Thiram is a dithiocarbamate compound widely used for industrial processes and agriculture. Animal studies reveal that this compound may afftct the male reproductive system. Aim of this study was to test, using sensiti...Thiram is a dithiocarbamate compound widely used for industrial processes and agriculture. Animal studies reveal that this compound may afftct the male reproductive system. Aim of this study was to test, using sensitive testicular parameters, whether thiram directly affects germinal cells. For this purpose, B6C3F1 mice were intraperitoneally injected with thiram in oil (single dose:75 mg/kg; repeated five daily doses: 25 mg/kg).Although both treatments were toxic, none of the parameters examined, i.e., testis weighi, spermatid head number,specific enzyme levels at different times after treatment (14, 28, 35, 56 days) showed significant variations from the controls, On the contrary, in the positive controls (treated with chlorambucil), a marked reduction of sperm head number as well as a deerease of lactate dehydrogenasex and sorbitol dehydrogenase activity letels were evidenced at day 28, with a tendency to recover at day 35. Under these conditions thiram did not cause cytotoxicity on differentiating spermatogonia and on late spermatocyte stages of mice gonads展开更多
Acute toxicity of 0.3 ppm mercuric chloride on the mucocytes of the branchial diverticulum and skin of Heteropneustes fossilis results in cyclic increases followed by decreases in the density, area occupancy and volum...Acute toxicity of 0.3 ppm mercuric chloride on the mucocytes of the branchial diverticulum and skin of Heteropneustes fossilis results in cyclic increases followed by decreases in the density, area occupancy and volume at different intervals of exposure. The alterations in the two tissues do not follow the same path perhaps due to different modes of action of the mercury salt: The skin comes under direct contact effects, while the branchial diverticulum may be affected by hormonal imbalance caused by a stress effect.展开更多
Objective To investigate the effect of fingolimod (FTY720)on RhoA expression after spinal cord injury (SCI)in rats,and explore the possible mechanism of FTY720in the treatment of SCI.Methods A rat model of acute SCI w...Objective To investigate the effect of fingolimod (FTY720)on RhoA expression after spinal cord injury (SCI)in rats,and explore the possible mechanism of FTY720in the treatment of SCI.Methods A rat model of acute SCI was established with a展开更多
Objective To investigate the effects of Glibenclamide on reduction of secondary damage after acute spinal cord injury in rats.Methods Ninety rats were randomly divided into control group(laminectomy alone),spinal cord...Objective To investigate the effects of Glibenclamide on reduction of secondary damage after acute spinal cord injury in rats.Methods Ninety rats were randomly divided into control group(laminectomy alone),spinal cord injury group(injury group),and treatment group(treated展开更多
Objective Air pollution is a leading public health issue.This study investigated the effect of air quality and pollutants on pulmonary function and inflammation in patients with asthma in Shanghai.Methods The study mo...Objective Air pollution is a leading public health issue.This study investigated the effect of air quality and pollutants on pulmonary function and inflammation in patients with asthma in Shanghai.Methods The study monitored 27 asthma outpatients for a year,collecting data on weather,patient self-management[daily asthma diary,peak expiratory flow(PEF)monitoring,medication usage],spirometry and serum markers.To explore the potential mechanisms of any effects,asthmatic mice induced by ovalbumin(OVA)were exposed to PM_(2.5).Results Statistical and correlational analyses revealed that air pollutants have both acute and chronic effects on asthma.Acute exposure showed a correlation between PEF and levels of ozone(O_(3))and nitrogen dioxide(NO_(2)).Chronic exposure indicated that interleukin-5(IL-5)and interleukin-13(IL-13)levels correlated with PM_(2.5)and PM_(10)concentrations.In asthmatic mouse models,exposure to PM_(2.5)increased cytokine levels and worsened lung function.Additionally,PM_(2.5)exposure inhibited cell proliferation by blocking the NF-κB and ERK phosphorylation pathways.Conclusion Ambient air pollutants exacerbate asthma by worsening lung function and enhancing Th2-mediated inflammation.Specifically,PM_(2.5)significantly contributes to these adverse effects.Further research is needed to elucidate the mechanisms by which PM_(2.5)impacts asthma.展开更多
