Purpose： We present a systematic review of the literature concerning major aspects of science mapping to serve two primary purposes： First, to demonstrate the use of a science mapping approach to perform the review ...Purpose： We present a systematic review of the literature concerning major aspects of science mapping to serve two primary purposes： First, to demonstrate the use of a science mapping approach to perform the review so that researchers may apply the procedure to the review of a scientific domain of their own interest, and second, to identify major areas of research activities concerning science mapping, intellectual milestones in the development of key specialties, evolutionary stages of major specialties involved, and the dynamics of transitions from one specialty to another.Design/methodology/approach： We first introduce a theoretical framework of the evolution of a scientific specialty. Then we demonstrate a generic search strategy that can be used to construct a representative dataset of bibliographic records of a domain of research. Next, progressively synthesized co-citation networks are constructed and visualized to aid visual analytic studies of the domain＇s structural and dynamic patterns and trends. Finally, trajectories of citations made by particular types of authors and articles are presented to illustrate the predictive potential of the analytic approach.Findings： The evolution of the science mapping research involves the development of a number of interrelated specialties. Four major specialties are discussed in detail in terms of four evolutionary stages： conceptualization, tool construction, application, and codification. Underlying connections between major specialties are also explored. The predictive analysis demonstrates citations trajectories of potentially transformative contributions.Research limitations： The systematic review is primarily guided by citation patterns in the dataset retrieved from the literature. The scope of the data is limited by the source of the retrieval, i.e. the Web of Science, and the composite query used. An iterative query refinement is possible if one would like to improve the data quality, although the current approach serves our purpose adequately.展开更多
Osteoarthritis （OA） is the most common degenerative joint disease and a major cause of pain and disability in adult individuals. The etiology of OA includes joint injury, obesity, aging, and heredity. However, the d...Osteoarthritis （OA） is the most common degenerative joint disease and a major cause of pain and disability in adult individuals. The etiology of OA includes joint injury, obesity, aging, and heredity. However, the detailed molecular mechanisms of OA initiation and progression remain poorly understood and, currently, there are no interventions available to restore degraded cartilage or decelerate disease progression. The diathrodial joint is a complicated organ and its function is to bear weight, perform physical activity and exhibit a joint-specific range of motion during movement. During OA development, the entire joint organ is affected, including articular cartilage, subchondral bone, synovial tissue and meniscus. A full understanding of the pathological mechanism of OA development relies on the discovery of the interplaying mechanisms among different OA symptoms, including articular cartilage degradation, osteophyte formation, subchondral sclerosis and synovial hyperplasia, and the signaling pathway（s） controlling these pathological processes.展开更多
Nonalcoholic fatty liver disease(NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consu...Nonalcoholic fatty liver disease(NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consumption, and other conditions that may lead to hepatic steatosis. NAFLD encompasses a broad clinical spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis(NASH), advanced fibrosis, cirrhosis, and finally hepatocellular carcinoma(HCC). NAFLD is the most common liver disease in the world and NASH may soon become the most common indication for liver transplantation. Ongoing persistence of obesity with increasing rate of diabetes will increase the prevalence of NAFLD, and as this population ages, many will develop cirrhosis and end-stage liver disease. There has been a general increase in the prevalence of NAFLD, with Asia leading the rise, yet the United States is following closely behind with a rising prevalence from 15% in 2005 to 25% within 5 years. NAFLD is commonly associated with metabolic comorbidities, including obesity, type Ⅱ diabetes, dyslipidemia, and metabolic syndrome. Our understanding of the pathophysiology of NAFLD is constantly evolving. Based on NAFLD subtypes, it has the potential to progress into advanced fibrosis, end-stage liver disease and HCC. The increasing prevalence of NAFLD with advanced fibrosis, is concerning because patients appear toexperience higher liver-related and non-liver-related mortality than the general population. The increased morbidity and mortality, healthcare costs and declining health related quality of life associated with NAFLD makes it a formidable disease, and one that requires more in-depth analysis.展开更多
