Publications by authors named "Mohammad S Khan"

48 Publications

HVD-LSTM based recognition of epileptic seizures and normal human activity.

Comput Biol Med 2021 Sep 27;136:104684. Epub 2021 Jul 27.

Faculty of Engineering and Information Technology, University of Technology Sydney, Ultimo, NSW, 2007, Australia. Electronic address:

In this paper, we detect the occurrence of epileptic seizures in patients as well as activities namely stand, walk, and exercise in healthy persons, leveraging EEG (electroencephalogram) signals. Using Hilbert vibration decomposition (HVD) on non-linear and non-stationary EEG signal, we obtain multiple monocomponents varying in terms of amplitude and frequency. After decomposition, we extract features from the monocomponent matrix of the EEG signals. The instantaneous amplitude of the HVD monocomponents varies because of the motion artifacts present in EEG signals. Hence, the acquired statistical features from the instantaneous amplitude help in identifying the epileptic seizures and the normal human activities. The features selected by correlation-based Q-score are classified using an LSTM (Long Short Term Memory) based deep learning model in which the feature-based weight update maximizes the classification accuracy. For epilepsy diagnosis using the Bonn dataset and activity recognition leveraging our Sensor Networks Research Lab (SNRL) data, we achieve testing classification accuracies of 96.00% and 83.30% respectively through our proposed method.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104684DOI Listing
September 2021

Type-2 Diabetes as a Risk Factor for Severe COVID-19 Infection.

Microorganisms 2021 Jun 3;9(6). Epub 2021 Jun 3.

Department of Pathology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.

The current outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), termed coronavirus disease 2019 (COVID-19), has generated a notable challenge for diabetic patients. Overall, people with diabetes have a higher risk of developing different infectious diseases and demonstrate increased mortality. Type 2 diabetes mellitus (T2DM) is a significant risk factor for COVID-19 progression and its severity, poor prognosis, and increased mortality. How diabetes contributes to COVID-19 severity is unclear; however, it may be correlated with the effects of hyperglycemia on systemic inflammatory responses and immune system dysfunction. Using the envelope spike glycoprotein SARS-CoV-2, COVID-19 binds to angiotensin-converting enzyme 2 (ACE2) receptors, a key protein expressed in metabolic organs and tissues such as pancreatic islets. Therefore, it has been suggested that diabetic patients are more susceptible to severe SARS-CoV-2 infections, as glucose metabolism impairments complicate the pathophysiology of COVID-19 disease in these patients. In this review, we provide insight into the COVID-19 disease complications relevant to diabetes and try to focus on the present data and growing concepts surrounding SARS-CoV-2 infections in T2DM patients.
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http://dx.doi.org/10.3390/microorganisms9061211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229474PMC
June 2021

Author's reply.

J Family Community Med 2021 May-Aug;28(2):141. Epub 2021 May 8.

Department of Restorative Dentistry, College of Dentistry, Umm Al-Qura University, Makkah, Saudi Arabia.

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http://dx.doi.org/10.4103/2230-8229.315732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213100PMC
May 2021

Proceedings of the North American Society of Head and Neck Pathology, Baltimore, MD, March 17, 2021: The Mistakes I Made When I Stepped Out of My Neck of the Woods.

Head Neck Pathol 2021 Mar 15;15(1):113-119. Epub 2021 Mar 15.

Department of Pathology, Yale School of Medicine, New Haven, CT, 06510, USA.

Rapidly growing, symptomatic, non-hematological, malignant neck masses are unusual in young adults. We report a case of a 34-year-old African American male with sickle cell trait who presented with a large left supraclavicular/cervical mass comprising of poorly differentiated malignant epithelial cells consistent with metastatic carcinoma of unknown origin. Upon immunohistochemistry, the tumor showed loss of INI1 (BAF47) and retained PAX-8 expression. After extensive clinical and radiological work-up the primary tumor was found to be a 2.6 cm renal medullary carcinoma. This case highlights the role of multidisciplinary approach to the diagnosis of a neck mass and to understanding that certain genetically-defined tumors can occur at and metastasize to any site.
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http://dx.doi.org/10.1007/s12105-021-01296-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010038PMC
March 2021

Breath can discriminate tuberculosis from other lower respiratory illness in children.

Sci Rep 2021 Feb 1;11(1):2704. Epub 2021 Feb 1.

Thayer School of Engineering, Dartmouth College, Hanover, NH, USA.

Pediatric tuberculosis (TB) remains a global health crisis. Despite progress, pediatric patients remain difficult to diagnose, with approximately half of all childhood TB patients lacking bacterial confirmation. In this pilot study (n = 31), we identify a 4-compound breathprint and subsequent machine learning model that accurately classifies children with confirmed TB (n = 10) from children with another lower respiratory tract infection (LRTI) (n = 10) with a sensitivity of 80% and specificity of 100% observed across cross validation folds. Importantly, we demonstrate that the breathprint identified an additional nine of eleven patients who had unconfirmed clinical TB and whose symptoms improved while treated for TB. While more work is necessary to validate the utility of using patient breath to diagnose pediatric TB, it shows promise as a triage instrument or paired as part of an aggregate diagnostic scheme.
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http://dx.doi.org/10.1038/s41598-021-80970-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851130PMC
February 2021

Application of the Kano model to determine quality attributes of patient's care at the primary healthcare centers of the Ministry of Health in Saudi Arabia, 2019.

J Family Community Med 2020 Sep-Dec;27(3):178-185. Epub 2020 Sep 25.

Department of Restorative Dentistry, College of Dentistry, Umm Al-Qura University, Makkah, Saudi Arabia.

Background: Patient satisfaction is the ultimate goal in any healthcare system. Together with other traditional quality indicators, patient satisfaction must be addressed to improve the quality of health care. The strategic objectives of the Ministry of Health (MOH) formulated by the Saudi National Transformation Program are to improve the quality of healthcare services, expand privatization of governmental services, and create an attractive environment for both local and international investors. The objective of this study was to apply Kano model to determine quality attributes of patient care at primary healthcare centers in Saudi Arabia.

