AIM To analyze liver tests before and following treatment with herbal Traditional Chinese Medicine(TCM) in order to evaluate the frequency of newly detected liver injury.METHODS Patients with normal values of alanine ...AIM To analyze liver tests before and following treatment with herbal Traditional Chinese Medicine(TCM) in order to evaluate the frequency of newly detected liver injury.METHODS Patients with normal values of alanine aminotransferase(ALT) as a diagnostic marker for ruling out pre-existing liver disease were enrolled in a prospective study of a safety program carried out at the First German Hospital of TCM from 1994 to 2015. All patients received herbal products, and their ALT values were reassessed 1-3 d prior to discharge. To verify or exclude causality for suspected TCM herbs, the Roussel Uclaf Causality Assessment Method(RUCAM) was used.RESULTS This report presents for the first time liver injury data derived from a prospective, hospital-based and largescale study of 21470 patients who had no liver disease prior to treatment with herbal TCM. Among these, ALT ranged from 1 × to < 5 × upper limit normal(ULN) in 844 patients(3.93%) and suggested mild or moderate liver adaptive abnormalities. However, 26 patients(0.12%) experienced higher ALT values of ≥ 5 × ULN(300.0 ± 172.9 U/L, mean ± SD). Causality for TCM herbs was RUCAM-based probable in 8/26 patients, possible in 16/26, and excluded in 2/26 cases. Bupleuri radix and Scutellariae radix were the two TCM herbs most commonly implicated. CONCLUSION In 26(0.12%) of 21470 patients treated with herbal TCM, liver injury with ALT values of ≥ 5 × ULN was found, which normalized shortly following treatment cessation, also substantiating causality.展开更多
Three genetic mechanisms activate oncogenes in human neoplasms: 1) mutations, 2) gene amplification, and 3) chromosome rearrangements. These mechanisms result in either an alteration of protooncogene structure or an i...Three genetic mechanisms activate oncogenes in human neoplasms: 1) mutations, 2) gene amplification, and 3) chromosome rearrangements. These mechanisms result in either an alteration of protooncogene structure or an increase in protooncogene expression. The role of epigenetic aberrancies in carcinogenesis has been described earlier however to clinicians, the biological implications of epigenetic therapies to prevent cancer and the mechanisms involved have been a mystery. Furthermore, there is no biomarker suggested to track the carcinogenesis steps long before cancer develops, and this has caused a significant lack of proactive and preventive measures to be taken as all recommendations in preventive oncology are either deficiently and blindly made or through screening methods which are too late in the game. Here we explored a very different approach by applying our deepest understanding of epigenetics and carcinogenesis and even further we developed a framework where our clinical findings could translate to the research and vice versa by generating advanced and novel hypotheses on “how we get cancer”, by exploring the relation between the host and the tumor cells in a way no one had perceived before. The role of specific cancer stem cell pathways is dissected and how to inhibit each of these initiators using multitargeted epigenetic therapies and off-label medications are explained. We should admit that without considering this sophisticated amazing biological network, cancer will remain an unsolved challenge. Further, we were able to solve this unsolved puzzle by bridging the gap from a hypothetical point of view/hypothesis to possibilities that explain the clinical findings we had observed, and conclude that such an approach can completely change the way practitioners are treating cancer.展开更多
This article discusses the role of epithelial mesenchymal transition (EMT) and addresses the scientific merits on epigenetic regulation of EMT. The importance of EMT as a prognostic biomarker is explored and the ratio...This article discusses the role of epithelial mesenchymal transition (EMT) and addresses the scientific merits on epigenetic regulation of EMT. The importance of EMT as a prognostic biomarker is explored and the rationale on application of multitargeted epigenetic therapy is discussed. We describe a literature review of the epigenetic influence of such process and we present a potentially effective method to reverse the epigenetic switch in favor for MET, in a clinical setting. A case series of advanced solid tumors are summarized aiming at generating hypothesis for the future recommendations for clinical trials targeting the tumor’s biological behavior through inhibition of EMT. Hypothesis: We propose an integral and integrative approach that can modify tumor’s biological behavior through inhibition of EMT, and further reduce the chances of metastasis, that can translate to improved outcome and patient’s survival in advanced disease.展开更多
In most cases, cancer develops as a result of non-inheritable somatic mutations (epimutations), acquired by the individual adult cell, during the evolution of the cell, and propagated into an expanding clone of progen...In most cases, cancer develops as a result of non-inheritable somatic mutations (epimutations), acquired by the individual adult cell, during the evolution of the cell, and propagated into an expanding clone of progeny of the cells by natural selection [1]. The role of microenvironment in selection for such acquired mutations, or epimutations, is a focus of scientific research in carcinogenesis [2]. Here we describe a defective DNA response to hypoxia due to epigenetic aberrancies, in cancer cellular biology [3]. We also summarize a literature review on hypoxia mediated epigenetic responses, and its role in carcinogenesis and metastasis. Further, we review a novel method of treating hypoxic solid tumors with a combination of epigenetic modifiers with both in vitro and in vivo results in human, translating to an improved prognosis and clinical outcome. We propose that this approach both independently and synergistically (with the current standard of care) can provide an improved outcome.展开更多
