The host environment is a crucial factor for considering the transplant of stem cell–derived immature pancreatic cells in patients with type 1 diabetes. Here, we investigated the effect of insulin (INS)-deficient diabetes on the fate of immature pancreatic endocrine cell grafts and the underlying mechanisms. Human induced pluripotent stem cell–derived pancreatic endocrine progenitor cells (EPCs), which contained a high proportion of chromogranin A⁺ NK6 homeobox 1⁺ cells and very few INS⁺ cells, were used. When the EPCs were implanted under the kidney capsule in immunodeficient mice, INS-deficient diabetes accelerated increase in plasma human C-peptide, a marker of graft-derived INS secretion. The acceleration was suppressed by INS infusion but not affected by partial attenuation of hyperglycemia by dapagliflozin, an INS-independent glucose-lowering agent. Immunohistochemical analyses indicated that the grafts from diabetic mice contained more endocrine cells including proliferative INS-producing cells compared with that from nondiabetic mice, despite no difference in whole graft mass between the two groups. These data suggest that INS-deficient diabetes upregulates the INS-secreting capacity of EPC grafts by increasing the number of endocrine cells including INS-producing cells without changing the graft mass. These findings provide useful insights into postoperative diabetic care for cell therapy using stem cell–derived pancreatic cells.

OBJECTIVE

In patients with type 1 diabetes and end-stage renal disease, it is controversial whether a simultaneous pancreas-kidney (SPK) transplantation improves survival compared with kidney transplantation alone. We compared long-term survival in SPK and living- or deceased-donor kidney transplant recipients.

OBJECTIVE

Reparixin is an inhibitor of CXCR1/2 chemokine receptor shown to be an effective anti-inflammatory adjuvant in a pilot clinical trial in allotransplant recipients.

Bernhard J. Hering
Jul 1, 2016; 39:1230-1240
Emerging Technologies and Therapeutics

Franca B. Barton
Jul 1, 2012; 35:1436-1445
Diabetes Care Symposium

Children undergoing stem cell transplantation are thought to be at risk for increased distress, adjustment difficulties, and impaired health-related quality of life. Few interventions to improve adjustment and quality-of-life outcomes in this setting have been tested.

The excellent outcomes observed in all patient groups, including controls, may be a result of improvements in standard supportive care. Stem cell transplantation may not be as demanding as previously thought to be, and children undergoing this procedure appear resilient to the challenge. (Read the full article)

The gap between organ availability and need continues to grow, and infants are among the most vulnerable candidates on the wait-list. The scarcity of donor organs has led the transplant community to look for alternative donor sources.

Children are receiving more grafts from pediatric donors, but they also continue to receive adult donor grafts. Donation after circulatory determination of death increases organ availability. Allocation changes have also helped increase pediatric transplantation and decrease wait-list deaths. (Read the full article)

End-stage kidney disease (ESKD) causes significant morbidity and mortality after solid organ transplantation. Adults commonly develop advanced kidney disease, particularly after liver and intestinal transplantation. Previous pediatric studies have not compared the relative incidence of ESKD by organ type.

This national cohort study shows the highest risk of ESKD among pediatric lung and intestinal transplant recipients, reflecting unique organ-specific causes of kidney injury. Our findings have implications for screening for and treating early kidney disease in transplant recipients. (Read the full article)

Low case volume has traditionally been associated with poor outcomes in complex surgical procedures, including pediatric liver transplantation.

This retrospective analysis supports the association between low case volume and poorer outcomes in pediatric liver transplantation, and, in addition, shows that candidates listed in low-volume centers have severely limited access to transplantation. (Read the full article)

“Thunder Over Dover” is a free, two-day event that will feature aerial demonstrations, displays of current and historical aircraft, and more.

Activities feature two special programs that explore 18th-century trades and pastimes that might have taken place at the property during the lifetime of the “Penman of the Revolution.”

Accreditation is the highest recognition afforded to museums in the United States.

Event explores Colonial-era job opportunities at the home of the “Penman of the Revolution.”

Program cancelled based on anticipated heavy rain and wind.

Day-long series of activities explores occupations of the 1700s including preserving food in the smokehouse, dyeing cloth, carpentry, blacksmithing and making bricks out of clay.

Bio-energy forest plantations will supplement woody biomass from other sources such as logging residues. In the southern U.S., projections are for an increase of up to 25 million “new” tons of woody biomass demand for bioenergy. To supply this woody biomass demand will require purpose grown plantations of various species including pine, eucalypts, sweetgum, hybrid poplar and cottonwood, amongst others. Forest plantation yields can be 8-15 green tons/acre/year on rotations of 5-12 years. Utilization of this renewable and sustainable biomass resource will be as feedstock “designed” for a large number of bio-energy applications.

The demand for transplantable solid organs far exceeds the supply of deceased donor organs. Patient selection criteria are determined by individual transplant programs; given the scarcity of solid organs for transplant, allocation to those most likely to benefit takes into consideration both medical and psychosocial factors. Children with intellectual and developmental disabilities have historically been excluded as potential recipients of organ transplants. When a transplant is likely to provide significant health benefits, denying a transplant to otherwise eligible children with disabilities may constitute illegal and unjustified discrimination. Children with intellectual and developmental disabilities should not be excluded from the potential pool of recipients and should be referred for evaluation as recipients of solid organ transplants.

