pavan patel - Academia.edu (original) (raw)
Papers by pavan patel
A sensitive, selective and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method... more A sensitive, selective and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of artemether (ART) and its active metabolite dihydroartemisinin (DHA) in human plasma using artemisinin (ARM) as the internal standard (IS). The analytes were extracted by liquid-liquid extraction and chromatographic separation was achieved on a reversed-phase Thermo HyPurity C18 (50 mm × 4.6 mm, 5 µm) column with a mobile phase consisting of 2 mM ammonium formate: methanol (15:85, v/v) in an isocratic mode at the flow rate of 0.600 mL/min. In order to quantify the analytes, triple quadrupole mass spectrometer equipped with electro spray ionization in the positive mode was used to obtain consistent precursor ammonium ion adducts [M + NH4]+ at m/z 316.5/163.5 for ART, 302.7/163.1 for DHA and 300.5/219.3 for ARM. The method was fully validated in the concentration range of 0.250 to 250 ng/mL using 50 µL human plasma. Intra- a...
Neurology, 2020
Objective: Examine mild traumatic brain injury (mTBI) in adolescents and its neuropsychiatric seq... more Objective: Examine mild traumatic brain injury (mTBI) in adolescents and its neuropsychiatric sequelae with an emphasis on structural brain changes and long-term consequences Background: TBI is a major public health issue with a high incidence of morbidity and mortality. Head injuries result in approximately 52,000 deaths, 275,000 hospitalizations and 1.4 million emergency department visits each year in the USA. The presentation of mTBI is individualized and highly variable, but the emotional and psychiatric manifestations are significantly under-investigated and poorly understood. Examination and management of these post-injury psychiatric outcomes is crucial to improving long-term outcomes. JS is an adolescent who suffered a concussion during a soccer game and was evaluated six months and one-year post injury with persistent mood-related symptoms including anxiety and depression. Design/Methods: Case report and literature review Results: JS underwent various tests to measure her e...
American Journal of Gastroenterology, 2020
Coronary Artery Disease, 2021
Introduction Multiple risk models are used to predict the presence of obstructive coronary artery... more Introduction Multiple risk models are used to predict the presence of obstructive coronary artery disease (CAD) in patients with chest pain. We aimed to compare the performance of these models to an experienced cardiologist’s assessment utilizing coronary angiography (CA) as a reference. Materials and methods We prospectively enrolled patients without known CAD referred for elective CA. We assessed pretest probability of CAD using the following risk models: Diamond–Forrester (original and updated), Duke Clinical score, ACC/AHA, CAD consortium (basic and clinical) and PROMISE minimal risk tool. All patients completed self-administrative Rose angina questionnaire. Independently, an experienced cardiologist assessed the patients to provide a binary prediction of obstructive CAD prior to CA. Obstructive CAD was defined as >80% stenosis in epicardial coronary arteries by visual assessment, or fractional flow reserve <0.80 in intermediate lesions (30–80%). Results A total of 150 patients were recruited (100 women, 50 men). Mean age was 58 (32–78) years. Obstructive CAD was found in 31 patients (21%). The area under the curve (AUC) for all the clinical risk prediction models (except the Duke Clinical Score, AUC 0.73, P = 0.07) was significantly lower compared with the clinician’s assessment (AUC 0.51–0.65 vs. 0.81, respectively, P < 0.01). The clinician’s assessment had sensitivity comparable to the Duke Clinical score, which was higher than all other clinical models. There was no difference in prediction performance on the basis of sex in this predominantly female population. Discussion/Conclusion In stable patients with chest pain and suspected CAD, current clinical risk models which are universally based upon the characteristics of the chest pain, show suboptimal performance in predicting obstructive CAD. These findings have important clinical implications, as current appropriateness criteria for recommending CA are on the basis of these risk models.
