A sodium ion conducting gel polymer electrolyte with counterbalance between 1-ethyl-3-methylimidazolium tetrafluoroborate and tetra ethylene glycol dimethyl ether for electrochemical applications.

For sodium batteries, the development of gel polymer electrolytes (GPEs) with remarkable electrochemical properties is in its early stage and persists to be a challenge. In this report we have synthesized a series of GPEs containing a poly(vinyllidene fluoride-co-hexafluoropropylene) (PVdF-HFP) and poly (methyl methacrylate) (PMMA) as blend polymer, sodium perchlorate (NaClO4) as ion-conducting salt and 1-ethyl-3-methylimidazolium tetrafluoroborate (EMIM-BF4) and tetra ethylene glycol dimethyl ether (TEGDME) as molecular solvents. The counter balance between EMIM-BF4 and TEGDME is maintained by the electrolyte, which is formed through the optimal weight ratio of 2 : 1. GPEs have an advantageous set of properties, including stability window of 5 V, Na+ transference number of 0.20, and a room-temperature ionic conductivity of 5.8 × 10-3 S cm-1. According to enthalpy and entropy calculations, optimized GPE yields the highest amount of disorder or amorphicity and contributes to greatest conductivity. XRD analysis supports this argument. Thermal investigations show that optimized GPE may preserve gel phase up to 125 °C. The prototype sodium cell fabricated with optimize GPE has a specific capacity of 281 mA h g-1 and open circuit voltage of 2.5 V. The optimized GPE exhibits potential for future electrochemical applications.

CTP-based estimated ischemic core: A comparative multicenter study between Olea and RAPID software.

BACKGROUND AND PURPOSE: CTP is increasingly used to assess eligibility for endovascular therapy (EVT) in patients with large vessel occlusions (LVO). There remain variability and inconsistencies between software packages for estimation of ischemic core. We aimed to use heterogenous data from four stroke centers to perform a comparative analysis for CTP-estimated ischemic core between RAPID (iSchemaView) and Olea (Olea Medical). METHODS: In this retrospective multicenter study, patients with anterior circulation LVO who underwent pretreatment CTP, successful EVT (defined TICI ≥ 2b), and follow-up MRI included. Automated CTP analysis was performed using Olea platform [rCBF < 25% and differential time-to-peak (dTTP)>5s] and RAPID (rCBF < 30%). The CTP estimated core volumes were compared against the final infarct volume (FIV) on post treatment MRI-DWI. RESULTS: A total of 151 patients included. The CTP-estimated ischemic core volumes (mean ± SD) were 18.7 ± 18.9 mL on Olea and 10.5 ± 17.9 mL on RAPID significantly different (p < 0.01). The correlation between CTP estimated core and MRI final infarct volume was r = 0.38, p < 0.01 for RAPID and r = 0.39, p < 0.01 for Olea. Both software platforms demonstrated a strong correlation with each other (r = 0.864, p < 0.001). Both software overestimated the ischemic core volume above 70 mL in 4 patients (2.6%). CONCLUSIONS: Substantial variation between Olea and RAPID CTP-estimated core volumes exists, though rates of overcalling of large core were low and identical. Both showed comparable core volume correlation to MRI infarct volume.

Arterial Collapse during Thrombectomy for Stroke: Clinical Evidence and Experimental Findings in Human Brains and In Vivo Models.

