This dissertation applies network science to three foundational problems in: epidemiology (the so... more This dissertation applies network science to three foundational problems in: epidemiology (the social gradient in mortality), health economics (the geographic variation in health care spending), and public health (the diffusion of knowledge and behavioral change). Chapter 1 investigates the relationship between social network position and fibrinogen, a biomarker of inflammation and cardiac risk. Socially isolated individuals face elevated rates of illness and death not explained by behavior alone. Conventional measures of social connectedness reflect an individual’s perceived network and are subject to bias and variation in reporting. In this study of a large social network, I find that greater indegree, a sociocentric measure of friendship and familial ties identified by the ego’s connections rather than the ego herself, predicts significantly lower ego fibrinogen, after controlling for demographics, education, medical history, and known predictors of cardiac risk. The effect size of social isolation, as measured by low indegree, is comparable to that of smoking, and greater than that of low education, a conventional measure of socioeconomic disadvantage. By contrast, outdegree, which reflects an individual’s perceived connectedness, is weakly associated with fibrinogen. Chapter 2 turns to the networks of physicians whose behavior governs the cost and quality of health care across the country. Using data on hundreds of millions of patient-sharing relationships from 2009-2014, I construct comprehensive longitudinal networks of Medicare providers. For all providers billing for at least 100 office visits in 2012, I calculate six specialty-adjusted measures of billing intensity. After accounting for attributes of individual physicians, pairs of physicians who share patients are more similar on six dimensions of billing intensity than physicians who do not share patients but share a common colleague, who in turn are more similar than pairs of physicians separated in the network by three degrees or more. Moreover, patterns of physician clustering differ dramatically by region, with implications for efforts to reduce healthcare spending, and for the detection of fraud and abuse. Chapter 3 describes the first real-world, large-scale randomized trial of network interventions for public health. In 32 villages of rural Honduras, we delivered two dissimilar public health interventions: chlorine for water purification, and multivitamins for micronutrient deficiencies. Using a block randomized design, we assigned villages to one of three targeting methods, introducing interventions to 5% samples composed either of: randomly selected villagers, villagers with the most social ties, or nominated friends of random villagers (the last strategy exploiting the “friendship paradox” of social networks). We compared the diffusion of the products and of related knowledge across the three methods of network targeting. Targeting the most highly connected individuals produced no greater diffusion of knowledge and behavior than random targeting. Targeting nominated friends, by contrast, increased adoption of the nutritional intervention by 12.2% compared to random targeting, and also improved villagers’ knowledge of the intervention’s usage and benefits at follow-up. This method has the additional advantage of scalability, because it can be implemented without mapping the network. Deploying certain types of health interventions via network targeting, without increasing the number of individuals targeted or the resources used, may enhance the adoption and efficiency of those interventions, and thereby improve population health.Health Polic
The goal of this study was to find out how well Korean EFL learners produce the English articles ... more The goal of this study was to find out how well Korean EFL learners produce the English articles - the definite, indefinite and the zero article. This study has established the zero article to be the most difficult for Korean EFL learners followed by the indefinite and definite article respectively by assessing the results of the cloze tests. Also, the use(s) of the definite and indefinite articles which Korean EFL learners seem to have the greatest difficulty are pointed out by this study. In order to establish the above this study used a cloze test. The cloze test in total had twenty-one blanks - 9 each for the definite and indefinite articles and 3 for the zero articles. It was impossible to make a 'natural' cloze with the same number of the zero articles as the other two types of articles. Also, it is 'unnatural' to find the same nwnber of each type of articles in a 'natural' oral discourse. The cloze test on purpose had a Korean content to make the readi...
Background: Acupuncture and herbal medicine have been of great benefit to Asian people for centur... more Background: Acupuncture and herbal medicine have been of great benefit to Asian people for centuries. However, the discipline has not been subjected systematically and thoroughly to the rigors of scientific testing. Objective: This article reviews experimental evidence in regard to the vascular mechanisms of acupuncture and herbal medicine in hypertension. We focus on our hypothesis that acupuncture and herbal medicine reduce hypertension through activation of microvascular endothelial nitric oxide synthesis (eNOS). We also examine whether or not our results in experimental renovascular hypertension conform to the meridian theory. Results and conclusion: Acupuncture and herbal medicine 1) reduce experimental renovascular hypertension; 2) increase production of nitric oxide (NO), and contribute to vasodilation in the microvasculature and reduction of peripheral vascular resistance. We concluded that acupuncture and herbal medicine target eNOS and activate its signaling mechanisms, an...