<div style="text-align:justify;"> <span style="font-family:Verdana;">Enteroviruses are responsible for emerging diseases which cause diverse symptoms and may result in neurological comp...<div style="text-align:justify;"> <span style="font-family:Verdana;">Enteroviruses are responsible for emerging diseases which cause diverse symptoms and may result in neurological complications. An antiviral with multiple mechanisms of action can help prevent enterovirus mediated disease despite differences in the pathogenesis between enteroviruses, including the recently identified enterovirus 69 (EV-69) for which pathogenesis is not well understood. This study investigated the efficacy of epigallocatechin-3-gallate stearate (EGCG-S), a modified form of the antioxidant green tea catechin epigallocatechin-3-gallate (EGCG), in inhibiting EV-69 infection of lung fibroblast cells </span><i><span style="font-family:Verdana;">in vitro</span></i><span style="font-family:Verdana;">. Treatment with EGCG-S resulted in moderate protection from EV-69 mediated cytotoxicity as demonstrated by increased metabolic activity as well as maintenance of cell morphology and mitochondrial function. These effects were correlated with reduced hydrogen peroxide production in infected cells following EGCG-S treatment with concentrations less than 100 μM, suggesting a role for inhibition of EV-69 mediated oxidative stress. This study provides insight into characteristics of EV-69 infection as well as the efficacy of EGCG-S mediated inhibition of EV-69 infection.</span> </div>展开更多
Purpose: To evaluate Charcot neuroarthropathy in diabetic foot patients at tertiary hospital. Methods and Material: It is a retrospective study from 2005 to 2015 of Charcot foot patients in diabetic patients admitted ...Purpose: To evaluate Charcot neuroarthropathy in diabetic foot patients at tertiary hospital. Methods and Material: It is a retrospective study from 2005 to 2015 of Charcot foot patients in diabetic patients admitted in King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Sixty-four patients were admitted as diabetic foot disease and were studied by reviewing patients records of demography, pain, discharge, duration of disease, duration and types of diabetes IDDM [Insulin Dependant Diabetes Mellitus] NIDDM [Non Insulin Dependent Diabetes Mellitus], history of trauma, peripheral vascular disease, obesity, hypertension, co-morbid conditions, previous surgery, involvement of fore foot/midfoot/hindfoot, deformity, ulcer and treatment like casts, offloading devices, pharmacological like biphosphonates, debridement, osteotomy, arthrodesis, exostectomy, and amputation. Results: Majority of patients were males (81.2%). Mean age was 61.75 years. Pain was reported in 25% of patients, numbness in 12.5%, foot deformity in 23.4%, pus discharge in 73.4%, difficulty in walking in 12.5%, and 10.9% had history of trauma. Majority of patients were NIDDM 68.8%, IDDM 31.3%, (62.5% had DM more than 10 years and 36.9% had DM less than 10 years), controlled DM in 21.9% and uncontrolled DM in 73.4%, nephropathy in 46.3%, neuropathy in 59.4%, retinopathy in 40.6%, cardiomyopathy in 48.4% and vasculopathy in 56.3%. Charcot arthropathy was in 28.1% of cases and forefoot was involved in 65.5%, midfoot in 4.7% and hindfoot/ankle in 21.9%. It was forefoot which was mainly involved in Charcot joint disease. It was demonstrated by X-rays which showed subluxation in 40.6%, dislocation in 54.7%, disorganized foot joints in 42.2%, bone resorption in 23.4%, osteomyelitis in 14.1%, fractures in 50%, joint collapse in 39.1% and destruction of articular surfaces in 37.5%. Debridement was done in 25% of cases while 75% of patients underwent some sort of amputation. 14.1% of patients underwent above knee amputation, 10.9% below knee amputation, 10.展开更多
Aim:To assess the relation of reactive oxygen species(ROS)and antioxidants in the internal spermatic vein blood compared to the peripheral venous blood.Methods:Sixty-eight infertile oligoasthenozoospemic patients asso...Aim:To assess the relation of reactive oxygen species(ROS)and antioxidants in the internal spermatic vein blood compared to the peripheral venous blood.Methods:Sixty-eight infertile oligoasthenozoospemic patients associated with varicocele were investigated.During inguinal varicocelectomy,blood samples of internal sper- matic as well as median cubital veins were withdrawn.Three ROS factors(malondialdehyde[MDA],hydrogen peroxide H_2O_2,nitric oxide[NO])and four antioxidants(superoxide dismutase[SOD],catalase[Cat],glutathione peroxidase[GPx] and vitamin C)were estimated in these blood samples.Results:Mean levels of tested ROS factors were significantly higher in the internal spermatic venous blood compared to those in the peripheral one (mean±SD)(MDA 18.7±1.4 nmol/mL vs.15.4±1.4 nmol/mL,H_2O_2 43.6±8.0 μmol/mL vs.30.8±8.1 μmol/mL,NO 2.3±0.5 nmol/L vs.1.6±0.4 nmol/L,P<0.01).Mean levels of tested antioxidants were significantly lower in the internal spermatic venous blood compared to those in the peripheral one(superoxide dismutase 1690.7±130.0 U/mL vs.1818.5±143.0 U/mL,catalase 38.9±6.1 mol/L vs.47.9±10.2 mol/L,GPx 20.4±8.1 U/mL vs.23.0±8.4 U/mL,vita- min C 0.3±0.1 vs.0.4±0.1 mg/dL,P<0.05).Conclusion:Internal spermatic venous blood of infertile male cases associated with varicocele demonstrated elevated levels of ROS and decreased levels of antioxidants compared to peripheral venous circulation.(Asian J Androl 2006 Jul;8:451-454)展开更多