BACKGROUND AND PURPOSE: Aspiration thrombectomy has become a preferred approach to recanalize large-vessel occlusion in stroke with a growing trend toward using larger-bore catheters and stronger vacuum pumps. However, the mechanical response of the delicate cerebral arteries to aspiration force has not been evaluated. Here, we provide preclinical and clinical evidence of intracranial arterial collapse in aspiration thrombectomy. MATERIALS AND METHODS: We presented a clinical case of arterial collapse with previously implanted flow diverters. We then evaluated the effect of vacuum with conventional aspiration catheters (with and without stent retrievers) in a rabbit model (n = 3) using fluoroscopy and intravascular optical coherence tomography. Then, in a validated human cadaveric brain model, we conducted 168 tests of direct aspiration thrombectomy following an experimental design modifying the catheter inner diameter (0.064 inch, 0.068 inch, and 0.070 inch), cerebral perfusion pressures (mean around 60 and 90 mm Hg), and anterior-versus-posterior circulation. Arterial wall response was recorded and graded via direct transluminal observation. RESULTS: Arterial collapse was observed in both the patient and preclinical experimental models. In the human brain model, arterial collapse was observed in 98% of cases in the M2 and in all the cases with complete proximal flow arrest. A larger bore size of the aspiration catheter, a lower cerebral perfusion pressure, and the posterior circulation in comparison with the anterior circulation were associated with a higher probability of arterial collapse. CONCLUSIONS: Arterial collapse does occur during aspiration thrombectomy and is more likely to happen with larger catheters, lower perfusion pressure, and smaller arteries.

Outcomes among preterm infants with patent ductus arteriosus: Relationship with treatment, gestational age, hemodynamic status and timing of treatment.

BACKGROUND: There remains controversy regarding the outcomes resulting from treatment versus conservative management of patent ductus arteriosus (PDA) among preterm infants. The effects of extreme prematurity, hemodynamic status of the PDA, and age at treatment remain poorly defined. STUDY DESIGN: This retrospective case-control study including infants < 1250 gm who were categorized into 3 groups: Group 1: without PDA, Group 2: with untreated PDA, and Group 3: treated PDA. Diagnosis and treatment of PDA extracted from the medical records. Demographics, clinical characteristics, and outcomes compared using chi-square and analysis of variance. Logistic regression used to estimate adjusted odds ratios. RESULTS: The study included 734 infants, with 141(19%) in Group 1, 329 (45%) in 2, and 264 (36%) in 3. Group 3 had higher incidence of bronchopulmonary dysplasia (BPD) (aOR, 2.9; 95%CI 1.7-4.8). Infant treated for hemodynamically significant PDA (HSPDA) had higher incidence of BPD (aOR, 1.9; 95%CI 1.0-3.8) and retinopathy of prematurity (ROP) (aOR, 3.4; 95%CI 1.6-6.9). There were no differences in outcome associated with treatment among≤26 weeks gestation and the age when treated. CONCLUSION: Infants with PDA who were treated had higher incidence of BPD. Among those who were treated, those with HSPDA had a higher incidence of BPD and ROP.

Bi-maxillary Protrusion: An Orthodontic Management.

Bi-maxillary protrusion is a condition with protrusive and proclined upper and lower incisors and the patient is not able to close lips without strain. The presented case reported with the chief complaint of forwardly placed teeth, with skeletal class II malocclusion, and Angle's class I malocclusion with protrusive and forwardly placed upper and lower incisors. The treatment was performed with the extraction of all first premolars and retraction under absolute anchorage. The retraction of upper and lower lips of about 3 mm and 3.5 mm was achieved respectively and the patient was able to close lips without strain. With proper anchorage preparation, bi-maxillary protrusion can be successfully managed orthodontically.

Radiation-Induced Imaging Changes and Cerebral Edema following Stereotactic Radiosurgery for Brain AVMs.

