Background:Different homeopathic approaches have been used as supportive care for coronavirus disease 2019(COVID-19)cases,but none has been tested in a clinical trial.Objectives:To investigate the effectiveness and sa...Background:Different homeopathic approaches have been used as supportive care for coronavirus disease 2019(COVID-19)cases,but none has been tested in a clinical trial.Objectives:To investigate the effectiveness and safety of the homeopathic medicine,Natrum muriaticum LM2,for mild cases of COVID-19.Design,setting,participants,and interventions:A randomized,double-blind,two-armed,parallel,singlecenter,placebo-controlled clinical trial was conducted from June 2020 to April 2021 in S?o-Carlos,Brazil.Participants aged>18 years,with influenza-like symptoms and positive result from a real-time polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 were recruited and randomized(1:1)into two groups that received different treatments during a period of at-homeisolation.One group received the homeopathic medicine Natrum muriaticum,prepared with the second degree of the fifty-millesimal dynamization(LM2;Natrum muriaticum LM2),while the other group received a placebo.Outcome measures:The primary endpoint was time until recovery from COVID-19 influenza-like symptoms.Secondary measures included a survival analysis of the number and severity of COVID-19 symptoms(influenza-like symptoms plus anosmia and ageusia)from a symptom grading scale that was informed by the participant,hospital admissions,and adverse events.Kaplan-Meier curves were used to estimate time-to-event(survival)measures.Results:Data from 86 participants were analyzed(homeopathy,n=42;placebo,n=44).There was no difference in time to recovery between two groups among participants who were reporting influenzalike symptoms at the beginning of monitoring(homeopathy,n=41;placebo,n=41;P=0.56),nor in a sub-group that had at least 5 moderate to severe influenza-like symptoms at the beginning of monitoring(homeopathy,n=15;placebo,n=17;P=0.06).Secondary outcomes indicated that a 50%reduction in symptom score was achieved significantly earlier in the homeopathy group(homeopathy,n=24;placebo,n=25;P=0.04),among the participants with a basal symptom s展开更多
This paper introduces an electrical drives control architecture combining a fractional-order controller and a setpoint pre-filter. The former is based on a fractional-order proportional-integral(PI) unit, with a non-i...This paper introduces an electrical drives control architecture combining a fractional-order controller and a setpoint pre-filter. The former is based on a fractional-order proportional-integral(PI) unit, with a non-integer order integral action, while the latter can be of integer or non-integer type. To satisfy robustness and dynamic performance specifications, the feedback controller is designed by a loop-shaping technique in the frequency domain. In particular, optimality of the feedback system is pursued to achieve input-output tracking. The setpoint pre-filter is designed by a dynamic inversion technique minimizing the difference between the ideal synthesized command signal(i.e., a smooth monotonic response) and the prefilter step response. Experimental tests validate the methodology and compare the performance of the proposed architecture with well-established control schemes that employ the classical PIbased symmetrical optimum method with a smoothing pre-filter.展开更多
Objective:Bone metastasis is a clinically important outcome of prostate carcinoma(PC).We focused on the phenotypic and functional characterization of a particularly aggressive phenotype within the androgen-independent...Objective:Bone metastasis is a clinically important outcome of prostate carcinoma(PC).We focused on the phenotypic and functional characterization of a particularly aggressive phenotype within the androgen-independent bone metastasis-derived PC3 cell line.These cells,originated from the spontaneous conversion of a CD44-negative subpopulation,stably express the CD44 v8-10 isoform(CD44 v8-10 pos)and display stem cell-like features and a marked invasive phenotype in vitro that is lost upon CD44 v8-10 silencing.Methods:Flow cytometry,enzyme-linked immunoassay,immunofluorescence,and Western blot were used for phenotypic and immunologic characterization.Real-time quantitative polymerase chain reaction and functional assays were used to assess osteomimicry.Results:Analysis of epithelial–mesenchymal transition markers showed that CD44 v8-10 pos PC3 cells surprisingly display epithelial phenotype and can undergo osteomimicry,acquiring bone cell phenotypic and behavioral traits.Use of specific si RNA evidenced the ability of CD44 v8-10 variant to confer osteomimetic features,hence the potential to form bone-specific metastasis.Moreover,the ability of tumors to activate immunosuppressive mechanisms which counteract effective immune responses is a sign of the aggressiveness of a tumor.Here we report that CD44 v8-10 pos cells express programmed death ligand 1,a negative regulator of anticancer immunity,and secrete exceptionally high amounts of interleukin-6,favoring osteoclastogenesis and immunosuppression in bone microenvironment.Notably,we identified a novel pathway activated by CD44 v8-10,involving tafazzin(TAZ)and likely the Wnt/TAZ axis,known to play a role in upregulating osteomimetic genes.Conclusions:CD44 v8-10 could represent a marker of a more aggressive bone metastatic PC population exerting a driver role in osteomimicry in bone.A novel link between TAZ and CD44 v8-10 is also shown.展开更多
