BACKGROUND Crohn’s disease(CD)is a chronic inflammatory bowel disease with unknown etiology.Inflammatory chemical mediators synthesized from arachidonic acid,an n-6 polyunsaturated fatty acid(PUFA),have been shown to...BACKGROUND Crohn’s disease(CD)is a chronic inflammatory bowel disease with unknown etiology.Inflammatory chemical mediators synthesized from arachidonic acid,an n-6 polyunsaturated fatty acid(PUFA),have been shown to activate CD.Additionally,n-3 PUFAs are metabolized by the same enzyme as n-6 PUFAs and known to inhibit the arachidonic acid cascade.Our previous study noted that the presence of erythrocyte membrane fatty acids is a characteristic finding in Japanese CD patients.It was thus speculated that FADS2 gene polymorphisms,which induce PUFA metabolizing enzymes,are involved in the pathogenesis of CD,though no such relationship was found.AIM To investigate the relationship of FADS2 polymorphisms with serum and erythrocyte membrane fatty acid composition ratios,and disease activity.METHODS Using previously reported findings regarding FADS2 genetic polymorphisms,the records of 52 CD patients undergoing treatment at Jikei University Kashiwa Hospital were analyzed.Mutations noted were divided into three groups;wild-type(GG),heterozygous mutants(GA),and homozygous(AA),with the activities of delta-6 and delta-5 desaturases compared using redefined d6d index(rd.d6di)and d5d index(d5di).Additionally,comparisons of serum and erythrocyte membranes for fatty acid composition,and also gene polymorphisms and CD activity index(CDAI)were performed.RESULTS The presence of the rs174538 mutation in FADS2 resulted in reduction of only rd.d6di in the erythrocyte membrane(P<0.01).In contrast,that mutation was found to be associated with d5di induced by FADS1 in serum(P=0.019)as well as the erythrocyte membrane(P<0.0001),and also with reduction in the fatty acid composition of arachidonic acid in both serum(P<0.0001)and the erythrocyte membrane(P<0.01).Regarding disease activity,a positive correlation of CDAI score with rd.d6di in both serum(P<0.05)and the erythrocyte membrane(P<0.05)was found only in the rs174538 wild-type group.In contrast,there was no correction between CDAI and d5di in either serum or erythrocyte membrane samples.CONCLUSION The rs174538 mutation alters the fatty acid profile through strong linkage to the FADS1 gene.In wild-type individuals,rd.d6di was positively correlated with CDAI,suggesting predictive utility of disease severity.展开更多
Background Conditional relative survival(CRS),the probability of survival given that an individual has already survived a certain period post-diagnosis,is a more clinically relevant measure for long-term survival than...Background Conditional relative survival(CRS),the probability of survival given that an individual has already survived a certain period post-diagnosis,is a more clinically relevant measure for long-term survival than standard relative survival(RS).This study aims to evaluate the 5-year CRS among adolescent and young adult(AYA)breast cancer patients by age,tumor stage,and receptor subtype to guide disclosure periods for insurance.Methods Data of all females aged 18–39 years and diagnosed with invasive breast cancer between 2003 and 2021(n=13,075)were obtained from The Netherlands Cancer Registry(NCR).The five-year CRS was calculated annually up to 10 years post-diagnosis using a hybrid analysis approach.Results For the total AYA breast cancer study population the 5-year CRS exceeded 90%from diagnosis and increased beyond 95%7 years post-diagnosis.Patients aged 18–24 reached 95%9 years post-diagnosis,those aged 25–29 after 5 years,and those aged 30–34 and 35–39 after 8 years.For stage I,the 5-year CRS reached 95%from diagnosis,for stage II after 6 years,while the 5-year CRS for stages III and IV did not reach the 95%threshold during the 10-year follow-up.Triple-negative tumors exceeded 95%after 4 years,human epidermal growth factor receptor 2(HER2)positive tumors after 6 years,while hormone receptor(HR)positive tumors did not reach 95%.Conclusion Excess mortality among AYA breast cancer patients tends to be little(CRS 90%–95%)from diagnosis and becomes minimal(CRS>95%)over time compared to the general population.These results can enhance expectation management and inform policymakers,suggesting a shorter disclosure period.展开更多