BACKGROUND AND PURPOSE: T2 signal and FLAIR changes in patients undergoing stereotactic radiosurgery for brain AVMs may occur posttreatment and could result in adverse radiation effects. We aimed to evaluate outcomes in patients with these imaging changes, the frequency and degree of this response, and factors associated with it. MATERIALS AND METHODS: Through this retrospective cohort study, consecutive patients treated with stereotactic radiosurgery for brain AVMs who had at least 1 year of follow-up MR imaging were identified. Logistic regression analysis was used to evaluate predictors of outcomes. RESULTS: One-hundred-sixty AVMs were treated in 148 patients (mean, 35.6 years of age), including 42 (26.2%) pediatric AVMs. The mean MR imaging follow-up was 56.5 months. The median Spetzler-Martin grade was III. The mean maximal AVM diameter was 2.8 cm, and the mean AVM target volume was 7.4 mL. The median radiation dose was 16.5 Gy. New T2 signal and FLAIR hyperintensity were noted in 40% of AVMs. T2 FLAIR volumes at 3, 6, 12, 18, and 24 months were, respectively, 4.04, 55.47, 56.42, 48.06, and 29.38 mL Radiation-induced neurologic symptoms were encountered in 34.4%. In patients with radiation-induced imaging changes, 69.2% had new neurologic symptoms versus 9.5% of patients with no imaging changes (P = .0001). Imaging changes were significantly associated with new neurologic findings (P < .001). Larger AVM maximal diameter (P = .04) and the presence of multiple feeding arteries (P = .01) were associated with radiation-induced imaging changes. CONCLUSIONS: Radiation-induced imaging changes are common following linear particle accelerator-based stereotactic radiosurgery for brain AVMs, appear to peak at 12 months, and are significantly associated with new neurologic findings.

Effect of Doublesynch and Estradoublesynch protocols on estrus induction, conception rate, plasma progesterone, protein, and cholesterol profile in anestrus Gir heifers.

AIM: This study aimed to evaluate the efficacy of Doublesynch and Estradoublesynch protocols on estrus induction, conception rates, plasma progesterone, protein, and cholesterol profile in anestrus Gir heifers. MATERIALS AND METHODS: In this study, 50 pubertal anestrus Gir heifers were selected from the field and farm conditions. The heifers were dewormed (injection ivermectin, 100 mg, s/c) and supplemented with minerals and vitamins (injection organic phosphorus 800 mg and injection Vitamin AD3E and Biotin 10 ml i/m) and multi-mineral bolus at 1 bolus daily for 7 days. The heifers were randomly divided into three groups: Doublesynch (n=20), Estradoublesynch (n=20), and control (n=10). The animals were monitored for estrus response, estrus interval, behavioral signs, and conception rates after induced/first, second, and third cycle post-treatment. Blood samples were obtained on day 0, day 9, day 12, and on day 12 post-artificial insemination (AI) for determination of plasma progesterone, protein, and cholesterol profile. RESULTS: The estrus response rate between Doublesynch and Estradoublesynch protocols was similar between treated heifers (85% and 95%). The interval from the second prostaglandin F2α (PGF2α) injection to estrus induction did not differ between the groups (63.87±4.19 vs. 58.27±3.83 h). The conception rates following induced estrus (20% vs. 30%), at the second cycle (23.07% vs. 16.66%), at the third cycle (22.22% vs. 30.00%), and the overall conception rate (45% and 55%) within 27.89±5.75 and 26.45±5.48 days were the same across the treatment groups. The mean plasma progesterone concentrations were significantly (p<0.01) higher on day 9 (second PGF2α injection) and day 12 post-AI compared to day 0 (first PGF2α injection) and the day of fixed-timed artificial insemination. The concentrations were also significantly (p<0.05) higher in conceived than non-conceived heifers on day 9 of treatment and day 12 post-AI in both the protocols. The mean plasma cholesterol concentrations were significantly higher during peak follicular and luteal phases compared to the initial anestrus phase in both the protocols. The values were also higher in non-conceived than conceived animals in both the protocols. The plasma protein profile was not influenced by the sampling days or conceived and non-conceived status. CONCLUSION: The results showed that both Doublesynch and Estradoublesynch protocols resulted in similar estrus induction and conception rates with modulation of plasma progesterone and cholesterol profile in anestrus Gir heifers.

INDUCED CYTOMICTIC VARIATIONS AND SYNCYTE FORMATION DURING MICROSPOROGENESIS IN PHASEOLUS VULGARIS L.