The present study aims to investigate the genotype-phenotype correlation of the hereditary hemochromatosis （HH）, a genetic disorder of iron metabolism, in Matera province （Basilicata, Italy）. Integrating both epid...The present study aims to investigate the genotype-phenotype correlation of the hereditary hemochromatosis （HH）, a genetic disorder of iron metabolism, in Matera province （Basilicata, Italy）. Integrating both epidemiological and molecular approaches, the authors studied： （a） the frequency of the HH main mutations; （b） the association between mutations and HH cases. The majority of patients with HH are homozygous for the C282Y mutation of the HFE gene. A second mutation （H63D） is more widely distributed and its connection with HH isn＇t clear, but a low penetrance is attributed to this variant. The population-based study consists of three steps： （1） determination of iron biochemical parameters, （2） genetic test, and （3） sequencing of HFE gene and bioinformatics studies. A case report is presented in a 41-year-old male （genotype： H63D/wt） with biochemical and clinical evidences of HH, in absence of secondary iron overload factors. In the cohort of studied patients （150M：62F）, there are 18 homozygous patients; H63D/H63D genotype is found in 11 cases. In the heterozygous group, H63D/wt is the predominant genotype （61/68 subjects）. All the H63D/wt residents in the same village （Mont.） show altered biochemical parameter levels. In our case study, a substitution localized into the HFE promoter （nt225A 〉 C） is found. Results show that the H63D genotype is responsible for most cases of HH. The peculiar clinical manifestation found in Mont. suggests a founder effect. In our case, the iron overload is related to a presence of an undetected mutation, critical for the transcriptional regulation of the HFE gene.展开更多
The aim of this paper is to present and analyze the factors, motivations and criteria considered in the decision-making processes of the actors belonging to the biodiesel production chain in Brazil. The biodiesel prod...The aim of this paper is to present and analyze the factors, motivations and criteria considered in the decision-making processes of the actors belonging to the biodiesel production chain in Brazil. The biodiesel production chain consists of three main agents： the farmers, the soybean processing plants and the oil refinery/distributor. For the farmers organized in cooperatives the central decision is whether to sell oil-bearing crops for the production of biodiesel. In contrast, for the soybean processing plants that convert the crops into vegetable and/or biodiesel, the decision to produce this fuel is based on the wish to expand their market portfolio. Government tax incentives strongly influence both decisions regarding which oil-bearing crop to use and the amount of vegetable oil to be transformed into biodiesel. Finally, the oil refinery/distributor is obliged by law to mix the biodiesel with the mineral diesel and perceives this as a liability. The results show the existence of different characteristics linked to the decision-making process and a significant lack of synchronicity in the aims and motivations behind the agents＇ decisions. This state of decisional misalignment leads to heightened uncertainty regarding the sustainability of the Brazilian biodiesel production program.展开更多
Obesity and its associated diseases are a worldwide epidemic disease. Usual weight loss cures- as diets, physical activity, behavior therapy and pharmacotherapy- have been continuously implemented but still have relat...Obesity and its associated diseases are a worldwide epidemic disease. Usual weight loss cures- as diets, physical activity, behavior therapy and pharmacotherapy- have been continuously implemented but still have relatively poor long-term success and mainly scarce adherence. Bariatric surgery is to date the most effective long term treatment for morbid obesity and it has been proven to reduce obesity-related co-morbidities, among them nonalcoholic fatty liver disease, and mortality. This article summarizes such variations in gut hormones following the current metabolic surgery procedures. The profile of gut hormonal changes after bariatric surgery represents a strategy for the individuation of the most performing surgical procedures to achieve clinical results. About this topic, experts suggest that the individuation of the crosslink among the gut hormones, microbiome, the obesity and the bariatric surgery could lead to new and more specific therapeutic interventions for severe obesity and its co-morbidities, also non surgical.展开更多
This paper focuses on a new approach to design(possibly fractional) set-point filters for fractional control systems.After designing a smooth and monotonic desired output signal,the necessary command signal is obtaine...This paper focuses on a new approach to design(possibly fractional) set-point filters for fractional control systems.After designing a smooth and monotonic desired output signal,the necessary command signal is obtained via fractional input-output inversion.Then,a set-point filter is determined based on the synthesized command signal.The filter is computed by minimizing the 2-norm of the difference between the command signal and the filter step response.The proposed methodology allows the designer to synthesize both integer and fractional setpoint filters.The pros and cons of both solutions are discussed in details.This approach is suitable for the design of two degreeof-freedom controllers capable to make the set-point tracking performance almost independent from the feedback part of the controller.Simulation results show the effectiveness of the proposed methodology.展开更多
