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1.  National Pharmaceutical Stockpile drill analysis using XML data collection on wireless Java phones. 
This study describes an informatics effort to track subjects through a National Pharmaceutical Stockpile (NPS) distribution drill. The drill took place in Seattle on 1/24/2002. Washington and the State Department of Health are among the first in the nation to stage a NPS drill testing the distribution of medications to mock patients, thereby testing the treatment capacity of the plan given a post-anthrax exposure scenario. The goal of the Public Health Informatics Group at the University of Washington ( was to use informatics approaches to monitor subject numbers and elapsed time. This study compares accuracy of time measurements using a mobile phone Java application to traditional paper recording in a live drill of the NPS. Pearson correlation = 1.0 in 2 of 3 stations. Differences in last station measurements can be explained by delay in recording of the exit time. We discuss development of the application itself and lessons learned. (MeSH Bioterrorism, Informatics, Public Health)
PMCID: PMC2244171  PMID: 12463848
2.  Colonization of the gut of the blue crab (Callinectes sapidus) by Vibrio cholerae. 
Attachment of Vibrio cholerae to the mucosal surface of the intestine is considered to be an important virulence characteristic. Vibrio cholerae, an autochthonous member of brackish water and estuarine bacterial communities, also attaches to crustacea, a significant factor in multiplication and survival of V. cholerae in nature. The ability of V. cholerae to attach to the gut wall of the blue crab (Callinectes sapidus) was examined, and attachment was observed only in the hindgut and not the midgut of crabs, confirming a requirement for chitin in the attachment of V. cholerae to invertebrate and zooplankton surfaces. The new finding of attachment of V. cholerae to the hindgut of crabs may be correlated with the epidemiology and transmission of cholera in the aquatic environment. The crab model may also prove useful in elucidating the mechanism(s) of ion transport in crustacea.
PMCID: PMC203579  PMID: 3767362
3.  Influence of water temperature, salinity, and pH on survival and growth of toxigenic Vibrio cholerae serovar 01 associated with live copepods in laboratory microcosms. 
The influence of water temperature, salinity, and pH on the multiplication of toxigenic Vibrio cholerae serovar O1 cells and their attachment to live planktonic crustaceans, i.e., copepods, was investigated by using laboratory microcosms. By increasing water temperatures up to 30 degrees C, a pronounced effect on the multiplication of V. cholerae was demonstrated, as was attachment of the cells to live copepods. These were measured by culturable counts on agar plates and direct observation by scanning electron microscopy, respectively. Of the three salinities examined (5, 10, and 15%), maximum growth of V. cholerae and attachment to copepods occurred at 15%. An alkaline pH (8.5) was optimal both for attachment and multiplication of V. cholerae, as compared with pH 6.5 and 7.5. It is concluded that conditions affecting attachment of V. cholerae serovar O1 to live copepods observed under laboratory conditions may also occur in the natural estuarine environment and, thereby, are significant in the epidemiology of cholera.
PMCID: PMC241529  PMID: 6486784
4.  Ecological relationships between Vibrio cholerae and planktonic crustacean copepods. 
Strains of Vibrio cholerae, both O1 and non-O1 serovars, were found to attach to the surfaces of live copepods maintained in natural water samples collected from the Chesapeake Bay and Bangladesh environs. The specificity of attachment of V. cholerae to live copepods was confirmed by scanning electron microscopy, which revealed that the oral region and egg sac were the most heavily colonized areas of the copepods. In addition, survival of V. cholerae in water was extended in the presence of live copepods. Attachment of viable V. cholerae cells to copepods killed by exposure to -60 degrees C was not observed. Furthermore, survival of V. cholerae was not as long in the presence of dead copepods as in the live copepod system. A strain of Vibrio parahaemolyticus was also seen to attach to copepod surfaces without effect on survival of the organism in water. The attachment of vibrios to copepods was concluded to be significant since strains of other bacteria, including Pseudomonas sp. and Escherichia coli, did not adhere to live or dead copepods. Attachment of V. cholerae to live copepods is suggested to be an important factor of the ecology of this species in the aquatic environment, as well as in the epidemiology of cholera, for which V. cholerae serovar O1 is the causative agent.