The intercellular translocation of chromatin material along with other cytoplasmic contents among the proximate meiocytes lying in close contact with each other commonly referred as cytomixis was reported during microsporogenesis in Phaseolus vulgaris L., a member of the family Fabaceae. The phenomenon of cytomixis was observed at three administered doses of gamma rays viz. 100, 200, 300 Gy respectively in the diploid plants of Phaseolus vulgaris L. The gamma rays irradiated plants showed the characteristic feature of inter-meiocyte chromatin/chromosomes transmigration through various means.such as channel formation, beak formation or by direct adhesion between the PMC's (Pollen mother cells). The present study also reports the first instance of syncyte formation induced via cytomictic transmigration in Phaseolus vulgaris L. Though the frequency of syncyteformation was rather low yet these could play a significant role in plant evolution. It is speculated that syncyte enhances the ploidy level of plants by forming 2n gametes and may lead to the production ofpolyploid plants. The phenomenon of cytomixis shows a gradual inclination along with the increasing treatment doses of gamma rays. The preponderance of cytomixis was more frequent during meiosis I as compared to meiosis II. An interesting feature noticed during the present study was the channel formation among the microspores and fusion among the tetrads due to cell wall dissolution. The impact of this phenomenon is also visible on the development of post-meiotic products. The formation of heterosized pollen grains; a deviation from the normal pollen grains has also been reported. The production of gametes with unbalanced chromosomes is of utmost importance and should be given more attention in future studies as they possess the capability of inducing variations at the genomic level and can be further utilized in the improvement of germplasm.

Transmission dynamics & epidemiology of malaria in two tribal districts in Madhya Pradesh, India.

BACKGROUND AND OBJECTIVES: Epidemiology and transmission of malaria vary within the tribal areas with the variation in topography, forest cover and type of forest. For the control of disease, understanding of the dynamics of transmission in the varied ecological situation is essential. This study was carried out in the two distinct tribal areas- Baiga Chak (thick forested area) of Dindori district and Bichhia block (forest fringe area) of Mandla district, Madhya Prasdesh, India, to understand the epidemiology and transmission dynamics of malaria. METHODS: Mosquitoes were collected using hand catch and whole night collections to determine the proportion of vectors, their density and seasonality. Vector incrimination was done by sporozoite ELISA and feeding preferences of vector by gel diffusion method. Active fever surveys were carried out fortnightly to determine the age specific malaria parasite rates among the inhabitants of two areas. RESULTS: Density of Anopheles culicifacies was significantly higher in Bichhia while the density of An. fluviatilis was higher in Baiga Chak. An. culicifacies was incriminated from both the areas while An. fluviatilis was incriminated from Baiga Chak only. Malaria slide positivity rate (SPR) was significantly higher (OR=3.7 95%CI, 3.1-4.4) in Baiga Chak (28.2%) than Bichhia (9.6%). INTERPRETATION & CONCLUSIONS: The features of malaria transmission in tribal areas differed from those reported in rural or semirural population. Site-specific and region-specific studies are required to develop appropriate intervention measures to control malaria.

Human behavior. Sex equality can explain the unique social structure of hunter-gatherer bands.

The social organization of mobile hunter-gatherers has several derived features, including low within-camp relatedness and fluid meta-groups. Although these features have been proposed to have provided the selective context for the evolution of human hypercooperation and cumulative culture, how such a distinctive social system may have emerged remains unclear. We present an agent-based model suggesting that, even if all individuals in a community seek to live with as many kin as possible, within-camp relatedness is reduced if men and women have equal influence in selecting camp members. Our model closely approximates observed patterns of co-residence among Agta and Mbendjele BaYaka hunter-gatherers. Our results suggest that pair-bonding and increased sex egalitarianism in human evolutionary history may have had a transformative effect on human social organization.

Relationship of Oxygen Saturation with Neonatal and Maternal factors in Vaginal and Cesarean Deliveries.

