CONCLUSION The majority of renal transplant recipients aged ≥60 fail to tolerate full-dose MPA. In this group, MPA dose reduction is associated with low rejection rates, but full-dose MPA is associated with high infection rates. We suggest that a tailored approach to immunosuppression in elderly recipients incorporating lower doses of MPA may be appropriate. © 2020 Asian Pacific Society of Nephrology.The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has a drastic impact on national health care systems. Given the overwhelming demand on facility capacity, the impact on all health care sectors has to be addressed. Solid organ transplantation represents a field with a high demand on staff, intensive care units, and follow-up facilities. The great therapeutic value of organ transplantation has to be weighed against mandatory constraints of health care capacities. In addition, the management of immunosuppressed recipients has to be reassessed during the ongoing coronavirus disease 2019 (COVID-19) pandemic. In addressing these crucial questions, transplant physicians are facing a total lack of scientific evidence. Therefore, the aim of this study was to offer an approach of consensus-based guidance, derived from individual information of 22 transplant societies. Key recommendations were extracted and the degree of consensus among different organizations was calculated. A high degree of consensus was found for temporarily suspending nonurgent transplant procedures and living donation programs. Systematic polymerase chain reaction-based testing of donors and recipients was broadly recommended. Additionally, more specific aspects (eg, screening of surgical explant teams and restricted use of marginal donor organs) were included in our analysis. This study offers a novel approach to informed guidance for health care management when a priori no scientific evidence is available. © 2020 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.Replicative senescence during in vitro augmentation, which is mostly induced by the loss of physiological microenvironment, hinders the application of mesenchymal stem cells (****) in the clinic. Here, we investigated whether **** senescence could be prevented by bio-scaffold mimicking the natural tissue matrix. Human umbilical cord mesenchymal stem cells (hUCMSCs) exhibited a senescent phenotype during a long-term passage in the conventional culture dish. To fabricate the bone matrix, a naturally based matrix composed of nano-hydroxyapatite/chitosan/poly lactide-co-glycolide (nHA/CS/PLGA) was produced. Long-term passage resulted in an obvious increase in the expression of senescence markers and a reduction in the expression of master genes involved in tissue regeneration. Functional assay confirmed that nHA/CS/PLGA scaffold preserved the proliferation and differentiation of hUCMSCs even after being passaged 27 times. https://www.selleckchem.com/products/favipiravir-t-705.html Moreover, in vivo ectopic bone formation assay revealed that the bone formation of hUCMSCs cultured on the nano-scaffolds for the long term was as robust as the cells in the early passage. In summary, our results demonstrate that nHA/CS/PLGA scaffold effectively preserves the stemness and youth of hUCMSCs in the long-term passage. Taken advantage of its compatibility and bioactivity, nHA/CS/PLGA scaffold is of great potential in large-scale expansion of **** for stem cell therapy and tissue engineering. © 2020 Wiley Periodicals, Inc.Because acellular vascular xenografts induce an immunological reaction through macrophage infiltration, they are conventionally crosslinked with glutaraldehyde (GA). However, the GA crosslinking reaction inhibits not only the host immune reaction around the graft but also the graft's enzymatic degradability, which is one of the key characteristics of acellular grafts that allow them to be replaced by host tissue. In this study, we used an 8-arm polyethylene glycol (PEG) to successfully suppress macrophage infiltration, without eliminating graft degradation. Decellularized ostrich carotid arteries were modified with GA or N-hydroxysuccinimide-activated 8-arm PEG (8-arm PEG-NHS), which has a molecular weight of 17 kDa. To evaluate the enzymatic degradation in vitro, the graft was immersed in a collagenase solution for 12 hr. The 8-arm PEG-modified graft was degraded to the same extent as the unmodified graft, but the GA-modified graft was not degraded. The graft was transplanted into rat subcutaneous tissue for up to 8 weeks. Although CD68-positive cells accumulated in the unmodified graft, they did not infiltrate into either modified graft. However, the GA-modified grafts calcified, but the 8-arm PEG-modified graft did not calcify after transplantation. These data suggested that 8-arm PEG-NHS is a promising modification agent for biodegradable vascular xenografts, to suppress acute macrophage infiltration only. © 2020 Wiley Periodicals, Inc.Direct selection for litter size or weight at weaning in pigs is often hindered by external interventions such as cross-fostering. The objective of this study was to infer the causal structure among phenotypes of reproductive traits in pigs to enable subsequent direct selection for these traits. Examined traits included number born alive (NBA), litter size on day 21 (LS21), and litter weight on day 21 (LW21). The study included 6,240 litters from 1,673 Landrace dams and 5,393 litters from 1,484 Large White dams. The inductive causation (IC) algorithm was used to infer the causal structure, which was then fitted to a structural equation model (SEM) to estimate causal coefficients and genetic parameters. Based on the IC algorithm and temporal and biological information, the causal structure among traits was identified as NBA → LS21 → LW21 and NBA → LW21. Owing to the causal effect of NBA on LS21 and LW21, the genetic, permanent environmental, and residual variances of LS21 and LW21were **** lower in the SEM than in the multiple-trait model for both breeds. Given the strong effect of NBA on LS21 and LW21, the SEM and causal information might assist with selective breeding for LS21 and LW21 when cross-fostering occurs. © 2020 The Authors. Animal Science Journal published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Animal Science.
