Therapeutic role of bone marrow mesenchymal stem cells in diabetic neuronal alternations of rat hippocampus

Background: As the hippocampus is the main brain region for many forms of learning and memory functions and is acutely sensitive to blood glucose changes, diabetes mellitus, which is a serious metabolic disease, is often accompanied by learning and memory deficits. Through scientific literatures, mesenchymal stem cells (MSCs) promote functional recovery in rats with traumatic brain injury, so the present work was conducted to study MSCs as a possible treatment for the diabetic neuronal degeneration and functional impairment of rat hippocampus. Materials and methods: It was carried out using male albino rats: non-diabetic control groups (4, 8, 12 weeks) (n = 15), diabetic groups by i.v. injection of streptozotocin for (4, 8, 12 weeks) (n = 15) and MSCs treatment to diabetic groups for (8, 12 weeks) (n = 10). Hippocampal learning and memory functions were assessed by the Morris Water Maze test and its results were statistically analysed. The rat hippocampal regions (CA1 and CA3) were subjected to histological, ultrastructural examination and morphometrical analyse of pyramidal neurons. Results: Neurons of the diabetic groups showed disturbed function and architecture; shrunken hyperchromatic nuclei and vacuolated eosinophilic cytoplasm (apoptotic changes) also MSCs treatment improved hippocampal learning and memory functions plus its architectural changes; increasing populations and normal regular distribution. Conclusions: It can be concluded that diabetic hippocampal neuronal alternations and functional impairment can be ameliorated by MSCs treatment

An evaluation of the performance of the twentieth century reanalysis version 3

The performance of a new historical reanalysis, the NOAA–CIRES–DOE Twentieth Century Reanalysis version 3 (20CRv3), is evaluated via comparisons with other reanalyses and independent observations. This dataset provides global, 3-hourly estimates of the atmosphere from 1806 to 2015 by assimilating only surface pressure observations and prescribing sea surface temperature, sea ice concentration, and radiative forcings. Comparisons with independent observations, other reanalyses, and satellite products suggest that 20CRv3 can reliably produce atmospheric estimates on scales ranging from weather events to long-term climatic trends. Not only does 20CRv3 recreate a ‘‘best estimate’’ of the weather, including extreme events, it also provides an estimate of its confidence through the use of an ensemble. Surface pressure statistics suggest that these confidence estimates are reliable. Comparisons with independent upper-air observations in the Northern Hemisphere demonstrate that 20CRv3 has skill throughout the twentieth century. Upper-air fields from 20CRv3 in the late twentieth century and early twenty-first century correlate well with full-input reanalyses, and the correlation is predicted by the confidence fields from 20CRv3. The skill of analyzed 500-hPa geopotential heights from 20CRv3 for 1979–2015 is comparable to that of modern operational 3–4-day forecasts. Finally, 20CRv3 performs well on climate time scales. Long time series and multidecadal averages of mass, circulation, and precipitation fields agree well with modern reanalyses and station- and satellite-based products. 20CRv3 is also able to capture trends in tropospheric-layer temperatures that correlate well with independent products in the twentieth century, placing recent trends in a longer historical context.The research work of R. Przybylak and P. Wyszynski was supported by the National Science Centre, Poland (Grants DEC-2012/07/B/ST10/04002 and 2015/19/B/ST10/02933)

An Evaluation of the Performance of the Twentieth Century Reanalysis Version 3

The performance of a new historical reanalysis, the NOAA–CIRES–DOE Twentieth Century Reanalysis version 3 (20CRv3), is evaluated via comparisons with other reanalyses and independent observations. This dataset provides global, 3-hourly estimates of the atmosphere from 1806 to 2015 by assimilating only surface pressure observations and prescribing sea surface temperature, sea ice concentration, and radiative forcings. Comparisons with independent observations, other reanalyses, and satellite products suggest that 20CRv3 can reliably produce atmospheric estimates on scales ranging from weather events to long-term climatic trends. Not only does 20CRv3 recreate a “best estimate” of the weather, including extreme events, it also provides an estimate of its confidence through the use of an ensemble. Surface pressure statistics suggest that these confidence estimates are reliable. Comparisons with independent upper-air observations in the Northern Hemisphere demonstrate that 20CRv3 has skill throughout the twentieth century. Upper-air fields from 20CRv3 in the late twentieth century and early twenty-first century correlate well with full-input reanalyses, and the correlation is predicted by the confidence fields from 20CRv3. The skill of analyzed 500-hPa geopotential heights from 20CRv3 for 1979–2015 is comparable to that of modern operational 3–4-day forecasts. Finally, 20CRv3 performs well on climate time scales. Long time series and multidecadal averages of mass, circulation, and precipitation fields agree well with modern reanalyses and station- and satellite-based products. 20CRv3 is also able to capture trends in tropospheric-layer temperatures that correlate well with independent products in the twentieth century, placing recent trends in a longer historical context