BACKGROUND Chronic hepatitis B virus(HBV)and hepatitis C virus(HCV)infections are known risk factors for liver disease,cirrhosis and hepatocellular carcinoma(HCC).There is substantial global variation in HBV and HCV p...BACKGROUND Chronic hepatitis B virus(HBV)and hepatitis C virus(HCV)infections are known risk factors for liver disease,cirrhosis and hepatocellular carcinoma(HCC).There is substantial global variation in HBV and HCV prevalence resulting in variations in cirrhosis and HCC.We previously reported high prevalence of HBV and HCV infections in Somali immigrants seen at an academic medical center in Minnesota.AIM To determine the prevalence of chronic viral hepatitis in Somali immigrants in Minnesota through a community-based screening program.METHODS We conducted a prospective community-based participatory research study in the Somali community in Minnesota in partnership with community advisory boards,community clinics and local mosques between November 2010 and December 2015(data was analyzed in 2020).Serum was tested for hepatitis B surface antigen,hepatitis B core antibody,hepatitis B surface antibody and anti-HCV antibody.RESULTS Of 779 participants,15.4%tested positive for chronic HBV infection,50.2%for prior exposure to HBV and 7.6%for chronic HCV infection.Calculated age-adjusted frequencies in males and females for chronic HBV were 12.5%and 11.6%;for prior exposure to HBV were 44.8%and 41.3%;and for chronic HCV were 6.7%and 5.7%,respectively.Seven participants developed incident HCC during follow up.CONCLUSION Chronic HBV and HCV are major risk factors for liver disease and HCC among Somali immigrants,with prevalence of both infections substantially higher than in the general United States population.Community-based screening is essential for identifying and providing health education and linkage to care for diagnosed patients.展开更多
A polyhedral active set algorithm PASA is developed for solving a nonlinear optimization problem whose feasible set is a polyhedron. Phase one of the algorithm is the gradient projection method, while phase two is any...A polyhedral active set algorithm PASA is developed for solving a nonlinear optimization problem whose feasible set is a polyhedron. Phase one of the algorithm is the gradient projection method, while phase two is any algorithm for solving a linearly constrained optimization problem. Rules are provided for branching between the two phases. Global convergence to a stationary point is established, while asymptotically PASA performs only phase two when either a nondegeneracy assumption holds, or the active constraints are linearly independent and a strong second-order sufficient optimality condition holds.展开更多
BACKGROUND The rising number of people using methamphetamine leads to an increasing need for treatment options for this patient group.Evidence-based research on the efficacy of treatment programs for methamphetamine u...BACKGROUND The rising number of people using methamphetamine leads to an increasing need for treatment options for this patient group.Evidence-based research on the efficacy of treatment programs for methamphetamine users is limited.Due to specific characteristics of methamphetamine users,the question arises whether established treatment methods for individuals using other substances can be effective for the treatment of methamphetamine dependence as well.We hypothesize that there are significant differences between the two groups that may affect the effectiveness of treatment and worsen the prognosis of treatment outcomes for methamphetamine users compared to consumers of other substances.AIM To investigate potential differences in cognitive functioning and psychopathology between methamphetamine users and other substance users and possible correlations with treatment outcomes.METHODS A total of 110 subjects were recruited for an observational,longitudinal study from a German inpatient addiction treatment center:55 patients with methamphetamine dependence and 55 patients with dependence of other substances(“OS group”).Both groups were examined at beginning(baseline)and end of treatment(after 6 mo)with regard to treatment retention,craving,cognitive functioning,psychosocial resources,personality traits,depression,and other psychiatric symptoms.Instruments used were Raven’s IQ test,Mannheimer craving scale,cognitrone cognitive test battery,NEO personality factors inventory,Hamilton depression scale,Becks depression inventory,and a symptom checklist.The statistical methods used were χ^(2)-test,t-test and multiple mixed ANOVAs.RESULTS A total drop-out rate of 40%(methamphetamine-group:36.4%;OS-group:43.6%)was observed without significant differences between groups.At baseline,methamphetamine-group subjects significantly differed from OS-group individuals in terms of a lower intelligence quotient,fewer years of education,slower working speed,and decreased working accuracy,as well as less cannabinoid and cocain展开更多
Skin-inspired soft and stretchable electronic devices based on functional nanomaterials have broad applications such as health monitoring,human-machine interface,and the Internet of things.Solution-processed conductiv...Skin-inspired soft and stretchable electronic devices based on functional nanomaterials have broad applications such as health monitoring,human-machine interface,and the Internet of things.Solution-processed conductive nanocomposites have shown great promise as a building block of soft and stretchable electronic devices.However,realizing conductive nanocomposites with high conductivity,electromechanical stability,and low modulus over a large area at sub-100μm resolution remains challenging.Here,we report a moldable,transferrable,high-performance conductive nanocomposite comprised of an interpenetrating network of silver nanowires and poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate).The stacked structure of the nanocomposite synergistically integrates the complementary electrical and mechanical properties of the individual components.We patterned the nanocomposite via a simple,low-cost micromolding process and then transferred the patterned large-area electrodes onto various substrates to realize soft,skin-interfaced electrophysiological sensors.Electrophysiological signals measured using the nanocomposite electrodes exhibit a higher signal-to-noise ratio than standard gel electrodes.The nanocomposite design and fabrication approach presented here can be broadly employed for soft and stretchable electronic devices.展开更多