Mfd couples transcription to nucleotide excision repair, and acts on RNA polymerases when elongat... more Mfd couples transcription to nucleotide excision repair, and acts on RNA polymerases when elongation is impeded. Depending on impediment severity, this action results in either transcription termination or elongation rescue, which rely on ATP-dependent Mfd translocation on DNA. Due to its role in antibiotic resistance, Mfd is also emerging as a prime target for developing anti-evolution drugs. Here we report the structure of DNA-bound Mfd, which reveals large DNA-induced structural changes that are linked to the active site via ATPase motif VI. These changes relieve autoinhibitory contacts between the N- and C-termini and unmask UvrA recognition determinants. We also demonstrate that translocation relies on a threonine in motif Ic, widely conserved in translocases, and a family-specific histidine near motif IVa, reminiscent of the “arginine clamp” of RNA helicases. Thus, Mfd employs a mode of DNA recognition that at its core is common to ss/ds translocases that act on DNA or RNA.
Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics, 2003
Head and neck squamous cell carcinoma (HNSCC) ranks as the sixth most frequent cancer worldwide. ... more Head and neck squamous cell carcinoma (HNSCC) ranks as the sixth most frequent cancer worldwide. HNSCC cell lines are typically refractory to transforming growth factor-beta (TGF-beta)-mediated cell cycle arrest. A number of these cell lines carry inactivating mutations of the TGF-beta type II (TbetaR-II) receptor, and fail to phosphorylate receptor-associated Smads, Smad2 and Smad3. In addition, we identified several intragenic mutations of the TbetaR-I gene in a small series of metastatic HNSCC specimens, suggesting that disruptions of TGF-beta signaling might contribute to the development and progression of HNSCC. To test this idea, we have now embarked on a larger scale analysis of the patterns of expression and activation of Smads in 170 HNSCC specimens assembled in tissue microarrays. Smad2 protein was expressed by 99% (95% CI: 96-100%) of tumors. The activated form of Smad2, pSmad2, was expressed in 86% (95% CI: 80-91%) of HNSCC, indicating their ability to survive and proliferate in spite of the presence of bioactive TGF-beta within the tissue microenvironment. In the 24 remaining cases (14%; 95% CI: 9-20%), pSmad2 was not detected in the tumor cells, although it was expressed by surrounding stromal cells and capillaries. In addition, 38 tumors (22%; 95% CI: 16-29%) failed to express Smad4 protein. Thus, we found evidence of loss of TGF-beta/Smad signaling in approximately 15-20% of HNSCC specimens, which is consistent with the phenotype of established human SCC lines. Moreover, we found that these Smad signaling defects were associated with a greater tendency for metastatic spread and regional or distant recurrence of HNSCC. These results indicate that inactivation of TGF-beta/Smad signaling occurs frequently in HNSCC and might have an adverse effect on patient outcome.
Antidepressants are one of the most prescribed classes of medications. A number of case reports h... more Antidepressants are one of the most prescribed classes of medications. A number of case reports have linked these drugs to extrapyramidal symptoms (EPSs), but no large epidemiologic study to date has examined this association. We sought to quantify the association of EPSs with different antidepressants by undertaking a large pharmacoepidemiologic study. A nested case-control study was conducted using a large health claims database in the United States from June 2006 to December 2015. Subjects with a diagnosis of primary Parkinson disease and those who received prescriptions of levodopa, ropinirole, pramipexole, domperidone, metoclopramide, entacapone, benztropine, selegiline, rasagiline, diphenhydramine, trihexyphenidyl, typical and atypical antipsychotics, and tricyclic antidepressants were excluded. Cases were followed to the first billing code for an extrapyramidal event or last date of enrollment in the cohort. For each case, 10 control subjects were matched by follow-up time, c...