The Cooper Rowan Medical Journal, 2020
Acupuncture is an complementary form of medicine that has relatively recently become a component ... more Acupuncture is an complementary form of medicine that has relatively recently become a component of traditional Chinese medicine (TCM). It involves the application of thin needles at specific points throughout the body, although initially, general areas instead of points were used. There are estimated to be about 395 different points that can be utilized, and the technique behind using these points can vary widely between practitioners. In addition to acupuncture points, TCM is said to use meridians or pathways along with qi, or energy flows. In terms of acupunctures’ utility, it has been known to treat a variety of ailments ranging from pain and headaches to sleep disturbances, but it's true benefits continue to be questioned. To date, thousands of studies have been performed in regards to its efficacy with varying conclusions. Once considered to be “pseudomedicine”, this ancient technique has been found to provide long-term benefits for patients with chronic pain. This manuscr...
Frontiers in Cellular Neuroscience, 2021
Aggregation of misfolded α-synuclein (α-syn) is the major component of Lewy bodies and neurites i... more Aggregation of misfolded α-synuclein (α-syn) is the major component of Lewy bodies and neurites in Parkinson’s disease (PD) and related α-synucleinopathies. Some α-syn mutations (e.g., A53T) in familial PD recapitulate the α-syn pathology in transgenic mice, which supports the importance of pathologic α-syn in driving the pathogenesis of α-synucleinopathies. Lymphocyte activation gene 3 (Lag3) is a receptor of α-syn fibrils facilitating pathologic α-syn spread; however, the role of Lag3 in mediating the pathogenesis in α-syn transgenic mice is not clear. Here, we report that depletion of Lag3 in human α-syn A53T transgenic (hA53T) mice significantly reduces the level of detergent-insoluble α-syn aggregates and phosphorylated ser129 α-syn, and inhibits activation of microglia and astrocytes. The absence of Lag3 significantly delays disease progression and reduces the behavioral deficits in hA53T transgenic mice leading to prolonged survival. Taken together, these results show that La...
The extracellular matrix (ECM) is a complex mixture composed of fibrillar collagens as well as ad... more The extracellular matrix (ECM) is a complex mixture composed of fibrillar collagens as well as additional protein and carbohydrate components. Proteoglycans (PGs) contribute to the heterogeneity of the ECM and play an important role in its structure and function. While the small leucine rich proteoglycans (SLRPs), including decorin and lumican, have been studied extensively as mediators of collagen fibrillogenesis and organization, the function of large matrix PGs in collagen matrices is less well known. In this study, we showed that different matrix PGs have distinct roles in regulating collagen behaviors. We found that versican, a large chondroitin sulfate PG, promotes collagen fibrillogenesis in a turbidity assay and upregulates cell-mediated collagen compaction and reorganization, whereas aggrecan, a structurally-similar large PG, has different and often opposing effects on collagen. Compared to versican, decorin and lumican also have distinct functions in regulating collagen be...
Neurology: Clinical Practice, 2020
Coronavirus disease 2019 (COVID-19) is a novel infectious disease caused by severe acute respirat... more Coronavirus disease 2019 (COVID-19) is a novel infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Patients can be asymptomatic or symptomatic with severity determined by age and comorbid conditions. Common early symptoms are fever, cough, dyspnea, myalgia, headache, and diarrhea. In addition to respiratory complications, other systems involved include genitourinary, gastrointestinal and cardiac.1
Gastrointestinal Endoscopy, 2020
BMJ Case Reports, 2019
Erythromelalgia (EM) is a rare disorder of small nerve fibres that leads to painful flushing and ... more Erythromelalgia (EM) is a rare disorder of small nerve fibres that leads to painful flushing and burning paresthesisas of the distal extremities and is typically associated with heat or physical activity; relief is found using cooling measures. Its effects are often debilitating in the general population, but this patient had an excellent response to specific treatment options and continues to maintain employment, something many individuals suffering from EM are unable to do. His presentation was also unique in that he had isolated, proximal involvement as his condition progressed whereas typically only the distal extremities are affected. Routine electromyography and nerve conduction studies were normal, whereas nerve biopsy demonstrated findings of small fibre neuropathy. Ultimately, his condition was managed with carbamazepine and his symptoms have almost entirely resolved to date.
