Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 29
Filter
1.
Gene Expr Patterns ; 45: 119261, 2022 09.
Article in English | MEDLINE | ID: mdl-35817289

ABSTRACT

A recommendation system is an imaginative resolution for managing the restrictions in e-commerce services with item details and user details. Also, it is used to determine the user preferences to recommend the items they expected to buy. Several conventional collaborative filtering techniques are devised in the recommender model, but it has some complexities. Hence, an innovative optimization-driven deep residual network is devised in this paper for a product recommendation system. Here, the product of images is used for extracting features where the Convolutional neural network (CNN) features are computed, and then it is given as input to the deep residual network aimed at product recommendation. The deep residual network is trained using developed Elephant Herding Feedback Artificial Optimization (EHFAO), which is obtained by integrating Elephant Herding optimization (EHO) into the Feedback Artificial Tree (FAT). Here, the item grouping is carried out on input data based on K-means clustering. After item grouping, Cosine similarity is used to perform matching of groups, where the best group is acquired among all the available groups. Extraction of list of visitors is done from the best group. Then, the list of items is obtained from the sequence of best visitor. Next, the corresponding binary sequence is obtained for the applicable sequence of visitor. From this sequence of best visitor, the recommended product is acquired. Then, the recommended product is subjected to the sentiment analysis for which the score is determined. Here, the sentiment analysis helps to decide whether the product is recommended or not recommended. If the score is positive, then the same product is recommended; otherwise, the new product is recommended. The proposed EHFAO-based deep residual network attained better performance in comparison to the other techniques with a maximal F-measure at 84.061%, 84.061% precision, 87.845% recall along with minimal Mean Squared Error (MSE) of 0.216.


Subject(s)
Commerce , Deep Learning , Commerce/methods , Computer Simulation , Models, Economic
2.
Acad Forensic Pathol ; 12(1): 15-22, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35694009

ABSTRACT

Introduction: Violence with physical assault is a common cause of morbidity and mortality prevalent but not limited to underdeveloped countries. The opinion of the forensic expert is often indispensable in such cases to determine the penalties. This study was planned to describe the pattern of presentation of the victims and evaluate the strengths and limitations in formulating a scientific medicolegal opinion based on the findings of the victim. Methods: A retrospective descriptive study based on the case records of the victims of assault admitted to Colombo North Teaching Hospital, Ragama, Sri Lanka, was conducted for four years. Results: Out of the 400 victims, the majority (72% n = 290) were males and of the age-group of 21 to 40 (n = 216). The reason for assault in the majority was sudden provocation (n = 99, 25%), followed by previous long-duration enmity (n = 89, 22%). The majority (83%) had isolated blunt force trauma, and the injuries were nongrievous (74%). Defense injuries were significantly associated with attempted defense (p = 0.000) and sharp force trauma (p = 0.002). The underlying reason for the assault was not significantly associated with the causative weapon (p = 0.228) or body region injured (p = 0.195). Conclusions: Even though the presentation and the pattern of injures are definitely of value in formulating a scientific opinion, the study identified the limitations of the forensic experts, and the need for a holistic approach at the investigations was highlighted.

3.
Biomed Res Int ; 2022: 7799812, 2022.
Article in English | MEDLINE | ID: mdl-35480141

ABSTRACT

Brain cancer is one of the cell synthesis diseases. Brain cancer cells are analyzed for patient diagnosis. Due to this composite cell, the conceptual classifications differ from each and every brain cancer investigation. In the gene test, patient prognosis is identified based on individual biocell appearance. Classification of advanced artificial neural network subtypes attains improved performance compared to previous enhanced artificial neural network (EANN) biocell subtype investigation. In this research, the proposed features are selected based on improved gene expression programming (IGEP) with modified brute force algorithm. Then, the maximum and minimum term survivals are classified by using PCA with enhanced artificial neural network (EANN). In this, the improved gene expression programming (IGEP) effectual features are selected by using remainder performance to improve the prognosis efficiency. This system is estimated by using the Cancer Genome Atlas (CGA) dataset. Simulation outputs present improved gene expression programming (IGEP) with modified brute force algorithm which achieves accurate efficiency of 96.37%, specificity of 96.37%, sensitivity of 98.37%, precision of 78.78%, F-measure of 80.22%, and recall of 64.29% when compared to generalized regression neural network (GRNN), improved extreme learning machine (IELM) with minimum redundancy maximum relevance (MRMR) method, and support vector machine (SVM).