Mussels from two sites within the Baltic mussel (Mytilus edulis × M. trossulus) hybrid zone were used in a comparative study on the effects of salinity-changing rates on filtration activity. The acute effect of v...Mussels from two sites within the Baltic mussel (Mytilus edulis × M. trossulus) hybrid zone were used in a comparative study on the effects of salinity-changing rates on filtration activity. The acute effect of varying salinity-changing rates was found to be similar in M. edulis from the brackish Great Belt and in M. trossulus from the low saline Central Baltic Sea, and the relationships could be described by linear regression lines through 0.0 indicating that the acute effect of deteriorating conditions at decreasing salinities is the opposite as for improving conditions when the salinity is subsequently increased. Further, both M. edulis and M. trossulus acclimatized to 20 psu reacted to an acute salinity change to 6.5 psu by immediately closing their valves whereupon the filtration rate gradually increased during the following days, but only M. trossulus had completely acclimatized to 6.5 psu within 5 days which may be explained by different genotypes of M. edulis and M. trossulus which probably reflected an evolutionary adaptation of the latter to survive in the stable low-salinity Baltic Sea.展开更多
The oil spill impact analysis (OSIA) software system has been developed to supply a tool for comprehensive, quantitative environmental impact assessments resulting from oil spills. In the system, a biological componen...The oil spill impact analysis (OSIA) software system has been developed to supply a tool for comprehensive, quantitative environmental impact assessments resulting from oil spills. In the system, a biological component evaluates potential effects on exposed organisms based on results from a physico chemical fates component, including the extent and characteristics of the surface slick, and dissolved and total concentrations of hydrocarbons in the water column. The component includes a particle based exposure model for migratory adult fish populations, a particle based exposure model for spawning planktonic organisms (eggs and larvae), and an exposure model for wildlife species (sea birds or marine mammals). The exposure model for migratory adult fish populations simulates the migration behaviors of fish populations migrating to or staying in their feeding areas, over wintering areas or spawning areas, and determines the acute effects (mortality) and chronic accumulation (body burdens) from the dissolved contaminant. The exposure model for spawning planktonic organisms simulates the release of eggs and larvae, also as particles, from specific spawning areas during the spawning period, and determines their potential exposure to contaminants in the water or sediment. The exposure model for wild species calculates the exposure to surface oil of wildlife (bird and marine mammal) categories inhabiting the contaminated area. Compared with the earlier models in which all kinds of organisms are assumed evenly and randomly distributed, the updated biological exposure models can more realistically estimate potential effects on marine ecological system from oil spill pollution events.展开更多
Objective: To investigate the level of acute phase proteins (APP)-synthesized in hepatocytes in pathogenic process of multiple organ dysfunction syndrome (MODS) and the effect of Dachengqi Decoction (DCQD) on it. Met...Objective: To investigate the level of acute phase proteins (APP)-synthesized in hepatocytes in pathogenic process of multiple organ dysfunction syndrome (MODS) and the effect of Dachengqi Decoction (DCQD) on it. Methods: The levels of C-reactive protein (CRP),α1-acid glycoprotein (AAG), α1-antitrypsin total (α1AT), α2-macroglobulin (α2-MG), ceruloplasmine (CP), hepatoglobin (HP) and transferrin (TF) synthesis were determined in 32 cases of MODS patients and rat models of MODS induced by acute infective peritonitis and mesenterial artery ischemia-reperfusion.Results: The serum APP level in MODS patients was increased and higher than that in the control group (P < 0. 01 ). After 3 days of DCQD treatment it reduced significantly (P <0. 05). Serum APP level in MODS model was also increased significantly, and after 3 days of DCQD treatment, it reduced significantly (P < 0. 05). The APP secreting level of rat hepatocytes cultured in vitro raised after stimulated and activated by lipopolysacchride, which was reduced after cultured with rabbits serum containing different concentration of effective ingredients of DCQD. The APP inhibiting effect of DCQD was dose dependent. Conclusion: Purgation therapy with DCQD could reduce the stimulation of pathogenic factors on hepatocytes, protect tissues and organs from damage caused by excessive inflammatory reaction.Original article on CJIM(Chin) 1998; 18(8): 453展开更多