Linear and nonlinear dust acoustic(DA)waves have been investigated in an opposite polarity dusty plasma comprising negatively and positively charged dust grains,Maxwellian electrons and ions,including the generalized ...Linear and nonlinear dust acoustic(DA)waves have been investigated in an opposite polarity dusty plasma comprising negatively and positively charged dust grains,Maxwellian electrons and ions,including the generalized polarization force effect.The properties of linear DA waves have been significantly altered by the dual dust polarity and polarization force.Large amplitude DA solitons have been discussed in the framework of the Sagdeev potential technique.Our results show that both rarefactive and compressive solitons can exist in such a dusty plasma.The basic features of the Sagdeev potential have been examined under the effect of the polarization force parameter R,the ratio of the charge number of the positive dust to that of the negative dust Z,and the Mach number M.The results show that these parameters play a significant role in determining the region of existence of large amplitude DA solitons.展开更多
The disagreements in clinical data and therapy recommendations extracted from different sources/studies are a common finding in oncology research. Knowingly “biology is less reproducible than physics and mechanic eng...The disagreements in clinical data and therapy recommendations extracted from different sources/studies are a common finding in oncology research. Knowingly “biology is less reproducible than physics and mechanic engineering”, in order to overcome the disagreements and to find common grounds, we still rely on meta-analysis and systemic reviews for the highest level of evidence. To gather systemic review data base, a bibliographic search usually is conducted in the PubMed and in Cochrane Central Register of Controlled Trials databases to address a common clinical challenge. That said, frequently due to common conflicts between articles outcomes, an opinion of a third investigator is sought. Here in this article, we propose a rationale that could explain the differences in outcomes as a result of imperfect understanding of the current research database secondary to the unique biology of the tumor, rather than statistical interpretation on findings. We believe that the differences in findings merely are based on blinded inclusion criteria, and lack of accurate companion diagnostics to correlate the magnitude of response to each therapy. The objective of this article is to discuss a strategy to overcome such discordance by providing quantitative biological measures for genomic classification and correlation of tumor response to the selected targeted therapy. We further review such analysis in a case series of Her 2 positive breast cancer and conclude that translational research would be clinically relevant when customized to the biological findings.展开更多
The introduction of PARP inhibitors as active agents to inhibit the DNA repair was a revolution in the cancer therapeutics, however, such approach only has shown promising results for a short time in majority of cases...The introduction of PARP inhibitors as active agents to inhibit the DNA repair was a revolution in the cancer therapeutics, however, such approach only has shown promising results for a short time in majority of cases due to secondary mutations and promoter gene methylation, and most of patients with triple negative breast cancer when treated with such agents only benefit for a short time, until the tumor shows resistance and further the therapy fails [1]. Considering this category of drugs and their mechanism of action in DNA repair [2] [3], several recent studies have focused on combination of PARP inhibitors with chemotherapy, immune therapy and interestingly relevant to this article, epigenetic therapies [4]. That said, to our knowledge the human data in this regard is missing. Here we discuss a case report of a patient with stage four refractory and resistant BRCA1 mutated triple negative breast cancer who responded in matter of two weeks to a combinational therapy, consisting of PARP inhibitor and epigenetic therapies. As the patient already had exhausted the PARP inhibitor by excessive presence of BRCA positive altered circulatory DNA, the response merely reflects the epigenetic therapy as back bone of treatment. The liquid biopsy repeated after two weeks of combination therapy showed complete disappearance (resolution of positive BRCA gene/c DNA), reflecting a synergism by proposed modulation of resistance as mechanism of action. (The initial c DNA showed 93 percent mutation allele fraction of BRCA gene.) To our knowledge, this is the first study on combinational therapy in human. The finding in this case could potentially change the standard of care in treating BRCA positive tumors, by providing a superior treatment to current standards.展开更多
The vehicular ad hoc network (VANET) technology based on the approved IEEE 802.11p standard and the appendant inter-vehicle communication (IVC) has the potential to dramatically change the way transportation systems w...The vehicular ad hoc network (VANET) technology based on the approved IEEE 802.11p standard and the appendant inter-vehicle communication (IVC) has the potential to dramatically change the way transportation systems work. The fundamental idea is to change the individual behavior of each vehicle by exchanging information among traffic participants to realize a cooperative and more efficient transportation system. Certainly, the evaluation of such systems is a comprehensive and challenging task in a real world test bed, therefore, simulation frameworks are a key tool to analyze IVC. Several models are needed to emulate the real behavior of a VANET in all aspects as much realistically as necessary. The intention of this survey is to provide a comprehensive overview of publications concerning IVC simulations of the year 2013 and to see how IVC simulation has changed since 2009. Based on this analysis, we will answer the following questions: What simulation techniques are applied to IVC? Which aspects of IVS have been evaluated? What has changed within five years of IVC simulations? We also take a closer look at commonly used software tools and discuss their functionality and drawbacks. Finally, we present open questions concerning IVC simulations.展开更多