PMCID: PMC242265  PMID: 6337551
5.  Occurrence of Vibrio cholerae serotype O1 in Maryland and Louisiana estuaries. 
Vibrio cholerae serotype O1 has been isolated from Chesapeake Bay in Maryland and estuaries and sewers in Louisiana. The occurrence of V. cholerae O1 in the aquatic environment in the absence of human disease suggests that this organism survives and multiples in the natural environment.
PMCID: PMC243732  PMID: 7235699
6.  Development of Highly Selective Kv1.3-Blocking Peptides Based on the Sea Anemone Peptide ShK 
Marine Drugs  2015;13(1):529-542.
ShK, from the sea anemone Stichodactyla helianthus, is a 35-residue disulfide-rich peptide that blocks the voltage-gated potassium channel Kv1.3 at ca. 10 pM and the related channel Kv1.1 at ca. 16 pM. We developed an analog of this peptide, ShK-186, which is currently in Phase 1b-2a clinical trials for the treatment of autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. While ShK-186 displays a >100-fold improvement in selectivity for Kv1.3 over Kv1.1 compared with ShK, there is considerable interest in developing peptides with an even greater selectivity ratio. In this report, we describe several variants of ShK that incorporate p-phophono-phenylalanine at the N-terminus coupled with internal substitutions at Gln16 and Met21. In addition, we also explored the combinatorial effects of these internal substitutions with an alanine extension at the C-terminus. Their selectivity was determined by patch-clamp electrophysiology on Kv1.3 and Kv1.1 channels stably expressed in mouse fibroblasts. The peptides with an alanine extension blocked Kv1.3 at low pM concentrations and exhibited up to 2250-fold selectivity for Kv1.3 over Kv1.1. Analogs that incorporates p-phosphono-phenylalanine at the N-terminus blocked Kv1.3 with IC50s in the low pM range and did not affect Kv1.1 at concentrations up to 100 nM, displaying a selectivity enhancement of >10,000-fold for Kv1.3 over Kv1.1. Other potentially important Kv channels such as Kv1.4 and Kv1.6 were only partially blocked at 100 nM concentrations of each of the ShK analogs.
PMCID: PMC4306950  PMID: 25603346
immunomodulator; T lymphocyte; potassium channel; disulfide-rich peptide; sea anemone toxin; K+ channel blocker
7.  Attitudes of Cairo University medical students toward smoking: the need for tobacco control programs in medical education 
Tobacco smoking rates are increasing in developing countries and so are tobacco-related chronic diseases. Reported figures from the WHO show rates of smoking in Egypt as high as 20% but limited information is available about smoking specifically among physicians and medical students.
Materials and methods
Final-year medical students of Cairo University were surveyed regarding their tobacco behavior and attitudes using a modified Global Health Professions Student Survey. We approached 220 students by randomly selecting clinical units into which they were assigned and requested completion of the survey.
Ever users of some form of tobacco comprised 46.7% of students sampled, current users of cigarettes comprised 17.4%, and current users of water pipe ‘sheesha’ comprised 17.6%. The vast majority (87.7%) of students believed that smoking is a public health problem in Cairo and supported restriction of tobacco. Yet, only 58.5% stated that they were taught it is important for physicians to provide tobacco education materials to patients. Among ever users of cigarettes, 54.4% believed health professionals do not serve as health role models for patients, and only a small percentage of all students (34.2%) stated that they had received some form of training on smoking cessation in their medical curriculum to be able to instruct patients.
Conclusion and recommendations
A high rate of smoking was revealed among medical students in Cairo. Overall, approximately 23.4% of students were currently smoking cigarettes and/or sheesha, and 46.7% were ever users of some form of tobacco. A formal antitobacco program for medical students should be incorporated into their medical curriculum to change the attitudes of medical students and overcome the anticipated increase in chronic diseases in Egypt.
PMCID: PMC4274946  PMID: 22415329
curriculum; Egypt; medical students; tobacco
8.  Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children 
Nature  2014;510(7505):417-421.