INTRODUCTION: Hypoxemia is the major cause of neonatal morbidity and mortality. The study aims to determine the influence of birth weight, Apgar score, gestation age, body mass index and hemoglobin of mother on levels of SpO2 in healthy newborns born vaginally and through cesarean section. METHODS: A hospital Based, observational study conducted in Department of Pediatrics, Universal College of Medical Sciences-Teaching Hospital, Bhairahawa, Lumbini, Nepal; on 49 vaginal and 49 cesarean deliveries with Apgar Score ≥ 6. SpO2 was estimated by pulse oximeter post-ductally between 1 to 30 minutes of birth. The observed SpO2 values were correlated with neonatal and maternal factors. RESULTS: Vaginal and Cesarean deliveries SpO2 were comparable for birth weight, gestational age, Apgar score of neonates, body mass index and hemoglobin of the mother. Birth weight in vaginally delivered babies and Apgar score in cesarean births showed significant change in SpO2 (P<0.05). At all points of time the SpO2 values were higher in neonates, born by cesarean than those born out of spontaneous vaginal deliveries (P<0.001). CONCLUSIONS: SpO2 levels in neonates born through cesarean section were higher in comparison to thoseborn by vaginal route. Birth weight and Apgar score had correlation with SpO2 in vaginal and cesarean births, respectively.

SMAR1 coordinates HDAC6-induced deacetylation of Ku70 and dictates cell fate upon irradiation.

Acetylation status of DNA end joining protein Ku70 dictates its function in DNA repair and Bax-mediated apoptosis. Despite the knowledge of HDACs and HATs that are reported to modulate the acetylation dynamics of Ku70, very little is known about proteins that critically coordinate these key modifications. Here, we demonstrate that nuclear matrix-associated protein scaffold/matrix-associated region-binding protein 1 (SMAR1) is a novel interacting partner of Ku70 and coordinates with HDAC6 to maintain Ku70 in a deacetylated state. Our studies revealed that knockdown of SMAR1 results in enhanced acetylation of Ku70, which leads to impaired recruitment of Ku70 in the chromatin fractions. Interestingly, ionizing radiation (IR) induces the expression of SMAR1 and its redistribution as distinct nuclear foci upon ATM-mediated phosphorylation at serine 370. Furthermore, SMAR1 regulates IR-induced G2/M cell cycle arrest by facilitating Chk2 phosphorylation. Alternatively, SMAR1 provides radioresistance by modulating the association of deacetylated Ku70 with Bax, abrogating the mitochondrial translocation of Bax. Thus, we provide mechanistic insights of SMAR1-mediated regulation of repair and apoptosis via a complex crosstalk involving Ku70, HDAC6 and Bax.

Large-volume blood patch to multiple sites in the epidural space through a single-catheter access site for treatment of spontaneous intracranial hypotension.

BACKGROUND AND PURPOSE: Spontaneous intracranial hypotension can be a therapeutic challenge to the treating physician. In this study, we present our experience with the administration of a large-volume blood patch to multiple sites in the epidural space through a single-catheter access site. MATERIALS AND METHODS: A retrospective review was conducted of patients with spontaneous intracranial hypotension who underwent a large-volume blood patch to multiple sites in the epidural space through a single-catheter access site from 2010 to 2012. Patient demographic data, clinical charts, indications for treatment, radiographic images, procedure notes, and postprocedure hospital course were reviewed. RESULTS: Overall, 9 patients were identified who underwent 20 blood patch procedures. Patients were selected to undergo the large-volume procedure either because they had a failed site-directed epidural blood patch or if imaging demonstrated multiple possible leak sites. There were 6 women and 3 men, with an average age of 33.5 years. The mean volume of blood injected per procedure was 54.1 mL (median=55 mL; range=38-70 mL). All patients had an orthostatic headache as one of their presenting symptoms; 22% also presented with neurocognitive decline and behavioral changes; 89% of patients had improvement or resolution of their symptoms; and 80% of patients who had a previously failed site-directed epidural blood or fibrin glue patch improved with a large volume catheter-directed blood patch. CONCLUSIONS: Our experience supports the use of a large-volume blood patch to multiple sites in the epidural space through a single-catheter access site for the treatment of spontaneous intracranial hypotension. Additionally, our results indicate a role for this procedure in refractory cases of spontaneous intracranial hypotension.

Pediatric Precursor B-cell Lymphoblastic Lymphoma Presenting with Extensive Skeletal Lesions.