Although antipsychotics are used to treat Tourette syndrome, there have been reports of paradoxic... more Although antipsychotics are used to treat Tourette syndrome, there have been reports of paradoxical induction of tics by first- and second-generation antipsychotics. The objective of this systematic review was to better characterize tics as the potential adverse effect of antipsychotics. A literature search was performed, with no language restriction, using the MEDLINE, EMBASE, and PsycINFO databases for all publications up to January 2018. To be included, studies utilizing any study design had to meet the following criteria: (1) a temporal association of tics with antipsychotic use where tics emerged during treatment or after discontinuation and (2) no diagnosis of Tourette syndrome before tic emergence. More stringent criteria were used for individuals under 18 years of age that included (1) no personal or family history of primary tic disorder and either (2) tics occurring during antipsychotic treatment improved significantly upon discontinuation or dose reduction or (3) tics eme...
Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia and has minimal ri... more Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia and has minimal risk for extrapyramidal symptoms. Therapeutic benefits, however, are accompanied by a myriad of cardiometabolic side-effects. The specific reasons for clozapine's high propensity to cause adverse cardiometabolic events remain unknown, but it is believed that autonomic dysfunction may play a role in many of these. This systematic review summarizes the literature on autonomic dysfunction and related cardiovascular side effects associated with clozapine treatment. A search of the EMBASE, MEDLINE, and EBM Cochrane databases was conducted using the search terms antipsychotic agents, antipsychotic drug, antipsychotic, schizophrenia, schizophren, psychos, psychotic, mental ill, mental disorder, neuroleptic, cardiovascular, cardiovascular diseases, clozapine, clozaril, autonomic, sympathetic, catecholamine, norepinephrine, noradrenaline, epinephrine, adrenaline. The search yielded 37 studies t...
American journal of physiology. Heart and circulatory physiology, 1998
To better understand the mechanisms of ischemia-reperfusion (I/R) injury, we tested the hypothesi... more To better understand the mechanisms of ischemia-reperfusion (I/R) injury, we tested the hypothesis that protein synthesis is involved in the production of tumor necrosis factor (TNF) and in the microvascular transport changes in I/R. To evaluate the hypothesis, we inhibited protein synthesis with topically applied actinomycin D (AMD), measured I/R-induced changes in microvascular transport, and bioassayed the venous plasma levels of TNF. The rat cremaster muscle I/R model consisted of 4 h of ischemia followed by 2 h of reperfusion. Changes in transport were determined by integrated optical intensity (IOI) using FITC-Dextran 150 as tracer. Animals were separated into four groups: 1) control (C), 2) control treated with AMD (C + AMD), 3) I/R, and 4) I/R treated with AMD (I/R + AMD). The mean (±SE) maximal IOI in C and C + AMD were 3.0 ± 1.0 and 3.7 ± 0.7 units, respectively. I/R elevated mean maximal IOI to 21.8 ± 1.9 units ( P < 0.05 vs. C, C + AMD, I/R + AMD). Treatment with AMD ...
Nearly all virulence factors in Bordetella pertussis are activated by a master two-component syst... more Nearly all virulence factors in Bordetella pertussis are activated by a master two-component system, BvgAS, composed of the sensor kinase BvgS and the response regulator BvgA. When BvgS is active, BvgA is phosphorylated (BvgA~P), and virulence-activated genes (vags) are expressed [Bvg(+) mode]. When BvgS is inactive and BvgA is not phosphorylated, virulence-repressed genes (vrgs) are induced [Bvg(-) mode]. Here, we have used transcriptome sequencing (RNA-seq) and reverse transcription-quantitative PCR (RT-qPCR) to define the BvgAS-dependent regulon of B. pertussis Tohama I. Our analyses reveal more than 550 BvgA-regulated genes, of which 353 are newly identified. BvgA-activated genes include those encoding two-component systems (such as kdpED), multiple other transcriptional regulators, and the extracytoplasmic function (ECF) sigma factor brpL, which is needed for type 3 secretion system (T3SS) expression, further establishing the importance of BvgA~P as an apex regulator of transcr...