Corals record long-term Leeuwin current variability including Ningaloo Niño/Niña since 1795

Variability of the Leeuwin current (LC) off Western Australia is a footprint of interannual and decadal climate variations in the tropical Indo-Pacific. La Niña events often result in a strengthened LC, high coastal sea levels and unusually warm sea surface temperatures (SSTs), termed Ningaloo Niño. The rarity of such extreme events and the response of the southeastern Indian Ocean to regional and remote climate forcing are poorly understood owing to the lack of long-term records. Here we use well-replicated coral SST records from within the path of the LC, together with a reconstruction of the El Niño-Southern Oscillation to hindcast historical SST and LC strength from 1795 to 2010. We show that interannual and decadal variations in SST and LC strength characterized the past 215 years and that the most extreme sea level and SST anomalies occurred post 1980. These recent events were unprecedented in severity and are likely aided by accelerated global ocean warming and sea-level rise. © 2014 Macmillan Publishers Limited

Graft-versus-host disease in recipients of male unrelated donor compared with parous female sibling donor transplants

Optimal donor selection is critical for successful allogeneic hematopoietic cell transplantation (HCT). Donor sex and parity are well-established risk factors for graft-versus-host disease (GVHD), with male donors typically associated with lower rates of GVHD. Well-matched unrelated donors (URDs) have also been associated with increased risks of GVHD as compared with matched sibling donors. These observations raise the question of whether male URDs would lead to more (or less) favorable transplant outcomes as compared with parous female sibling donors. We used the Center for International Blood and Marrow Transplant Research registry to complete a retrospective cohort study in adults with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome, who underwent T-cell replete HCT from these 2 donor types (parous female sibling or male URD) between 2000 and 2012. Primary outcomes included grade 2 to 4 acute GVHD (aGVHD), chronic GVHD (cGVHD), and overall survival. Secondary outcomes included disease-free survival, transplant-related mortality, and relapse. In 2813 recipients, patients receiving male URD transplants (n = 1921) had 1.6 times higher risk of grade 2 to 4 aGVHD (P \u3c .0001). For cGVHD, recipient sex was a significant factor, so donor/recipient pairs were evaluated. Female recipients of male URD grafts had a higher risk of cGVHD than those receiving parous female sibling grafts (relative risk [RR] = 1.43, P \u3c .0001), whereas male recipients had similar rates of cGVHD regardless of donor type (RR = 1.09, P = .23). Donor type did not significantly affect any other end point. We conclude that when available, parous female siblings are preferred over male URDs

Comparative Analysis of Calcineurin Inhibitor-Based Methotrexate and Mycophenolate Mofetil-Containing Regimens for Prevention of Graft-versus-Host Disease after Reduced-Intensity Conditioning Allogeneic Transplantation

The combination of a calcineurin inhibitor (CNI) such as tacrolimus (TAC) or cyclosporine (CYSP) with methotrexate (MTX) or with mycophenolate mofetil (MMF) has been commonly used for graft-versus-host disease (GVHD) prophylaxis after reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (alloHCT), but there are limited data comparing efficacy of the 2 regimens. We evaluated 1564 adult patients who underwent RIC alloHCT for acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), and myelodysplastic syndrome (MDS) from 2000 to 2013 using HLA-identical sibling (matched related donor [MRD]) or unrelated donor (URD) peripheral blood graft and received CYSP or TAC with MTX or MMF for GVHD prophylaxis. Primary outcomes of the study were acute and chronic GVHD and overall survival (OS). The study divided the patient population into 4 cohorts based on regimen: MMF-TAC, MMF-CYSP, MTX-TAC, and MTX-CYSP. In the URD group, MMF-CYSP was associated with increased risk of grade II to IV acute GVHD (relative risk [RR], 1.78; P <.001) and grade III to IV acute GVHD (RR, 1.93; P =.006) compared with MTX-TAC. In the URD group, use of MMF-TAC (versus MTX-TAC) lead to higher nonrelapse mortality. (hazard ratio, 1.48; P =.008). In either group, no there was no difference in chronic GVHD, disease-free survival, and OS among the GVHD prophylaxis regimens. For RIC alloHCT using MRD, there are no differences in outcomes based on GVHD prophylaxis. However, with URD RIC alloHCT, MMF-CYSP was inferior to MTX-based regimens for acute GVHD prevention, but all the regimens were equivalent in terms of chronic GVHD and OS. Prospective studies, targeting URD recipients are needed to confirm these results

