Impact of leptin on memory function and hippocampal structure in mild cognitive impairment

Metabolic changes have been suggested to contribute to dementia and its precursor mild cognitive impairment (MCI), yet previous results particularly for the “satiety hormone” leptin are mixed. Therefore, we aimed to determine if MCI patients show systematic differences in leptin, independent of sex, adipose mass, age, and glucose and lipid metabolism, and whether leptin levels correlated with memory performance and hippocampal integrity. Forty MCI patients (20 females, aged 67 years ± 7 SD) were compared to 40 healthy controls (HC) that were pair‐wise matched for sex, age, and body fat. Memory performance was assessed using the auditory verbal learning test. Volume and microstructure of the hippocampus were determined using 3T‐neuroimaging. Fasting serum markers of leptin, glucose and lipid metabolism, and other confounding factors were assayed. MCI patients, compared with HC, showed lower serum leptin, independent of sex, age, and body fat (P < 0.001). Glucose and lipid markers did not attenuate these results. Moreover, MCI patients exhibited poorer memory and lower volume and microstructural integrity within hippocampal subfields. While leptin and memory were not significantly correlated, mediation analyses indicated that lower leptin contributed to poorer memory through its negative effect on right hippocampus volume and left hippocampus microstructure. We demonstrated that MCI is associated with lower serum leptin independent of sex, age, body fat, glucose, and lipid metabolism. Our data further suggest that inefficient leptin signaling could partly contribute to decreases in memory performance through changes in hippocampus structure, a hypothesis that should now be verified in longitudinal studies. Hum Brain Mapp 37:4539–4549, 2016. © 2016 Wiley Periodicals, Inc.     

Living Legends: Students' Responses to an Intergenerational Life Review Writing Program

The purpose of the study was to examine the effects of participation in the Living Legends program upon health science students' image of older adults and interest in working with older people. A multisite quasi‐experimental control group design with a connected qualitative component was used. Program sites included three Naturally Occurring Retirement Communities (NORCs) and one senior center. Health science students (n = 43) from two universities and two community colleges and community‐dwelling seniors (n = 39) participated in the program. A baseline questionnaire was used to ascertain demographic characteristics and prior type and amount of contact with older adults. The Image of Aging Scale and Likert‐style questions to measure interest in working with older adults were the primary outcome measures. Written responses to program experiences were also collected. Analysis of covariance was used to compare changes in Image of Aging subscale scores from pre‐ to posttest. Mean change in positive image of older adults subscale scores was 4.6 (SD = 4.4) for the intervention group and ?0.6 (SD = 4.8) for the control group. The difference between groups was significant (F = 22.0, P < .001), and the effect size was large (Cohen's d = 1.07). Nine of the 22 students in the intervention group had a greater interest in working with seniors after the program. Qualitative themes that emerged included a positive and beneficial experience, life lessons, seeing the person beyond the visible, power of the written word, and shared lives. Living Legends is an effective program to enhance positive images of older adults in future healthcare professionals and may have a positive impact on some students with regard to interest in working with older adults.     

Palliative care consultation services in hospitals in the Netherlands: the design of the COMPASS study

Background

Patients with an advanced incurable disease are often hospitalised for some time during the last phase of life. Care in hospitals is generally focussed at curing disease and prolonging life and may therefore not in all cases adequately address the needs of such patients. We present the COMPASS study, a study on the effects and costs of consultation teams for palliative care in hospitals.This observational study aims to investigate the use, effects and costs of PCT consultation services for hospitalized patients with incurable cancer in the Netherlands.

Methods/design

The study consists of 3 parts:1. A questionnaire, interviews and a focus group discussion to investigate the characteristics of PCT consultation in 12 hospitals. PCTs will register their activities to calculate the costs of PCT consultation.2. Cancer patients for whom the attending physician would not be surprised that they would die within 12 month will be included in a medical file search in three hospitals. Medical records will be investigated to compare care, treatment and hospital costs between patients with and patients without PCT consultation.3. In the other nine hospitals, we will perform a longitudinal study, and compare quality of life between 100 patients for whom a PCT was consulted with 200 patients without PCT consultation. Propensity score matching will be used to adjust for differences between both patient groups. Patients will be followed for three months after inclusion. Quality of life will be assessed with the Palliative Outcome Scale, the EuroQol-5d and the EORTC-QLQ-C15 PAL. Satisfaction with care in the hospital is measured with the IN-PATSAT32. The cost impact of PCT consultation will also be explored.