文摘AIM To analyze liver tests before and following treatment with herbal Traditional Chinese Medicine(TCM) in order to evaluate the frequency of newly detected liver injury.METHODS Patients with normal values of alanine aminotransferase(ALT) as a diagnostic marker for ruling out pre-existing liver disease were enrolled in a prospective study of a safety program carried out at the First German Hospital of TCM from 1994 to 2015. All patients received herbal products, and their ALT values were reassessed 1-3 d prior to discharge. To verify or exclude causality for suspected TCM herbs, the Roussel Uclaf Causality Assessment Method(RUCAM) was used.RESULTS This report presents for the first time liver injury data derived from a prospective, hospital-based and largescale study of 21470 patients who had no liver disease prior to treatment with herbal TCM. Among these, ALT ranged from 1 × to < 5 × upper limit normal(ULN) in 844 patients(3.93%) and suggested mild or moderate liver adaptive abnormalities. However, 26 patients(0.12%) experienced higher ALT values of ≥ 5 × ULN(300.0 ± 172.9 U/L, mean ± SD). Causality for TCM herbs was RUCAM-based probable in 8/26 patients, possible in 16/26, and excluded in 2/26 cases. Bupleuri radix and Scutellariae radix were the two TCM herbs most commonly implicated. CONCLUSION In 26(0.12%) of 21470 patients treated with herbal TCM, liver injury with ALT values of ≥ 5 × ULN was found, which normalized shortly following treatment cessation, also substantiating causality.
文摘Three genetic mechanisms activate oncogenes in human neoplasms: 1) mutations, 2) gene amplification, and 3) chromosome rearrangements. These mechanisms result in either an alteration of protooncogene structure or an increase in protooncogene expression. The role of epigenetic aberrancies in carcinogenesis has been described earlier however to clinicians, the biological implications of epigenetic therapies to prevent cancer and the mechanisms involved have been a mystery. Furthermore, there is no biomarker suggested to track the carcinogenesis steps long before cancer develops, and this has caused a significant lack of proactive and preventive measures to be taken as all recommendations in preventive oncology are either deficiently and blindly made or through screening methods which are too late in the game. Here we explored a very different approach by applying our deepest understanding of epigenetics and carcinogenesis and even further we developed a framework where our clinical findings could translate to the research and vice versa by generating advanced and novel hypotheses on “how we get cancer”, by exploring the relation between the host and the tumor cells in a way no one had perceived before. The role of specific cancer stem cell pathways is dissected and how to inhibit each of these initiators using multitargeted epigenetic therapies and off-label medications are explained. We should admit that without considering this sophisticated amazing biological network, cancer will remain an unsolved challenge. Further, we were able to solve this unsolved puzzle by bridging the gap from a hypothetical point of view/hypothesis to possibilities that explain the clinical findings we had observed, and conclude that such an approach can completely change the way practitioners are treating cancer.
文摘This article discusses the role of epithelial mesenchymal transition (EMT) and addresses the scientific merits on epigenetic regulation of EMT. The importance of EMT as a prognostic biomarker is explored and the rationale on application of multitargeted epigenetic therapy is discussed. We describe a literature review of the epigenetic influence of such process and we present a potentially effective method to reverse the epigenetic switch in favor for MET, in a clinical setting. A case series of advanced solid tumors are summarized aiming at generating hypothesis for the future recommendations for clinical trials targeting the tumor’s biological behavior through inhibition of EMT. Hypothesis: We propose an integral and integrative approach that can modify tumor’s biological behavior through inhibition of EMT, and further reduce the chances of metastasis, that can translate to improved outcome and patient’s survival in advanced disease.
文摘In most cases, cancer develops as a result of non-inheritable somatic mutations (epimutations), acquired by the individual adult cell, during the evolution of the cell, and propagated into an expanding clone of progeny of the cells by natural selection [1]. The role of microenvironment in selection for such acquired mutations, or epimutations, is a focus of scientific research in carcinogenesis [2]. Here we describe a defective DNA response to hypoxia due to epigenetic aberrancies, in cancer cellular biology [3]. We also summarize a literature review on hypoxia mediated epigenetic responses, and its role in carcinogenesis and metastasis. Further, we review a novel method of treating hypoxic solid tumors with a combination of epigenetic modifiers with both in vitro and in vivo results in human, translating to an improved prognosis and clinical outcome. We propose that this approach both independently and synergistically (with the current standard of care) can provide an improved outcome.