Key Points

Background

Kidney injury associated with cold storage is a determinant of delayed graft function and the long-term outcome of transplanted kidneys, but the underlying mechanism remains elusive. We previously reported a role of protein kinase C- (PKC) in renal tubular injury during cisplatin nephrotoxicity and albumin-associated kidney injury, but whether PKC is involved in ischemic or transplantation-associated kidney injury is unknown.

Background

COPD patients account for a large proportion of lung transplants; lung transplantation survival benefit for COPD patients is not well established.

Testosterone is an important determinant of endothelial function and vascular health in men. As both factors play a role in mortality after allogeneic stem cell transplantation (alloSCT), we retrospectively evaluated the impact of pre-transplant testosterone levels on outcome in male patients undergoing alloSCT. In the discovery cohort (n=346), an impact on outcome was observed only in the subgroup of patients allografted for acute myeloid leukemia (AML) (n=176, hereafter termed ‘training cohort’). In the training cohort, lower pre-transplant testosterone levels were significantly associated with shorter overall survival (OS) [hazard ratio (HR) for a decrease of 100 ng/dL: 1.11, P=0.045]. This was based on a higher hazard of non-relapse mortality (NRM) (cause-specific HR: 1.25, P=0.013), but not relapse (cause-specific HR: 1.06, P=0.277) in the multivariable models. These findings were replicated in a confirmation cohort of 168 male patients allografted for AML in a different center (OS, HR: 1.15, P=0.012 and NRM, cause-specific HR: 1.23; P=0.008). Next, an optimized cut-off point for pre-transplant testosterone was derived from the training set and evaluated in the confirmation cohort. In multivariable models, low pre-transplant testosterone status (<250 ng/dL) was associated with worse OS (hazard ratio 1.95, P=0.021) and increased NRM (cause-specific HR 2.68, P=0.011) but not with relapse (cause-specific HR: 1.28, P=0.551). Our findings may provide a rationale for prospective studies on testosterone/androgen assessment and supplementation in male patients undergoing alloSCT for AML.

Cytogenetic risk stratification at diagnosis has long been one of the most useful tools to assess prognosis in acute lymphoblastic leukemia (ALL). To examine the prognostic impact of cytogenetic abnormalities on outcomes after allogeneic hematopoietic cell transplantation, we studied 1731 adults with Philadelphia-negative ALL in complete remission who underwent myeloablative or reduced intensity/non-myeloablative conditioning transplant from unrelated or matched sibling donors reported to the Center for International Blood and Marrow Transplant Research. A total of 632 patients had abnormal conventional metaphase cytogenetics. The leukemia-free survival and overall survival rates at 5 years after transplantation in patients with abnormal cytogenetics were 40% and 42%, respectively, which were similar to those in patients with a normal karyotype. Of the previously established cytogenetic risk classifications, modified Medical Research Council-Eastern Cooperative Oncology Group score was the only independent prognosticator of leukemia-free survival (P=0.03). In the multivariable analysis, monosomy 7 predicted post-transplant relapse [hazard ratio (HR)=2.11; 95% confidence interval (95% CI): 1.04-4.27] and treatment failure (HR=1.97; 95% CI: 1.20-3.24). Complex karyotype was prognostic for relapse (HR=1.69; 95% CI: 1.06-2.69), whereas t(8;14) predicted treatment failure (HR=2.85; 95% CI: 1.35-6.02) and overall mortality (HR=3.03; 95% CI: 1.44-6.41). This large study suggested a novel transplant-specific cytogenetic scheme with adverse [monosomy 7, complex karyotype, del(7q), t(8;14), t(11;19), del(11q), tetraploidy/near triploidy], intermediate (normal karyotype and all other abnormalities), and favorable (high hyperdiploidy) risks to prognosticate leukemia-free survival (P=0.02). Although some previously established high-risk Philadelphia-negative cytogenetic abnormalities in ALL can be overcome by transplantation, monosomy 7, complex karyotype, and t(8;14) continue to pose significant risks and yield inferior outcomes.