European psychiatry : the journal of the Association of European Psychiatrists, Feb 8, 2017
There is irrefutable evidence that routine physical activity or exercise can offer considerable h... more There is irrefutable evidence that routine physical activity or exercise can offer considerable health benefits to individuals living with various mental disorders. However, it is not clear what effect physical activity has on the symptoms of Tourette syndrome. Despite a paucity of evidence, physical activity or exercise has already been recommended by various health organizations for the management of tics. We provide a systematic review of the effects of physical activity or exercise on tic symptomology in individuals with Tourette syndrome. Major electronic databases were searched for all available publications before August 2017. Keywords and MeSH terms included "physical activity" or "exercise" or "exercise therapy" or "physical exertion" or "sports" and "tics" or "tic disorders" or "Tourette." Eight studies were included, the majority of which were case reports. Despite a number of methodological l...
International Journal of Automotive Technology, 2009
The large-scale shear flows over the sunroof opening of a mid-sized SUV measured using a PIV syst... more The large-scale shear flows over the sunroof opening of a mid-sized SUV measured using a PIV system were investigated. The shear flows were measured for five different cases of deflector protrusion (one case was the baseline test without deflector) at two different free stream flow velocities below the critical velocity where the buffeting noise level reached a maximum. The structures
Clinical schizophrenia & related psychoses, Jan 4, 2017
Antipsychotic medications can effectively treat psychotic symptoms in individuals with schizophre... more Antipsychotic medications can effectively treat psychotic symptoms in individuals with schizophrenia. However, side effects including cardiovascular and extrapyramidal symptoms are often inevitable. Exercise has proven effective in ameliorating cardiometabolic abnormalities in individuals with schizophrenia. In addition, exercise has consistently been an effective intervention for improving the symptoms associated with schizophrenia. We report here two cases in which individuals with schizoaffective disorder treated with a long-acting injectable antipsychotic medication displayed worsening of extrapyramidal symptoms over the course of a 12-week exercise program. This can be attributed to an increase in blood flow to the depot site during exercise, accelerating the rate of absorption and bioavailability of the antipsychotic medication and subsequently increasing dopamine D2 blockade. Clinicians need to be vigilant when patients receiving long-acting injectable antipsychotic medicatio...
Clinical autonomic research : official journal of the Clinical Autonomic Research Society, Jan 3, 2017
To explore the relationship between antipsychotic-associated antagonism of alpha2-adrenergic rece... more To explore the relationship between antipsychotic-associated antagonism of alpha2-adrenergic receptors and resting heart rate in individuals with schizophrenia. Thirty-one inpatients treated with antipsychotics were included in this exploratory analysis. Antipsychotic doses were converted to haloperidol equivalents for alpha2-adrenergic receptor antagonism. Resting heart rate was measured with the patient in the seated upright posture. After controlling for confounding variables, the relationship between alpha2-adrenergic receptor antagonism and resting heart rate demonstrated a positive linear effect (P = 0.002) as well as a nonlinear effect that accounted for an additional 14% of the variability in resting heart rate (P = 0.005). The observed inverted-U relationship between alpha2-adrenergic receptor antagonism and resting heart rate can possibly be attributed to an altered response of beta1-adrenergic receptors to increased norepinephrine release. Further investigations are requi...
American journal of physiology. Heart and circulatory physiology, Jan 5, 2017
Approaches to reduce excessive edema due to the microvascular hyperpermeability that occurs durin... more Approaches to reduce excessive edema due to the microvascular hyperpermeability that occurs during ischemia-reperfusion (I/R) are needed to prevent muscle compartment syndrome. We tested the hypothesis that cAMP-activated mechanisms actively restore barrier integrity in postischemic striated muscle. We found, using I/R in intact muscles and hypoxia-reoxygenation (H/R, an I/R mimic) in human microvascular endothelial cells (HMVEC), that hyperpermeability can be deactivated by increasing cAMP levels through application of forskolin. This effect was seen whether or not the hyperpermeability was accompanied by increased mRNA expression of vascular endothelial growth factor (VEGF), which occurred only after 4 hours of ischemia. We found that cAMP increases in HMVEC following H/R, suggesting that cAMP-mediated restoration of barrier function is a physiological mechanism. We explored the mechanisms underlying this effect of cAMP. We found that Epac1, a downstream effector of cAMP that stim...
David B. Kim. 2015. The Perspectives and Alerters on Request for EFL Learners of English. Studies... more David B. Kim. 2015. The Perspectives and Alerters on Request for EFL Learners of English. Studies in British and American Language and Literature...