Lymphoblastic lymphoma (LL) of the B cell type is uncommon, and extranodal presentation is even rarer. It is difficult to suspect this diagnosis without clinically obvious lymph nodal mass or bone marrow involvement. A 3-year-old girl presented with progressive pain and swelling of the right knee joint of 3 months duration. Radiograph revealed expansile lytic lesion at the supracondylar area of the right femur; with pathological fracture and multiple lytic areas in both femora. She neither had lymphadenopathy nor organomegaly. Her blood counts, peripheral smear examination and bone marrow examination were normal. Right supracondylar biopsy revealed diagnosis of a precursor B cell LL. Computerized tomography scan revealed a hypodense, poorly enhancing lesion in the left adnexal region. Although rare, precursor B-cell LL may present with extensive bone lesions. Early and accurate diagnosis of this entity is very important due to its high cure rates.

Management of bleeding in extrahepatic portal venous obstruction.

Extrahepatic portal venous obstruction, although rare in the western world, is a common cause of major and life threatening upper gastrointestinal bleeding among the poor in developing countries. Patients have large spleens and stunted growth. The diagnosis is easily confirmed by Doppler ultrasonography. Endoscopy sclerotherapy is the best option for the control of acute variceal bleeding. For secondary prophylaxis of bleeding, the choice lies between repeated sclerotherapy and a portosystemic shunt. We believe that due consideration should be given to performing a splenectomy and a lienorenal shunt. Performed by experienced surgeons, it carries a low operative mortality of 1%, a rebleeding rate of about 10%, removes the large spleen, reverses hypersplenism, and is not followed by portosystemic encephalopathy. Most importantly, it is a onetime procedure particularly suited to those who have little access to blood transfusion and sophisticated medical facilities.

Spinal dural arteriovenous fistulas: clinical experience with endovascular treatment as a primary therapy at 2 academic referral centers.

BACKGROUND AND PURPOSE: Spinal dural arteriovenous fistulas are a rare entity that, if left untreated, can lead to considerable morbidity with progressive spinal cord symptoms. The aim of this study was to evaluate the clinical outcome of patients with spinal dural arteriovenous fistulas that were primarily treated with endovascular embolization. MATERIALS AND METHODS: A retrospective review was performed of all patients from 1997-2010 who underwent treatment at 2 academic referral centers for a spinal dural arteriovenous fistula. Follow-up was performed by clinical examination, and functional status was measured by use of the Aminoff-Logue Disability Scale, McCormick classification grading, and mRS scores. The nonparametric Wilcoxon signed rank test was used to compare pretreatment and posttreatment Aminoff-Logue Disability Scale gait and micturition scores, McCormick classification grading, and mRS scores. P values < .05 were considered significant. RESULTS: A total of 38 patients were included. Five patients (2 endovascular, 3 surgical) were lost to follow-up and therefore were excluded from the analysis, 29 patients were initially treated from an endovascular approach (9 Onyx, 20 cyanoacrylate), and 4 patients were treated from a standard surgical approach. Five patients in the endovascular group subsequently underwent surgery for various reasons. The clinical improvements in the Aminoff-Logue Disability Scale gait and micturition scores, McCormick classification grading, and the mRS scores were statistically significant (P < .05, Wilcoxon signed rank test). CONCLUSIONS: We conclude that endovascular treatment of spinal dural arteriovenous fistulas can result in good clinical outcomes. Surgery remains the treatment of choice when safe embolization of the proximal radicular draining vein cannot be obtained or because the shunting artery of the spinal dural arteriovenous fistula also supplies the anterior spinal, posterior spinal, or a radiculomedullary artery.

Influence of IL-6 haplotypes on clinical and inflammatory response in aggressive periodontitis.