Materials And Methods: This cross-sectional study was conducted at primary healthcare centers (PHCs) under the MOH in Saudi Arabia between October 2018 and February 2019. Study included all Saudi adult patients aged 18 years or older attending the selected PHCs of MOH. Patients who had difficulty in comprehending were excluded. Data was collected by using a structured questionnaire based on the Kano model for the assessment of patients' expectations of the quality of care and provided services. Data was entered and analysed using SPSS. Chi-square test and -test were used to test for statistical significance.

Results: The study included a total of 243 patients from 10 PHCs, 51% from consulting PHCs and 49% from nonconsulting PHCs. Response rate was 97.2%, and 44.9% respondents were males. Of the 18 attributes chosen for our study, 14 were one-dimensional, three belonged to the attractive type, and one was indifferent type. The top three one-dimensional attributes were "friendliness and respectfulness of the clinic receptionist," "friendliness and respectfulness of the nurses and laboratory staff," and "care and attention of the doctor".

Conclusion: The investors and policymakers need to turn their attention to assisting in the privatization of governmental services by creating a good climate for both local and international investors.
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http://dx.doi.org/10.4103/jfcm.JFCM_92_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745778PMC
September 2020

Tele-education for hepatology residents in Bangladesh during the Covid-19 pandemic.

J Family Med Prim Care 2020 Aug 25;9(8):4476-4477. Epub 2020 Aug 25.

Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan.

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http://dx.doi.org/10.4103/jfmpc.jfmpc_1001_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586574PMC
August 2020

Computed Tomography Scan Overestimates the Size of Pericardial Effusion Compared to Echocardiography.

Cureus 2019 Jul 20;11(7):e5182. Epub 2019 Jul 20.

Cardiology, University of Toledo Medical Center, Toledo, USA.

Objective:  Pericardial effusion is not an uncommon finding in hospitalized patients. Many pericardial effusions are found incidentally through computed tomography (CT) performed for other indications. Echocardiography is usually ordered when an incidentally discovered pericardial effusion is found on the CT to examine the effect of the effusion on hemodynamics and to detect early signs of tamponade. However, in clinical practice, the discrepancy between CT and echocardiography regarding the size of pericardial effusions is common. The accuracy of CT in the evaluation of the size of pericardial effusions is not well-studied. Our study aims to evaluate the accuracy of CT in assessing the size of a pericardial effusion compared with the gold standard echocardiography.

Methods:  This is a retrospective study examining patients presenting to the University of Toledo Medical Center (UTMC) with pericardial effusions. One hundred and forty-one patient charts were reviewed and 45 subjects were excluded. Ninety-six patients in whom both CT and echocardiography were performed were enrolled in the final analysis. The time interval between both imaging modalities was limited to less than 14 days and no interventions on the effusion (e.g., pericardiocentesis) occurred in the time interval between the two imaging modalities.

Results:  The size of the pericardial effusion was assessed similarly between CT and echocardiography in 50% of the cases (48/96). In the other half of the study population, the results were discrepant; CT was found to overestimate the size of pericardial effusion in 44% of the cases (42/96). The agreement rate between the two modalities is significantly low kappa = 0.111, P = 0.028. The independent variables age, gender, body mass index (BMI), use of anticoagulants, and renal function had no effect on the agreement between CT and echocardiography.

Conclusion:  Computerized tomography tends to overestimate the size of the pericardial effusion compared to echocardiography. Based on an incidental finding of pericardial effusion on CT scan, this discrepancy should be recognized prior to ordering an echocardiogram. Echocardiography can be considered in relevant clinical settings.
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http://dx.doi.org/10.7759/cureus.5182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6758974PMC
July 2019

Pulmonary capillary hemangiomatosis: a lesson learned.

Autops Case Rep 2019 Jul-Sep;9(3):e2019111. Epub 2019 Aug 22.

Cedars Sinai Medical Center, Departments of Pathology & Radiology. Los Angeles, CA, United States of America.

Pulmonary capillary hemangiomatosis (PCH) is a rare and controversial entity that is known to be a cause of pulmonary hypertension and is microscopically characterized by proliferation of dilated capillary-sized channels along and in the alveolar walls. Clinically, it is mostly seen in adults. Clinical features are characterized by nonspecific findings such as shortness of breath, cough, chest pain, and fatigue. It can be clinically indistinguishable from pre-capillary pulmonary arterial hypertension disorders such as primary pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension. However, the diagnostic distinction, which usually requires a multidisciplinary approach, is crucial in order to avoid inappropriate treatment with vasodilator medications usually used for PAH treatment. Prognosis of PCH remains poor with lung transplant being the only definitive treatment. We report an autopsy case of pulmonary capillary hemangiomatosis unmasked at autopsy that was treated with a prostacyclin analog, usually contraindicated in such patients. We emphasize that this entity should always be on the differential diagnosis in a patient with pulmonary hypertension and requires great vigilance on the part of the clinician, radiologist and pathologist to make the diagnosis and guide appropriate management.
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http://dx.doi.org/10.4322/acr.2019.111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6709648PMC
August 2019

Critical Care Utilization in Patients with Diabetic Ketoacidosis, Stroke, and Gastrointestinal Bleed: Two Hospitals Experience.

Cureus 2019 May 21;11(5):e4698. Epub 2019 May 21.

Internal Medicine, Good Samaritan Hospital, Cincinnati, USA.

Introduction: Intensive Care Units (ICUs) are among the most expensive components of hospital care. Experts believe that ICUs are overused; however, hospitals vary in their ICU admission rate. Our hypothesis is based on clinical observations that many patients with diabetic ketoacidosis (DKA), stroke, and gastrointestinal (GI) bleeding admitted to the ICU don't really need it and could be managed safely in a non-ICU level of care. Reducing inappropriate admissions would reduce healthcare costs and improve outcomes. Our primary objective was to determine the frequency of inappropriate ICU admissions. Secondary objectives were to evaluate which diagnoses were more unnecessarily admitted to the ICU, evaluate different variables and comorbidities, and determine the mortality rates during ICU admissions.