This dissertation applies network science to three foundational problems in: epidemiology (the so... more This dissertation applies network science to three foundational problems in: epidemiology (the social gradient in mortality), health economics (the geographic variation in health care spending), and public health (the diffusion of knowledge and behavioral change). Chapter 1 investigates the relationship between social network position and fibrinogen, a biomarker of inflammation and cardiac risk. Socially isolated individuals face elevated rates of illness and death not explained by behavior alone. Conventional measures of social connectedness reflect an individual’s perceived network and are subject to bias and variation in reporting. In this study of a large social network, I find that greater indegree, a sociocentric measure of friendship and familial ties identified by the ego’s connections rather than the ego herself, predicts significantly lower ego fibrinogen, after controlling for demographics, education, medical history, and known predictors of cardiac risk. The effect size of social isolation, as measured by low indegree, is comparable to that of smoking, and greater than that of low education, a conventional measure of socioeconomic disadvantage. By contrast, outdegree, which reflects an individual’s perceived connectedness, is weakly associated with fibrinogen. Chapter 2 turns to the networks of physicians whose behavior governs the cost and quality of health care across the country. Using data on hundreds of millions of patient-sharing relationships from 2009-2014, I construct comprehensive longitudinal networks of Medicare providers. For all providers billing for at least 100 office visits in 2012, I calculate six specialty-adjusted measures of billing intensity. After accounting for attributes of individual physicians, pairs of physicians who share patients are more similar on six dimensions of billing intensity than physicians who do not share patients but share a common colleague, who in turn are more similar than pairs of physicians separated in the network by three degrees or more. Moreover, patterns of physician clustering differ dramatically by region, with implications for efforts to reduce healthcare spending, and for the detection of fraud and abuse. Chapter 3 describes the first real-world, large-scale randomized trial of network interventions for public health. In 32 villages of rural Honduras, we delivered two dissimilar public health interventions: chlorine for water purification, and multivitamins for micronutrient deficiencies. Using a block randomized design, we assigned villages to one of three targeting methods, introducing interventions to 5% samples composed either of: randomly selected villagers, villagers with the most social ties, or nominated friends of random villagers (the last strategy exploiting the “friendship paradox” of social networks). We compared the diffusion of the products and of related knowledge across the three methods of network targeting. Targeting the most highly connected individuals produced no greater diffusion of knowledge and behavior than random targeting. Targeting nominated friends, by contrast, increased adoption of the nutritional intervention by 12.2% compared to random targeting, and also improved villagers’ knowledge of the intervention’s usage and benefits at follow-up. This method has the additional advantage of scalability, because it can be implemented without mapping the network. Deploying certain types of health interventions via network targeting, without increasing the number of individuals targeted or the resources used, may enhance the adoption and efficiency of those interventions, and thereby improve population health.Health Polic
The goal of this study was to find out how well Korean EFL learners produce the English articles ... more The goal of this study was to find out how well Korean EFL learners produce the English articles - the definite, indefinite and the zero article. This study has established the zero article to be the most difficult for Korean EFL learners followed by the indefinite and definite article respectively by assessing the results of the cloze tests. Also, the use(s) of the definite and indefinite articles which Korean EFL learners seem to have the greatest difficulty are pointed out by this study. In order to establish the above this study used a cloze test. The cloze test in total had twenty-one blanks - 9 each for the definite and indefinite articles and 3 for the zero articles. It was impossible to make a 'natural' cloze with the same number of the zero articles as the other two types of articles. Also, it is 'unnatural' to find the same nwnber of each type of articles in a 'natural' oral discourse. The cloze test on purpose had a Korean content to make the readi...
Background: Acupuncture and herbal medicine have been of great benefit to Asian people for centur... more Background: Acupuncture and herbal medicine have been of great benefit to Asian people for centuries. However, the discipline has not been subjected systematically and thoroughly to the rigors of scientific testing. Objective: This article reviews experimental evidence in regard to the vascular mechanisms of acupuncture and herbal medicine in hypertension. We focus on our hypothesis that acupuncture and herbal medicine reduce hypertension through activation of microvascular endothelial nitric oxide synthesis (eNOS). We also examine whether or not our results in experimental renovascular hypertension conform to the meridian theory. Results and conclusion: Acupuncture and herbal medicine 1) reduce experimental renovascular hypertension; 2) increase production of nitric oxide (NO), and contribute to vasodilation in the microvasculature and reduction of peripheral vascular resistance. We concluded that acupuncture and herbal medicine target eNOS and activate its signaling mechanisms, an...