Hepatocellular carcinoma(HCC) represents a unique challenge for physicians and patients.There is no definitively curative treatment.Rather,many treatment and management modalities exist with differing advantages and d...Hepatocellular carcinoma(HCC) represents a unique challenge for physicians and patients.There is no definitively curative treatment.Rather,many treatment and management modalities exist with differing advantages and disadvantages.Both current guidelines and individual patient concerns must be taken into account in order to properly manage HCC.In addition,quality of life issues are particularly complex in patients with HCC and these concerns must also be factored into treatment strategies.Thus,considering all the options and their various pros and cons can quickly become complex for both clinicians and patients.In this review,we systematically discuss the current treatment modalities available for HCC,detailing relevant clinical data,risks and rewards and overall outcomes for each approach.Surgical options discussed include resection,transplantation and ablation.We also discuss the radiation modalities:conformal radiotherapy,yttrium 90 microspheres and proton and heavy ion radiotherapy.The biologic agent Sorafenib is discussed as a promising new approach,and recent clinical trials are reviewed.We then detail currently described molecular pathways implicated in the initiation and progression of HCC,and we explore the potential of each pathway as an avenue for drug exploitation.We hope this comprehensive and forward-looking review enables both clinicians and patients to understand various options and thereby make more informed decisions regarding this disease.展开更多
Acute pancreatitis (AP) is a rare event in pregnancy, occurring in approximately 3 in 10 000 pregnancies. The spectrum of AP in pregnancy ranges from mild pancreatitis to serious pancreatitis associated with necrosis,...Acute pancreatitis (AP) is a rare event in pregnancy, occurring in approximately 3 in 10 000 pregnancies. The spectrum of AP in pregnancy ranges from mild pancreatitis to serious pancreatitis associated with necrosis, abscesses, pseudocysts and multiple organ dysfunction syndromes. Pregnancy related hematological and biochemical alterations infl uence the interpretation of diagnostic tests and assessment of severity of AP. As in any other disease associated with pregnancy, AP is associated with greater concerns as it deals with two lives rather than just one as in the non-pregnant population. The recent advances in clinical gastroenterology have improved the early diagnosis and effective management of biliary pancreatitis. Diagnostic studies such as endoscopic ultrasound, magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography and therapeutic modalities that include endoscopic sphincterotomy, biliary stenting, common bile duct stone extraction and laparoscopic cholecystectomy are major milestones in gastroenterology. When properly managed AP in pregnancy does not carry a dismal prognosis as in the past.展开更多
Tourette syndrome(TS) is a neurodevelopmental disorder characterized by multiple chronic motor and vocal tics beginning in childhood. Several studies describe the association between TS and attention deficit hyperacti...Tourette syndrome(TS) is a neurodevelopmental disorder characterized by multiple chronic motor and vocal tics beginning in childhood. Several studies describe the association between TS and attention deficit hyperactivity disorder(ADHD). Fifty percent of children diagnosed with ADHD have comorbid tic disorder. ADHD related symptoms have been reported in 35% to 90% of children with TS. Since ADHD is the most prevalent comorbid condition with TS and those with concomitant TS and ADHD present with considerable psychosocial and behavioral impairments, it is essential for clinicians to be familiar with these diagnoses and their management. This paper highlights the association between treating ADHD with stimulants and the development of tic disorders. The two cases discussed underscore the fact that children with TS may present with ADHD symptomatology prior to the appearance of any TS related symptoms. Appropriate management of TS in a patient diagnosed with ADHD can lead to quality of life improvements and a reduction in psychosocial impairments.展开更多
Inflammation plays an important role in cardiac dysfunction under different situations. Acute systemic inflammation occurring in patients with severe burns, trauma, and inflammatory diseases causes cardiac dysfunction...Inflammation plays an important role in cardiac dysfunction under different situations. Acute systemic inflammation occurring in patients with severe burns, trauma, and inflammatory diseases causes cardiac dysfunction, which is one of the leading causes of mortality in these patients. Acute sepsis decreases cardiac contractility and impairs myocardial compliance. Chronic inflammation such as that occurring in Duchenne muscular dystropshy and myocarditis may cause adverse cardiac remodeling including myocyte hypertrophy and death, fibrosis, and altered myocyte function. However, the underlying cellular and molecular mechanisms for inflammatory cardiomyopathy are still controversial probably due to multiple factors involved. Potential mechanisms include the change in circulating blood volume;a direct inhibition of myocyte contractility by cytokines (tumor necrosis factor (TNF)-?, interleukin (IL)-1?);abnormal nitric oxide and reactive oxygen species (ROS) signaling;mitochondrial dysfunction;abnormal excitation-contraction coupling;and reduced calcium sensitivity at the myofibrillar level and blunted ?-adrenergic signaling. This review will summarize recent advances in diagnostic technology, mechanisms, and potential therapeutic strategies for inflammation-induced cardiac dysfunction.展开更多