文摘<div style="text-align:justify;"> <span style="font-family:Verdana;">Enteroviruses are responsible for emerging diseases which cause diverse symptoms and may result in neurological complications. An antiviral with multiple mechanisms of action can help prevent enterovirus mediated disease despite differences in the pathogenesis between enteroviruses, including the recently identified enterovirus 69 (EV-69) for which pathogenesis is not well understood. This study investigated the efficacy of epigallocatechin-3-gallate stearate (EGCG-S), a modified form of the antioxidant green tea catechin epigallocatechin-3-gallate (EGCG), in inhibiting EV-69 infection of lung fibroblast cells </span><i><span style="font-family:Verdana;">in vitro</span></i><span style="font-family:Verdana;">. Treatment with EGCG-S resulted in moderate protection from EV-69 mediated cytotoxicity as demonstrated by increased metabolic activity as well as maintenance of cell morphology and mitochondrial function. These effects were correlated with reduced hydrogen peroxide production in infected cells following EGCG-S treatment with concentrations less than 100 μM, suggesting a role for inhibition of EV-69 mediated oxidative stress. This study provides insight into characteristics of EV-69 infection as well as the efficacy of EGCG-S mediated inhibition of EV-69 infection.</span> </div>
文摘Purpose: To evaluate Charcot neuroarthropathy in diabetic foot patients at tertiary hospital. Methods and Material: It is a retrospective study from 2005 to 2015 of Charcot foot patients in diabetic patients admitted in King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Sixty-four patients were admitted as diabetic foot disease and were studied by reviewing patients records of demography, pain, discharge, duration of disease, duration and types of diabetes IDDM [Insulin Dependant Diabetes Mellitus] NIDDM [Non Insulin Dependent Diabetes Mellitus], history of trauma, peripheral vascular disease, obesity, hypertension, co-morbid conditions, previous surgery, involvement of fore foot/midfoot/hindfoot, deformity, ulcer and treatment like casts, offloading devices, pharmacological like biphosphonates, debridement, osteotomy, arthrodesis, exostectomy, and amputation. Results: Majority of patients were males (81.2%). Mean age was 61.75 years. Pain was reported in 25% of patients, numbness in 12.5%, foot deformity in 23.4%, pus discharge in 73.4%, difficulty in walking in 12.5%, and 10.9% had history of trauma. Majority of patients were NIDDM 68.8%, IDDM 31.3%, (62.5% had DM more than 10 years and 36.9% had DM less than 10 years), controlled DM in 21.9% and uncontrolled DM in 73.4%, nephropathy in 46.3%, neuropathy in 59.4%, retinopathy in 40.6%, cardiomyopathy in 48.4% and vasculopathy in 56.3%. Charcot arthropathy was in 28.1% of cases and forefoot was involved in 65.5%, midfoot in 4.7% and hindfoot/ankle in 21.9%. It was forefoot which was mainly involved in Charcot joint disease. It was demonstrated by X-rays which showed subluxation in 40.6%, dislocation in 54.7%, disorganized foot joints in 42.2%, bone resorption in 23.4%, osteomyelitis in 14.1%, fractures in 50%, joint collapse in 39.1% and destruction of articular surfaces in 37.5%. Debridement was done in 25% of cases while 75% of patients underwent some sort of amputation. 14.1% of patients underwent above knee amputation, 10.9% below knee amputation, 10.