Subject(s)
Brain Neoplasms , Neural Networks, Computer , Algorithms , Brain Neoplasms/diagnosis , Brain Neoplasms/genetics , Computer Simulation , Humans , Support Vector Machine
4.
Photodiagnosis Photodyn Ther ; 38: 102753, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35139339

ABSTRACT

BACKGROUND: The treatment of patients after mechanical ventilation of lungs suffering from a multi-species infection of the tracheobronchial tree can be complicated.. The situation is aggravated in patients with post-intubation tracheal stenosis, where infection plays a leading pathogenetic role in damage to the tracheal wall. As a result of such a pathological process, cicatricial stenosis of the trachea of purulent-inflammatory infectious genesis or infected tracheal stenosis (ITS) may occur. METHODS: In this work, we studied the possibility of photodynamic inactivation of pathogenic microbiota typical for patients with ITS using methylene blue (MB) as a photosensitizer. RESULTS: 13 clinical isolates of 8 species of bacteria from 9 patients were susceptible to photodynamic inactivation with MB. 30 µM of MB at a light irradiation dose of 25 J/cm2 and incubation with MB for 15 min allows to completely inactivate bacteria found in the tracheobronchial secretions of patients with ITS. CONCLUSIONS: MB retains its optico-physical properties in the range of 3-30 µM and provides effective inactivation of isolated Gram-positive and Gram-negative bacteria, including multi- and pan-resistant to antibiotics.


Subject(s)
Microbiota , Photochemotherapy , Tracheal Stenosis , Anti-Bacterial Agents/therapeutic use , Bacteria , Gram-Negative Bacteria , Gram-Positive Bacteria , Humans , Methylene Blue/pharmacology , Methylene Blue/therapeutic use , Photochemotherapy/methods , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Tracheal Stenosis/drug therapy
5.
Reprod Sci ; 28(1): 37-42, 2021 01.
Article in English | MEDLINE | ID: mdl-32748221

ABSTRACT

There is a growing evidence for the public health hazards associated with waterpipe tobacco smoking (WTS). While the adverse effects of WTS exposure during pregnancy on the offspring are widely reported, its impact during breastfeeding remains less understood. The effects of WTS exposure during lactation on the reproductive hormones and oxidative stress biomarkers of adult male progeny were examined. Lactating rats received either fresh air (controls) or mainstream WTS for 1 h twice/day from day 4 to day 21 of lactation. The offspring was then followed up until week 20. The data indicated that WTS exposure in the lactating animals reduced the levels of follicle-stimulating hormone (FSH), prolactin (P < 0.05), luteinizing hormone (LH) (P = 0.1146), and estradiol (P = 0.0773) in the blood in male progeny. While the activities of testicular superoxide dismutase (SOD), glutathione peroxidase (GPx) and the levels of thiobarbituric acid reactive substances (TBARS) and blood levels of testosterone (P >0.05) remained unaltered, the activity of catalase increased significantly indicating an increased oxidant load in the WTS exposed rats compared to the controls. WTS exposure during lactation impairs male reproductive hormonal profile, augments oxidative damage, and potentially affects male fertility in male offspring rats.


Subject(s)
Hormones/blood , Lactation , Oxidative Stress , Reproduction , Smoke/adverse effects , Testis/metabolism , Tobacco, Waterpipe/adverse effects , Vaping/adverse effects , Animals , Biomarkers/metabolism , Female , Fertility , Male , Pregnancy , Rats, Wistar , Testis/pathology
6.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 1816-1819, 2020 07.
Article in English | MEDLINE | ID: mdl-33018352

ABSTRACT

The measure of White Blood Cells (WBC) in the blood is an important indicator of pathological conditions. Computer vision based methods for differential counting of WBC are increasing due to their advantages over traditional methods. However, most of these methods are proposed for single WBC images which are pre-processed, and do not generalize for raw microscopic images with multiple WBC. Moreover, they do not have the capability to detect the absence of WBC in the images. This paper proposes an image processing algorithm based on K-Means clustering to detect the presence of WBC in raw microscopic images and to localize them, and a VGG-16 classifier to classify those cells with a classification accuracy of 95.89%.