Therapeutic food interventions have reduced mortality in children with severe acute malnutrition (SAM) but incomplete restoration of healthy growth remains a major problem1,2. The relationships between the type of nutritional intervention, the gut microbiota, and therapeutic responses are unclear. In the current study, bacterial species whose proportional representation define a healthy gut microbiota as it assembles during the first two postnatal years were identified by applying a machine-learning-based approach to 16S rRNA datasets generated from monthly fecal samples obtained from a birth-cohort of children, living in an urban slum of Dhaka, Bangladesh, who exhibited consistently healthy growth. These age-discriminatory bacterial species were incorporated into a model that computes a ‘relative microbiota maturity index’ and ‘microbiota-for-age Z-score’ that compare development (defined here as maturation) of a child’s fecal microbiota relative to healthy children of similar chronologic age. The model was applied to twins and triplets (to test for associations of these indices with genetic and environmental factors including diarrhea), children with SAM enrolled in a randomized trial of two food interventions, and children with moderate acute malnutrition. Our results indicate that SAM is associated with significant relative microbiota immaturity that is only partially ameliorated following two widely used nutritional interventions. Immaturity is also evident in less severe forms of malnutrition and correlates with anthropometric measurements. Microbiota maturity indices provide a microbial measure of human postnatal development, a way of classifying malnourished states, and a parameter for judging therapeutic efficacy. More prolonged interventions with existing or new therapeutic foods and/or addition of gut microbes may be needed to achieve enduring repair of gut microbiota immaturity in childhood malnutrition and improve clinical outcomes.
PMCID: PMC4189846  PMID: 24896187
9.  Letter to the Editor 
PMCID: PMC3905995  PMID: 24497771
10.  Population Vulnerability to Biannual Cholera Outbreaks and Associated Macro-Scale Drivers in the Bengal Delta 
The highly populated floodplains of the Bengal Delta have a long history of endemic and epidemic cholera outbreaks, both coastal and inland. Previous studies have not addressed the spatio-temporal dynamics of population vulnerability related to the influence of underlying large-scale processes. We analyzed spatial and temporal variability of cholera incidence across six surveillance sites in the Bengal Delta and their association with regional hydroclimatic and environmental drivers. More specifically, we use salinity and flood inundation modeling across the vulnerable districts of Bangladesh to test earlier proposed hypotheses on the role of these environmental variables. Our results show strong influence of seasonal and interannual variability in estuarine salinity on spring outbreaks and inland flooding on fall outbreaks. A large segment of the population in the Bengal Delta floodplains remain vulnerable to these biannual cholera transmission mechanisms that provide ecologic and environmental conditions for outbreaks over large geographic regions.
PMCID: PMC3820342  PMID: 24019441
11.  Interceptor and Phantom Trials of EDNS at UPMC 
Health physics  2013;105(5 0 2):S199-S208.
University of Pittsburgh Medical Center (UPMC) installed an Emergency Department Notification System (EDNS) in one of its hospitals. The system, manufactured by Thermo Fisher Scientific (Thermo Fisher Scientific, Inc., 81 Wyman Street, Waltham, MA 02454), consists of four NaI(Tl) scintillation detectors, a 2.5 L PVT gamma counter, a 512 channels multi-channel analyzer, a system controller, and a database-monitoring server. We evaluated a portable Interceptor™ hand-held detector as part of the system for potential ambulance-based early detection and warning unit. We present the minimum detectable activity, distance, and isotope identification success rates along with the change in detector response to various radioisotope sources placed in a Rando® humanoid phantom. The present paper reports these results.
PMCID: PMC3805965  PMID: 24077079
12.  A new integrative conjugative element detected in Haitian isolates of Vibrio cholerae non-O1/non-O139 
Research in microbiology  2013;164(9):891-893.
The presence of SXT/R391-related integrating conjugative elements (ICEs) in V. cholerae O1 and non-O1/non-O139 isolated from clinical and environmental samples in Haiti in 2010 was studied. The main finding of this work was the identification of the novel ICEVchHai2 among closely related V. cholerae non-O1/non-O139 clinical strains. The mosaic structure of this element confirms the role of ICEs as efficient recombination systems whereby new genetic material can be acquired and exchanged, according V. cholerae strains new accessory functions.