Objective: To study the utility of Doppler velocimetry and computerized cardiotocography in the management of intrauterine growth restriction and prediction of neonatal outcome. Patients and methods: Seventy-two pregn...Objective: To study the utility of Doppler velocimetry and computerized cardiotocography in the management of intrauterine growth restriction and prediction of neonatal outcome. Patients and methods: Seventy-two pregnant women with fetuses showing growth restriction and delivered within 48 h of their last Doppler velocimetry evaluation. The last computerized cardiotocographic trace from these fetuses was used for statistical analysis, and the last trace from the healthy fetuses of 93 consecutive women undergoing cesarean section was used as control. Umbilical artery pulsatility index (UA PI), middle cerebral artery pulsatility index (MCA PI), UA PI / MCA PI ratio, and uterine artery resistance index (Ut RI) were assessed. Results: Among women with growth-restricted fetuses, all parameters were significantly higher in those who had hypertension; and in those who had diabetes, only the UAPI /MCA ratio was significantly higher. Umbilical artery PI values and the UA PI / MCA ratio were higher in those who had a nonreassuring result to computerized nonstress test immediately before delivery. A multiple logistic analysis showed that the UA PI / MCA ratio was the only Doppler velocimetry parameter predicting cardiotocographic nonreactivity; furthermore, the predictivity of extended newborn hospitalization (longer than 15 days) was verified,with a sensitivity of 56%and a specificity of 92%when the ratio was higher than 1.26. Conclusion: The MCA PI of fetuses with growth restriction should be assessed. The UA PI / MCA ratio is predictive of a nonreactive computerized cardiotocography trace and of prolonged neonatal hospitalization.展开更多
文摘Background:Different homeopathic approaches have been used as supportive care for coronavirus disease 2019(COVID-19)cases,but none has been tested in a clinical trial.Objectives:To investigate the effectiveness and safety of the homeopathic medicine,Natrum muriaticum LM2,for mild cases of COVID-19.Design,setting,participants,and interventions:A randomized,double-blind,two-armed,parallel,singlecenter,placebo-controlled clinical trial was conducted from June 2020 to April 2021 in S?o-Carlos,Brazil.Participants aged>18 years,with influenza-like symptoms and positive result from a real-time polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 were recruited and randomized(1:1)into two groups that received different treatments during a period of at-homeisolation.One group received the homeopathic medicine Natrum muriaticum,prepared with the second degree of the fifty-millesimal dynamization(LM2;Natrum muriaticum LM2),while the other group received a placebo.Outcome measures:The primary endpoint was time until recovery from COVID-19 influenza-like symptoms.Secondary measures included a survival analysis of the number and severity of COVID-19 symptoms(influenza-like symptoms plus anosmia and ageusia)from a symptom grading scale that was informed by the participant,hospital admissions,and adverse events.Kaplan-Meier curves were used to estimate time-to-event(survival)measures.Results:Data from 86 participants were analyzed(homeopathy,n=42;placebo,n=44).There was no difference in time to recovery between two groups among participants who were reporting influenzalike symptoms at the beginning of monitoring(homeopathy,n=41;placebo,n=41;P=0.56),nor in a sub-group that had at least 5 moderate to severe influenza-like symptoms at the beginning of monitoring(homeopathy,n=15;placebo,n=17;P=0.06).Secondary outcomes indicated that a 50%reduction in symptom score was achieved significantly earlier in the homeopathy group(homeopathy,n=24;placebo,n=25;P=0.04),among the participants with a basal symptom s
基金partially supported by the Australian Research Council(DP160104994)
文摘This paper introduces an electrical drives control architecture combining a fractional-order controller and a setpoint pre-filter. The former is based on a fractional-order proportional-integral(PI) unit, with a non-integer order integral action, while the latter can be of integer or non-integer type. To satisfy robustness and dynamic performance specifications, the feedback controller is designed by a loop-shaping technique in the frequency domain. In particular, optimality of the feedback system is pursued to achieve input-output tracking. The setpoint pre-filter is designed by a dynamic inversion technique minimizing the difference between the ideal synthesized command signal(i.e., a smooth monotonic response) and the prefilter step response. Experimental tests validate the methodology and compare the performance of the proposed architecture with well-established control schemes that employ the classical PIbased symmetrical optimum method with a smoothing pre-filter.