Subject(s)
Image Processing, Computer-Assisted , Leukocytes , Algorithms , Cluster Analysis , Leukocyte Count
7.
Am J Physiol Renal Physiol ; 319(4): F686-F696, 2020 10 01.
Article in English | MEDLINE | ID: mdl-32830535

ABSTRACT

Renal proximal tubular apoptosis plays a critical role in kidney health and disease. However, cellular molecules that trigger renal apoptosis remain elusive. Here, we evaluated the effect of inhibiting protein disulfide isomerase (PDI), a critical thioredoxin chaperone protein, on apoptosis as well as the underlying mechanisms in human renal proximal tubular (HK2) cells. HK2 cells were transfected with PDI-specific siRNA in the absence and presence of an antioxidant, tempol. PDI siRNA transfection resulted in a decrease of ~70% in PDI protein expression and enzyme activity. PDI inhibition increased caspase-3 activity and induced profound cell apoptosis. Mitochondrial function, as assessed by mitochondrial cytochrome c levels, mitochondrial membrane potential, oxygen consumption, and ATP levels, was significantly reduced in PDI-inhibited cells. Also, PDI inhibition caused nuclear factor erythroid 2-related factor 2 (Nrf2; a redox-sensitive transcription factor) cytoplasmic sequestration, decreased superoxide dismutase and glutathione-S-transferase activities, and increased oxidative stress. In PDI-inhibited cells, tempol reduced apoptosis, caspase-3 activity, and oxidative stress and also restored Nrf2 nuclear translocation and mitochondrial function. Silencing Nrf2 in the cells abrogated the beneficial effect of tempol, whereas Kelch-like ECH-associated protein 1 (an Nrf2 regulatory protein) silencing protected cells from PDI inhibitory effects. Collectively, our data indicate that PDI inhibition diminishes Nrf2 nuclear translocation, causing oxidative stress that further triggers mitochondrial dysfunction and renal cell apoptosis. This study suggests an important role for PDI in renal cell apoptosis involving Nrf2 and mitochondrial dysfunction.


Subject(s)
Apoptosis , Epithelial Cells/enzymology , Kelch-Like ECH-Associated Protein 1/metabolism , Kidney Tubules, Proximal/enzymology , Mitochondria/enzymology , NF-E2-Related Factor 2/metabolism , Protein Disulfide-Isomerases/metabolism , Active Transport, Cell Nucleus , Antioxidants/pharmacology , Apoptosis/drug effects , Cell Line , Cyclic N-Oxides/pharmacology , Energy Metabolism , Epithelial Cells/drug effects , Epithelial Cells/pathology , Humans , Kelch-Like ECH-Associated Protein 1/genetics , Kidney Tubules, Proximal/drug effects , Kidney Tubules, Proximal/pathology , Mitochondria/drug effects , Mitochondria/genetics , Mitochondria/pathology , NF-E2-Related Factor 2/genetics , Oxidative Stress , Protein Disulfide-Isomerases/genetics , RNA Interference , Signal Transduction , Spin Labels
8.
Toxicol Rep ; 6: 809-818, 2019.
Article in English | MEDLINE | ID: mdl-31453112

ABSTRACT

INTRODUCTION: Russell's viper envenoming in dogs is a significant problem in Sri Lanka. The current study focused on investigating clinical profile, laboratory findings of three selected tests and to develop a treatment strategy with Indian polyvalent Anti-Venom Serum (AVS). It was also intended to report adverse effects and complications caused by both Russell's viper venom (RVV) and AVS in Russell's Viper (RV) envenomed dogs. OBJECTIVE: To evaluate and report the clinical manifestations, to find out the minimum effective vials of AVS and to record AVS induced adverse reactions of RV envenoming in dogs. MATERIALS AND METHODS: A prospective study was conducted on Russell's viper bitten dogs (n = 65) admitted to the Veterinary Teaching Hospital (VTH) in Sri Lanka. Indian polyvalent AVS was used to treat all the envenomed dogs. The number of vials of AVS that was administered to a patient was decided upon by a second degree polynomial model with a number of vials of AVS in the X axis verses Prothrombine Time (PT), Activated Partial Thromboplastine Time (aPTT) and Clotting Time (CT) in the Y axis respectively. RESULTS: Varying degrees of pain were exhibited by all the victim dogs. Mild swelling and necrosis at the site of bite was seen in 54% (n = 35) and 37% (n = 24) of dogs respectively. Prolonged values of, PT, aPTT and CT were seen from all the RV envenomed dogs. The mean leukocyte count in these dogs was 39.79 × 103/µL (normal range; 4-20 × 103/µL) (IQR:29.05 × 103/µL-45.92 × 103/µL). Statistical analysis showed that the initial vials of 7 AVS would be the minimum required vials. Therefore, a range of 6-15 AVS vials in total were administered to these dogs and in 7.6% (n = 5) of dogs, the results of PT, aPTT and CT became normal with 6 AVS vials at 32-97 minutes. Acute Renal Failure (ARF) was detected from 29% (n = 19) of dogs as a complication. CONCLUSIONS: Systemic clinical signs of haemorrhagic lesions, cardio respiratory toxicities were common in Russell's viper envenomed dogs. Initially 6 vials of AVS must be administered. AVS induced reactions were reported commonly. Russell's viper envenoming was found to be lethal in dogs.