PMCID: PMC3999591  PMID: 23994142
Vibrio cholera; Non-O1/non-O139; Haiti; Integrative conjugative elements
13.  Paratesticular sarcomas: A report of seven cases 
Oncology Letters  2014;9(1):308-312.
Primary tumors of the paratesticular region are rare, with paratesticular sarcomas constituting a major proportion of these tumors, particularly in the elderly. The paratesticular region consists of mesothelial, various epithelial and mesenchymal cells and may therefore give rise to a number of tumors with various behaviors. Defining the association between the paratesticular mass and the testicle, and differentiation between benign and malignant masses using radiology is challenging, therefore the mass is usually considered to be malignant and radical orchiectomy with high ligation is performed. The present study reports the cases of seven patients with tumors of the paratesticular region and presents the clinical and significant histological features of the tumors. In total, two patients suffered from dedifferentiated liposarcoma (DDLS), two exhibited leiomyosarcoma, two exhibited low-grade fibromyxoid sarcoma and one case of undifferentiated pleomorphic sarcoma was identified. Radical orchiectomy with high ligation was performed in five cases; simple orchiectomy was performed in one case and excisional biopsy was performed in the remaining case. A leiomyosarcomatous and epithelial membrane antigen (EMA) positive whorl pattern was observed during microscopy in the two DDLS cases. Additionally, one of the low-grade fibromyxoid sarcoma patients exhibited pleomorphism and mitosis in focal areas. To the best of our knowledge, the present study is the second time low-grade fibromyxoid sarcoma cases with paratesticular localization have been reported in the literature. Of the seven cases, four patients succumbed to the disease, one patient is living with the disorder and the two cases of DDLS are living without the disease. Paratesticular sarcomas are often aggressive and a multidisciplinary approach is required for the diagnosis and treatment of these tumors.
PMCID: PMC4246635  PMID: 25435981
paratestis; sarcomas; dedifferentiated liposarcoma; fibromyxois sarcoma; leiomyosarcoma; spindle cell liposarcoma; pleomorphic sarcoma; whorl pattern
14.  Environmental Factors Influencing Epidemic Cholera 
Cholera outbreak following the earthquake of 2010 in Haiti has reaffirmed that the disease is a major public health threat. Vibrio cholerae is autochthonous to aquatic environment, hence, it cannot be eradicated but hydroclimatology-based prediction and prevention is an achievable goal. Using data from the 1800s, we describe uniqueness in seasonality and mechanism of occurrence of cholera in the epidemic regions of Asia and Latin America. Epidemic regions are located near regional rivers and are characterized by sporadic outbreaks, which are likely to be initiated during episodes of prevailing warm air temperature with low river flows, creating favorable environmental conditions for growth of cholera bacteria. Heavy rainfall, through inundation or breakdown of sanitary infrastructure, accelerates interaction between contaminated water and human activities, resulting in an epidemic. This causal mechanism is markedly different from endemic cholera where tidal intrusion of seawater carrying bacteria from estuary to inland regions, results in outbreaks.
PMCID: PMC3771306  PMID: 23897993
15.  Field-testing of the rapid assessment of disability questionnaire 
BMC Public Health  2014;14(1):900.
The Rapid Assessment of Disability (RAD) questionnaire measures the magnitude and impact of disability and aims to inform the design of disability inclusive development programs. This paper reports the psychometric evaluation of the RAD.
The initial version of the RAD comprised five sections: 1) demographics, 2) functioning, 3) rights awareness, 4) well-being, and 5) access to the community. Item functioning and construct validity were assessed in a population-based study in Bangladesh. Data were analysed using descriptive statistics (sections 2 and 5) and Rasch modelling (sections 3 and 4). A subsequent case–control study in Fiji tested the refined questionnaire in a cross-cultural setting and assessed the sensitivity and specificity of the RAD section 2 to identify people with disability.