Previously,it was shown that the use of a symptom diary for two weeks,even in generally healthy subjects,results in increased recall of daily symptoms and increased perception of symptom severity(Ferrari and Russell,2...Previously,it was shown that the use of a symptom diary for two weeks,even in generally healthy subjects,results in increased recall of daily symptoms and increased perception of symptom severity(Ferrari and Russell,2010).In that study,generally healthy female subjects were asked to recall symptoms experienced in the previous two weeks,after keeping a symptom diary for two weeks,while a control group was asked to recall symptoms experienced in the previous two weeks without having kept a symptom diary.While both groups had展开更多
Background Intravascular volume expansion represents a beneficial measure against contrast-induced acute kidney injury (CI-AKI) in patients undergoing elective angiographic procedures. However, the efficacy of this ...Background Intravascular volume expansion represents a beneficial measure against contrast-induced acute kidney injury (CI-AKI) in patients undergoing elective angiographic procedures. However, the efficacy of this preventive strategy has not yet been established for patients with ST-elevation-myocardial infarction (STEMI), who are at higher risk of this complication after primary percutaneous coronary intervention (PCI). In this randomized study we investigated the possible beneficial role of periprocedural intravenous volume expansion and we compared the efficacy of 2 different hydration strategies in patients with STEMI undergoing primary PCI.展开更多
Objective To evaluate the role of acute kidney injury(AKI)in predicting early(30-day)and late(30-day to5-year)mortality of acute myocardial infarction(AMI)patients during hospitalization.Methods A total of 1371adult p...Objective To evaluate the role of acute kidney injury(AKI)in predicting early(30-day)and late(30-day to5-year)mortality of acute myocardial infarction(AMI)patients during hospitalization.Methods A total of 1371adult patients diagnosed with AMI in the First People’s Hospital of Changzhou from January 2008 to December2012 were analyzed retrospectively while their展开更多
Objective:To explore the effect of Wulong Dan (WLD) on treatment of acute cerebral infarction and change of hormones in hypothalamus-pituitary-thyroid axis. Methods:Thirty five cases of the treated group treated with ...Objective:To explore the effect of Wulong Dan (WLD) on treatment of acute cerebral infarction and change of hormones in hypothalamus-pituitary-thyroid axis. Methods:Thirty five cases of the treated group treated with WLD by taken orally and 31 cases of the control group treated with nimoton taken orally. And dextran was given intravenously to both groups. Blood level of triiodothyronine (T3), free triiodothyronine (FT3), thyroxine (T4), free throxine (FT4) and thyroid stimulating hormone (TSH) of all patients were determined before and after treatment by radioimmunoassay. Results: After 4 weeks of treatment, there were significant difference between the treated group and the control group in cure rate, markedly effective rate,cure score and disappearance of clinical symptoms (P < 0. 01 ). The levels of T3, FT3,TSH of all patients were lower than those of the normal control before treatment. After treatment with WLD and dextran, the abovementioned indexes turned to normal. Conclusions: WLD has a significant effect on patients with cerebral infarction on the basis of improved microcirculation induced by dextran. It also has regulatory effect on the hypothalamuspituitary-thyroid axis disorder so as to be helpful in maintaining the homeostasis.展开更多
The effects of chemical spills on aquatic nontarget organisms were evaluated in this study.Based on a review of three types of current eco-toxicological models of chemicals,i.e.,ACQUATOX model of the US-EPA,Hudson Riv...The effects of chemical spills on aquatic nontarget organisms were evaluated in this study.Based on a review of three types of current eco-toxicological models of chemicals,i.e.,ACQUATOX model of the US-EPA,Hudson River Model of PCBs,and critical body residual(CBR)model and dynamic energy budget(DEBtox)model,this paper presents an uncoupled numerical ecotoxicological model.The transport and transformation of spilled chemicals were simulated by a chemical transport model(including flow and sediment transport),and the mortalities of an organism caused by the chemicals were simulated by the extended threshold damage model,separately.Due to extreme scarcity of data,this model was applied to two hypothetical cases of chemical spills happening upstream of a lake.Theoretical analysis and simulated results indicated that this model is capable of reasonably predicting the acute effects of chemical spills on aquatic ecosystems or organism killings.展开更多