Methods:  Patients admitted to the ICU, from the Emergency Department (ED) or transferred from the floor, during a one-year period were evaluated in this retrospective study. Patients 18-years old and above who had an admitting diagnosis of DKA, GI bleed, ischemic stroke, or hemorrhagic stroke were included. Patients in a comatose state, intubated, on vasopressors, hemodynamically unstable or had an unstable comorbid disease, subarachnoid hemorrhage, surgery during hospitalization prior to the ICU admission were excluded. Patients were categorized as having an appropriate or inappropriate ICU admission based on our institutional ICU admission criteria and data from available literature and guidelines.

Results: A total of 95 patients were included in our cohort. Seventy-two out of 95 (76%) were considered as inappropriate ICU admissions. When comparing each of the four admitting diagnoses, a significantly higher proportion of DKA patients were considered inappropriate ICU admissions when compared to the other diagnoses ( = 0.001). The overall mortality rate of ICU admissions was 16%, 15 patients out of 95 study population. When comparing each of the four admitting diagnoses, there was a significant difference in mortality rate with DKA having the lowest mortality (3%) and GI bleed having the highest mortality (43%). Out of the 15 patients who died, only 1 patient was categorized as an inappropriate ICU admission.

Conclusions:  More than three-quarters of our study population was admitted to the ICU inappropriately. Incorporating severity scores in ICU admission criteria could improve the appropriateness of ICU admission and financial feasibility. This article is based on a poster: Alsamman S, Alsamman MA, Castro M, Koselka H, Steinbrunner J: ICU admission patterns in patients with DKA, stroke and GI bleed: do they all need ICU? J Hosp Med. March 2015.
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http://dx.doi.org/10.7759/cureus.4698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6649872PMC
May 2019

Trends in Incidence and Outcomes of Clostridium difficile Colitis in Hospitalized Patients of Febrile Neutropenia: A Nationwide Analysis.

J Clin Gastroenterol 2019 10;53(9):e376-e381

Gastroenterology & Hepatology, University of Toledo Medical Center, Toledo, OH.

Introduction: Clostridium difficile infection (CDI) has been attracting attention lately as the most common hospital acquired infection. Patients with neutropenia because of malignancy seem to be at an increased risk for developing CDI. There is currently limited data that assesses the national burden and outcomes of CDI in Febrile Neutropenia (FN).

Methods: We analyzed the National Inpatient Sample (NIS) database for all subjects with discharge diagnosis of FN with or without CDI (ICD-9 codes 288.00, 288.03,780.60, and 008.45) as primary or secondary diagnosis during the period from 2008 to 2014. All analyses were performed with SAS, version 9.4 (SAS Institute).

Results: From 2008 to 2014 there were total 19422 discharges of FN patients with CDI. There was a rising incidence of CDI in patients with FN from 4.11% (in 2008) to 5.83% (in 2014). The In-hospital mortality showed a decreasing trend from 7.79% (in 2008) to 5.32% (in 2014), likely because of improvements in diagnostics and treatment. The overall mortality (6.37% vs. 4.61%), length of stay >5 days (76.45% vs. 50.98%), hospital charges >50,000 dollars (64.43% vs. 40.29%), colectomy and colostomy (0.35% vs. 0.15%), and discharge to skilled nursing facility (10.47% vs. 6.43%) was significantly more in FN patients with CDI versus without CDI over 7 years (2008 to 2014). Age above 65 years, Hispanic race, hematological malignancies, urban hospital settings, and sepsis were significant predictors of mortality in febrile neutropenia patients with CDI.

Discussion: Despite the significant decrease in mortality, the incidence of CDI is rising in hospitalized FN patients with underlying hematological malignancies. Risk factor modification, with the best possible empiric antibiotic regimen is imperative for reducing mortality and health care costs in this cohort.
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http://dx.doi.org/10.1097/MCG.0000000000001171DOI Listing
October 2019

Outer Membrane Vesicle Vaccines from Biosafe Surrogates Prevent Acute Lethal Glanders in Mice.

Vaccines (Basel) 2018 Jan 10;6(1). Epub 2018 Jan 10.

Department of Infectious Diseases and Immunology, College of Veterinary Medicine; University of Florida, Gainesville, FL 32608, USA.

is a host-adapted Gram-negative mammalian pathogen that causes the severe disease glanders. Glanders can manifest as a rapid acute progression or a chronic debilitating syndrome primarily affecting solipeds and humans in close association with infected animals. In USA, is classified as one of the most important bacterial biothreat agents. Presently, there is no licensed glanders vaccine available for humans or animals. In this work, outer membrane vesicles (OMVs) were isolated from three attenuated biosafe bacterial strains, Bp82, E555, and TxDOH and used to vaccinate mice. OMVs induced significantly higher antibody responses that were investigated. specific serum antibody responses were of higher magnitude in mice vaccinated with OMVs compared to levels in mice vaccinated with OMVs. OMVs derived from biosafe strains protected mice from acute lethal glanders with vesicles from the two strains affording significant protection (>90%) up to 35 days post-infection with some up to 60 days. Organ loads from 35-day survivors indicated bacteria colonization of the lungs, liver, and spleen while those from 60 days had high CFUs in the spleens. The highest antibody producing vaccine ( E555 OMVs) also protected C57BL/6 mice from acute inhalational glanders with evidence of full protection.
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http://dx.doi.org/10.3390/vaccines6010005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5874646PMC
January 2018

Onion Peel Ethylacetate Fraction and Its Derived Constituent Quercetin 4'--β-D Glucopyranoside Attenuates Quorum Sensing Regulated Virulence and Biofilm Formation.