2,057 adults took part in the study (1,855 in Bangladesh and 202 in Fiji). The prevalence of disability estimated using RAD section 2 in Bangladesh was 10.5% (95% CI 8.8-12.2), with satisfactory sensitivity and specificity (62.4% and 81.2%, respectively). Section 3 exhibited multidimensionality and poor differentiation between levels of rights awareness in both Bangladesh (person separation index [PSI] = 0.71) and Fiji (PSI = 0.0), and was unable to distinguish between people with and without disability (Bangladesh p = 0.786, Fiji p = 0.403). This section was subsequently removed from the questionnaire pending re-development. Section 4 had good ability to differentiate between levels of well-being (PSI = 0.82). In both countries, people with disability had significantly worse well-being scores than people without disability (p < 0.001) and also access to all sectors of community except legal assistance, drinking water and toilets (p < 0.001).
Filed-testing in Bangladesh and Fiji confirmed the psychometric robustness of functioning, well-being, and community access sections of the RAD. Information from the questionnaire can be used to inform and evaluate disability inclusive development programs.
PMCID: PMC4246465  PMID: 25179800
Disability; Rapid assessment; Validation; Questionnaire; Inclusive development
16.  Toll free mobile communication: overcoming barriers in maternal and neonatal emergencies in Rural Bangladesh 
Reproductive Health  2014;11:52.
Toll free mobile telephone intervention to support mothers in pregnancy and delivery period was tested in one sub district of Bangladesh. Qualitative research was conducted to measure the changes of mobile phone use in increasing communication for maternal and neonatal complications.
In-depth interviews were conducted among twelve Community Skilled Birth Attendants and fourteen mothers along with their husbands prior to intervention. At intervention end, six Community Skilled Birth Attendants were purposively selected for in-depth interview. Semi structured interviews were conducted among all 27 Community Skilled Birth Attendants engaged in the intervention. One Focus Group Discussion was conducted with 10 recently delivered mothers. Thematic analysis and triangulation of different responses were conducted.
Prior to intervention, Community Skilled Birth Attendants reported that mobile communication was not a norm. It was also revealed that poor mothers had poor accessibility to mobile services. Mothers, who communicated through mobile phone with providers noted irritability from Community Skilled Birth Attendants and sometimes found phones switched off. At the end of the project, 85% of mothers who had attended orientation sessions of the intervention communicated with Community Skilled Birth Attendants through mobile phones during maternal health complications. Once a complication is reported or anticipated over phone, Community Skilled Birth Attendants either made a prompt visit to mothers or advised for direct referral. More than 80% Community Skilled Birth Attendants communicated with Solution Linked Group for guidance on maternal health management. Prior to intervention, Solution Linked Group was not used to receive phone call from Community Skilled Birth Attendants. Community Skilled Birth Attendants were valued by the mothers. Mothers viewed that Community Skilled Birth Attendants are becoming confident in managing complication due to communication with Solution Linked Group.
The use of mobile technology in this intervention took a leap from simply rendering information to providing more rapid services. Active participation of service providers along with mothers’ accessibility motivated both the service providers and mothers to communicate through mobile phone for maternal health issues. These altogether made the shift towards adoption of an innovation.
PMCID: PMC4107484  PMID: 25015126
Toll free mobile phone; Maternal health complications; Rural Bangladesh
17.  The Price Sensitivity of Cigarette Consumption in Bangladesh: Evidence from the International Tobacco Control (ITC) Bangladesh Wave 1 (2009) and Wave 2 (2010) Surveys 
Tobacco control  2013;23(0 1):i39-i47.
In Bangladesh, the average excise tax on cigarettes accounted for merely 38% in 2009 and 45% in 2010 of the average retail price of cigarettes. It is well below the WHO recommended share of 70% of the retail price at a minimum. There is thus ample room for raising taxes on cigarettes in Bangladesh.
The objective of the paper is to estimate the price elasticity of demand for cigarettes and the effect of tax increases on the consumption of cigarettes and on tax revenue in Bangladesh.
Based on data from Wave 1 (2009) and Wave 2 (2010) of the International Tobacco Control Bangladesh Survey, we estimate the overall impact of a price change on cigarette demand using a two-part model. The total price elasticity of cigarettes is measured by the sum of the elasticity of smoking prevalence and the elasticity of average daily consumption conditional on smoking participation. The price elasticity estimates are used in a simulation model to predict changes in cigarette consumption and tax revenue from tax and price increases.