Mfd couples transcription to nucleotide excision repair, and acts on RNA polymerases when elongat... more Mfd couples transcription to nucleotide excision repair, and acts on RNA polymerases when elongation is impeded. Depending on impediment severity, this action results in either transcription termination or elongation rescue, which rely on ATP-dependent Mfd translocation on DNA. Due to its role in antibiotic resistance, Mfd is also emerging as a prime target for developing anti-evolution drugs. Here we report the structure of DNA-bound Mfd, which reveals large DNA-induced structural changes that are linked to the active site via ATPase motif VI. These changes relieve autoinhibitory contacts between the N- and C-termini and unmask UvrA recognition determinants. We also demonstrate that translocation relies on a threonine in motif Ic, widely conserved in translocases, and a family-specific histidine near motif IVa, reminiscent of the “arginine clamp” of RNA helicases. Thus, Mfd employs a mode of DNA recognition that at its core is common to ss/ds translocases that act on DNA or RNA.
Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics, 2003
Head and neck squamous cell carcinoma (HNSCC) ranks as the sixth most frequent cancer worldwide. ... more Head and neck squamous cell carcinoma (HNSCC) ranks as the sixth most frequent cancer worldwide. HNSCC cell lines are typically refractory to transforming growth factor-beta (TGF-beta)-mediated cell cycle arrest. A number of these cell lines carry inactivating mutations of the TGF-beta type II (TbetaR-II) receptor, and fail to phosphorylate receptor-associated Smads, Smad2 and Smad3. In addition, we identified several intragenic mutations of the TbetaR-I gene in a small series of metastatic HNSCC specimens, suggesting that disruptions of TGF-beta signaling might contribute to the development and progression of HNSCC. To test this idea, we have now embarked on a larger scale analysis of the patterns of expression and activation of Smads in 170 HNSCC specimens assembled in tissue microarrays. Smad2 protein was expressed by 99% (95% CI: 96-100%) of tumors. The activated form of Smad2, pSmad2, was expressed in 86% (95% CI: 80-91%) of HNSCC, indicating their ability to survive and proliferate in spite of the presence of bioactive TGF-beta within the tissue microenvironment. In the 24 remaining cases (14%; 95% CI: 9-20%), pSmad2 was not detected in the tumor cells, although it was expressed by surrounding stromal cells and capillaries. In addition, 38 tumors (22%; 95% CI: 16-29%) failed to express Smad4 protein. Thus, we found evidence of loss of TGF-beta/Smad signaling in approximately 15-20% of HNSCC specimens, which is consistent with the phenotype of established human SCC lines. Moreover, we found that these Smad signaling defects were associated with a greater tendency for metastatic spread and regional or distant recurrence of HNSCC. These results indicate that inactivation of TGF-beta/Smad signaling occurs frequently in HNSCC and might have an adverse effect on patient outcome.
Antidepressants are one of the most prescribed classes of medications. A number of case reports h... more Antidepressants are one of the most prescribed classes of medications. A number of case reports have linked these drugs to extrapyramidal symptoms (EPSs), but no large epidemiologic study to date has examined this association. We sought to quantify the association of EPSs with different antidepressants by undertaking a large pharmacoepidemiologic study. A nested case-control study was conducted using a large health claims database in the United States from June 2006 to December 2015. Subjects with a diagnosis of primary Parkinson disease and those who received prescriptions of levodopa, ropinirole, pramipexole, domperidone, metoclopramide, entacapone, benztropine, selegiline, rasagiline, diphenhydramine, trihexyphenidyl, typical and atypical antipsychotics, and tricyclic antidepressants were excluded. Cases were followed to the first billing code for an extrapyramidal event or last date of enrollment in the cohort. For each case, 10 control subjects were matched by follow-up time, c...