Introduction of arsenic trioxide(ATO, As_2O_3) to the treatment of acute promyelocytic leukemia in the 1970s enlightened an effective treatment approach for the disease. Decades later, knowledge on this agent's fur...Introduction of arsenic trioxide(ATO, As_2O_3) to the treatment of acute promyelocytic leukemia in the 1970s enlightened an effective treatment approach for the disease. Decades later, knowledge on this agent's further functions has rapidly advanced so that it has entered common use in hematology and oncology. In addition, As_2O_3 reportedly induces DNA and chromosomal damage, inhibits DNA repair, and alters DNA methylation in mammalian cells. The compound is becoming increasingly reasonable as a treatment modality to rectify genetic blood disorders and other cancer types. Nevertheless, limitations of As_2O_3 typically emerged from drug resistance, adverse effects and secondary tumors, which may result in a myriad of outcomes. Though prolonged exposure to As_2O_3 ensues poisons and genome alternations that do not permanently change the DNA sequence, other synergistic alterations should be considered as replacement. In this review, we recollect the discovery and clinical implementation of As_2O_3, describe its advantages and shortcomings for leukemia and solid cancer treatment, and consider future prospects for engendering useful impacts.展开更多
文摘Thiram is a dithiocarbamate compound widely used for industrial processes and agriculture. Animal studies reveal that this compound may afftct the male reproductive system. Aim of this study was to test, using sensitive testicular parameters, whether thiram directly affects germinal cells. For this purpose, B6C3F1 mice were intraperitoneally injected with thiram in oil (single dose:75 mg/kg; repeated five daily doses: 25 mg/kg).Although both treatments were toxic, none of the parameters examined, i.e., testis weighi, spermatid head number,specific enzyme levels at different times after treatment (14, 28, 35, 56 days) showed significant variations from the controls, On the contrary, in the positive controls (treated with chlorambucil), a marked reduction of sperm head number as well as a deerease of lactate dehydrogenasex and sorbitol dehydrogenase activity letels were evidenced at day 28, with a tendency to recover at day 35. Under these conditions thiram did not cause cytotoxicity on differentiating spermatogonia and on late spermatocyte stages of mice gonads
文摘Acute toxicity of 0.3 ppm mercuric chloride on the mucocytes of the branchial diverticulum and skin of Heteropneustes fossilis results in cyclic increases followed by decreases in the density, area occupancy and volume at different intervals of exposure. The alterations in the two tissues do not follow the same path perhaps due to different modes of action of the mercury salt: The skin comes under direct contact effects, while the branchial diverticulum may be affected by hormonal imbalance caused by a stress effect.
文摘Objective To investigate the effect of fingolimod (FTY720)on RhoA expression after spinal cord injury (SCI)in rats,and explore the possible mechanism of FTY720in the treatment of SCI.Methods A rat model of acute SCI was established with a
文摘Objective To investigate the effects of Glibenclamide on reduction of secondary damage after acute spinal cord injury in rats.Methods Ninety rats were randomly divided into control group(laminectomy alone),spinal cord injury group(injury group),and treatment group(treated
基金supported by Shanghai Science and Technology Commission with Project(No.14411951100,No.21s31900400)。
文摘Objective Air pollution is a leading public health issue.This study investigated the effect of air quality and pollutants on pulmonary function and inflammation in patients with asthma in Shanghai.Methods The study monitored 27 asthma outpatients for a year,collecting data on weather,patient self-management[daily asthma diary,peak expiratory flow(PEF)monitoring,medication usage],spirometry and serum markers.To explore the potential mechanisms of any effects,asthmatic mice induced by ovalbumin(OVA)were exposed to PM_(2.5).Results Statistical and correlational analyses revealed that air pollutants have both acute and chronic effects on asthma.Acute exposure showed a correlation between PEF and levels of ozone(O_(3))and nitrogen dioxide(NO_(2)).Chronic exposure indicated that interleukin-5(IL-5)and interleukin-13(IL-13)levels correlated with PM_(2.5)and PM_(10)concentrations.In asthmatic mouse models,exposure to PM_(2.5)increased cytokine levels and worsened lung function.Additionally,PM_(2.5)exposure inhibited cell proliferation by blocking the NF-κB and ERK phosphorylation pathways.Conclusion Ambient air pollutants exacerbate asthma by worsening lung function and enhancing Th2-mediated inflammation.Specifically,PM_(2.5)significantly contributes to these adverse effects.Further research is needed to elucidate the mechanisms by which PM_(2.5)impacts asthma.