The total price elasticity of demand for cigarettes is estimated at −0.49. The elasticity of smoking prevalence accounts for 59% of the total price elasticity. The price elasticity of cigarette consumption is higher for people belonging to lower socio-economic status. Increases in taxes would result in significant reduction in cigarette consumption while tax revenue increases.
Raising cigarette price through increased taxation can lead to a win-win-win situation in Bangladesh—it will reduce cigarette consumption, increase tobacco tax revenue and potentially decrease socio-economic inequities.
PMCID: PMC4090419  PMID: 24105828
cigarette; price elasticity; tobacco tax revenue
18.  SCN2A mutation is associated with infantile spasms and bitemporal glucose hypometabolism 
Pediatric neurology  2013;49(1):10.1016/j.pediatrneurol.2013.03.002.
Genetic mutations play crucial role in the etiology of cryptogenic infantile spasms but the cause is still unknown in a significant proportion of patients. Whole exome sequencing technology shows great promise in identifying genetic causes of infantile spasms.
We performed whole exome sequencing and 2-deoxy-2-(18F)fluoro-D-glucose positron emission tomography scan of a male child with infantile spasms. Exome sequencing was also performed in parents to identify any de novo mutations.
The positron emission tomography scan showed a pattern of bilateral symmetric temporal lobe glucose hypometabolism. A total of 8171 non-synonymous variants were identified in the child. Despite the large number of nonsynonymous variants, there was only a single de novo missense mutation in SCN2A in the child (NCBI hg19 assembly, position: Chr2:166234116, K1422E). Subsequent Sanger sequencing confirmed the de novo status of this variant. This mutation has never been reported in 6500 individuals of the exome variant server database. Similarly, this variant is not reported in online mendelian inheritance in man database or human gene mutation database. It has previously been shown that SCN2A mutations are associated with hippocampal hyperexcitability. Therefore, we speculate that IS and bitemporal hypometabolism in our patient might have been caused by hippocampal hyperexcitability due to SCN2A mutation.
The simultaneous presence of an SCN2A mutation and bitemporal hypometabolism in this patient with infantile spasms suggests a plausible hippocampal origin. However, additional mechanistic and clinical studies are required to validate this link.
PMCID: PMC3868437  PMID: 23827426
Infantile Spasms; Exome sequencing; Positron Emission Tomography; Genetics; Ion channel gene defects
19.  Improved Survival of Mice After Total Body Irradiation with 10 MV Photon, 2400 MU/min SRS Beam 
In vivo (Athens, Greece)  2014;28(1):1-12.
We evaluated the radiobiological effects of stereotactic radiosurgery (SRS) photon beams on survival of C57BL/6NTac mice following total body irradiation.
Materials and Methods
Survival of Lewis lung carcinoma (3LL) cells was tested after irradiation using 6 MV: 300 MU/min or 1400 MU/min; or 10 MV: 300 MU/min or 2400 MU/min. Survival of C57BL/6NTac mice after a dose which is lethal to 50% of the mice in 30 days (LD50/30) (9.25 Gy) total body irradiation (TBI) and 21 Gy to orthotopic 3LL tumors was tested. We quantitated levels of organ-specific gene transcripts by Real Time Polymerase Chain Reaction (RT-PCR).
While 3LL cell survival and inhibition of orthotopic tumor growth was uniform, 10 MV photons at 2400 MU/min TBI led to significantly greater survival (p=0.0218), with higher levels of intestinal (Sod2), (Gpx1), (Nrf2), and (NFκB) RNA transcripts.
Clinical 10 MV-2400 cGy/min SRS beams led to unexpected protection of mice on TBI and increased radioprotective gene transcripts.
PMCID: PMC4046118  PMID: 24425830
Stereotactic radiosurgery; dose rate; photon energy
20.  A water marker monitored by satellites to predict seasonal endemic cholera 
Remote sensing letters (Print)  2013;4(8):822-831.