Front Microbiol 2017 5;8:1675. Epub 2017 Sep 5.

Department of Food Science and Nutrition, Faculty of Food and Agricultural Sciences, King Saud UniversityRiyadh, Saudi Arabia.

The resistance and pathogenesis of bacteria could be related to their ability to sense and respond to population density, termed quorum sensing (QS). Inhibition of the QS system is considered as a novel strategy for the development of antipathogenic agents, especially for combating drug-resistant bacterial infections. In the present study, the anti-QS activity of Onion peel ethylacetate fraction (ONE) was tested against CV12472 and PAO1. ONE inhibit the QS-mediated virulence factors production such as violacein in and elastase, pyocyanin in . Further, the treatment with sub-MICs of ONE significantly inhibited the QS-mediated biofilm formation, EPS (Extracellular polymeric substances) production and swarming motility. Further, quercetin 4'--β-D glucopyranoside (QGP) was isolated from ONE and its anti-QS potential was confirmed after observing significant inhibition of QS-controlled virulence factors such as violacein, elastase, pyocyanin and biofilm formation in test pathogens. Molecular docking analysis predicted that QGP should be able to bind at the active sites of Vfr and LasR, and if so blocks the entry of active sites in Vfr and LasR.
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http://dx.doi.org/10.3389/fmicb.2017.01675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5591837PMC
September 2017

Alveolar Soft Part Sarcoma with Unusual Cardiac Metastasis: A Case Report and Review of the Literature.

Case Rep Cardiol 2017 6;2017:7248727. Epub 2017 Aug 6.

Department of Internal Medicine, University of Toledo Medical Center, 3000 Arlington Avenue, MS 1150, Toledo, OH 43614, USA.

Alveolar soft part sarcoma is a very uncommon soft tissue malignancy which accounts for <1% of soft tissue sarcoma. It is a malignant and highly vascular tumor arising most commonly in the musculature of the lower extremities, with metastasis primarily to the lungs, bones, and brain. Cardiac metastasis is very rare and only 5 cases have been reported in the literature so far. We report a case of a young woman with a history of surgically resected alveolar soft part sarcoma of left thigh who presented with persistent dry cough and was found to have a cardiac mass, which on biopsy proved to be alveolar soft part sarcoma.
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http://dx.doi.org/10.1155/2017/7248727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5563395PMC
August 2017

Impact of Transgenic Harboring the Antifungal Synthetic Chitinase (NiC) Gene on Rhizosphere Microbial Diversity and Enzyme Activities.

Front Plant Sci 2017 25;8:1307. Epub 2017 Jul 25.

Genomics and Bioinformatics Laboratory, Institute of Biotechnology and Genetic Engineering (IBGE), Faculty of Crop Production Sciences, University of AgriculturePeshawar, Pakistan.

Transgenic harboring the synthetic chitinase () gene exhibits broad-spectrum antifungal resistance. As the rhizosphere microorganisms play an important role in element cycling and nutrient transformation, therefore, biosafety assessment of containing transgenic plants on soil ecosystem is a regulatory requirement. The current study is designed to evaluate the impact of gene on the rhizosphere enzyme activities and microbial community structure. The transgenic lines with the synthetic chitinase gene () showed resistance to , a common disease causing fungal pathogen. The rhizosphere enzyme analysis showed no significant difference in the activities of fivesoil enzymes: alkalyine phosphomonoestarase, arylsulphatase, β-glucosidase, urease and sucrase between the transgenic and non-transgenic lines of varieties, Durr-e-NIFA (DN) and Abasyne-95 (AB-95). However, varietal differences were observed based on the analysis of molecular variance. Some individual enzymes were significantly different in the transgenic lines from those of non-transgenic but the results were not reproducible in the second trail and thus were considered as environmental effect. Genotypic diversity of soil microbes through 16S-23S rRNA intergenic spacer region amplification was conducted to evaluate the potential impact of the transgene. No significant diversity (4% for bacteria and 12% for fungal) between soil microbes of and the non-transgenic lines was found. However, significant varietal differences were observed between DN and AB-95 with 79% for bacterial and 54% for fungal diversity. We conclude that the lines may not affect the microbial enzyme activities and community structure of the rhizosphere soil. Varietal differences might be responsible for minor changes in the tested parameters.
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http://dx.doi.org/10.3389/fpls.2017.01307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5524829PMC
July 2017

Development of a patient and institutional-based model for estimation of operative times for robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium.

BJU Int 2017 11 16;120(5):695-701. Epub 2017 Jul 16.

School of Medicine, Ankara Ataturk Training and Research Hospital, Yildirim Beyazit University, Ankara, Turkey.

Objectives: To design a methodology to predict operative times for robot-assisted radical cystectomy (RARC) based on variation in institutional, patient, and disease characteristics to help in operating room scheduling and quality control.

Patients And Methods: The model included preoperative variables and therefore can be used for prediction of surgical times: institutional volume, age, gender, body mass index, American Society of Anesthesiologists score, history of prior surgery and radiation, clinical stage, neoadjuvant chemotherapy, type, technique of diversion, and the extent of lymph node dissection. A conditional inference tree method was used to fit a binary decision tree predicting operative time. Permutation tests were performed to determine the variables having the strongest association with surgical time. The data were split at the value of this variable resulting in the largest difference in means for the surgical time across the split. This process was repeated recursively on the resultant data sets until the permutation tests showed no significant association with operative time.

Results: In all, 2 134 procedures were included. The variable most strongly associated with surgical time was type of diversion, with ileal conduits being 70 min shorter (P < 0.001). Amongst patients who received neobladders, the type of lymph node dissection was also strongly associated with surgical time. Amongst ileal conduit patients, institutional surgeon volume (>66 RARCs) was important, with those with a higher volume being 55 min shorter (P < 0.001). The regression tree output was in the form of box plots that show the median and ranges of surgical times according to the patient, disease, and institutional characteristics.