文摘Mussels from two sites within the Baltic mussel (Mytilus edulis × M. trossulus) hybrid zone were used in a comparative study on the effects of salinity-changing rates on filtration activity. The acute effect of varying salinity-changing rates was found to be similar in M. edulis from the brackish Great Belt and in M. trossulus from the low saline Central Baltic Sea, and the relationships could be described by linear regression lines through 0.0 indicating that the acute effect of deteriorating conditions at decreasing salinities is the opposite as for improving conditions when the salinity is subsequently increased. Further, both M. edulis and M. trossulus acclimatized to 20 psu reacted to an acute salinity change to 6.5 psu by immediately closing their valves whereupon the filtration rate gradually increased during the following days, but only M. trossulus had completely acclimatized to 6.5 psu within 5 days which may be explained by different genotypes of M. edulis and M. trossulus which probably reflected an evolutionary adaptation of the latter to survive in the stable low-salinity Baltic Sea.
基金theChinaScholarshipCouncil (CSC)andOceanographicScientificFundsforYouthfromtheStateOceanographicAdministration (No .96 80 1)
文摘The oil spill impact analysis (OSIA) software system has been developed to supply a tool for comprehensive, quantitative environmental impact assessments resulting from oil spills. In the system, a biological component evaluates potential effects on exposed organisms based on results from a physico chemical fates component, including the extent and characteristics of the surface slick, and dissolved and total concentrations of hydrocarbons in the water column. The component includes a particle based exposure model for migratory adult fish populations, a particle based exposure model for spawning planktonic organisms (eggs and larvae), and an exposure model for wildlife species (sea birds or marine mammals). The exposure model for migratory adult fish populations simulates the migration behaviors of fish populations migrating to or staying in their feeding areas, over wintering areas or spawning areas, and determines the acute effects (mortality) and chronic accumulation (body burdens) from the dissolved contaminant. The exposure model for spawning planktonic organisms simulates the release of eggs and larvae, also as particles, from specific spawning areas during the spawning period, and determines their potential exposure to contaminants in the water or sediment. The exposure model for wild species calculates the exposure to surface oil of wildlife (bird and marine mammal) categories inhabiting the contaminated area. Compared with the earlier models in which all kinds of organisms are assumed evenly and randomly distributed, the updated biological exposure models can more realistically estimate potential effects on marine ecological system from oil spill pollution events.
文摘Objective: To investigate the level of acute phase proteins (APP)-synthesized in hepatocytes in pathogenic process of multiple organ dysfunction syndrome (MODS) and the effect of Dachengqi Decoction (DCQD) on it. Methods: The levels of C-reactive protein (CRP),α1-acid glycoprotein (AAG), α1-antitrypsin total (α1AT), α2-macroglobulin (α2-MG), ceruloplasmine (CP), hepatoglobin (HP) and transferrin (TF) synthesis were determined in 32 cases of MODS patients and rat models of MODS induced by acute infective peritonitis and mesenterial artery ischemia-reperfusion.Results: The serum APP level in MODS patients was increased and higher than that in the control group (P < 0. 01 ). After 3 days of DCQD treatment it reduced significantly (P <0. 05). Serum APP level in MODS model was also increased significantly, and after 3 days of DCQD treatment, it reduced significantly (P < 0. 05). The APP secreting level of rat hepatocytes cultured in vitro raised after stimulated and activated by lipopolysacchride, which was reduced after cultured with rabbits serum containing different concentration of effective ingredients of DCQD. The APP inhibiting effect of DCQD was dose dependent. Conclusion: Purgation therapy with DCQD could reduce the stimulation of pathogenic factors on hepatocytes, protect tissues and organs from damage caused by excessive inflammatory reaction.Original article on CJIM(Chin) 1998; 18(8): 453
文摘Previously,it was shown that the use of a symptom diary for two weeks,even in generally healthy subjects,results in increased recall of daily symptoms and increased perception of symptom severity(Ferrari and Russell,2010).In that study,generally healthy female subjects were asked to recall symptoms experienced in the previous two weeks,after keeping a symptom diary for two weeks,while a control group was asked to recall symptoms experienced in the previous two weeks without having kept a symptom diary.While both groups had
文摘Background Intravascular volume expansion represents a beneficial measure against contrast-induced acute kidney injury (CI-AKI) in patients undergoing elective angiographic procedures. However, the efficacy of this preventive strategy has not yet been established for patients with ST-elevation-myocardial infarction (STEMI), who are at higher risk of this complication after primary percutaneous coronary intervention (PCI). In this randomized study we investigated the possible beneficial role of periprocedural intravenous volume expansion and we compared the efficacy of 2 different hydration strategies in patients with STEMI undergoing primary PCI.