The ability to predict an occurrence of cholera, a water-related disease, offers a significant public health advantage. Satellite based estimates of chlorophyll, a surrogate for plankton abundance, have been linked to cholera incidence. However, cholera bacteria can survive under a variety of coastal ecological conditions, thus constraining the predictive ability of the chlorophyll, since it provides only an estimate of greenness of seawater. Here, a new remote sensing based index is proposed: Satellite Water Marker (SWM), which estimates condition of coastal water, based on observed variability in the difference between blue (412 nm) and green (555 nm) wavelengths that can be related to seasonal cholera incidence. The index is bounded between physically separable wavelengths for relatively clear (blue) and turbid (green) water. Using SWM, prediction of cholera with reasonable accuracy, with at least two month in advance, can potentially be achieved in the endemic coastal regions.
PMCID: PMC3714106  PMID: 23878762
21.  Mapping of dose distribution from IMRT onto MRI-guided high dose rate brachytherapy using deformable image registration for cervical cancer treatments: preliminary study with commercially available software 
For patients undergoing external beam radiation therapy (EBRT) and brachytherapy, recommendations for target doses and constraints are based on calculation of the equivalent dose in 2 Gy fractions (EQD2) from each phase. At present, the EBRT dose distribution is assumed to be uniform throughout the pelvis. We performed a preliminary study to determine whether deformable dose distribution mapping from the EBRT onto magnetic resonance (MR) images for the brachytherapy would yield differences in doses for organs at risk (OARs) and high-risk clinical target volume (HR-CTV).
Material and methods
Nine cervical cancer patients were treated to a total dose of 45 Gy in 25 fractions using intensity-modulated radiation therapy (IMRT), followed by MRI-based 3D high dose rate (HDR) brachytherapy. Retrospectively, the IMRT planning CT images were fused with the MR image for each fraction of brachytherapy using deformable image registration. The deformed IMRT dose onto MR images were converted to EQD2 and compared to the uniform dose assumption.
For all patients, the EQD2 from the EBRT phase was significantly higher with deformable registration than with the conventional uniform dose distribution assumption. The mean EQD2 ± SD for HR-CTV D90 was 45.7 ± 0.7 Gy vs. 44.3 Gy for deformable vs. uniform dose distribution, respectively (p < 0.001). The dose to 2 cc of the bladder, rectum, and sigmoid was 46.4 ± 1.2 Gy, 46.2 ± 1.0 Gy, and 48.0 ± 2.5 Gy, respectively with deformable dose distribution, and was significantly higher than with uniform dose distribution (43.2 Gy for all OAR, p < 0.001).
This study reveals that deformed EBRT dose distribution to HR-CTV and OARs in MR images for brachytherapy is technically feasible, and achieves differences compared to a uniform dose distribution. Therefore, the assumption that EBRT contributes the same dose value may need to be carefully investigated further based on deformable image registration.
PMCID: PMC4105642  PMID: 25097559
cervical cancer; deformable image registration; IMRT; MRI
22.  Cytological features of pure micropapillary carcinoma of various organs: A report of eight cases 
Oncology Letters  2014;8(2):705-710.
Micropapillary carcinoma (MPC) is a rare aggressive tumor, which generally accompanies the primary carcinoma of the organ of its origin, while the pure form is extremely uncommon. Angiolymphatic involvement is widespread and a considerable proportion of the cases present with metastases. The current study presents eight pure MPC cases arising from the breast (n=3), urinary bladder (n=3), parotid gland (n=1) and lung (n=1, presenting with pericardial effusion), with the cytological findings. The eight patients included three female and five male cases aged between 48 and 74 years. The most common cytological findings were three-dimensional aggregates, cell clusters with angulated or scalloped borders, single cells with a columnar configuration and eccentric nuclei, and high-grade nuclear features. Histopathological sections showed accompanying in situ ductal carcinoma in the cases of MPC arising in the parotid gland and breast (n=3), and one case in the bladder exhibited only in situ MPC. The average follow-up period was 20 months (range, 6–54 months) and, during this period, three patients succumbed to the disease. At present, four patients are alive with disease and one patient is alive and disease-free. In conclusion, cytology is an important tool for the diagnosis and management of MPC.