OBJECTIVES: The aim of this study was to investigate the inflammatory response in aggressive periodontitis (AgP) patients after periodontal therapy and associate these changes to subjects' interleukin-6 (IL-6) genetic variants. MATERIALS AND METHODS: Twelve non-smoking UK Caucasian patients with AgP were selected based on their IL6 haplotypes (six haplotype positive and six haplotype negative based on polymorphisms rs 2069827 and rs 2069825) and underwent full mouth non-surgical periodontal therapy, followed by open flap surgery. Gingival crevicular fluid (GCF) and peripheral blood samples were taken at baseline and at six different time points after treatment. Gingival biopsy samples were harvested during surgery and underwent immunohistochemical analysis for identification of IL-6. RESULTS: An overall improvement in clinical periodontal parameters was observed following periodontal therapy. Haplotype status was associated with clinical presentation, Aggregatibacter actinomycetemcomitans counts in subgingival plaque samples, white cell count, neutrophils, red cell count and haemoglobin. GCF IL-6 concentrations increased dramatically 1 day after surgery and IL-6 haplotype-positive subjects exhibited a higher magnitude in this increase. CONCLUSIONS: IL6 haplotypes may have an effect on clinical presentation and magnitude and kinetics of local and systemic inflammatory responses following non-surgical and surgical periodontal therapy in aggressive periodontitis. CLINICAL RELEVANCE: Detecting IL-6 haplotype-positive periodontitis patients might become helpful in identifying subjects prone to excessive inflammatory response and increased periodontal breakdown.

Genomic impact of cigarette smoke, with application to three smoking-related diseases.

There is considerable evidence that inhaled toxicants such as cigarette smoke can cause both irreversible changes to the genetic material (DNA mutations) and putatively reversible changes to the epigenetic landscape (changes in the DNA methylation and chromatin modification state). The diseases that are believed to involve genetic and epigenetic perturbations include lung cancer, chronic obstructive pulmonary disease (COPD), and cardiovascular disease (CVD), all of which are strongly linked epidemiologically to cigarette smoking. In this review, we highlight the significance of genomics and epigenomics in these major smoking-related diseases. We also summarize the in vitro and in vivo findings on the specific perturbations that smoke and its constituent compounds can inflict upon the genome, particularly on the pulmonary system. Finally, we review state-of-the-art genomics and new techniques such as high-throughput sequencing and genome-wide chromatin assays, rapidly evolving techniques which have allowed epigenetic changes to be characterized at the genome level. These techniques have the potential to significantly improve our understanding of the specific mechanisms by which exposure to environmental chemicals causes disease. Such mechanistic knowledge provides a variety of opportunities for enhanced product safety assessment and the discovery of novel therapeutic interventions.

Investigation of 3'-debenzoyl-3'-(3-([¹²4I]-iodobenzoyl))paclitaxel analog as a radio-tracer to study multidrug resistance in vivo.

A study was carried out to identify a suitable radioactive paclitaxel analog and to use it to investigate tumor multidrug resistance in vivo. 3'-Debenzoyl-3'-(3-([(124)I]-iodobenzoyl))paclitaxel was prepared by aromatic iodination of 3'-debenzoyl-3'-(3-trimethylstannylbenzoyl)paclitaxel. Uptake of the labeled paclitaxel analog in nude mice bearing tumor with the paclitaxel sensitive cancer cell lines MCF7 and MDA-435/LCC6(WT), and multidrug resistant cell lines NCI/ADR-RES and MDA-435/LCC6(MDR), was studied. There was no difference in drug level between the sensitive and resistant MDA-435/LCC6 tumors at 6h post-injection. However, at 6h, there was a significant increase in drug level for the MCF7 tumor as compared with the NCI/ADR-RES tumor, presumably due to increased drug retention. At 24h, drug uptake/retention was significantly higher in both sensitive tumor cell lines as compared to their drug resistant counterparts. Pretreatment of mice with MDR transport modulators, Cyclosporine or tRA 96029, did not increase the level of labeled paclitaxel analog in the drug resistant MDA-435/LCC6(MDR) tumor. On the other hand, at 24h Cyclosporine apparently increased analog level in the drug sensitive MDA-435/LCC6(WT) tumor, aiding drug imaging studies.