As obligate intracellular parasites,viruses need a host cell to provide a milieu favorable to viral replication.Consequently,viruses often adopt mechanisms to subvert host cellular signaling processes.While beneficial...As obligate intracellular parasites,viruses need a host cell to provide a milieu favorable to viral replication.Consequently,viruses often adopt mechanisms to subvert host cellular signaling processes.While beneficial for the viral replication cycle,virus-induced deregulation of host cellular signaling processes can be detrimental to host cell physiology and can lead to virus-associated pathogenesis,including,for oncogenic viruses,cell transformation and cancer progression.Included among these oncogenic viruses is the hepatitis B virus(HBV).Despite the availability of an HBV vaccine,350-500 million people worldwide are chronically infected with HBV,and a significant number of these chronically infected individuals will develop hepatocellular carcinoma(HCC).Epidemiological studies indicate that chronic infection with HBV is the leading risk factor for the development of HCC.Globally,HCC is the second highest cause of cancer-associated deaths,underscoring the need for understanding mechanisms that regulate HBV replication and the development of HBV-associated HCC.HBV is the prototype member of the Hepadnaviridae family;members of this family of viruses have a narrow host range and predominately infect hepatocytes in their respective hosts.The extremely small and compact hepadnaviral genome,the unique arrangement of open reading frames,and a replication strategy utilizing reverse transcription of an RNA intermediate to generate the DNA genome are distinguishing features of the Hepadnaviridae.In this review,the authors provide a comprehensive description of HBV biology,summarize the model systems used for studying HBV infections,and highlight potential mechanisms that link a chronic HBV-infection to the development of HCC.For example,the HBV X protein(HBx),a key regulatory HBV protein that is important for HBV replication,is thought to play a cofactor role in the development of HBV-induced HCC,and the authors highlight the functions of HBx that may contribute to the development of HBV-associated HCC.展开更多
Chronic infection with the hepatitis B virus(HBV) is the leading risk factor for the development of hepatocellular carcinoma(HCC). With nearly 750000 deaths yearly, hepatocellular carcinoma is the second highest cause...Chronic infection with the hepatitis B virus(HBV) is the leading risk factor for the development of hepatocellular carcinoma(HCC). With nearly 750000 deaths yearly, hepatocellular carcinoma is the second highest cause of cancer-related death in the world. Unfortunately, the molecular mechanisms that contribute to the development of HBV-associated HCC remain incompletely understood. Recently, micro RNAs(mi RNAs), a family of small non-coding RNAs that play a role primarily in post-transcriptional gene regulation, have been recognized as important regulators of cellular homeostasis, and altered regulation of mi RNA expression has been suggested to play a significant role in virus-associated diseases and the development of many cancers. With this in mind, many groups have begun to investigate the relationship between mi RNAs and HBV replication and HBV-associated disease. Multiple findings suggest that some mi RNAs, such as mi R-122, and mi R-125 and mi R-199 family members, are playing a role in HBV replication and HBV-associated disease, including the development of HBV-associated HCC. In this review, we discuss the current state of our understanding of the relationship between HBV and mi RNAs, including how HBV affects cellular mi RNAs, how these mi RNAs impact HBV replication, and the relationship between HBV-mediated mi RNA regulation and HCC development. We also address the impact of challenges in studying HBV, such as the lack of an effective model system for infectivity and a reliance on transformed cell lines, on our understanding of the relationship between HBV and mi RNAs, and proposepotential applications of mi RNA-related techniques that could enhance our understanding of the role mi RNAs play in HBV replication and HBV-associated disease, ultimately leading to new therapeutic options and improved patient outcomes.展开更多
Ornithine transcarbamylase （OTC） deficiency is an X-linked trait that accounts for nearly half of all inherited disorders of the urea cycle. OTC is one of the enzymes common to both the urea cycle and the bacterial ...Ornithine transcarbamylase （OTC） deficiency is an X-linked trait that accounts for nearly half of all inherited disorders of the urea cycle. OTC is one of the enzymes common to both the urea cycle and the bacterial arginine biosynthesis pathway; however, the role of OTC has changed over evolution. For animals with a urea cycle, defects in OTC can trigger hyperammonemic episodes that can lead to brain damage and death. This is the fifth mutation update for human OTC with previous updates reported in 1993, 1995, 2002, and 2006. In the 2006 update, 341 mutations were reported. This current update contains 417 disease-causing mutations, and also is the first report of this series to incorporate information about natural variation of the OTC gene in the general population through examination of publicly available genomic data and examination of phenotype/genotype correlations from patients participating in the Urea Cycle Disorders Consortium Longitudinal Study and the first to evaluate the suitability of systematic computational approaches to predict severity of disease associated with different types of OTC mutations.展开更多