Although studies of mixed chimerism following hematopoietic stem cell transplantation in patients with sickle cell disease (SCD) may provide insights into the engraftment needed to correct the disease and into immunological reconstitution, an extensive multilineage analysis is lacking. We analyzed chimerism simultaneously in peripheral erythroid and granulomonocytic precursors/progenitors, highly purified B and T lymphocytes, monocytes, granulocytes and red blood cells (RBC). Thirty-four patients with mixed chimerism and ≥12 months of follow-up were included. A selective advantage of donor RBC and their progenitors/precursors led to full chimerism in mature RBC (despite partial engraftment of other lineages), and resulted in the clinical control of the disease. Six patients with donor chimerism <50% had hemolysis (reticulocytosis) and higher HbS than their donor. Four of them had donor chimerism <30%, including a patient with AA donor (hemoglobin >10 g/dL) and three with AS donors (hemoglobin <10 g/dL). However, only one vaso-occlusive crisis occurred with 68.7% HbS. Except in the patients with the lowest chimerism, the donor engraftment was lower for T cells than for the other lineages. In a context of mixed chimerism after hematopoietic stem cell transplantation for SCD, myeloid (rather than T cell) engraftment was the key efficacy criterion. Results show that myeloid chimerism as low as 30% was sufficient to prevent a vaso-occlusive crisis in transplants from an AA donor but not constantly from an AS donor. However, the correction of hemolysis requires higher donor chimerism levels (i.e. ≥50%) in both AA and AS recipients. In the future, this group of patients may need a different therapeutic approach.

Plasma DNA fragmentomics is an emerging area of research covering plasma DNA sizes, end points, and nucleosome footprints. In the present study, we found a significant increase in the diversity of plasma DNA end motifs in patients with hepatocellular carcinoma (HCC). Compared with patients without HCC, patients with HCC showed a preferential pattern of 4-mer end motifs. In particular, the abundance of plasma DNA motif CCCA was much lower in patients with HCC than in subjects without HCC. The aberrant end motifs were also observed in patients with other cancer types, including colorectal cancer, lung cancer, nasopharyngeal carcinoma, and head and neck squamous cell carcinoma. We further observed that the profile of plasma DNA end motifs originating from the same organ, such as the liver, placenta, and hematopoietic cells, generally clustered together. The profile of end motifs may therefore serve as a class of biomarkers for liquid biopsy in oncology, noninvasive prenatal testing, and transplantation monitoring.

Preimplantation genetic testing (PGT) is a reproductive technology that, in the course of in vitro fertilization (IVF), allows prospective parents to select their future offspring based on genetic characteristics. PGT could be seen as an exercise of reproductive liberty, thus potentially raising significant socioethical and legal controversy. In this review, we examine—from a comparative perspective—variations in policy approaches to the regulation of PGT. We draw on a sample of 19 countries (Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, India, Israel, Italy, Japan, Mexico, Netherlands, Singapore, South Korea, Switzerland, United Kingdom, and the United States) to provide a global landscape of the spectrum of policy and legislative approaches (e.g., restrictive to permissive, public vs. private models). We also explore central socioethical and policy issues and contentious applications, including permissibility criteria (e.g., medical necessity), nonmedical sex selection, and reproductive tourism. Finally, we further outline genetic counseling requirements across policy approaches.

Souplantation's owner says there was no way the restaurants' longtime self-serve model could survive in the era of COVID-19

The agriculture department had earlier fixed May 10 as the date to begin sowing of paddy nursery and June 20 for paddy transplantation, during the current kharif season. The farmers had raised concerns about meeting the cultivation/sowing requirements in view of the labour shortage resulting from migrant labourers returning to their homes in view of the COVID-19 crisis.

Forest department is utterly displeased with the way the Navi Mumbai Municipal Corporation (NMMC) is going about implementing its tree belt project. On Friday, a range forest officer carried out a panchnama, a copy of which is with mid-day, listing the violations so far.

The panchnama states that the tree plantation done by NMMC contractors is inappropriate — the forest department had warned that plantation should be at least 50 metres away from the buffer zone surrounding the mangroves; and yet, it has been done right next to the boundary. The contractors have also allegedly cut the grown trees improperly and dumped the debris amid the mangroves.

Seeing red over green
An environment activist of Vashi, Rohit Malhotra, said, "NMMC removed 200 trees from the plot opposite Fortis Hospital, while dozens of fully grown and numbered trees inside the Rajiv Gandhi Joggers Park adjoining this plot have been felled, on the ground that were Subabul trees. All this has been done with much impunity... I had lodged a complaint with Prakesh Choudhary, range forest officer of Thane Division, who then deputed range officer Pandurang Gaikwad to survey the site. Mr Gaikwad has prepared the panchnama."

Residents had emailed their complaint to Dinesh Kumar Jain, chief secretary of Maharashtra, who has forwarded it to secretary of the forest department for necessary action.

A forest officer, confirming all violations, said, "I shouted at the contractors when I saw that some trees that were not on the list had been cut. Also, they removed soil from around others in such a way that the trees have tilted.

"However, senior forest officers have refused to sign the panchnama, saying they will settle the matter." "NMMC had taken permission from us to cut the Subabul trees in June 20... But I didn't know they dumped the debris amid mangroves. Also, the plantation in the buffer zone was done without our knowledge. I will visit the spot and decide on further action," said Choudhary.

The other side
NMMC Commissioner N Ramaswamy said, "We took all required permissions to cut the trees and for the project. About this particular complaint, I will check and take action accordingly."

The violations

• Planting trees close to mangroves, in violation of buffer zone distance restrictions
• Hacking full-grown trees inappropriately
• Dumping the cut parts amid the mangroves

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Cycling's drug problem has been well documented for years, but for once the sport was happy to assist in catching those committing doping violations - albeit accidentally.