9.
J Neurosurg Sci ; 61(3): 283-290, 2017 Jun.
Article in English | MEDLINE | ID: mdl-26354185

ABSTRACT

BACKGROUND: Diffusion tensor imaging (DTI) is an advanced and sensitive technique that detects sub-threshold pathology in normal imaging brain injury patients. Currently, there are no longitudinal DTI studies to look for time-based changes. The present study has investigated longitudinal imaging and its association with cognitive deficits. METHODS: Twenty-one patients were available for MRI and neuropsychological test (NPT) assessment for all the 3 time points. Initially (<36 hours), all patients presented with GCS 15 and normal scan findings. The DTI (P<0.0001) and NPT scores (P<0.05) were analyzed using repeated-measure of analysis. The tensor values were correlated with specific time-point NPT scores using partial correlation (0.05). RESULTS: Right cerebral-hemisphere showed significant alterations in both anisotropy and diffusivity values overtime. Cingulate gyrus and occipital lobe showed prominent changes in anisotropy value. Significant improvement in thalamo-cortical anisotropy value after 3-4 months after injury was seen. The changes in diffusivity values were mainly seen in frontal, parietal lobe, right inferior fronto-occipital and superior longitudinal fasciculus, and posterior supramarginal gyrus. Time-related changes of tensor values of thalamus, frontal and temporal lobe had persistent and significant association with attention and learning/memory aspects. CONCLUSIONS: The findings of this study suggest that DTI detects and observes natural-recovery of brain regions affected by sub-threshold force.


Subject(s)
Brain Concussion , Cerebral Cortex/diagnostic imaging , Cognitive Dysfunction , Diffusion Tensor Imaging/methods , Thalamus/diagnostic imaging , Adult , Brain Concussion/complications , Brain Concussion/diagnostic imaging , Brain Concussion/physiopathology , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/etiology , Cognitive Dysfunction/physiopathology , Female , Humans , Longitudinal Studies , Male , Neuropsychological Tests , Recovery of Function , Young Adult
10.
Front Hum Neurosci ; 9: 513, 2015.
Article in English | MEDLINE | ID: mdl-26441610

ABSTRACT

Brains reveal amplified plasticity as they recover from an injury. We aimed to define time dependent plasticity changes in patients recovering from mild traumatic brain injury (mTBI). Twenty-five subjects with mild head injury were longitudinally evaluated within 36 h, 3 and 6 months using resting state functional connectivity (RSFC). Region of interest (ROI) based connectivity differences over time within the patient group and in comparison with a healthy control group were analyzed at p < 0.005. We found 33 distinct ROI pairs that revealed significant changes in their connectivity strength with time. Within 3 months, the majority of the ROI pairs had decreased connectivity in mTBI population, which increased and became comparable to healthy controls at 6 months. Within this diffuse decreased connectivity in the first 3 months, there were also few regions with increased connections. This hyper connectivity involved the salience network and default mode network within 36 h, and lingual, inferior frontal and fronto-parietal networks at 3 months. Our findings in a fairly homogenous group of patients with mTBI evaluated during the 6 month window of recovery defines time varying brain connectivity changes as the brain recovers from an injury. A majority of these changes were seen in the frontal and parietal lobes between 3 and 6 months after injury. Hyper connectivity of several networks supported normal recovery in the first 6 months and it remains to be seen in future studies whether this can predict an early and efficient recovery of brain function.