Minocycline hydrochloride（MH）, a semi-synthetic tetracycline derivative, is a clinically available antibiotic and anti-inflammatory drug that also exhibits potent neuroprotective activities. It has been shown to tar...Minocycline hydrochloride（MH）, a semi-synthetic tetracycline derivative, is a clinically available antibiotic and anti-inflammatory drug that also exhibits potent neuroprotective activities. It has been shown to target multiple secondary injury mechanisms in spinal cord injury, via its anti-inflammatory, anti-oxidant, and anti-apoptotic properties. The secondary injury mechanisms that MH can potentially target include inflammation, free radicals and oxidative stress, glutamate excitotoxicity, calcium influx, mitochondrial dysfunction, ischemia, hemorrhage, and edema. This review discusses the potential mechanisms of the multifaceted actions of MH. Its anti-inflammatory and neuroprotective effects are partially achieved through conserved mechanisms such as modulation of p38 mitogen-activated protein kinase（MAPK） and phosphoinositide 3-kinase（PI3K）/Akt signaling pathways as well as inhibition of matrix metalloproteinases（MMPs）. Additionally, MH can directly inhibit calcium influx through the N-methyl-D-aspartate（NMDA） receptors, mitochondrial calcium uptake, poly（ADP-ribose） polymerase-1（PARP-1） enzymatic activity, and iron toxicity. It can also directly scavenge free radicals. Because it can target many secondary injury mechanisms, MH treatment holds great promise for reducing tissue damage and promoting functional recovery following spinal cord injury.展开更多
We briefly summarized how to design and fabricate an insect-mimicking flapping-wing system and demonstrate how to implement inherent pitching stability for stable vertical takeoff. The effect of relative locations of ...We briefly summarized how to design and fabricate an insect-mimicking flapping-wing system and demonstrate how to implement inherent pitching stability for stable vertical takeoff. The effect of relative locations of the Center of Gravity （CG） and the mean Aerodynamic Center （AC） on vertical flight was theoretically examined through static force balance considera- tion. We conducted a series of vertical takeoff tests in which the location of the mean AC was determined using an unsteady Blade Element Theory （BET） previously developed by the authors. Sequential images were captured during the takeoff tests using a high-speed camera. The results demonstrated that inherent pitching stability for vertical takeoff can be achieved by controlling the relative position between the CG and the mean AC of the flapping system.展开更多
AIMTo examine the epidemic of diabetes mellitus (DM) and its impact on mortality from all-cause and cardiovascular disease (CVD), and to test the effect of antidiabetic therapy on the mortality in United States adults...AIMTo examine the epidemic of diabetes mellitus (DM) and its impact on mortality from all-cause and cardiovascular disease (CVD), and to test the effect of antidiabetic therapy on the mortality in United States adults. METHODS The analysis included a randomized population sample of 272149 subjects ages ≥ 18 years who participated in the National Health Interview Surveys (NHIS) in2000-2009. Chronic conditions (hypertension, DM and CVD) were classified by participants’ self-reports of physician diagnosis. NHIS-Mortality Linked Files, and NHIS-Medical Expenditure Panel Survey Linkage Fileson prescribed medicines for patients with DM were used to test the research questions. χ 2, Poisson and Cox’s regression models were applied in data analysis.RESULTS Of all participants, 22305 (8.2%) had DM. The prevalence of DM significantly increased from 2000 to 2009 in all age groups (P < 0.001). Within an average 7.39 (SD= 3) years of follow-up, male DM patients had 1.56 times higher risk of death from all-cause (HR = 1.56, 95%CI:1.49-1.64), 1.72 times higher from heart disease [1.72 (1.53-1.93)], 1.48 times higher from cerebrovascular disease [1.48 (1.18-1.85)], and 1.67 times higher from CVD [1.67 (1.51-1.86)] than subjects without DM,respectively. Similar results were observed in females. In males, 10% of DM patients did not use any antidiabetic medications, 38.1% used antidiabetic monotherapy, and 51.9% used ≥ 2 antidiabetic medications. These corresponding values were 10.3%, 40.4% and 49.4% in females. A significant protective effect of metformin monotherapy or combination therapy (except for insulin) on all-cause mortality and a protective but non-significant effect on CVD mortality were observed. CONCLUSION This is the first study using data from multiple linkage files to confirm a significant increased prevalence of DM in the last decade in the United States. Patients with DM have significantly higher risk of death from all-cause and CVD than those without DM. Antidiabetic mediations,specifically for metformin展开更多