基金supported by funding by Ateneo Sapienza University(Grant Nos.RP 11816427B97420 and RG11916B7AF0C02D)to A.R.
文摘Objective:Bone metastasis is a clinically important outcome of prostate carcinoma(PC).We focused on the phenotypic and functional characterization of a particularly aggressive phenotype within the androgen-independent bone metastasis-derived PC3 cell line.These cells,originated from the spontaneous conversion of a CD44-negative subpopulation,stably express the CD44 v8-10 isoform(CD44 v8-10 pos)and display stem cell-like features and a marked invasive phenotype in vitro that is lost upon CD44 v8-10 silencing.Methods:Flow cytometry,enzyme-linked immunoassay,immunofluorescence,and Western blot were used for phenotypic and immunologic characterization.Real-time quantitative polymerase chain reaction and functional assays were used to assess osteomimicry.Results:Analysis of epithelial–mesenchymal transition markers showed that CD44 v8-10 pos PC3 cells surprisingly display epithelial phenotype and can undergo osteomimicry,acquiring bone cell phenotypic and behavioral traits.Use of specific si RNA evidenced the ability of CD44 v8-10 variant to confer osteomimetic features,hence the potential to form bone-specific metastasis.Moreover,the ability of tumors to activate immunosuppressive mechanisms which counteract effective immune responses is a sign of the aggressiveness of a tumor.Here we report that CD44 v8-10 pos cells express programmed death ligand 1,a negative regulator of anticancer immunity,and secrete exceptionally high amounts of interleukin-6,favoring osteoclastogenesis and immunosuppression in bone microenvironment.Notably,we identified a novel pathway activated by CD44 v8-10,involving tafazzin(TAZ)and likely the Wnt/TAZ axis,known to play a role in upregulating osteomimetic genes.Conclusions:CD44 v8-10 could represent a marker of a more aggressive bone metastatic PC population exerting a driver role in osteomimicry in bone.A novel link between TAZ and CD44 v8-10 is also shown.
文摘The present study aims to investigate the genotype-phenotype correlation of the hereditary hemochromatosis （HH）, a genetic disorder of iron metabolism, in Matera province （Basilicata, Italy）. Integrating both epidemiological and molecular approaches, the authors studied： （a） the frequency of the HH main mutations; （b） the association between mutations and HH cases. The majority of patients with HH are homozygous for the C282Y mutation of the HFE gene. A second mutation （H63D） is more widely distributed and its connection with HH isn＇t clear, but a low penetrance is attributed to this variant. The population-based study consists of three steps： （1） determination of iron biochemical parameters, （2） genetic test, and （3） sequencing of HFE gene and bioinformatics studies. A case report is presented in a 41-year-old male （genotype： H63D/wt） with biochemical and clinical evidences of HH, in absence of secondary iron overload factors. In the cohort of studied patients （150M：62F）, there are 18 homozygous patients; H63D/H63D genotype is found in 11 cases. In the heterozygous group, H63D/wt is the predominant genotype （61/68 subjects）. All the H63D/wt residents in the same village （Mont.） show altered biochemical parameter levels. In our case study, a substitution localized into the HFE promoter （nt225A 〉 C） is found. Results show that the H63D genotype is responsible for most cases of HH. The peculiar clinical manifestation found in Mont. suggests a founder effect. In our case, the iron overload is related to a presence of an undetected mutation, critical for the transcriptional regulation of the HFE gene.