11.
Forensic Sci Med Pathol ; 11(3): 416-20, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26148811

ABSTRACT

We report a case of acute hemorrhagic leukoencephalomyelitis in a man with viral myocarditis. A 48-year-old previously healthy male was found dead in his locked apartment. At autopsy he was found to be malnourished, and his lungs showed gross evidence of bilateral pneumonia with abscess formation and bullous emphysema. Multiple petechial hemorrhages were observed in the brain and mainly involved white matter in the cerebral hemispheres including the corpus callosum and internal capsule, as well as the cerebellum, brainstem, and spinal cord. Microscopy of the brain and spinal cord revealed perivenular hemorrhages, central microthrombi in venules with fibrin exudation into the subcortical white matter, and early perivenular demyelination associated with scanty mixed cellular infiltrates. Other microscopic features included widespread diffuse viral myocarditis, extensive suppurative bronchopneumonia, and chronic bronchitis. This case illustrates the death of a man with a rare fatal disease associated with two other potentially lethal diseases. The case also illustrates the importance of a holistic approach when determining the cause of death, especially when there are competing causes of death.


Subject(s)
Leukoencephalitis, Acute Hemorrhagic/pathology , Myocarditis/virology , Brain/pathology , Bronchitis, Chronic/pathology , Bronchopneumonia/pathology , Humans , Male , Middle Aged , Myocarditis/pathology , Purpura/pathology , Spinal Cord/pathology
12.
Br J Neurosurg ; 28(5): 626-30, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24377669

ABSTRACT

OBJECTIVE: Fourth ventricular neurocysticercal cyst (FVNCC) usually presents with acute hydrocephalus, requiring surgery. Though endoscopic intervention is preferable, there is no consensus on the method and/or the extent of endoscopic intervention. We share our experience of endoscopic intervention for FVNCC and propose an algorithm of management. METHOD: We reviewed the clinicoradiological details of consecutive patients, who underwent endoscopic intervention for the FVNCC at our institute from 1998 to 2009. Details of cyst excision, endoscopic intervention(s), cerebrospinal fluid (CSF) diversion (internal and external), complications and the outcome were analyzed. RESULTS: There were 21 patients. Cyst could be totally excised in 13 patients, while two patients had only partial excision of cyst. Excision of cyst could not be done in five patients due to ependymitis/adhesion, intraventricular hemorrhage (IVH) and poor visibility of CSF due to hazy CSF. One patient only underwent endoscopic third ventriculostomy (ETV), as cyst excision was not planned in view of calcified FVNCC. Three patients had only cyst excision, as the sole endoscopic intervention, while 12 patients underwent ETV along with excision. Two patients had symptomatic periaqueductal injury with partial recovery (one each with rigid and flexible scope). The mean available follow-up was 22 months. Shunt was avoided in 90% of patients. All patients who are available for follow-up are asymptomatic, irrespective of the type of endoscopic intervention and extent of cyst excision status. CONCLUSION: Relieving the acute symptomatic hydrocephalus by endoscopic internal CSF diversion (ETV) should be the primary therapeutic goal. Cyst excision (partial or total) should be attempted, only where feasible. The rigid scope is safe and satisfactory for the endoscopic intervention for FVNCC.


Subject(s)
Fourth Ventricle/surgery , Neuroendoscopy , Adolescent , Adult , Aged , Child , Cysts/surgery , Female , Humans , Hydrocephalus/surgery , Male , Middle Aged , Neuroendoscopy/methods , Retrospective Studies , Treatment Outcome , Ventriculostomy/methods , Young Adult
13.
Med Sci Law ; 54(2): 74-7, 2014 Apr.
Article in English | MEDLINE | ID: mdl-23966353