American Journal of Gastroenterology, 2019
American Journal of Gastroenterology, 2019
American Journal of Gastroenterology, 2019
American Journal of Gastroenterology, 2013
American Journal of Gastroenterology, 2014
Fungal Genetics and Biology, 2018
The formation of a glucan/chitin/glycoprotein cell wall matrix is vital for fungal survival, grow... more The formation of a glucan/chitin/glycoprotein cell wall matrix is vital for fungal survival, growth, and morphogenesis. The cell wall proteins are important cell wall components and function in adhesion, signal transduction, and as cell wall structural elements. In this report we demonstrate that Neurospora crassa GH72 glucan transferases function to crosslink cell wall glycoproteins into the cell wall. With an in vitro assay, we show that the glucan transferases are able to attach lichenin, a cell wall glucan with a repeating β-1,4-glucose-β-1,4glucose-β-1,3-glucose structure, to cell wall glycoproteins. We propose that the pathway for attachment of lichenin to the glycoprotein has four steps. First, N-linked oligosaccharides present on the glycoproteins are modified by the addition of a galactomannan. As part of our report we have characterized the structure of the galactomannan, which consists of an α-1,6-mannose backbone with galactofuranose side chains. In the second step, the galactomannan is processed by members of the GH76 α-1,6-mannanases. In the third step, the glucan transferases cleave the lichenin and create substrate-enzyme intermediates. In the final step, the transferases transfer the lichenin to the processed galactomannan. We demonstrate that the N. crassa glucan transferases have demonstrate specificity for the processed galactomannan and for lichenin. The energy from the cleaved glycosidic bond in lichenin is retained in the substrate-enzyme intermediate and used to create a new glycosidic bond between the lichenin and the processed galactomannan. The pathway effectively crosslinks glycoproteins into the fungal cell wall.
A sensitive, selective and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method... more A sensitive, selective and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of artemether (ART) and its active metabolite dihydroartemisinin (DHA) in human plasma using artemisinin (ARM) as the internal standard (IS). The analytes were extracted by liquid-liquid extraction and chromatographic separation was achieved on a reversed-phase Thermo HyPurity C18 (50 mm × 4.6 mm, 5 µm) column with a mobile phase consisting of 2 mM ammonium formate: methanol (15:85, v/v) in an isocratic mode at the flow rate of 0.600 mL/min. In order to quantify the analytes, triple quadrupole mass spectrometer equipped with electro spray ionization in the positive mode was used to obtain consistent precursor ammonium ion adducts [M + NH4]+ at m/z 316.5/163.5 for ART, 302.7/163.1 for DHA and 300.5/219.3 for ARM. The method was fully validated in the concentration range of 0.250 to 250 ng/mL using 50 µL human plasma. Intra- a...
Neurology, 2020
Objective: Examine mild traumatic brain injury (mTBI) in adolescents and its neuropsychiatric seq... more Objective: Examine mild traumatic brain injury (mTBI) in adolescents and its neuropsychiatric sequelae with an emphasis on structural brain changes and long-term consequences Background: TBI is a major public health issue with a high incidence of morbidity and mortality. Head injuries result in approximately 52,000 deaths, 275,000 hospitalizations and 1.4 million emergency department visits each year in the USA. The presentation of mTBI is individualized and highly variable, but the emotional and psychiatric manifestations are significantly under-investigated and poorly understood. Examination and management of these post-injury psychiatric outcomes is crucial to improving long-term outcomes. JS is an adolescent who suffered a concussion during a soccer game and was evaluated six months and one-year post injury with persistent mood-related symptoms including anxiety and depression. Design/Methods: Case report and literature review Results: JS underwent various tests to measure her e...