Diabetes mellitus(DM)is a growing epidemic with global proportions.It is estimated that in 2019,463 million adults aged 20-79 years were living with DM.The latest evidence shows that DM continues to be a significant g...Diabetes mellitus(DM)is a growing epidemic with global proportions.It is estimated that in 2019,463 million adults aged 20-79 years were living with DM.The latest evidence shows that DM continues to be a significant global health challenge and is likely to continue to grow substantially in the next decades,which would have major implications for healthcare expenditures,particularly in developing countries.Hence,new conceptual and methodological approaches to tackle the epidemic are long overdue.Spatial epidemiology has been a successful approach to control infectious disease epidemics like malaria and human immunodeficiency virus.The implementation of this approach has been expanded to include the study of non-communicable diseases like cancer and cardiovascular diseases.In this review,we discussed the implementation and use of spatial epidemiology and Geographic Information Systems to the study of DM.We reviewed several spatial methods used to understand the spatial structure of the disease and identify the potential geographical drivers of the spatial distribution of DM.Finally,we discussed the use of spatial epidemiology on the design and implementation of geographically targeted prevention and treatment interventions against DM.展开更多
文摘Purpose： We present a systematic review of the literature concerning major aspects of science mapping to serve two primary purposes： First, to demonstrate the use of a science mapping approach to perform the review so that researchers may apply the procedure to the review of a scientific domain of their own interest, and second, to identify major areas of research activities concerning science mapping, intellectual milestones in the development of key specialties, evolutionary stages of major specialties involved, and the dynamics of transitions from one specialty to another.Design/methodology/approach： We first introduce a theoretical framework of the evolution of a scientific specialty. Then we demonstrate a generic search strategy that can be used to construct a representative dataset of bibliographic records of a domain of research. Next, progressively synthesized co-citation networks are constructed and visualized to aid visual analytic studies of the domain＇s structural and dynamic patterns and trends. Finally, trajectories of citations made by particular types of authors and articles are presented to illustrate the predictive potential of the analytic approach.Findings： The evolution of the science mapping research involves the development of a number of interrelated specialties. Four major specialties are discussed in detail in terms of four evolutionary stages： conceptualization, tool construction, application, and codification. Underlying connections between major specialties are also explored. The predictive analysis demonstrates citations trajectories of potentially transformative contributions.Research limitations： The systematic review is primarily guided by citation patterns in the dataset retrieved from the literature. The scope of the data is limited by the source of the retrieval, i.e. the Web of Science, and the composite query used. An iterative query refinement is possible if one would like to improve the data quality, although the current approach serves our purpose adequately.
基金supported by NIH grants AR055915 and AR054465 to DC
文摘Osteoarthritis （OA） is the most common degenerative joint disease and a major cause of pain and disability in adult individuals. The etiology of OA includes joint injury, obesity, aging, and heredity. However, the detailed molecular mechanisms of OA initiation and progression remain poorly understood and, currently, there are no interventions available to restore degraded cartilage or decelerate disease progression. The diathrodial joint is a complicated organ and its function is to bear weight, perform physical activity and exhibit a joint-specific range of motion during movement. During OA development, the entire joint organ is affected, including articular cartilage, subchondral bone, synovial tissue and meniscus. A full understanding of the pathological mechanism of OA development relies on the discovery of the interplaying mechanisms among different OA symptoms, including articular cartilage degradation, osteophyte formation, subchondral sclerosis and synovial hyperplasia, and the signaling pathway（s） controlling these pathological processes.
文摘Nonalcoholic fatty liver disease(NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consumption, and other conditions that may lead to hepatic steatosis. NAFLD encompasses a broad clinical spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis(NASH), advanced fibrosis, cirrhosis, and finally hepatocellular carcinoma(HCC). NAFLD is the most common liver disease in the world and NASH may soon become the most common indication for liver transplantation. Ongoing persistence of obesity with increasing rate of diabetes will increase the prevalence of NAFLD, and as this population ages, many will develop cirrhosis and end-stage liver disease. There has been a general increase in the prevalence of NAFLD, with Asia leading the rise, yet the United States is following closely behind with a rising prevalence from 15% in 2005 to 25% within 5 years. NAFLD is commonly associated with metabolic comorbidities, including obesity, type Ⅱ diabetes, dyslipidemia, and metabolic syndrome. Our understanding of the pathophysiology of NAFLD is constantly evolving. Based on NAFLD subtypes, it has the potential to progress into advanced fibrosis, end-stage liver disease and HCC. The increasing prevalence of NAFLD with advanced fibrosis, is concerning because patients appear toexperience higher liver-related and non-liver-related mortality than the general population. The increased morbidity and mortality, healthcare costs and declining health related quality of life associated with NAFLD makes it a formidable disease, and one that requires more in-depth analysis.