ABSTRACT

INTRODUCTION: Unnatural childhood deaths are not only associated with intense trauma and separation distress, but also relate to a sense of neglect to protect children from harm. Accurate information on causes and circumstances of such deaths through a process of medico-legal investigations is essential in creating an awareness among the policy makers and educators/caregivers, to prevent these tragic deaths. OBJECTIVE: The aim of the study was to determine the causes and the circumstances of unnatural deaths of children among the medico-legal autopsy population presented to North Colombo Teaching Hospital, Sri Lanka. STUDY DESIGN: A retrospective descriptive study was carried out based on Reports of Postmortem Examination performed in a Tertiary Care Hospital, on children who died of unnatural causes during the period from 2009 to 2011. RESULTS: Out of 48 unnatural childhood deaths, 24 (50%) children were older than 10 years of age. The most frequent circumstance of death was accidental 39 (81%), while the most frequent cause of death was drowning 16 (33%). Fifteen died due to accidental drowning while one was a homicidal drowning. Suicidal deaths were found only among the children older than 16 years of age. Fifty-four percent of the accidental deaths had taken place at or around the home. CONCLUSION: Accidents accounted for the majority (or greatest number) of tragic childhood deaths. The presence of drowning as the most common cause of death indicates that an immense responsibility lies with the parents and caregivers to prevent such deaths.


Subject(s)
Cause of Death , Accidents/mortality , Adolescent , Age Distribution , Child , Child, Preschool , Drowning/mortality , Homicide/statistics & numerical data , Hospitals, Teaching , Humans , Infant , Infant, Newborn , Retrospective Studies , Sri Lanka/epidemiology , Suicide/statistics & numerical data
14.
Am J Physiol Renal Physiol ; 305(4): F560-7, 2013 Aug 15.
Article in English | MEDLINE | ID: mdl-23698121

ABSTRACT

A recent study demonstrated that the dopamine D1 receptor (D1R) is nonfunctional in human kidney cells, HK2 cells, in terms of their inability to couple to Gs protein in response to the D1R agonist fenoldopam. Since D1R also couples to Gq protein, we tested whether D1R is functional in HK2 cells in terms of their ability to couple to Gq and produce downstream signaling. For comparison, we also studied another receptor, angiotensin II type 1 receptor (AT1R) known to couple to Gq. Protein kinase C (PKC) and (86)rubidium transport activities were determined as surrogate downstream signaling markers. Fenoldopam and angiotensin II increased PKC activity, which decreased in the presence of respective receptor antagonists (SCH23390 for D1R; candesartan for AT1R), PKC (chelerythrine chloride) and Gi protein (pertussis toxin) inhibitors and Gq/11α siRNA. Furthermore, fenoldopam and angiotensin II increased (35)S-GTPγS binding, an index of receptor-G protein coupling, which decreased with pertussis toxin and in Gq/11α-depleted cells. Also, fenoldopam-mediated inhibition of (86)rubidium transport (an index of Na-K-ATPase activity) was attenuated with SCH23390, chelerythrine chloride, pertussis toxin, and Gq/11α siRNA. Moreover, fenoldopam caused a decrease in cytosolic and increase in membranous abundance of Gq/11α. The immunoprecipitated levels of Gq/11α in the membranes were greater in fenoldopam-treated cells, and Giα coimmunoprecipitated with Gq/11α. Our results suggest that both D1R and AT1R are functional in HK2 cells, enabling Gq-mediated downstream signaling in a Gi dependent manner.


Subject(s)
GTP-Binding Protein alpha Subunits, Gi-Go/metabolism , GTP-Binding Protein alpha Subunits, Gq-G11/metabolism , Kidney Tubules, Proximal/metabolism , Kidney/metabolism , Receptors, Dopamine D1/metabolism , Biological Transport , Cell Culture Techniques , Epithelial Cells/metabolism , Fenoldopam/pharmacology , Humans , Kidney/drug effects , Kidney Tubules, Proximal/drug effects , Receptor, Angiotensin, Type 1/metabolism , Signal Transduction/drug effects
15.
PLoS One ; 7(12): e51736, 2012.
Article in English | MEDLINE | ID: mdl-23272153