American Journal of Gastroenterology, 2020
Coronary Artery Disease, 2021
Introduction Multiple risk models are used to predict the presence of obstructive coronary artery... more Introduction Multiple risk models are used to predict the presence of obstructive coronary artery disease (CAD) in patients with chest pain. We aimed to compare the performance of these models to an experienced cardiologist’s assessment utilizing coronary angiography (CA) as a reference. Materials and methods We prospectively enrolled patients without known CAD referred for elective CA. We assessed pretest probability of CAD using the following risk models: Diamond–Forrester (original and updated), Duke Clinical score, ACC/AHA, CAD consortium (basic and clinical) and PROMISE minimal risk tool. All patients completed self-administrative Rose angina questionnaire. Independently, an experienced cardiologist assessed the patients to provide a binary prediction of obstructive CAD prior to CA. Obstructive CAD was defined as >80% stenosis in epicardial coronary arteries by visual assessment, or fractional flow reserve <0.80 in intermediate lesions (30–80%). Results A total of 150 patients were recruited (100 women, 50 men). Mean age was 58 (32–78) years. Obstructive CAD was found in 31 patients (21%). The area under the curve (AUC) for all the clinical risk prediction models (except the Duke Clinical Score, AUC 0.73, P = 0.07) was significantly lower compared with the clinician’s assessment (AUC 0.51–0.65 vs. 0.81, respectively, P < 0.01). The clinician’s assessment had sensitivity comparable to the Duke Clinical score, which was higher than all other clinical models. There was no difference in prediction performance on the basis of sex in this predominantly female population. Discussion/Conclusion In stable patients with chest pain and suspected CAD, current clinical risk models which are universally based upon the characteristics of the chest pain, show suboptimal performance in predicting obstructive CAD. These findings have important clinical implications, as current appropriateness criteria for recommending CA are on the basis of these risk models.
The Cooper Rowan Medical Journal, 2020
Acupuncture is an complementary form of medicine that has relatively recently become a component ... more Acupuncture is an complementary form of medicine that has relatively recently become a component of traditional Chinese medicine (TCM). It involves the application of thin needles at specific points throughout the body, although initially, general areas instead of points were used. There are estimated to be about 395 different points that can be utilized, and the technique behind using these points can vary widely between practitioners. In addition to acupuncture points, TCM is said to use meridians or pathways along with qi, or energy flows. In terms of acupunctures’ utility, it has been known to treat a variety of ailments ranging from pain and headaches to sleep disturbances, but it's true benefits continue to be questioned. To date, thousands of studies have been performed in regards to its efficacy with varying conclusions. Once considered to be “pseudomedicine”, this ancient technique has been found to provide long-term benefits for patients with chronic pain. This manuscr...
Frontiers in Cellular Neuroscience, 2021
Aggregation of misfolded α-synuclein (α-syn) is the major component of Lewy bodies and neurites i... more Aggregation of misfolded α-synuclein (α-syn) is the major component of Lewy bodies and neurites in Parkinson’s disease (PD) and related α-synucleinopathies. Some α-syn mutations (e.g., A53T) in familial PD recapitulate the α-syn pathology in transgenic mice, which supports the importance of pathologic α-syn in driving the pathogenesis of α-synucleinopathies. Lymphocyte activation gene 3 (Lag3) is a receptor of α-syn fibrils facilitating pathologic α-syn spread; however, the role of Lag3 in mediating the pathogenesis in α-syn transgenic mice is not clear. Here, we report that depletion of Lag3 in human α-syn A53T transgenic (hA53T) mice significantly reduces the level of detergent-insoluble α-syn aggregates and phosphorylated ser129 α-syn, and inhibits activation of microglia and astrocytes. The absence of Lag3 significantly delays disease progression and reduces the behavioral deficits in hA53T transgenic mice leading to prolonged survival. Taken together, these results show that La...