Conclusion: We developed a method to estimate operative times for RARC based on patient, disease, and institutional metrics that can help operating room scheduling for RARC.
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http://dx.doi.org/10.1111/bju.13934DOI Listing
November 2017

Glycation Induced Generation of Amyloid Fibril Structures by Glucose Metabolites.

Protein Pept Lett 2016 ;23(10):892-897

Department of Biochemistry, College of Science, King Saud University, KSA.

The non-enzymatic reaction (glycation) of reducing sugars with proteins has received increased interest in dietary and therapeutic research lately. In the present work, the impact of glycation on structural alterations of camel serum albumin (CSA) by different glucose metabolites was studied. Glycation of CSA was evaluated by specific fluorescence of advanced glycation end-products (AGEs) and determination of available amino groups. Further, conformational changes in CSA during glycation were also studied using 8-analino 1-nephthlene sulfonic acid (ANS) binding assay, circular dichroism (CD) and thermal analysis. Intrinsic fluorescence measurement of CSA showed a 22 nm red shift after methylglyoxal treatment, suggesting glycation induced denaturation of CSA. Rayleigh scattering analysis showed glycation induced turbidity and aggregation in CSA. Furthermore, ANS binding to native and glycated-CSA reflected perturbation in the environment of hydrophobic residues. However, CD spectra did not reveal any significant modifications in the secondary structure of the glycated-CSA. Thioflavin T (ThT) fluorescence of CSA increased after glycation, illustrated cross β-structure and amyloid formation. Transmission electron microscopy (TEM) analysis further reaffirms the formation of aggregate and amyloid. In summary, glucose metabolites induced conformational changes in CSA and produced aggregate and amyloid structures.
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http://dx.doi.org/10.2174/0929866523666160831153858DOI Listing
February 2017

Assessing Utilization and Environmental Risks of Important Genes in Plant Abiotic Stress Tolerance.

Front Plant Sci 2016 24;7:792. Epub 2016 Jun 24.

Faculty of Crop Production Sciences, Institute of Biotechnology and Genetic Engineering, The University of Agriculture, Peshawar Pakistan.

Transgenic plants with improved salt and drought stress tolerance have been developed with a large number of abiotic stress-related genes. Among these, the most extensively used genes are the glycine betaine biosynthetic codA, the DREB transcription factors, and vacuolar membrane Na(+)/H(+) antiporters. The use of codA, DREBs, and Na(+)/H(+) antiporters in transgenic plants has conferred stress tolerance and improved plant phenotype. However, the future deployment and commercialization of these plants depend on their safety to the environment. Addressing environmental risk assessment is challenging since mechanisms governing abiotic stress tolerance are much more complex than that of insect resistance and herbicide tolerance traits, which have been considered to date. Therefore, questions arise, whether abiotic stress tolerance genes need additional considerations and new measurements in risk assessment and, whether these genes would have effects on weediness and invasiveness potential of transgenic plants? While considering these concerns, the environmental risk assessment of abiotic stress tolerance genes would need to focus on the magnitude of stress tolerance, plant phenotype and characteristics of the potential receiving environment. In the present review, we discuss environmental concerns and likelihood of concerns associated with the use of abiotic stress tolerance genes. Based on our analysis, we conclude that the uses of these genes in domesticated crop plants are safe for the environment. Risk assessment, however, should be carefully conducted on biofeedstocks and perennial plants taking into account plant phenotype and the potential receiving environment.
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http://dx.doi.org/10.3389/fpls.2016.00792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4919908PMC
July 2016

Sub-MICs of Mentha piperita essential oil and menthol inhibits AHL mediated quorum sensing and biofilm of Gram-negative bacteria.

Front Microbiol 2015 13;6:420. Epub 2015 May 13.

Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University Riyadh, Saudi Arabia.

Bacterial quorum sensing (QS) is a density dependent communication system that regulates the expression of certain genes including production of virulence factors in many pathogens. Bioactive plant extract/compounds inhibiting QS regulated gene expression may be a potential candidate as antipathogenic drug. In this study anti-QS activity of peppermint (Mentha piperita) oil was first tested using the Chromobacterium violaceum CVO26 biosensor. Further, the findings of the present investigation revealed that peppermint oil (PMO) at sub-Minimum Inhibitory Concentrations (sub-MICs) strongly interfered with acyl homoserine lactone (AHL) regulated virulence factors and biofilm formation in Pseudomonas aeruginosa and Aeromonas hydrophila. The result of molecular docking analysis attributed the QS inhibitory activity exhibited by PMO to menthol. Assessment of ability of menthol to interfere with QS systems of various Gram-negative pathogens comprising diverse AHL molecules revealed that it reduced the AHL dependent production of violacein, virulence factors, and biofilm formation indicating broad-spectrum anti-QS activity. Using two Escherichia coli biosensors, MG4/pKDT17 and pEAL08-2, we also confirmed that menthol inhibited both the las and pqs QS systems. Further, findings of the in vivo studies with menthol on nematode model Caenorhabditis elegans showed significantly enhanced survival of the nematode. Our data identified menthol as a novel broad spectrum QS inhibitor.
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http://dx.doi.org/10.3389/fmicb.2015.00420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4429619PMC
June 2015

A single genotype of Acinetobacter baumannii expresses multiple antibiotic susceptibility phenotypes.

Am J Infect Control 2014 May;42(5):556-8

Division of Infectious Diseases, University of Louisville School of Medicine, Louisville, KY.

It is common practice to define a bacterium with unequal antibiotic susceptibility phenotypes as a different genotype. Here, we describe the utility of this practice for Acinetobacter baumannii. We determined antibiotic susceptibility for 19 clinical isolates of A baumannii. Repetitive sequence polymerase chain reaction method was used to determine genotypes. Although all isolates were of the same genotype, 79% were predicted to be different based on susceptibility patterns. The antibiotic susceptibility phenotype does not accurately predict the genotype of A baumannii.
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http://dx.doi.org/10.1016/j.ajic.2014.01.003DOI Listing
May 2014

Comparative study of non-high density lipoproteins cholesterol level and lipid profile in pre-diabetic and diabetic patients.