ABSTRACT

The development and clinical testing of drug combinations for the treatment of Non-Hodgkin Lymphoma (NHL) and other cancers has recently shown great promise. However, determining the optimum combination and its associated dosages for maximum efficacy and minimum side effects is still a challenge. This paper describes a parametric analysis of the dynamics of malignant B-cells and the effects of an anti-sense oligonucleotide targeted to BCL-2 (as-bcl-2), anti-CD-20 (rituximab) and their combination, for a SCID mouse human lymphoma xenograft model of NHL. Our parametric model is straightforward. Several mechanisms of malignant B-cell birth and death in the nodal micro-environment are simulated. Cell death is accelerated by hypoxia and starvation induced by tumor scale, by modification of anti-apoptosis with as-bcl-2, and by direct kill effects of rituximab (cell kill by cytotoxic immune cells is not included, due to the absence of an immune system in the corresponding experiments). We show that the cell population dynamics in the control animals are primarily determined by K*, the ratio of rate constants for malignant cell death, K(d), and cell birth, K(b). Tumor growth with independent treatments is reproduced by the model, and is used to predict their effect when administered in combination. Malignant cell lifetimes are derived to provide a quantitative comparison of the efficacy of these treatments. Future experimental and clinical applications of the model are discussed.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Antineoplastic Agents/administration & dosage , Lymphoma, Non-Hodgkin/drug therapy , Models, Biological , Oligonucleotides/administration & dosage , Animals , Combined Modality Therapy , Disease Models, Animal , Drug Therapy, Combination , Humans , Lymphoma, Non-Hodgkin/diagnosis , Mice , Xenograft Model Antitumor Assays
16.
J Health Care Poor Underserved ; 21(3 Suppl): 132-47, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20675951

ABSTRACT

BACKGROUND/OBJECTIVES: Colorectal cancer (CRC) is the third cause of cancer deaths for African Americans. OBJECTIVES: 1) increase CRC knowledge, 2) decrease cancer fatalism, and 3) increase colonoscopy screening for CRC among African Americans in North Carolina. METHODS: Churches and community-based organizations were randomized into intervention and control groups. The intervention group received a 90-minute culturally targeted educational program on colorectal health. Pre-test and post-test questionnaires were completed by both groups. RESULTS: A total of 539 African American men and women 50 years of age and older participated in this study. The intervention group had a significantly greater proportion of those receiving a colonoscopy within three months after the educational session than the control group. In the intervention group, CRC knowledge significantly increased and cancer fatalism attitudes significantly decreased. CONCLUSIONS: A culturally targeted faith/community-based educational intervention can increase CRC knowledge, decrease cancer fatalism, and increase screening for CRC among African Americans.


Subject(s)
Black or African American/education , Colorectal Neoplasms/ethnology , Culture , Health Education/methods , Health Knowledge, Attitudes, Practice , Black or African American/psychology , Black or African American/statistics & numerical data , Colonoscopy/statistics & numerical data , Colorectal Neoplasms/psychology , Community-Based Participatory Research , Early Detection of Cancer , Female , Humans , Male , Middle Aged , North Carolina , Religion and Medicine , Surveys and Questionnaires
17.
Forensic Sci Med Pathol ; 6(1): 13-9, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20091145

ABSTRACT

Fifty-six cases of sudden death from myocarditis were reviewed to characterize the range of histologic appearances of myocarditis. All autopsy cases of myocarditis over 13 years (1996-2008) in the Toronto Forensic Pathology Unit, Ontario Forensic Pathology Service, were studied. In each case, historical documentation and histological slides were reviewed. The severity of myocarditis was graded qualitatively and quantitatively (the inflammatory index). We established the inflammatory index in order to classify the severity of myocarditis, by counting the mean number of inflammatory foci per section of myocardium. Based on the inflammatory index, myocardial inflammation was classified into four grades. Based on this classification, 47% of the cases were classified as marked myocarditis having an inflammatory index over 5, with the number of foci per slide varying from 3 to more than 10, while 20% were classified as mild myocarditis with an inflammatory index between 1.1 and 1.9 with the number of foci per slide varying from 0 to 6. The diagnosis of mild myocarditis is dependent on adequate sampling. We believe that the use of this inflammatory index enhances the post-mortem diagnostic sensitivity of myocarditis, especially in its mild form and correlates with qualitative assessment of the histologic severity of myocarditis.