PMCID: PMC4081296  PMID: 25013488
micropapillary carcinoma; cytology; parotid; lung; urinary bladder; breast
23.  Synthesis and activity of three new trinuclear platinums with cis-geometry for terminal metal centres 
As compared to cisplatin, trinuclear platinum compounds such as BBR3464 and DH6Cl have an altered spectrum of activity possibly because they form long-range adducts with DNA as against mainly intrastrand 1,2-bifunctional adducts formed by cisplatin and its analogues. Because of the labilizing effect associated with the trans-geometry, the compounds are expected to break down inside the cell thus serving to reduce the number of long-range adducts formed. In contrast, trinuclear platinum complexes with cis-geometry for the terminal metal centres would be less subject to such breakdown and hence may produce a greater number of long-range inter- and intrastrand adducts with the DNA. This paper describes the synthesis and activity against human ovarian tumour models of of three new trinuclear platinum complexes with cis-geometry for terminal platinum centres, coded as QH4, QH7 and QH8. The paper also describes cellular accumulation of platinum, level of drug−DNA binding, and nature of interaction of the compounds with pBR322 plasmid DNA.
Methods of synthesis, elemental analysis, spectral studies and molar conductivity measurements provide support to the suggested structures of the compounds. QH4 and QH8 are found to be more cytotoxic than cisplatin against the parental A2780 cell line; QH8 is more active than cisplatin against the resistant A2780cisR and A2780ZD0473R cell lines as well. The least compound QH7 shows a greater activity against the resistant cell lines than the parental cell line; it is most damaging to pBR322 plasmid DNA and most able to induce changes in DNA conformation. The variations in activity of the compounds, changes in intracellular drug accumulation and levels of Pt−DNA binding with the changes in number of planaramine ligands bound to central platinum and the length of the linking diamines, can be seen (1) to illustrate structure-activity relationships and (2) to highlight that the relationship between antitumour activity and interaction with cellular platinophiles including DNA can be quite complex as the cell death is carried out by downstream processes in the cell cycle where many proteins are involved.
Among the three designed trinuclear platinum complexes with cis-geometry for the terminal metal centres, the most active compound QH8 is found to be more active than cisplatin against the parental A2780 and the resistant A2780cisR and A2780ZD0473R cell lines.
PMCID: PMC4022405  PMID: 24884683
Ovarian cancer; Platinum drug; Trinuclear; A2780; pBR322 plasmid; Drug resistance; Pt−DNA binding
24.  Octyl (2E)-2-[2-(di­phenyl­phosphan­yl)benzyl­idene]hydrazinecarbodi­thio­ate 
The title compound, C28H33N2S2P, adopts the thione tautomeric form, as supported by the C—S distance [1.6744 (18) Å]. The Schiff base exhibits an E conformation about the C=N bond but a Z conformation about the C—N bond. The terminal chain is disordered over two sets of sites with an occupancy ratio of 0.732 (3):0.268 (3). In the crystal, pairs of N—N—H hydrogen bonds between the thione groups link neighbouring mol­ecules into centrosymmetric dimers.
PMCID: PMC4051045  PMID: 24940222
25.  Ethnobotanical, Phytochemical, Pharmacological, and Toxicological Aspects of Persicaria hydropiper (L.) Delarbre 
Persicaria hydropiper (L.) Delarbre, belonging to Polygonaceae family, is a common weed found in most of the temperate countries including Bangladesh, China, Malaysia, and Japan. The plant is also referred to as “marsh pepper” or “smart weed.” It appears to be a useful herb with evidence-based medicinal properties. The present work addresses the botanical description, traditional uses, phytochemistry, pharmacology, and toxicology of P. hydropiper. All plant parts have been commonly used in the traditional systems of medicines. Flavonoids are the major group of phytochemical components followed by drimane-type sesquiterpenes and sesquiterpenoids, as well as phenylpropanoids. Different extracts and plant parts showed remarkable pharmacological activities including antioxidant, antibacterial, antifungal, antihelminth, antifeedant, cytotoxicity, anti-inflammatory, antinociceptive, oestrogenicity, antifertility, antiadipogenicity, and neuroprotection. Mutagenicity and acute and subchronic toxicities of the plant were also reported. P. hydropiper has tremendous medicinal properties that could further be investigated for the development of evidence-based herbal products.
PMCID: PMC4009190  PMID: 24834098

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