The extracellular matrix (ECM) is a complex mixture composed of fibrillar collagens as well as ad... more The extracellular matrix (ECM) is a complex mixture composed of fibrillar collagens as well as additional protein and carbohydrate components. Proteoglycans (PGs) contribute to the heterogeneity of the ECM and play an important role in its structure and function. While the small leucine rich proteoglycans (SLRPs), including decorin and lumican, have been studied extensively as mediators of collagen fibrillogenesis and organization, the function of large matrix PGs in collagen matrices is less well known. In this study, we showed that different matrix PGs have distinct roles in regulating collagen behaviors. We found that versican, a large chondroitin sulfate PG, promotes collagen fibrillogenesis in a turbidity assay and upregulates cell-mediated collagen compaction and reorganization, whereas aggrecan, a structurally-similar large PG, has different and often opposing effects on collagen. Compared to versican, decorin and lumican also have distinct functions in regulating collagen be...
Neurology: Clinical Practice, 2020
Coronavirus disease 2019 (COVID-19) is a novel infectious disease caused by severe acute respirat... more Coronavirus disease 2019 (COVID-19) is a novel infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Patients can be asymptomatic or symptomatic with severity determined by age and comorbid conditions. Common early symptoms are fever, cough, dyspnea, myalgia, headache, and diarrhea. In addition to respiratory complications, other systems involved include genitourinary, gastrointestinal and cardiac.1
Gastrointestinal Endoscopy, 2020
BMJ Case Reports, 2019
Erythromelalgia (EM) is a rare disorder of small nerve fibres that leads to painful flushing and ... more Erythromelalgia (EM) is a rare disorder of small nerve fibres that leads to painful flushing and burning paresthesisas of the distal extremities and is typically associated with heat or physical activity; relief is found using cooling measures. Its effects are often debilitating in the general population, but this patient had an excellent response to specific treatment options and continues to maintain employment, something many individuals suffering from EM are unable to do. His presentation was also unique in that he had isolated, proximal involvement as his condition progressed whereas typically only the distal extremities are affected. Routine electromyography and nerve conduction studies were normal, whereas nerve biopsy demonstrated findings of small fibre neuropathy. Ultimately, his condition was managed with carbamazepine and his symptoms have almost entirely resolved to date.
American Journal of Gastroenterology, 2019
American Journal of Gastroenterology, 2019
American Journal of Gastroenterology, 2019
American Journal of Gastroenterology, 2013
American Journal of Gastroenterology, 2014
Fungal Genetics and Biology, 2018
The formation of a glucan/chitin/glycoprotein cell wall matrix is vital for fungal survival, grow... more The formation of a glucan/chitin/glycoprotein cell wall matrix is vital for fungal survival, growth, and morphogenesis. The cell wall proteins are important cell wall components and function in adhesion, signal transduction, and as cell wall structural elements. In this report we demonstrate that Neurospora crassa GH72 glucan transferases function to crosslink cell wall glycoproteins into the cell wall. With an in vitro assay, we show that the glucan transferases are able to attach lichenin, a cell wall glucan with a repeating β-1,4-glucose-β-1,4glucose-β-1,3-glucose structure, to cell wall glycoproteins. We propose that the pathway for attachment of lichenin to the glycoprotein has four steps. First, N-linked oligosaccharides present on the glycoproteins are modified by the addition of a galactomannan. As part of our report we have characterized the structure of the galactomannan, which consists of an α-1,6-mannose backbone with galactofuranose side chains. In the second step, the galactomannan is processed by members of the GH76 α-1,6-mannanases. In the third step, the glucan transferases cleave the lichenin and create substrate-enzyme intermediates. In the final step, the transferases transfer the lichenin to the processed galactomannan. We demonstrate that the N. crassa glucan transferases have demonstrate specificity for the processed galactomannan and for lichenin. The energy from the cleaved glycosidic bond in lichenin is retained in the substrate-enzyme intermediate and used to create a new glycosidic bond between the lichenin and the processed galactomannan. The pathway effectively crosslinks glycoproteins into the fungal cell wall.