Subject(s)
Death, Sudden , Myocarditis/mortality , Adolescent , Adult , Aged , Aged, 80 and over , Autopsy , Child , Documentation , Forensic Pathology/methods , Humans , Inflammation/pathology , Middle Aged , Muscle Cells/pathology , Myocarditis/epidemiology , Myocarditis/pathology , Ontario , Seasons , Severity of Illness Index
18.
Indian J Dermatol ; 55(4): 397-8, 2010 Oct.
Article in English | MEDLINE | ID: mdl-21430901

ABSTRACT

Glomus tumors are relatively rare vascular tumors with reported incidence of 1.6% of all soft tissue tumors. It is variously regarded as a hamartoma or a neoplasm of neuromyoarterial glomus, which consists of dilated vascular channels, surrounded by proliferating glomus, nerve cells, and plays an important role in temperature regulation. We report the case of glomangioma in a 43-year-old male who came to dermatology OPD with a painful lesion over the right elbow of six months duration. Cutaneous examination revealed a single round reddish blue papule of about 0.5 cm in size on the flexor aspect of the right elbow. The papule was firm in consistency and tender. The excision biopsy showed stratified squamous lining with well circumscribed tumor in the dermis. The tumor consisted of sheets of uniform cells with pale cytoplasm; round to ovoid centrally placed punched out nuclei and well defined cell margins. There were numerous dilated thin walled vascular spaces surrounded by a layer of tumor cells and the histopathology was consistent with glomangioma.

19.
Blood ; 114(19): 4233-42, 2009 Nov 05.
Article in English | MEDLINE | ID: mdl-19729518

ABSTRACT

The tightly regulated production of distinct erythrocyte protein 4.1R isoforms involves differential splicing of 3 mutually exclusive first exons (1A, 1B, 1C) to the alternative 3' splice sites (ss) of exon 2'/2. Here, we demonstrate that exon 1 and 2'/2 splicing diversity is regulated by a transcription-coupled splicing mechanism. We also implicate distinctive regulatory elements that promote the splicing of exon 1A to the distal 3' ss and exon 1B to the proximal 3' ss in murine erythroleukemia cells. A hybrid minigene driven by cytomegalovirus promoter mimicked 1B-promoter-driven splicing patterns but differed from 1A-promoter-driven splicing patterns, suggesting that promoter identity affects exon 2'/2 splicing. Furthermore, splicing factor SF2/ASF ultraviolet (UV) cross-linked to the exon 2'/2 junction CAGAGAA, a sequence that overlaps the distal U2AF(35)-binding 3' ss. Consequently, depletion of SF2/ASF allowed exon 1B to splice to the distal 3' ss but had no effect on exon 1A splicing. These findings identify for the first time that an SF2/ASF binding site also can serve as a 3' ss in a transcript-dependent manner. Taken together, our results suggest that 4.1R gene expression involves transcriptional regulation coupled with a complex splicing regulatory network.


Subject(s)
Alternative Splicing , Blood Proteins/genetics , Cytoskeletal Proteins/genetics , Membrane Proteins/genetics , 5' Untranslated Regions , Animals , Base Sequence , Binding Sites/genetics , Blood Proteins/biosynthesis , Cell Line , Cytoskeletal Proteins/biosynthesis , DNA Polymerase II/metabolism , DNA Primers/genetics , Exons , Humans , Leukemia, Erythroblastic, Acute/genetics , Leukemia, Erythroblastic, Acute/metabolism , Membrane Proteins/biosynthesis , Mice , Microfilament Proteins , Models, Genetic , Molecular Sequence Data , Nuclear Proteins/metabolism , Promoter Regions, Genetic , Protein Isoforms/biosynthesis , Protein Isoforms/genetics , RNA-Binding Proteins/metabolism , Ribonucleoproteins/metabolism , Serine-Arginine Splicing Factors , Splicing Factor U2AF , Tissue Distribution , Transcription, Genetic , Transcriptional Activation , Tumor Cells, Cultured
20.
J Pediatr Surg ; 44(5): 1044-6, 2009 May.
Article in English | MEDLINE | ID: mdl-19433196

ABSTRACT

We report a case of type I tracheal agenesis with vertebral defects, anal atresia, tracheoesophageal fistula and/or esophageal atresia, radial dysplasia, renal defects, and cardiovascular defects association in which computed tomography was helpful in categorizing the diagnosis. This rare and fatal condition should always be considered when confronted with a neonate impossible to resuscitate at birth.


Subject(s)
Tomography, X-Ray Computed , Trachea/abnormalities , Abnormalities, Multiple , Anus, Imperforate , Diseases in Twins , Fatal Outcome , Female , Heart Defects, Congenital , Humans , Hypoplastic Left Heart Syndrome , Infant, Newborn , Intubation, Intratracheal , Polyhydramnios , Pregnancy , Trachea/diagnostic imaging
SELECTION OF CITATIONS
SEARCH DETAIL