文摘Aim:To assess the relation of reactive oxygen species(ROS)and antioxidants in the internal spermatic vein blood compared to the peripheral venous blood.Methods:Sixty-eight infertile oligoasthenozoospemic patients associated with varicocele were investigated.During inguinal varicocelectomy,blood samples of internal sper- matic as well as median cubital veins were withdrawn.Three ROS factors(malondialdehyde[MDA],hydrogen peroxide H_2O_2,nitric oxide[NO])and four antioxidants(superoxide dismutase[SOD],catalase[Cat],glutathione peroxidase[GPx] and vitamin C)were estimated in these blood samples.Results:Mean levels of tested ROS factors were significantly higher in the internal spermatic venous blood compared to those in the peripheral one (mean±SD)(MDA 18.7±1.4 nmol/mL vs.15.4±1.4 nmol/mL,H_2O_2 43.6±8.0 μmol/mL vs.30.8±8.1 μmol/mL,NO 2.3±0.5 nmol/L vs.1.6±0.4 nmol/L,P<0.01).Mean levels of tested antioxidants were significantly lower in the internal spermatic venous blood compared to those in the peripheral one(superoxide dismutase 1690.7±130.0 U/mL vs.1818.5±143.0 U/mL,catalase 38.9±6.1 mol/L vs.47.9±10.2 mol/L,GPx 20.4±8.1 U/mL vs.23.0±8.4 U/mL,vita- min C 0.3±0.1 vs.0.4±0.1 mg/dL,P<0.05).Conclusion:Internal spermatic venous blood of infertile male cases associated with varicocele demonstrated elevated levels of ROS and decreased levels of antioxidants compared to peripheral venous circulation.(Asian J Androl 2006 Jul;8:451-454)
基金Supported by the Mayo Clinic Center for Clinical and Translational Science from the National Center for Advancing Translational Sciences (5UL1TR000135-10)the Mayo Clinic Hepatobiliary SPORE from the National Cancer Institute (5P50CA210964-04)+1 种基金the Mayo Clinic Center for Cell Signaling in Gastroenterology (5P30DK084567-14)Gilead Sciences,Inc.(IN-US-174-0230)
文摘BACKGROUND Chronic hepatitis B virus(HBV)and hepatitis C virus(HCV)infections are known risk factors for liver disease,cirrhosis and hepatocellular carcinoma(HCC).There is substantial global variation in HBV and HCV prevalence resulting in variations in cirrhosis and HCC.We previously reported high prevalence of HBV and HCV infections in Somali immigrants seen at an academic medical center in Minnesota.AIM To determine the prevalence of chronic viral hepatitis in Somali immigrants in Minnesota through a community-based screening program.METHODS We conducted a prospective community-based participatory research study in the Somali community in Minnesota in partnership with community advisory boards,community clinics and local mosques between November 2010 and December 2015(data was analyzed in 2020).Serum was tested for hepatitis B surface antigen,hepatitis B core antibody,hepatitis B surface antibody and anti-HCV antibody.RESULTS Of 779 participants,15.4%tested positive for chronic HBV infection,50.2%for prior exposure to HBV and 7.6%for chronic HCV infection.Calculated age-adjusted frequencies in males and females for chronic HBV were 12.5%and 11.6%;for prior exposure to HBV were 44.8%and 41.3%;and for chronic HCV were 6.7%and 5.7%,respectively.Seven participants developed incident HCC during follow up.CONCLUSION Chronic HBV and HCV are major risk factors for liver disease and HCC among Somali immigrants,with prevalence of both infections substantially higher than in the general United States population.Community-based screening is essential for identifying and providing health education and linkage to care for diagnosed patients.
基金supported by the National Science Foundation of USA(Grant Nos.1522629 and 1522654)the Office of Naval Research of USA(Grant Nos.N00014-11-1-0068 and N00014-15-12048)+1 种基金the Air Force Research Laboratory of USA(Contract No.FA8651-08-D-0108/0054)National Natural Science Foundation of China(Grant No.11571178)
文摘A polyhedral active set algorithm PASA is developed for solving a nonlinear optimization problem whose feasible set is a polyhedron. Phase one of the algorithm is the gradient projection method, while phase two is any algorithm for solving a linearly constrained optimization problem. Rules are provided for branching between the two phases. Global convergence to a stationary point is established, while asymptotically PASA performs only phase two when either a nondegeneracy assumption holds, or the active constraints are linearly independent and a strong second-order sufficient optimality condition holds.
基金the German Federal Ministry of Health(partially).
文摘BACKGROUND The rising number of people using methamphetamine leads to an increasing need for treatment options for this patient group.Evidence-based research on the efficacy of treatment programs for methamphetamine users is limited.Due to specific characteristics of methamphetamine users,the question arises whether established treatment methods for individuals using other substances can be effective for the treatment of methamphetamine dependence as well.We hypothesize that there are significant differences between the two groups that may affect the effectiveness of treatment and worsen the prognosis of treatment outcomes for methamphetamine users compared to consumers of other substances.AIM To investigate potential differences in cognitive functioning and psychopathology between methamphetamine users and other substance users and possible correlations with treatment outcomes.METHODS A total of 110 subjects were recruited for an observational,longitudinal study from a German inpatient addiction treatment center:55 patients with methamphetamine dependence and 55 patients with dependence of other substances(“OS group”).Both groups were examined at beginning(baseline)and end of treatment(after 6 mo)with regard to treatment retention,craving,cognitive functioning,psychosocial resources,personality traits,depression,and other psychiatric symptoms.Instruments used were Raven’s IQ test,Mannheimer craving scale,cognitrone cognitive test battery,NEO personality factors inventory,Hamilton depression scale,Becks depression inventory,and a symptom checklist.The statistical methods used were χ^(2)-test,t-test and multiple mixed ANOVAs.RESULTS A total drop-out rate of 40%(methamphetamine-group:36.4%;OS-group:43.6%)was observed without significant differences between groups.At baseline,methamphetamine-group subjects significantly differed from OS-group individuals in terms of a lower intelligence quotient,fewer years of education,slower working speed,and decreased working accuracy,as well as less cannabinoid and cocain
基金funding from the Department of Biomedical Engineering at Texas A&M University,the Texas A&M Engineering Experiment Station,the National Science Foundation (Grant No.1648451)the National Institutes of Health (Grant No.1R21EB029064-01A1).