CNS Neurol Disord Drug Targets 2014 Apr;13(3):402-7

King Fahd Medical Research Centre, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Kingdom of Saudi Arabia.

Objectives: The present study compares the role and significance of non-high density lipoproteins (non-HDL) cholesterol level in pre-diabetic and diabetic patients. This study also compares non-HDL cholesterol level between males and females and with different age groups as well.

Methods: An observational study was conducted among 3830 randomly selected individuals to envisage the association of non-HDL cholesterol and other lipid parameters with age, gender, and diabetic status. On the basis of health status, the subjects were classified as diabetic, pre-diabetic and normal. Fasting blood samples were collected and analyzed on Roche p-800 modular system. Total cholesterol, high density lipoproteins (HDL), low density lipoproteins (LDL) and fasting triglycerides were also measured. From the above mentioned parameters, the level of non-HDL cholesterol level was also calculated.

Results: Significant association was observed with non-HDL cholesterol level and all other studied lipid parameters (total cholesterol, HDL, LDL and triglycerides) compared with age and gender of the subjects studied. Moreover, the calculated non-HDL level, total cholesterol and triglycerides were found to be significantly co-related with diabetic status of the patients involved in the study. However, HDL and LDL values did not show any significant association with diabetic status of the patients.

Conclusion: In this study, we found that age and gender of the studied subjects are associated with non-HDL cholesterol. Moreover, our data clearly indicates the positive association of non-HDL cholesterol level with pre-diabetic and diabetic status of the patients. Based on our study, we recommend estimation of non-HDL level in routine clinical practice to differentiate pre-diabetic and diabetic patients.
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http://dx.doi.org/10.2174/18715273113126660150DOI Listing
April 2014

Evaluation of robotic and laparoscopic partial nephrectomy for small renal tumours (T1a).

BJU Int 2013 Aug 11;112(4):E322-33. Epub 2013 Mar 11.

MRC Centre for Transplantation, King's College London, King's Health Partners, Hospital, London, UK.

Objective: To compare laparoscopic partial nephrectomy (LPN) with robotic PN (RPN) using meta-analytical techniques, since there has been a rise in the incidence of small renal masses (SRM; <4 cm) minimally invasive approaches are becoming more popular in dealing with such pathologies.

Materials And Methods: A systematic review of the literature was performed to identify studies comparing LPN and RPN. Comparative studies evaluating RPN and LPN that fulfilled the inclusion criteria were selected. Data on preoperative, operative (operative time, estimated blood loss [EBL], and warm ischaemia time [WIT]), postoperative (length of stay [LOS]) variables and complications were collected. A meta-analysis using random effect model was performed. A further Bland-Altman analysis of some of the operative variables was done to compare their reproducibility and mean difference in techniques.

Results: Six studies matched the selection criteria. In all, 256 patients were analysed (40% RPN and 60% LPN). There was no significant different in EBL (P = 0.12, 95% confidence interval [CI] -12.01 to 104.26). Similarly, there was no significant different in WIT between the groups (P = 0.23, 95% CI -15.22 to 3.70). Also, LOS (P = 0.22, 95% CI -0.38 to 0.09) and overall postoperative complication rates were not significantly different between the groups (P = 0.84, 95% CI -0.05 to 0.06).

Conclusions: Despite multiple studies reporting better perioperative variables for RPN, the present study found no significant differences between RPN and LPN. This has implications for both the surgeon and the patient. Lack of randomised controlled trials in addition to a lack of long-term oncological data for RPN are current limitations.
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http://dx.doi.org/10.1111/bju.12053DOI Listing
August 2013

Nerve growth factor (NGF): a potential urinary biomarker for overactive bladder syndrome (OAB)?

BJU Int 2013 Mar;111(3):372-80

Department of Uro-Neurology, National Hospital for Neurology and Neurosurgery, UCL Institute of Neurology, London, UK.

Unlabelled: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The search for a biomarker in overactive bladder syndrome (OAB) is an emerging field of interest, as bladder dysfunction is a common complaint that causes significant morbidity. A biomarker may give us insight as a diagnostic tool, and also inform us about how severe the condition is, how it may progress and how it may best be treated. The protein of interest here is nerve growth factor (NGF) and it has been shown to be a dynamic molecule in the bladder of patients with OAB. Urinary levels have been seen to rise in patients with OAB and fall in those who respond to treatment. However, there have also been many studies that examine this trend in numerous other conditions, e.g. interstitial cystitis, bladder outflow obstruction, renal stone disease and patients with neurological impairment after stroke. As a result the specificity of this as a potential urinary biomarker for OAB is questioned. This is a review of published studies, which discusses the pros and cons of NGF as a potential urinary biomarker. The evidence is examined and the studies are summarised together in a Table. Questions remain about the reliability, practicality and specificity of NGF as a biomarker for OAB. These questions need to be addressed by further studies that could clarify the points raised.

Objective: To review the current literature on the use of urinary nerve growth factor (NGF) as a potential biomarker for overactive bladder syndrome (OAB).

Method: A comprehensive electronic literature search was conducted using the PubMed database to identify publications relating to urinary NGF.

Results: There are a growing number of publications that have measured urinary NGF levels in different types of bladder dysfunction. These range from OAB, bladder pain syndrome, idiopathic and neurogenic detrusor overactivity, bladder oversensitivity and bladder outflow obstruction. Urinary NGF levels do appear to be raised in these pathological states when compared with healthy control samples. In patients with OAB, these raised urinary NGF levels appear to also reduce after successful treatment with antimuscarinics and botulinum toxin A, which indicates a potential use in monitoring responses to treatment. However, raised levels are not limited to OAB, which questions its specificity. Urinary NGF measurements are performed with an enzyme-linked immunosorbent assay using polyclonal antibodies to NGF. The technique requires standardisation, and the different antibodies to NGF require validating. Also a definition of what is the 'normal' range of NGF in urine is still required before it can be used as a diagnostic and prognostic tool.