CONCLUSION The majority of renal transplant recipients aged ≥60 fail to tolerate full-dose MPA. In this group, MPA dose reduction is associated with low rejection rates, but full-dose MPA is associated with high infection rates. We suggest that a tailored approach to immunosuppression in elderly recipients incorporating lower doses of MPA may be appropriate. © 2020 Asian Pacific Society of Nephrology.The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has a drastic impact on national health care systems. Given the overwhelming demand on facility capacity, the impact on all health care sectors has to be addressed. Solid organ transplantation represents a field with a high demand on staff, intensive care units, and follow-up facilities. The great therapeutic value of organ transplantation has to be weighed against mandatory constraints of health care capacities. In addition, the management of immunosuppressed recipients has to be reassessed during the ongoing coronavirus disease 2019 (COVID-19) pandemic. In addressing these crucial questions, transplant physicians are facing a total lack of scientific evidence. Therefore, the aim of this study was to offer an approach of consensus-based guidance, derived from individual information of 22 transplant societies. Key recommendations were extracted and the degree of consensus among different organizations was calculated. A high degree of consensus was found for temporarily suspending nonurgent transplant procedures and living donation programs. Systematic polymerase chain reaction-based testing of donors and recipients was broadly recommended. Additionally, more specific aspects (eg, screening of surgical explant teams and restricted use of marginal donor organs) were included in our analysis. This study offers a novel approach to informed guidance for health care management when a priori no scientific evidence is available. © 2020 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.Replicative senescence during in vitro augmentation, which is mostly induced by the loss of physiological microenvironment, hinders the application of mesenchymal stem cells (MSCs) in the clinic. Here, we investigated whether MSCs senescence could be prevented by bio-scaffold mimicking the natural tissue matrix. Human umbilical cord mesenchymal stem cells (hUCMSCs) exhibited a senescent phenotype during a long-term passage in the conventional culture dish. To fabricate the bone matrix, a naturally based matrix composed of nano-hydroxyapatite/chitosan/poly lactide-co-glycolide (nHA/CS/PLGA) was produced. Long-term passage resulted in an obvious increase in the expression of senescence markers and a reduction in the expression of master genes involved in tissue regeneration. Functional assay confirmed that nHA/CS/PLGA scaffold preserved the proliferation and differentiation of hUCMSCs even after being passaged 27 times. https://www.selleckchem.com/products/favipiravir-t-705.html Moreover, in vivo ectopic bone formation assay revealed that the bone formation of hUCMSCs cultured on the nano-scaffolds for the long term was as robust as the cells in the early passage. In summary, our results demonstrate that nHA/CS/PLGA scaffold effectively preserves the stemness and youth of hUCMSCs in the long-term passage. Taken advantage of its compatibility and bioactivity, nHA/CS/PLGA scaffold is of great potential in large-scale expansion of MSCs for stem cell therapy and tissue engineering. © 2020 Wiley Periodicals, Inc.Because acellular vascular xenografts induce an immunological reaction through macrophage infiltration, they are conventionally crosslinked with glutaraldehyde (GA). However, the GA crosslinking reaction inhibits not only the host immune reaction around the graft but also the graft's enzymatic degradability, which is one of the key characteristics of acellular grafts that allow them to be replaced by host tissue. In this study, we used an 8-arm polyethylene glycol (PEG) to successfully suppress macrophage infiltration, without eliminating graft degradation. Decellularized ostrich carotid arteries were modified with GA or N-hydroxysuccinimide-activated 8-arm PEG (8-arm PEG-NHS), which has a molecular weight of 17 kDa. To evaluate the enzymatic degradation in vitro, the graft was immersed in a collagenase solution for 12 hr. The 8-arm PEG-modified graft was degraded to the same extent as the unmodified graft, but the GA-modified graft was not degraded. The graft was transplanted into rat subcutaneous tissue for up to 8 weeks. Although CD68-positive cells accumulated in the unmodified graft, they did not infiltrate into either modified graft. However, the GA-modified grafts calcified, but the 8-arm PEG-modified graft did not calcify after transplantation. These data suggested that 8-arm PEG-NHS is a promising modification agent for biodegradable vascular xenografts, to suppress acute macrophage infiltration only. © 2020 Wiley Periodicals, Inc.Direct selection for litter size or weight at weaning in pigs is often hindered by external interventions such as cross-fostering. The objective of this study was to infer the causal structure among phenotypes of reproductive traits in pigs to enable subsequent direct selection for these traits. Examined traits included number born alive (NBA), litter size on day 21 (LS21), and litter weight on day 21 (LW21). The study included 6,240 litters from 1,673 Landrace dams and 5,393 litters from 1,484 Large White dams. The inductive causation (IC) algorithm was used to infer the causal structure, which was then fitted to a structural equation model (SEM) to estimate causal coefficients and genetic parameters. Based on the IC algorithm and temporal and biological information, the causal structure among traits was identified as NBA → LS21 → LW21 and NBA → LW21. Owing to the causal effect of NBA on LS21 and LW21, the genetic, permanent environmental, and residual variances of LS21 and LW21were much lower in the SEM than in the multiple-trait model for both breeds. Given the strong effect of NBA on LS21 and LW21, the SEM and causal information might assist with selective breeding for LS21 and LW21 when cross-fostering occurs. © 2020 The Authors. Animal Science Journal published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Animal Science.
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