文摘Skin-inspired soft and stretchable electronic devices based on functional nanomaterials have broad applications such as health monitoring,human-machine interface,and the Internet of things.Solution-processed conductive nanocomposites have shown great promise as a building block of soft and stretchable electronic devices.However,realizing conductive nanocomposites with high conductivity,electromechanical stability,and low modulus over a large area at sub-100μm resolution remains challenging.Here,we report a moldable,transferrable,high-performance conductive nanocomposite comprised of an interpenetrating network of silver nanowires and poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate).The stacked structure of the nanocomposite synergistically integrates the complementary electrical and mechanical properties of the individual components.We patterned the nanocomposite via a simple,low-cost micromolding process and then transferred the patterned large-area electrodes onto various substrates to realize soft,skin-interfaced electrophysiological sensors.Electrophysiological signals measured using the nanocomposite electrodes exhibit a higher signal-to-noise ratio than standard gel electrodes.The nanocomposite design and fabrication approach presented here can be broadly employed for soft and stretchable electronic devices.
文摘Linear and nonlinear dust acoustic(DA)waves have been investigated in an opposite polarity dusty plasma comprising negatively and positively charged dust grains,Maxwellian electrons and ions,including the generalized polarization force effect.The properties of linear DA waves have been significantly altered by the dual dust polarity and polarization force.Large amplitude DA solitons have been discussed in the framework of the Sagdeev potential technique.Our results show that both rarefactive and compressive solitons can exist in such a dusty plasma.The basic features of the Sagdeev potential have been examined under the effect of the polarization force parameter R,the ratio of the charge number of the positive dust to that of the negative dust Z,and the Mach number M.The results show that these parameters play a significant role in determining the region of existence of large amplitude DA solitons.
文摘The disagreements in clinical data and therapy recommendations extracted from different sources/studies are a common finding in oncology research. Knowingly “biology is less reproducible than physics and mechanic engineering”, in order to overcome the disagreements and to find common grounds, we still rely on meta-analysis and systemic reviews for the highest level of evidence. To gather systemic review data base, a bibliographic search usually is conducted in the PubMed and in Cochrane Central Register of Controlled Trials databases to address a common clinical challenge. That said, frequently due to common conflicts between articles outcomes, an opinion of a third investigator is sought. Here in this article, we propose a rationale that could explain the differences in outcomes as a result of imperfect understanding of the current research database secondary to the unique biology of the tumor, rather than statistical interpretation on findings. We believe that the differences in findings merely are based on blinded inclusion criteria, and lack of accurate companion diagnostics to correlate the magnitude of response to each therapy. The objective of this article is to discuss a strategy to overcome such discordance by providing quantitative biological measures for genomic classification and correlation of tumor response to the selected targeted therapy. We further review such analysis in a case series of Her 2 positive breast cancer and conclude that translational research would be clinically relevant when customized to the biological findings.
文摘The introduction of PARP inhibitors as active agents to inhibit the DNA repair was a revolution in the cancer therapeutics, however, such approach only has shown promising results for a short time in majority of cases due to secondary mutations and promoter gene methylation, and most of patients with triple negative breast cancer when treated with such agents only benefit for a short time, until the tumor shows resistance and further the therapy fails [1]. Considering this category of drugs and their mechanism of action in DNA repair [2] [3], several recent studies have focused on combination of PARP inhibitors with chemotherapy, immune therapy and interestingly relevant to this article, epigenetic therapies [4]. That said, to our knowledge the human data in this regard is missing. Here we discuss a case report of a patient with stage four refractory and resistant BRCA1 mutated triple negative breast cancer who responded in matter of two weeks to a combinational therapy, consisting of PARP inhibitor and epigenetic therapies. As the patient already had exhausted the PARP inhibitor by excessive presence of BRCA positive altered circulatory DNA, the response merely reflects the epigenetic therapy as back bone of treatment. The liquid biopsy repeated after two weeks of combination therapy showed complete disappearance (resolution of positive BRCA gene/c DNA), reflecting a synergism by proposed modulation of resistance as mechanism of action. (The initial c DNA showed 93 percent mutation allele fraction of BRCA gene.) To our knowledge, this is the first study on combinational therapy in human. The finding in this case could potentially change the standard of care in treating BRCA positive tumors, by providing a superior treatment to current standards.
文摘The vehicular ad hoc network (VANET) technology based on the approved IEEE 802.11p standard and the appendant inter-vehicle communication (IVC) has the potential to dramatically change the way transportation systems work. The fundamental idea is to change the individual behavior of each vehicle by exchanging information among traffic participants to realize a cooperative and more efficient transportation system. Certainly, the evaluation of such systems is a comprehensive and challenging task in a real world test bed, therefore, simulation frameworks are a key tool to analyze IVC. Several models are needed to emulate the real behavior of a VANET in all aspects as much realistically as necessary. The intention of this survey is to provide a comprehensive overview of publications concerning IVC simulations of the year 2013 and to see how IVC simulation has changed since 2009. Based on this analysis, we will answer the following questions: What simulation techniques are applied to IVC? Which aspects of IVS have been evaluated? What has changed within five years of IVC simulations? We also take a closer look at commonly used software tools and discuss their functionality and drawbacks. Finally, we present open questions concerning IVC simulations.