文摘The aim of this paper is to present and analyze the factors, motivations and criteria considered in the decision-making processes of the actors belonging to the biodiesel production chain in Brazil. The biodiesel production chain consists of three main agents： the farmers, the soybean processing plants and the oil refinery/distributor. For the farmers organized in cooperatives the central decision is whether to sell oil-bearing crops for the production of biodiesel. In contrast, for the soybean processing plants that convert the crops into vegetable and/or biodiesel, the decision to produce this fuel is based on the wish to expand their market portfolio. Government tax incentives strongly influence both decisions regarding which oil-bearing crop to use and the amount of vegetable oil to be transformed into biodiesel. Finally, the oil refinery/distributor is obliged by law to mix the biodiesel with the mineral diesel and perceives this as a liability. The results show the existence of different characteristics linked to the decision-making process and a significant lack of synchronicity in the aims and motivations behind the agents＇ decisions. This state of decisional misalignment leads to heightened uncertainty regarding the sustainability of the Brazilian biodiesel production program.
文摘Obesity and its associated diseases are a worldwide epidemic disease. Usual weight loss cures- as diets, physical activity, behavior therapy and pharmacotherapy- have been continuously implemented but still have relatively poor long-term success and mainly scarce adherence. Bariatric surgery is to date the most effective long term treatment for morbid obesity and it has been proven to reduce obesity-related co-morbidities, among them nonalcoholic fatty liver disease, and mortality. This article summarizes such variations in gut hormones following the current metabolic surgery procedures. The profile of gut hormonal changes after bariatric surgery represents a strategy for the individuation of the most performing surgical procedures to achieve clinical results. About this topic, experts suggest that the individuation of the crosslink among the gut hormones, microbiome, the obesity and the bariatric surgery could lead to new and more specific therapeutic interventions for severe obesity and its co-morbidities, also non surgical.
基金supported by the Australian Research Council(DP160104994)
文摘This paper focuses on a new approach to design(possibly fractional) set-point filters for fractional control systems.After designing a smooth and monotonic desired output signal,the necessary command signal is obtained via fractional input-output inversion.Then,a set-point filter is determined based on the synthesized command signal.The filter is computed by minimizing the 2-norm of the difference between the command signal and the filter step response.The proposed methodology allows the designer to synthesize both integer and fractional setpoint filters.The pros and cons of both solutions are discussed in details.This approach is suitable for the design of two degreeof-freedom controllers capable to make the set-point tracking performance almost independent from the feedback part of the controller.Simulation results show the effectiveness of the proposed methodology.
文摘Objective: To study the utility of Doppler velocimetry and computerized cardiotocography in the management of intrauterine growth restriction and prediction of neonatal outcome. Patients and methods: Seventy-two pregnant women with fetuses showing growth restriction and delivered within 48 h of their last Doppler velocimetry evaluation. The last computerized cardiotocographic trace from these fetuses was used for statistical analysis, and the last trace from the healthy fetuses of 93 consecutive women undergoing cesarean section was used as control. Umbilical artery pulsatility index (UA PI), middle cerebral artery pulsatility index (MCA PI), UA PI / MCA PI ratio, and uterine artery resistance index (Ut RI) were assessed. Results: Among women with growth-restricted fetuses, all parameters were significantly higher in those who had hypertension; and in those who had diabetes, only the UAPI /MCA ratio was significantly higher. Umbilical artery PI values and the UA PI / MCA ratio were higher in those who had a nonreassuring result to computerized nonstress test immediately before delivery. A multiple logistic analysis showed that the UA PI / MCA ratio was the only Doppler velocimetry parameter predicting cardiotocographic nonreactivity; furthermore, the predictivity of extended newborn hospitalization (longer than 15 days) was verified,with a sensitivity of 56%and a specificity of 92%when the ratio was higher than 1.26. Conclusion: The MCA PI of fetuses with growth restriction should be assessed. The UA PI / MCA ratio is predictive of a nonreactive computerized cardiotocography trace and of prolonged neonatal hospitalization.