The General Aviation Manufacturers Association(GAMA)published the First Quarter 2025 General Aviation Aircraft Shipment and Billing Report.The results for the first three months of 2025 when compared to the same perio...The General Aviation Manufacturers Association(GAMA)published the First Quarter 2025 General Aviation Aircraft Shipment and Billing Report.The results for the first three months of 2025 when compared to the same period in 2024 show increased shipments across all seet6rs and an increase in the overall value of aifcraft shipments.展开更多
文摘BACKGROUND Crohn’s disease(CD)is a chronic inflammatory bowel disease with unknown etiology.Inflammatory chemical mediators synthesized from arachidonic acid,an n-6 polyunsaturated fatty acid(PUFA),have been shown to activate CD.Additionally,n-3 PUFAs are metabolized by the same enzyme as n-6 PUFAs and known to inhibit the arachidonic acid cascade.Our previous study noted that the presence of erythrocyte membrane fatty acids is a characteristic finding in Japanese CD patients.It was thus speculated that FADS2 gene polymorphisms,which induce PUFA metabolizing enzymes,are involved in the pathogenesis of CD,though no such relationship was found.AIM To investigate the relationship of FADS2 polymorphisms with serum and erythrocyte membrane fatty acid composition ratios,and disease activity.METHODS Using previously reported findings regarding FADS2 genetic polymorphisms,the records of 52 CD patients undergoing treatment at Jikei University Kashiwa Hospital were analyzed.Mutations noted were divided into three groups;wild-type(GG),heterozygous mutants(GA),and homozygous(AA),with the activities of delta-6 and delta-5 desaturases compared using redefined d6d index(rd.d6di)and d5d index(d5di).Additionally,comparisons of serum and erythrocyte membranes for fatty acid composition,and also gene polymorphisms and CD activity index(CDAI)were performed.RESULTS The presence of the rs174538 mutation in FADS2 resulted in reduction of only rd.d6di in the erythrocyte membrane(P<0.01).In contrast,that mutation was found to be associated with d5di induced by FADS1 in serum(P=0.019)as well as the erythrocyte membrane(P<0.0001),and also with reduction in the fatty acid composition of arachidonic acid in both serum(P<0.0001)and the erythrocyte membrane(P<0.01).Regarding disease activity,a positive correlation of CDAI score with rd.d6di in both serum(P<0.05)and the erythrocyte membrane(P<0.05)was found only in the rs174538 wild-type group.In contrast,there was no correction between CDAI and d5di in either serum or erythrocyte membrane samples.CONCLUSION The rs174538 mutation alters the fatty acid profile through strong linkage to the FADS1 gene.In wild-type individuals,rd.d6di was positively correlated with CDAI,suggesting predictive utility of disease severity.
基金supported by The Netherlands Organization for Scientific Research VIDI(grant number:198.007).
文摘Background Conditional relative survival(CRS),the probability of survival given that an individual has already survived a certain period post-diagnosis,is a more clinically relevant measure for long-term survival than standard relative survival(RS).This study aims to evaluate the 5-year CRS among adolescent and young adult(AYA)breast cancer patients by age,tumor stage,and receptor subtype to guide disclosure periods for insurance.Methods Data of all females aged 18–39 years and diagnosed with invasive breast cancer between 2003 and 2021(n=13,075)were obtained from The Netherlands Cancer Registry(NCR).The five-year CRS was calculated annually up to 10 years post-diagnosis using a hybrid analysis approach.Results For the total AYA breast cancer study population the 5-year CRS exceeded 90%from diagnosis and increased beyond 95%7 years post-diagnosis.Patients aged 18–24 reached 95%9 years post-diagnosis,those aged 25–29 after 5 years,and those aged 30–34 and 35–39 after 8 years.For stage I,the 5-year CRS reached 95%from diagnosis,for stage II after 6 years,while the 5-year CRS for stages III and IV did not reach the 95%threshold during the 10-year follow-up.Triple-negative tumors exceeded 95%after 4 years,human epidermal growth factor receptor 2(HER2)positive tumors after 6 years,while hormone receptor(HR)positive tumors did not reach 95%.Conclusion Excess mortality among AYA breast cancer patients tends to be little(CRS 90%–95%)from diagnosis and becomes minimal(CRS>95%)over time compared to the general population.These results can enhance expectation management and inform policymakers,suggesting a shorter disclosure period.
文摘The General Aviation Manufacturers Association(GAMA)published the First Quarter 2025 General Aviation Aircraft Shipment and Billing Report.The results for the first three months of 2025 when compared to the same period in 2024 show increased shipments across all seet6rs and an increase in the overall value of aifcraft shipments.