Conclusions: Whilst the evidence for an increased urinary NGF in OAB appears convincing, many questions about its validity remain including: specificity, sensitivity, cost- and time-effectiveness. Many criteria for what constitutes a biomarker still need to be evaluated and met before this molecule can be considered for this role.
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http://dx.doi.org/10.1111/j.1464-410X.2012.11672.xDOI Listing
March 2013

Association between Pus Cells and Semen Parameters in Infertile Pakistani Males.

Sultan Qaboos Univ Med J 2012 Nov 20;12(4):479-84. Epub 2012 Nov 20.

Department of Biochemistry, Bannu Medical College, Khyber Pakhtunkhwa, Pakistan;

Objectives: This study evaluated the association between pus cells and semen parameters in infertile Pakistani males.

Methods: A cross-sectional descriptive study was carried out in the Department of Reproductive Physiology/Health, National Institute of Health, Islamabad, Pakistan, from 2004 to 2009. A total of 1,521 subjects were analysed, along with 97 proven fathers as controls.

Results: The mean of pus cells was 7.43 ± 0.43, 4.35 ± 0.34, and 4.26 ± 0.17 per high field in teratozoospermic, oligoasthenozoospermic, and asthenozoospermic groups, respectively, while it was 3.25 ± 0.26, 3.10 ± 0.19, and 2.98 ± 0.04 per high field in azoospermic, oligozoospermic and the proven father groups, respectively. The fewest pus cells were observed among proven fathers, which varied non-significantly (P >0.05) with all cases, except with teratozoospermic, oligozoospermic, and oligoasthenozoospermic cases. Pus cells showed an inverse relationship to sperm motility and count, except in azoospemia cases. Similarly, the fewest pus cells were observed among groups where normal forms where significantly more frequent (P <0.05). More pus cells were observed in cases where motility, and concentration or morphology was compromised. Similarly, low pus cell counts were seen in cases where sperm had the fewest head and neck defects. All kinds of sperm defects varied non-significantly (P >0.05) between proven fathers and normal concentration cases.

Conclusion: High pus cell counts were observed in various subclasses of infertile patients. Ignorance of this pyospermic factor will make pyospermic patients to be misdiagnosed as normozoospermic. Therefore, the presence of pyospermia must be considered by physicians as a male infertility factor.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3523998PMC
http://dx.doi.org/10.12816/0003174DOI Listing
November 2012

Antimicrobial activity of metal oxide nanoparticles against Gram-positive and Gram-negative bacteria: a comparative study.

Int J Nanomedicine 2012 5;7:6003-9. Epub 2012 Dec 5.

Centre of Nanotechnology, King Abdulaziz University, Jeddah, Saudi Arabia.

Background: Nanomaterials have unique properties compared to their bulk counterparts. For this reason, nanotechnology has attracted a great deal of attention from the scientific community. Metal oxide nanomaterials like ZnO and CuO have been used industrially for several purposes, including cosmetics, paints, plastics, and textiles. A common feature that these nanoparticles exhibit is their antimicrobial behavior against pathogenic bacteria. In this report, we demonstrate the antimicrobial activity of ZnO, CuO, and Fe(2)O(3) nanoparticles against Gram-positive and Gram-negative bacteria.

Methods And Results: Nanosized particles of three metal oxides (ZnO, CuO, and Fe(2)O(3)) were synthesized by a sol-gel combustion route and characterized by X-ray diffraction, Fourier-transform infrared spectroscopy, and transmission electron microscopy techniques. X-ray diffraction results confirmed the single-phase formation of all three nanomaterials. The particle sizes were observed to be 18, 22, and 28 nm for ZnO, CuO, and Fe(2)O(3), respectively. We used these nanomaterials to evaluate their antibacterial activity against both Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus and Bacillus subtilis) bacteria.

Conclusion: Among the three metal oxide nanomaterials, ZnO showed greatest antimicrobial activity against both Gram-positive and Gram-negative bacteria used in this study. It was observed that ZnO nanoparticles have excellent bactericidal potential, while Fe(2)O(3) nanoparticles exhibited the least bactericidal activity. The order of antibacterial activity was demonstrated to be the following: ZnO > CuO > Fe(2)O(3).
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http://dx.doi.org/10.2147/IJN.S35347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519005PMC
April 2013

The possible role of selenium concentration in hepatitis B and C patients.

Saudi J Gastroenterol 2012 Mar-Apr;18(2):106-10

Department of Biochemistry, Bannu Medical College, Khyber Pakhtunkhwa, Bannu, Pakistan.

Background/aim: The compelling evidence reported that selenium is an essential trace mineral for human beings. Selenium plays a pivotal role in the restoration of immune functions. High rates of hepatitis B and C are present in Pakistan. Epidemiologic surveys demonstrated an inverse association between selenium (Se) level and regional cancer incidence, as well as viral infection. The present study was designed to evaluate the concentration of selenium in the serum of patients suffering from hepatitis B and C.

Patients And Methods: In this cross-sectional descriptive analytical study, serum selenium concentration of 150 patients suffering from hepatitis B and C, along with 26 healthy controls, was determined by atomic absorption spectrophotometer equipped with hydride generation system, model Analytic Jena (Vario III).

Results: The mean and standard deviation of serum selenium concentration observed in male and female patients with hepatitis C were 101.60 ± 0.55 and 77.43 ± 0.47 μ g/L, respectively, whereas the mean and standard deviation of serum selenium concentration observed in male and female patients with hepatitis B were 107.58 ± 0.44 and 137.8 ± 0.36 μg/L. Analysis of t test showed significant difference between C and B (P<0.001) patients in serum selenium concentration, when compared with the control.

