binding of estradiol receptor to oligodeoxyribonucleotides.

Comparative incidence of the rearrangements of TEL/AML1 and ALL1 genes in pediatric precursor B acute lymphoblastic leukemias in India.

The TEL/AML1 translocation, which is specific for pre B-cell leukemias is predictive of a favorable treatment outcome. In contrast, translocations involving the ALL1 locus which are associated with both B and non B leukemias predict a poor outcome. To determine the relative distribution of high and low risk molecular subtypes of ALL in India, we analyzed the relative frequencies of these two translocations. The study included a random selection of 46 newly diagnosed patients of childhood ALL from the Tata Memorial Hospital, Bombay, India. Similar to the frequency observed in other world regions, we found an All1 rearrangement in less than 7% (3/46) of pre B-ALL patients. In contrast to the 25% frequency reported for other regions the low risk molecular subtype characterized by the TEL/AML1 translocation represented a comparatively smaller fraction (4/46) in this study. These results provide a preliminary support for a lower frequency of molecular subgroup of leukemias with a potential for favorable clinical outcome in precursor B-ALL from India.

The polynucleotide binding sites of estradiol receptor complexes.

As a model for interaction of steroid receptors with DNA, the binding of estradiol receptor complexes (E2R) to oligodeoxynucleotides, covalently linked to cellulose, was studied in detail. Binding was optimal at concentrations of monovalent cationic salts at, or near, isotonic levels and was selective for intracellular receptors in contrast to extracellular steroid binding proteins. Among the oligomers, the order of affinity was oligo dG greater than oligo dT greater than oligo dC greater than oligo dA greater than oligo dI. The binding to oligo dG was stable to 37 degrees C exposure and the processes of adsorption and desorption, while reactivity with oligo dT, oligo dC and oligo dA was labile. The decrease in binding following purification was restored by histone 2B. Oligo dG binding was the most resistant to inhibition by cibacron blue F3GA (CB) and pyridoxal-5-phosphate. On the basis of these data, a hypothesis is proposed for the interaction of mouse uterine cytosol E2R with prevalent nonspecific and putative specific sequences of DNA.

Comparative analysis of rat uterine estrogen-induced creatine kinase with monoclonal antibodies.

Monoclonal antibodies were generated against rat uterine estrogen-induced protein--creatine kinase (CK-EIP)--and two (MAb-28 and MAb-78) were studied. These antibodies were IgM but differed in their complementary antigenic determinants both of which were detectable on denatured but not on native CK-EIP. MAb-28 reacted with other CK-BBs but not with CK-MMs whereas MAb-78 reacted with both types of CKs. A measurement of antigenicity with the monoclonal antibodies under calibrated conditions showed differences among the CKs, notably between CK-BB from rat brain and CK-EIP when both were probed with MAb-28. The antigenicity of CK-BB (rat brain) was significantly lower than that of CK-EIP, indicating that the former either expresses less copies of the determinant recognized by MAb-28 than CK-EIP does, or possesses a determinant which interacts with the antibody with lower affinity. The monoclonal antibodies should help elucidate structure-function relationships in CK-BB and CK-EIP molecules, their anatomic distribution and their physiologic, pathologic and experimental variations in relation to gene expression induced by sex hormones.

Urticaria and angioedema: diagnostic and treatment considerations.

Urticaria and angioedema are common--and commonly frustrating--problems for physicians and patients alike. Patients often are in considerable distress with pruritus and uncomfortable lesions. They are frightened about their condition and frustrated when modern medicine cannot pinpoint the cause of the symptoms. Both urticaria and angioedema may be categorized as acute and chronic conditions. The dividing line between acute and chronic forms is relatively arbitrarily set at 6 weeks. A thorough history and physical examination may provide clues to the underlying cause, but in the majority of patients, the cause is rarely identified. One is more likely to discover the cause of acute than of chronic urticaria. A multitude of laboratory tests can be performed, but they often do not provide a diagnosis. It is not appropriate to do a large "screening" battery of laboratory tests. The dermal mast cells and their mediators play a central role in chronic urticaria. Chronic urticaria may have an autoimmune aspect. Recent evidence reveals that 50% of patients with chronic urticaria have a cutaneous autoimmune disorder mediated by autoantibodies to the high-affinity IgE receptor on mast cells. Biopsy may be necessary and may help with treatment.

Study of low productive value of rapid survey as a means of leprosy case detection in Kanpur urban project.

A study was undertaken in Kanpur city to identify the reasons for low yield of rapid survey in leprosy case detection and to intervene to overcome the shortcomings. By a random cluster sampling method, 200,000 persons were selected for the study. Rapid survey was undertaken in half the area and in another half similar survey was undertaken after additional inputs. The additional inputs were staff training, IEC activities, changing of the survey timings and addition of a female worker to the survey teams. The proportion of the population enumerated population showed a significant rise (from 58.35% to 72.21%) in the test area with additional inputs. The number and the type of cases detected did not show any difference. Significantly, addition of female workers to the team did not improve the proportion of the female population examined or of female cases detected.

SU-E-T-211: Peer Review System for Ensuring Quality of Radiation Therapy Treatments.

PURPOSE: To demonstrate a Web-based electronic peer review system that has the potential to improve quality of care for radiation therapy patients. The system provides tools that allow radiation oncologists to seek peer review of target and critical structure delineation, treatment plans, and share clinical data with peers to optimize radiation therapy treatments. MATERIAL AND METHODS: Peer review of radiation therapy treatment planning data prior to its initiation improves the quality of radiation therapy and clinical outcomes. Web-based access to radiation therapy treatment planning data and medical records mitigate existing geographical and temporal constraints. With internet access, the healthcare provider can access the data from any location and review it in an interactive and collaborative manner. Interoperability standard like DICOM-RT and IHE-RO compliant RT Systems have facilitated the design and implementation of PRS with Silverlight Web technology, .net Framework and SQL Server. Local DICOM-RT archive and cloud based services are deployed to facilitate remote peer reviews. RESULTS: To validate the PRS system, we tested the system for 100 patients with Philips Pinnacle v 9.0 and Varian Eclipse v 8.9 treatment planning system (TPS). We transmitted the DICOM RT data from the TPS to the cloud based services via the PRS local DICOM RT Archive. Various CT simulation based parameters such as orientation of CT, properties of RT structures etc. were compared between the TPS and PRS system. Data integrity of other parameters such as patient demographics (patient name, ID, attending physician etc.) and dose volume related parameters were also evaluated. Such rigorous testing allowed us to optimize the functionalities and clinical implementation of the PRS. CONCLUSIONS: We believe that the PRS will improve the quality and safety of a broad spectrum of radiation therapy patients treated in underserved areas while discouraging the overutilization of expensive radiation treatment modalities. This research and development project is supported by the James and Ester King Biomedical Research Program grant # RC1-09KW-09-26829.