文摘Hepatocellular carcinoma(HCC) represents a unique challenge for physicians and patients.There is no definitively curative treatment.Rather,many treatment and management modalities exist with differing advantages and disadvantages.Both current guidelines and individual patient concerns must be taken into account in order to properly manage HCC.In addition,quality of life issues are particularly complex in patients with HCC and these concerns must also be factored into treatment strategies.Thus,considering all the options and their various pros and cons can quickly become complex for both clinicians and patients.In this review,we systematically discuss the current treatment modalities available for HCC,detailing relevant clinical data,risks and rewards and overall outcomes for each approach.Surgical options discussed include resection,transplantation and ablation.We also discuss the radiation modalities:conformal radiotherapy,yttrium 90 microspheres and proton and heavy ion radiotherapy.The biologic agent Sorafenib is discussed as a promising new approach,and recent clinical trials are reviewed.We then detail currently described molecular pathways implicated in the initiation and progression of HCC,and we explore the potential of each pathway as an avenue for drug exploitation.We hope this comprehensive and forward-looking review enables both clinicians and patients to understand various options and thereby make more informed decisions regarding this disease.
文摘Acute pancreatitis (AP) is a rare event in pregnancy, occurring in approximately 3 in 10 000 pregnancies. The spectrum of AP in pregnancy ranges from mild pancreatitis to serious pancreatitis associated with necrosis, abscesses, pseudocysts and multiple organ dysfunction syndromes. Pregnancy related hematological and biochemical alterations infl uence the interpretation of diagnostic tests and assessment of severity of AP. As in any other disease associated with pregnancy, AP is associated with greater concerns as it deals with two lives rather than just one as in the non-pregnant population. The recent advances in clinical gastroenterology have improved the early diagnosis and effective management of biliary pancreatitis. Diagnostic studies such as endoscopic ultrasound, magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography and therapeutic modalities that include endoscopic sphincterotomy, biliary stenting, common bile duct stone extraction and laparoscopic cholecystectomy are major milestones in gastroenterology. When properly managed AP in pregnancy does not carry a dismal prognosis as in the past.
文摘Tourette syndrome(TS) is a neurodevelopmental disorder characterized by multiple chronic motor and vocal tics beginning in childhood. Several studies describe the association between TS and attention deficit hyperactivity disorder(ADHD). Fifty percent of children diagnosed with ADHD have comorbid tic disorder. ADHD related symptoms have been reported in 35% to 90% of children with TS. Since ADHD is the most prevalent comorbid condition with TS and those with concomitant TS and ADHD present with considerable psychosocial and behavioral impairments, it is essential for clinicians to be familiar with these diagnoses and their management. This paper highlights the association between treating ADHD with stimulants and the development of tic disorders. The two cases discussed underscore the fact that children with TS may present with ADHD symptomatology prior to the appearance of any TS related symptoms. Appropriate management of TS in a patient diagnosed with ADHD can lead to quality of life improvements and a reduction in psychosocial impairments.
文摘Inflammation plays an important role in cardiac dysfunction under different situations. Acute systemic inflammation occurring in patients with severe burns, trauma, and inflammatory diseases causes cardiac dysfunction, which is one of the leading causes of mortality in these patients. Acute sepsis decreases cardiac contractility and impairs myocardial compliance. Chronic inflammation such as that occurring in Duchenne muscular dystropshy and myocarditis may cause adverse cardiac remodeling including myocyte hypertrophy and death, fibrosis, and altered myocyte function. However, the underlying cellular and molecular mechanisms for inflammatory cardiomyopathy are still controversial probably due to multiple factors involved. Potential mechanisms include the change in circulating blood volume;a direct inhibition of myocyte contractility by cytokines (tumor necrosis factor (TNF)-?, interleukin (IL)-1?);abnormal nitric oxide and reactive oxygen species (ROS) signaling;mitochondrial dysfunction;abnormal excitation-contraction coupling;and reduced calcium sensitivity at the myofibrillar level and blunted ?-adrenergic signaling. This review will summarize recent advances in diagnostic technology, mechanisms, and potential therapeutic strategies for inflammation-induced cardiac dysfunction.
基金supported by an NIH predoctoral fellowship to RJLthe grant number is F31CA171712.
文摘As obligate intracellular parasites,viruses need a host cell to provide a milieu favorable to viral replication.Consequently,viruses often adopt mechanisms to subvert host cellular signaling processes.While beneficial for the viral replication cycle,virus-induced deregulation of host cellular signaling processes can be detrimental to host cell physiology and can lead to virus-associated pathogenesis,including,for oncogenic viruses,cell transformation and cancer progression.Included among these oncogenic viruses is the hepatitis B virus(HBV).Despite the availability of an HBV vaccine,350-500 million people worldwide are chronically infected with HBV,and a significant number of these chronically infected individuals will develop hepatocellular carcinoma(HCC).Epidemiological studies indicate that chronic infection with HBV is the leading risk factor for the development of HCC.Globally,HCC is the second highest cause of cancer-associated deaths,underscoring the need for understanding mechanisms that regulate HBV replication and the development of HBV-associated HCC.HBV is the prototype member of the Hepadnaviridae family;members of this family of viruses have a narrow host range and predominately infect hepatocytes in their respective hosts.The extremely small and compact hepadnaviral genome,the unique arrangement of open reading frames,and a replication strategy utilizing reverse transcription of an RNA intermediate to generate the DNA genome are distinguishing features of the Hepadnaviridae.In this review,the authors provide a comprehensive description of HBV biology,summarize the model systems used for studying HBV infections,and highlight potential mechanisms that link a chronic HBV-infection to the development of HCC.For example,the HBV X protein(HBx),a key regulatory HBV protein that is important for HBV replication,is thought to play a cofactor role in the development of HBV-induced HCC,and the authors highlight the functions of HBx that may contribute to the development of HBV-associated HCC.