Although antipsychotics are used to treat Tourette syndrome, there have been reports of paradoxic... more Although antipsychotics are used to treat Tourette syndrome, there have been reports of paradoxical induction of tics by first- and second-generation antipsychotics. The objective of this systematic review was to better characterize tics as the potential adverse effect of antipsychotics. A literature search was performed, with no language restriction, using the MEDLINE, EMBASE, and PsycINFO databases for all publications up to January 2018. To be included, studies utilizing any study design had to meet the following criteria: (1) a temporal association of tics with antipsychotic use where tics emerged during treatment or after discontinuation and (2) no diagnosis of Tourette syndrome before tic emergence. More stringent criteria were used for individuals under 18 years of age that included (1) no personal or family history of primary tic disorder and either (2) tics occurring during antipsychotic treatment improved significantly upon discontinuation or dose reduction or (3) tics eme...
Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia and has minimal ri... more Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia and has minimal risk for extrapyramidal symptoms. Therapeutic benefits, however, are accompanied by a myriad of cardiometabolic side-effects. The specific reasons for clozapine's high propensity to cause adverse cardiometabolic events remain unknown, but it is believed that autonomic dysfunction may play a role in many of these. This systematic review summarizes the literature on autonomic dysfunction and related cardiovascular side effects associated with clozapine treatment. A search of the EMBASE, MEDLINE, and EBM Cochrane databases was conducted using the search terms antipsychotic agents, antipsychotic drug, antipsychotic, schizophrenia, schizophren, psychos, psychotic, mental ill, mental disorder, neuroleptic, cardiovascular, cardiovascular diseases, clozapine, clozaril, autonomic, sympathetic, catecholamine, norepinephrine, noradrenaline, epinephrine, adrenaline. The search yielded 37 studies t...
American journal of physiology. Heart and circulatory physiology, 1998
To better understand the mechanisms of ischemia-reperfusion (I/R) injury, we tested the hypothesi... more To better understand the mechanisms of ischemia-reperfusion (I/R) injury, we tested the hypothesis that protein synthesis is involved in the production of tumor necrosis factor (TNF) and in the microvascular transport changes in I/R. To evaluate the hypothesis, we inhibited protein synthesis with topically applied actinomycin D (AMD), measured I/R-induced changes in microvascular transport, and bioassayed the venous plasma levels of TNF. The rat cremaster muscle I/R model consisted of 4 h of ischemia followed by 2 h of reperfusion. Changes in transport were determined by integrated optical intensity (IOI) using FITC-Dextran 150 as tracer. Animals were separated into four groups: 1) control (C), 2) control treated with AMD (C + AMD), 3) I/R, and 4) I/R treated with AMD (I/R + AMD). The mean (±SE) maximal IOI in C and C + AMD were 3.0 ± 1.0 and 3.7 ± 0.7 units, respectively. I/R elevated mean maximal IOI to 21.8 ± 1.9 units ( P < 0.05 vs. C, C + AMD, I/R + AMD). Treatment with AMD ...
Nearly all virulence factors in Bordetella pertussis are activated by a master two-component syst... more Nearly all virulence factors in Bordetella pertussis are activated by a master two-component system, BvgAS, composed of the sensor kinase BvgS and the response regulator BvgA. When BvgS is active, BvgA is phosphorylated (BvgA~P), and virulence-activated genes (vags) are expressed [Bvg(+) mode]. When BvgS is inactive and BvgA is not phosphorylated, virulence-repressed genes (vrgs) are induced [Bvg(-) mode]. Here, we have used transcriptome sequencing (RNA-seq) and reverse transcription-quantitative PCR (RT-qPCR) to define the BvgAS-dependent regulon of B. pertussis Tohama I. Our analyses reveal more than 550 BvgA-regulated genes, of which 353 are newly identified. BvgA-activated genes include those encoding two-component systems (such as kdpED), multiple other transcriptional regulators, and the extracytoplasmic function (ECF) sigma factor brpL, which is needed for type 3 secretion system (T3SS) expression, further establishing the importance of BvgA~P as an apex regulator of transcr...