Conclusion: The obtained results indicate that serum selenium concentration of hepatitis B and C patients is less than serum selenium concentration of healthy individuals. However, serum selenium decline is relative to severity of disease. Based on findings of this study, it is proposed that selenium should be supplemented in such patients in order to optimize nutritional support and to get better treatment response.
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http://dx.doi.org/10.4103/1319-3767.93811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3326970PMC
July 2012

Repeated botulinum toxin type A injections for refractory overactive bladder: medium-term outcomes, safety profile, and discontinuation rates.

Eur Urol 2012 Apr 13;61(4):834-9. Epub 2011 Dec 13.

Medical Research Council Centre for Transplantation, King's College London, King's Health Partners, Guy's Hospital, London, UK.

Background: Efficacy and safety of botulinum toxin type A (BoNTA) injection is supported by level 1 evidence, but data regarding repeated injections are limited in patients with refractory overactive bladder (OAB) and idiopathic detrusor overactivity (IDO).

Objectives: Describe medium-term outcomes and discontinuation rates for patients adopting repeated BoNTA as a management strategy for IDO.

Design, Setting, And Participants: Prospective data from a single centre were collected from the first 100 patients.

Intervention: Bladder injection of BoNTA (predominantly 200 U onabotulinumtoxinA; Allergan Ltd., Marlow, Buckinghamshire, UK) in an outpatient setting.

Measurements: OAB symptoms, quality of life, discontinuation rates, interinjection interval, and adverse events were recorded. Data comparisons were performed using a generalised linear model or a chi-square test where appropriate.

Results And Limitations: Two hundred seven injections were performed in 100 patients. All patients had 1 injection, 53 had a total of 2, 20 had 3, 13 had 4, 10 had 5, 5 had 6, 3 had 7, 1 had 8, 1 had 9, and 1 had 10 injections. Statistics were applied up to five repeated injections. A statistically significant reduction in frequency, urgency, and urge urinary incontinence were seen following the first BoNTA injection compared to baseline. This improvement was maintained after repeated injections and was not statistically different when comparing differences between injections. Thirty-seven patients stopped treatment after the first two injections; thereafter, dropouts were rare. The most common reasons for discontinuing treatment were poor efficacy (13%) and clean intermittent self-catheterisation (CISC)-related issues (11%). The incidence of CISC after the first injection was 35%. Bacteriuria was detected in 21% of patients. The mean interinjection interval was 322 d. Limitations included the concurrent use of antimuscarinic drugs in some patients.

Conclusions: BoNTA can provide a safe and effective medium-term management option for patients with refractory IDO. The most common reasons cited for stopping treatment were poor efficacy and CISC-related issues.
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http://dx.doi.org/10.1016/j.eururo.2011.12.011DOI Listing
April 2012

DNA nanotechnology for nucleic acid analysis: DX motif-based sensor.

Chembiochem 2011 Nov 18;12(17):2564-7. Epub 2011 Oct 18.

Chemistry Department, University of Central Florida, Orlando, FL 32816, USA.

A light on the tiles: A sensor that fluoresces in the presence of specific nucleic acids was designed and characterized. The sensor uses a molecular beacon probe and three adaptor strands to form a five-stranded assembly, a DX-tile, with a specific analyte. This sensor is a highly selective and affordable tool for the real-time analysis of DNA and RNA.
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http://dx.doi.org/10.1002/cbic.201100545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3221779PMC
November 2011

Insecticide-tolerant and plant-growth-promoting Rhizobium improves the growth of lentil (Lens esculentus) in insecticide-stressed soils.

Pest Manag Sci 2011 Apr;67(4):423-9

Department of Agricultural Microbiology, Faculty of Agricultural Sciences, Aligarh Muslim University, Aligarh, UP, India.

Background: Application of insecticides in modern agriculture in order to enhance legume production has led to their accumulation in soils to levels that adversely affect soil microflora such as rhizobia and exert a negative impact on the physiological activities associated with them. This study was therefore designed to identify rhizobial strains expressing higher tolerance to insecticides fipronil and pyriproxyfen and synthesising plant growth regulators even amid insecticide stress.

Results: The fipronil- and pyriproxyfen-tolerant Rhizobium sp. strain MRL3 produced plant-growth-promoting substances in substantial amounts, both in the presence and in the absence of the insecticides. In general, both insecticides at recommended and higher rates reduced plant dry biomass, symbiotic properties, nutrient uptake and seed yield of lentil plants. Interestingly, when applied with any concentration of the two insecticides, Rhizobium sp. strain MRL3 significantly increased the measured parameters compared with plants grown in soils treated solely with the same concentration of each insecticide but without inoculant.

Conclusion: This study suggests that Rhizobium strain MRL3 may be exploited as a bioinoculant to augment the efficiency of lentil exposed to insecticide-stressed soils.
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http://dx.doi.org/10.1002/ps.2080DOI Listing
April 2011

Prevalence and molecular diagnosis of Trypanosoma evansi in Nili-Ravi buffalo (Bubalus bubalis) in different districts of Punjab (Pakistan).

Trop Anim Health Prod 2010 Dec 31;42(8):1597-9. Epub 2010 Jul 31.

Livestock Production Research Institute Bahadurnagar, Okara, Punjab, Pakistan.

The prevalence of Trypanosoma evansi was investigated in 1,250 Nili-Ravi buffaloes of mixed age and sex by polymerase chain reaction (PCR) for the first time in Pakistan. DNA of the trypanosomes was isolated with TRIREAGENT®. The assay was employed using primers ESAG 6/7, specific for a 237-bp fragment from T. evansi genomic DNA. The samples were screened for the presence of T. evansi also by stained thin smear. Forty-four (3.5%) samples were positive by microscopy, while 97 (7.7%) samples were identified by PCR, indicating the high sensitivity of PCR for surveying the disease in epidemiological studies.
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http://dx.doi.org/10.1007/s11250-010-9616-0DOI Listing
December 2010
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