基金Supported by Pennsylvania state CURE grant,No.4100057658,[to Steel LF and Bouchard MJ(partially)]a Ruth L Kirschstein(F31)Predoctoral Fellowship,No.5F31CA171712-03,[to Lamontagne J(partially)]
文摘Chronic infection with the hepatitis B virus(HBV) is the leading risk factor for the development of hepatocellular carcinoma(HCC). With nearly 750000 deaths yearly, hepatocellular carcinoma is the second highest cause of cancer-related death in the world. Unfortunately, the molecular mechanisms that contribute to the development of HBV-associated HCC remain incompletely understood. Recently, micro RNAs(mi RNAs), a family of small non-coding RNAs that play a role primarily in post-transcriptional gene regulation, have been recognized as important regulators of cellular homeostasis, and altered regulation of mi RNA expression has been suggested to play a significant role in virus-associated diseases and the development of many cancers. With this in mind, many groups have begun to investigate the relationship between mi RNAs and HBV replication and HBV-associated disease. Multiple findings suggest that some mi RNAs, such as mi R-122, and mi R-125 and mi R-199 family members, are playing a role in HBV replication and HBV-associated disease, including the development of HBV-associated HCC. In this review, we discuss the current state of our understanding of the relationship between HBV and mi RNAs, including how HBV affects cellular mi RNAs, how these mi RNAs impact HBV replication, and the relationship between HBV-mediated mi RNA regulation and HCC development. We also address the impact of challenges in studying HBV, such as the lack of an effective model system for infectivity and a reliance on transformed cell lines, on our understanding of the relationship between HBV and mi RNAs, and proposepotential applications of mi RNA-related techniques that could enhance our understanding of the role mi RNAs play in HBV replication and HBV-associated disease, ultimately leading to new therapeutic options and improved patient outcomes.
基金the support of the Kettering Family FoundationThe Urea Cycle Disorders Consortium (U54HD061221) is a part of the National Institutes of Health (NIH) Rare Disease Clinical Research Network (RDCRN)+3 种基金supported through collaboration between the Office of Rare Diseases Research (ORDR)the National Center for Advancing Translational Science (NCATS)the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)The Urea Cycle Disorders Consortium is also supported by the O’Malley Foundation, the Rotenberg Family Fund, the Dietmar-Hopp Foundation, and the Kettering Fund
文摘Ornithine transcarbamylase （OTC） deficiency is an X-linked trait that accounts for nearly half of all inherited disorders of the urea cycle. OTC is one of the enzymes common to both the urea cycle and the bacterial arginine biosynthesis pathway; however, the role of OTC has changed over evolution. For animals with a urea cycle, defects in OTC can trigger hyperammonemic episodes that can lead to brain damage and death. This is the fifth mutation update for human OTC with previous updates reported in 1993, 1995, 2002, and 2006. In the 2006 update, 341 mutations were reported. This current update contains 417 disease-causing mutations, and also is the first report of this series to incorporate information about natural variation of the OTC gene in the general population through examination of publicly available genomic data and examination of phenotype/genotype correlations from patients participating in the Urea Cycle Disorders Consortium Longitudinal Study and the first to evaluate the suitability of systematic computational approaches to predict severity of disease associated with different types of OTC mutations.