European psychiatry : the journal of the Association of European Psychiatrists, Feb 8, 2017
There is irrefutable evidence that routine physical activity or exercise can offer considerable h... more There is irrefutable evidence that routine physical activity or exercise can offer considerable health benefits to individuals living with various mental disorders. However, it is not clear what effect physical activity has on the symptoms of Tourette syndrome. Despite a paucity of evidence, physical activity or exercise has already been recommended by various health organizations for the management of tics. We provide a systematic review of the effects of physical activity or exercise on tic symptomology in individuals with Tourette syndrome. Major electronic databases were searched for all available publications before August 2017. Keywords and MeSH terms included "physical activity" or "exercise" or "exercise therapy" or "physical exertion" or "sports" and "tics" or "tic disorders" or "Tourette." Eight studies were included, the majority of which were case reports. Despite a number of methodological l...
International Journal of Automotive Technology, 2009
The large-scale shear flows over the sunroof opening of a mid-sized SUV measured using a PIV syst... more The large-scale shear flows over the sunroof opening of a mid-sized SUV measured using a PIV system were investigated. The shear flows were measured for five different cases of deflector protrusion (one case was the baseline test without deflector) at two different free stream flow velocities below the critical velocity where the buffeting noise level reached a maximum. The structures
Clinical schizophrenia & related psychoses, Jan 4, 2017
Antipsychotic medications can effectively treat psychotic symptoms in individuals with schizophre... more Antipsychotic medications can effectively treat psychotic symptoms in individuals with schizophrenia. However, side effects including cardiovascular and extrapyramidal symptoms are often inevitable. Exercise has proven effective in ameliorating cardiometabolic abnormalities in individuals with schizophrenia. In addition, exercise has consistently been an effective intervention for improving the symptoms associated with schizophrenia. We report here two cases in which individuals with schizoaffective disorder treated with a long-acting injectable antipsychotic medication displayed worsening of extrapyramidal symptoms over the course of a 12-week exercise program. This can be attributed to an increase in blood flow to the depot site during exercise, accelerating the rate of absorption and bioavailability of the antipsychotic medication and subsequently increasing dopamine D2 blockade. Clinicians need to be vigilant when patients receiving long-acting injectable antipsychotic medicatio...
Clinical autonomic research : official journal of the Clinical Autonomic Research Society, Jan 3, 2017
To explore the relationship between antipsychotic-associated antagonism of alpha2-adrenergic rece... more To explore the relationship between antipsychotic-associated antagonism of alpha2-adrenergic receptors and resting heart rate in individuals with schizophrenia. Thirty-one inpatients treated with antipsychotics were included in this exploratory analysis. Antipsychotic doses were converted to haloperidol equivalents for alpha2-adrenergic receptor antagonism. Resting heart rate was measured with the patient in the seated upright posture. After controlling for confounding variables, the relationship between alpha2-adrenergic receptor antagonism and resting heart rate demonstrated a positive linear effect (P = 0.002) as well as a nonlinear effect that accounted for an additional 14% of the variability in resting heart rate (P = 0.005). The observed inverted-U relationship between alpha2-adrenergic receptor antagonism and resting heart rate can possibly be attributed to an altered response of beta1-adrenergic receptors to increased norepinephrine release. Further investigations are requi...
American journal of physiology. Heart and circulatory physiology, Jan 5, 2017
Approaches to reduce excessive edema due to the microvascular hyperpermeability that occurs durin... more Approaches to reduce excessive edema due to the microvascular hyperpermeability that occurs during ischemia-reperfusion (I/R) are needed to prevent muscle compartment syndrome. We tested the hypothesis that cAMP-activated mechanisms actively restore barrier integrity in postischemic striated muscle. We found, using I/R in intact muscles and hypoxia-reoxygenation (H/R, an I/R mimic) in human microvascular endothelial cells (HMVEC), that hyperpermeability can be deactivated by increasing cAMP levels through application of forskolin. This effect was seen whether or not the hyperpermeability was accompanied by increased mRNA expression of vascular endothelial growth factor (VEGF), which occurred only after 4 hours of ischemia. We found that cAMP increases in HMVEC following H/R, suggesting that cAMP-mediated restoration of barrier function is a physiological mechanism. We explored the mechanisms underlying this effect of cAMP. We found that Epac1, a downstream effector of cAMP that stim...
David B. Kim. 2015. The Perspectives and Alerters on Request for EFL Learners of English. Studies... more David B. Kim. 2015. The Perspectives and Alerters on Request for EFL Learners of English. Studies in British and American Language and Literature...
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