Climate Change Impact on Neotropical Social Wasps

Establishing a direct link between climate change and fluctuations in animal populations through long-term monitoring is difficult given the paucity of baseline data. We hypothesized that social wasps are sensitive to climatic variations, and thus studied the impact of ENSO events on social wasp populations in French Guiana. We noted that during the 2000 La Niña year there was a 77.1% decrease in their nest abundance along ca. 5 km of forest edges, and that 70.5% of the species were no longer present. Two simultaneous 13-year surveys (1997–2009) confirmed the decrease in social wasps during La Niña years (2000 and 2006), while an increase occurred during the 2009 El Niño year. A 30-year weather survey showed that these phenomena corresponded to particularly high levels of rainfall, and that temperature, humidity and global solar radiation were correlated with rainfall. Using the Self-Organizing Map algorithm, we show that heavy rainfall during an entire rainy season has a negative impact on social wasps. Strong contrasts in rainfall between the dry season and the short rainy season exacerbate this effect. Social wasp populations never recovered to their pre-2000 levels. This is probably because these conditions occurred over four years; heavy rainfall during the major rainy seasons during four other years also had a detrimental effect. On the contrary, low levels of rainfall during the major rainy season in 2009 spurred an increase in social wasp populations. We conclude that recent climatic changes have likely resulted in fewer social wasp colonies because they have lowered the wasps' resistance to parasitoids and pathogens. These results imply that Neotropical social wasps can be regarded as bio-indicators because they highlight the impact of climatic changes not yet perceptible in plants and other animals

Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide

Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P =.002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P <.001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus <29 years) was significantly associated with higher rates of grade 2 to 4 acute GVHD (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11 to 2.12; P =.01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR, 1.70; 95% CI, 1.11 to 2.62; P =.01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haplo-HCT. Our results indicate that in RIC haplo-HCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival

Haploidentical vs. sibling, unrelated, or cord blood hematopoietic cell transplantation for acute lymphoblastic leukemia

The role of haploidentical hematopoietic cell transplantation (HCT) using posttransplant cyclophosphamide (PTCy) for acute lymphoblastic leukemia (ALL) is being defined. We performed a retrospective, multivariable analysis comparing outcomes of HCT approaches by donor for adults with ALL in remission. The primary objective was to compare overall survival (OS) among haploidentical HCTs using PTCy and HLA-matched sibling donor (MSD), 8/8 HLAmatched unrelated donor (MUD), 7 /8 HLA-MUD, or umbilical cord blood (UCB) HCT. Comparing haploidentical HCT to MSD HCT, we found that OS, leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and acute graft-versus-host disease (aGVHD) were not different but chronic GVHD (cGVHD) was higher in MSD HCT. Compared with MUD HCT, OS, LFS, and relapse were not different, but MUD HCT had increased NRM (hazard ratio [HR], 1.42; P = .02), grade 3 to 4 aGVHD (HR, 1.59; P = .005), and cGVHD. Compared with 7/8 UD HCT, LFS and relapse were not different, but 7/8 UD HCT had worse OS (HR, 1.38; P = .01) and increased NRM (HR, 2.13; P <_ .001), grade 3 to 4 aGVHD (HR, 1.86; P = .003), and cGVHD (HR, 1.72; P <_ .001). Compared with UCB HCT, late OS, late LFS, relapse, and cGVHD were not different but UCB HCT had worse early OS (<_18 months; HR, 1.93; P < .001), worse early LFS (HR, 1.40; P = .007) and increased incidences of NRM (HR, 2.08; P < .001) and grade 3 to 4 aGVHD (HR, 1.97; P < .001). Haploidentical HCT using PTCy showed no difference in survival but less GVHD compared with traditional MSD and MUD HCT and is the preferred alternative donor HCT option for adults with ALL in complete remission