Discussion

This is the first multicenter study on PCT consultation in the Netherlands. The study will give valuable insight in the process, effects and costs of PCT consultation in hospitals. It is anticipated that PCT consultation has a positive effect on patients’ quality of life and satisfaction with care and will lead to less hospital care costs.

     

Adherence to a six-dose regimen of artemether-lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in Uganda

Measuring baseline levels of adherence and identifying risk factors for non-adherence are important steps before the introduction of new antimalarials. In Mbarara in southwestern Uganda, we assessed adherence to artemether-lumefantrine (Coartem) in its latest World Health Organization blister formulation. Patients with uncomplicated Plasmodium falciparum malaria were prescribed artemether-lumefantrine and received an explanation of how to take the following five doses at home. A tablet count was made and a questionnaire was completed during a home visit. Among 210 analyzable patients, 21 (10.0%) were definitely or probably non-adherent, whereas 189 (90.0%) were probably adherent. Age group was not associated with adherence. Lack of formal education was the only factor associated with non-adherence after controlling for confounders (odds ratio = 3.1, 95% confidence interval [CI] = 1.1-9.7). Mean lumefantrine blood levels were lower among non-adherent (n = 16) (2.76 microg/mL, 95% CI = 1.06-4.45) than among adherent (n = 171) (3.19 microg/mL, 95% CI = 2.84-3.54) patients, but this difference was not statistically significant. The high adherence to artemether-lumefantrine found in our study suggest that this drug is likely to be very effective in Mbarara provided that patients receive clear dosage explanations.     

Transplantation of mobilized peripheral blood cells to HLA-identical siblings with standard-risk leukemia

Allogeneic mobilized peripheral blood progenitor cells instead of bone marrow are increasingly used to restore hematopoiesis after myeloablative therapy. Data supporting this important change of clinical practice are scarce. We therefore assigned patients with early leukemias to peripheral blood or bone marrow transplantation; the occurrence of acute and chronic graft versus host disease, survival, transplantation-related mortality, and relapse rates were compared. A total of 350 patients between 18 and 55 years of age with acute leukemias in remission or chronic myelogenous leukemia in first chronic phase were randomized to receive either filgrastim-mobilized peripheral blood progenitor cells or bone marrow cells from HLA-identical sibling donors after standard high-dose chemoradiotherapy. Neutrophil and platelet recovery occurred significantly faster after transplantation of peripheral blood progenitor cells than after bone marrow transplantation. Acute graft versus host disease of grades II-IV was significantly more frequent in recipients of peripheral blood progenitor cells than in recipients of marrow cells (52% vs 39%, odds ratio 1.74, 95% confidence interval 1.12-2.69, P =.013). The cumulative incidence of chronic graft versus host disease was 67% with peripheral blood progenitor cells and 54% with bone marrow cells (hazard ratio 1.67, 95% confidence interval 1.15-2.42, P =.0066). The estimated overall probability of survival at 2 years was 65% with either source of stem cells (hazard ratio 1.15, 95% confidence interval 0.79-1.67, P =.46). Disease-free survival, transplantation-related mortality at day 100, and relapse rates did not significantly differ between treatment arms. Peripheral blood is an equivalent source of hematopoietic stem cells compared with bone marrow if administered to patients with standard-risk leukemias. Long-term observation of patients with different diseases and stages of disease is necessary to ultimately define the role of both sources of stem cells.     

Nitric oxide inhibits H2O2-induced transferrin receptor-dependent apoptosis in endothelial cells: Role of ubiquitin-proteasome pathway

We investigated here the mechanism of cytoprotection of nitric oxide (*NO) in bovine aortic endothelial cells treated with H2O2. NONOates were used as *NO donors that released *NO slowly at a well defined rate in the extracellular and intracellular milieus. H2O2-mediated intracellular dichlorofluorescein fluorescence and apoptosis were enhanced by the transferrin receptor (TfR)-mediated iron uptake. *NO inhibited the TfR-mediated iron uptake, dichlorofluorescein fluorescence, and apoptosis in H2O2-treated cells. *NO increased the proteasomal activity and degradation of nitrated TfR via ubiquitination. Nomega-nitro-L-arginine methyl ester, a nonspecific inhibitor of endogenous *NO biosynthesis, decreased the trypsin-like activity of 26S proteasome. *NO, by activating proteolysis, mitigates TfR-dependent iron uptake, dichlorodihydrofluorescein oxidation, and apoptosis in H2O2-treated bovine aortic endothelial cells. The relevance of biological nitration on redox signaling is discussed.