文摘Minocycline hydrochloride（MH）, a semi-synthetic tetracycline derivative, is a clinically available antibiotic and anti-inflammatory drug that also exhibits potent neuroprotective activities. It has been shown to target multiple secondary injury mechanisms in spinal cord injury, via its anti-inflammatory, anti-oxidant, and anti-apoptotic properties. The secondary injury mechanisms that MH can potentially target include inflammation, free radicals and oxidative stress, glutamate excitotoxicity, calcium influx, mitochondrial dysfunction, ischemia, hemorrhage, and edema. This review discusses the potential mechanisms of the multifaceted actions of MH. Its anti-inflammatory and neuroprotective effects are partially achieved through conserved mechanisms such as modulation of p38 mitogen-activated protein kinase（MAPK） and phosphoinositide 3-kinase（PI3K）/Akt signaling pathways as well as inhibition of matrix metalloproteinases（MMPs）. Additionally, MH can directly inhibit calcium influx through the N-methyl-D-aspartate（NMDA） receptors, mitochondrial calcium uptake, poly（ADP-ribose） polymerase-1（PARP-1） enzymatic activity, and iron toxicity. It can also directly scavenge free radicals. Because it can target many secondary injury mechanisms, MH treatment holds great promise for reducing tissue damage and promoting functional recovery following spinal cord injury.
基金Basic Science Research Program through the National Research Foundation of Korea (NRF)，The Ministry of Education,Science and Technology，The New & Renewable Energy R&D program of the Korea Institute of Energy Technology Evaluation and Planning (KETEP)，The Korea government Ministry of Knowledge Economy，M.J.Kim appreciates the financial support from National Science Foundation
文摘We briefly summarized how to design and fabricate an insect-mimicking flapping-wing system and demonstrate how to implement inherent pitching stability for stable vertical takeoff. The effect of relative locations of the Center of Gravity （CG） and the mean Aerodynamic Center （AC） on vertical flight was theoretically examined through static force balance considera- tion. We conducted a series of vertical takeoff tests in which the location of the mean AC was determined using an unsteady Blade Element Theory （BET） previously developed by the authors. Sequential images were captured during the takeoff tests using a high-speed camera. The results demonstrated that inherent pitching stability for vertical takeoff can be achieved by controlling the relative position between the CG and the mean AC of the flapping system.
基金Supported by A grant from the Drexel-Ameri Health Faculty Initiatives,No.282573
文摘AIMTo examine the epidemic of diabetes mellitus (DM) and its impact on mortality from all-cause and cardiovascular disease (CVD), and to test the effect of antidiabetic therapy on the mortality in United States adults. METHODS The analysis included a randomized population sample of 272149 subjects ages ≥ 18 years who participated in the National Health Interview Surveys (NHIS) in2000-2009. Chronic conditions (hypertension, DM and CVD) were classified by participants’ self-reports of physician diagnosis. NHIS-Mortality Linked Files, and NHIS-Medical Expenditure Panel Survey Linkage Fileson prescribed medicines for patients with DM were used to test the research questions. χ 2, Poisson and Cox’s regression models were applied in data analysis.RESULTS Of all participants, 22305 (8.2%) had DM. The prevalence of DM significantly increased from 2000 to 2009 in all age groups (P < 0.001). Within an average 7.39 (SD= 3) years of follow-up, male DM patients had 1.56 times higher risk of death from all-cause (HR = 1.56, 95%CI:1.49-1.64), 1.72 times higher from heart disease [1.72 (1.53-1.93)], 1.48 times higher from cerebrovascular disease [1.48 (1.18-1.85)], and 1.67 times higher from CVD [1.67 (1.51-1.86)] than subjects without DM,respectively. Similar results were observed in females. In males, 10% of DM patients did not use any antidiabetic medications, 38.1% used antidiabetic monotherapy, and 51.9% used ≥ 2 antidiabetic medications. These corresponding values were 10.3%, 40.4% and 49.4% in females. A significant protective effect of metformin monotherapy or combination therapy (except for insulin) on all-cause mortality and a protective but non-significant effect on CVD mortality were observed. CONCLUSION This is the first study using data from multiple linkage files to confirm a significant increased prevalence of DM in the last decade in the United States. Patients with DM have significantly higher risk of death from all-cause and CVD than those without DM. Antidiabetic mediations,specifically for metformin
文摘Diabetes mellitus(DM)is a growing epidemic with global proportions.It is estimated that in 2019,463 million adults aged 20-79 years were living with DM.The latest evidence shows that DM continues to be a significant global health challenge and is likely to continue to grow substantially in the next decades,which would have major implications for healthcare expenditures,particularly in developing countries.Hence,new conceptual and methodological approaches to tackle the epidemic are long overdue.Spatial epidemiology has been a successful approach to control infectious disease epidemics like malaria and human immunodeficiency virus.The implementation of this approach has been expanded to include the study of non-communicable diseases like cancer and cardiovascular diseases.In this review,we discussed the implementation and use of spatial epidemiology and Geographic Information Systems to the study of DM.We reviewed several spatial methods used to understand the spatial structure of the disease and identify the potential geographical drivers of the spatial distribution of DM.Finally,we discussed the use of spatial epidemiology on the design and implementation of geographically targeted prevention and treatment interventions against DM.