文摘Objective To evaluate the role of acute kidney injury(AKI)in predicting early(30-day)and late(30-day to5-year)mortality of acute myocardial infarction(AMI)patients during hospitalization.Methods A total of 1371adult patients diagnosed with AMI in the First People’s Hospital of Changzhou from January 2008 to December2012 were analyzed retrospectively while their
文摘Objective:To explore the effect of Wulong Dan (WLD) on treatment of acute cerebral infarction and change of hormones in hypothalamus-pituitary-thyroid axis. Methods:Thirty five cases of the treated group treated with WLD by taken orally and 31 cases of the control group treated with nimoton taken orally. And dextran was given intravenously to both groups. Blood level of triiodothyronine (T3), free triiodothyronine (FT3), thyroxine (T4), free throxine (FT4) and thyroid stimulating hormone (TSH) of all patients were determined before and after treatment by radioimmunoassay. Results: After 4 weeks of treatment, there were significant difference between the treated group and the control group in cure rate, markedly effective rate,cure score and disappearance of clinical symptoms (P < 0. 01 ). The levels of T3, FT3,TSH of all patients were lower than those of the normal control before treatment. After treatment with WLD and dextran, the abovementioned indexes turned to normal. Conclusions: WLD has a significant effect on patients with cerebral infarction on the basis of improved microcirculation induced by dextran. It also has regulatory effect on the hypothalamuspituitary-thyroid axis disorder so as to be helpful in maintaining the homeostasis.
基金This work was supported by the USDA Agriculture Research Service(No.58-6408-2-0062)the US State Department Agency for International Development(No.EE-G-00-02-00015-00)+3 种基金the Natural Science Foundation of Tianjin(Grant No.09ZCGYSF00400)National Key-Projects of Water Pollution Control and Prevention(2008ZX07209-001)the Commonweal Projects Specific for Scientific Research of the Ministry of Water Conservancy of China(No.200801135)the Open Fund of China Institute of Water Conservancy and Hydropower Research and the National Natural Science Foundation of China(Grant No.50479034).
文摘The effects of chemical spills on aquatic nontarget organisms were evaluated in this study.Based on a review of three types of current eco-toxicological models of chemicals,i.e.,ACQUATOX model of the US-EPA,Hudson River Model of PCBs,and critical body residual(CBR)model and dynamic energy budget(DEBtox)model,this paper presents an uncoupled numerical ecotoxicological model.The transport and transformation of spilled chemicals were simulated by a chemical transport model(including flow and sediment transport),and the mortalities of an organism caused by the chemicals were simulated by the extended threshold damage model,separately.Due to extreme scarcity of data,this model was applied to two hypothetical cases of chemical spills happening upstream of a lake.Theoretical analysis and simulated results indicated that this model is capable of reasonably predicting the acute effects of chemical spills on aquatic ecosystems or organism killings.
基金National Natural Science Foundation(81430088)Grants from Special Fund for Doctor Stations,Ministry of Education,China(20122307130003)
文摘Introduction of arsenic trioxide(ATO, As_2O_3) to the treatment of acute promyelocytic leukemia in the 1970s enlightened an effective treatment approach for the disease. Decades later, knowledge on this agent's further functions has rapidly advanced so that it has entered common use in hematology and oncology. In addition, As_2O_3 reportedly induces DNA and chromosomal damage, inhibits DNA repair, and alters DNA methylation in mammalian cells. The compound is becoming increasingly reasonable as a treatment modality to rectify genetic blood disorders and other cancer types. Nevertheless, limitations of As_2O_3 typically emerged from drug resistance, adverse effects and secondary tumors, which may result in a myriad of outcomes. Though prolonged exposure to As_2O_3 ensues poisons and genome alternations that do not permanently change the DNA sequence, other synergistic alterations should be considered as replacement. In this review, we recollect the discovery and clinical implementation of As_2O_3, describe its advantages and shortcomings for leukemia and solid cancer treatment, and consider future prospects for engendering useful impacts.