Differences in innate fear behaviour in native Japanese chickens.

1. Comprehensive knowledge of innate fear in chickens has important implications for understanding the adaptation of native Japanese chickens in modern production and behavioural changes caused by modern breeding goals. Innate fear behaviour seen in chicks from six native Japanese chicken breeds;, Ingie (IG), Nagoya (NAG), Oh-Shamo (OSM), Tosa-Jidori (TJI), Tosa-Kukin (TKU) and Ukokkei (UK), were compared with those in two lines of White Leghorn (WL-G and WL-T) in tonic immobility (TI) and open field (OF) tests.2. TI and OF tests were conducted for 267 chicks at 0-1 days of age in the eight breeds. Raw data for four TI traits and 13 OF traits were corrected for environmental factors. Breed differences were analysed by the Kruskal-Wallis test followed by the Steel Dwass post hoc test. Principal component (PC) analyses were conducted.3. The results showed that OSM was the least sensitive to fear in both the TI and OF tests. The WL-G birds showed higher sensitivity to TI fear but lower sensitivity to OF fear. The PC analysis of OF traits classified the tested breeds into three groups: least (OSM and WL-G), moderate (IG, WL-T, NAG, TJI and TKU) and most sensitive (UK).

Exploring experiences and health-related quality of life of caregivers of patients who start home dialysis: study protocol for a prospective, multicentre cohort study.

INTRODUCTION: Starting dialysis not only has a major impact on the life of patients but also on their informal caregivers. Previous research shows greater burden and lower quality of life among caregivers of dialysis patients compared with the general population. Unfortunately, the evidence on the course of both positive and negative experience in caregivers of incident dialysis patients is scarce. Furthermore, well-designed, prospective, multicentre studies comparing caregiving of home dialysis patients with in-centre dialysis patients are lacking. This paper proposes a protocol to assess the trajectory of experiences (both positive and negative) and quality of life of caregivers of home dialysis patients compared with caregivers of in-centre dialysis patients. METHODS AND ANALYSIS: This paper presents a protocol for a prospective, observational, multicentre cohort study which extends the ongoing Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes (DOMESTICO). This study will include at least 200 adult caregivers of patients who start dialysis therapy and have been included in the DOMESTICO study. Positive experiences of the caregivers will be the primary outcome parameter of this study, and negative experiences and health-related quality of life the secondary outcome parameters. Required support will be investigated as an exploratory finding. Outcome parameters will be assessed at baseline, and at 6 and 12 months after start of dialysis using validated questionnaires. ETHICS AND DISSEMINATION: Ethical approval for this study has been obtained from the Medical Research Ethics Committee of the Amsterdam University Medical Centre. The results of this study will be disseminated by publication in a peer-reviewed journal and through presentations at conferences and seminars.

Adverse reactions following transfusion of blood components, with a focus on some rare reactions: Reports to the International Haemovigilance Network Database (ISTARE) in 2012-2016.

OBJECTIVES: The International Haemovigilance Network's (IHN) ISTARE database collects surveillance data on all adverse reactions (AR) associated with transfusion of blood and blood components, facilitating the sharing of best practice and benchmarking for improving blood safety and quality. Up to 2012, no publications discussed certain rare AR. The aim of this study is to examine ISTARE data on AR from 2012 to 2016, focusing on hypotensive reactions, post-transfusion purpura (PTP), transfusion-associated graft versus host disease (TA-GvHD), hyperkalemia and hypocalcemia. MATERIALS AND METHODS: National Haemovigilance Systems (HVS), provided aggregate annual data on AR by type of reaction, severity, imputability to transfusion, and blood component implicated. Twenty-nine HVS provided 104 annual reports covering 107,778,290 blood units issued. RESULTS: Among AR reported, 25% were serious, including 368 deaths. The 284 transfusion-transmitted infections included 187 bacterial infections, 84 viral and 13 parasitic or fungal; nine deaths resulted. AR related to the respiratory system transfusion-associated circulatory overload, transfusion-related acute lung injury and transfusion-associated dyspnoea accounted for 8.3% of all AR, 20.1% of serious, and 52.2% of deaths. Of 1634 rare AR, 1565 were hypotensive, 38 PTP, 17 GvHD, 9 hyperkalemia and 5 hypercalcemia. Half were serious and 16 fatalities were recorded (13 hypotensive, 2 GvHD, one PTP). Among 14 countries that reported any hypotensive AR, incidences diverged widely. CONCLUSIONS: ARs in this group are frequently severe or life-threatening. Hypotensive AR are the most common, but may have been overlooked and counted under allergic and other AR presenting with hypotension. Compliance with the ISBT definition may be suboptimal, thus its real incidence may be higher. Data on GvHD may contribute to clarifying the role of leukodepletion with or without irradiation. ISTARE continues to be a useful surveillance tool for all transfusion AR and provides relevant insights into overlooked and rare AR, thus offering important contributions towards maximising transfusion safety.

Evaluation of risk factors for nephrotoxicity associated with high-dose vancomycin in Japanese patients.

Introduction: Considering the physique of the Japanese population, the standard daily vancomycin dose of 2 g/day and doses ≥ 3 g/day are high in terms of dose per body weight. Studies have reported that administering high-dose vancomycin to achieve a high target trough concentration has been associated with nephrotoxicity. The risk of high-dose vancomycin-associated nephrotoxicity is believed to be exceptionally high for Japanese patients because of their relatively low body weights, but data on the population is lacking. In this retrospective study, we aimed to evaluate risk factors associated with nephrotoxicity in Japanese patients treated with vancomycin. Methods: We examined the medical records of 107 Japanese patients who received vancomycin (3 to 4 g/day). They were divided into two groups based on the presence or absence of nephrotoxicity, and their demographics and clinical characteristics were compared. Results : The incidence of nephrotoxicity in patients receiving high-dose vancomycin was 13%. Age (≥ 60 years) and concurrent use of piperacillin/tazobactam were independent risk factors for vancomycin-associated nephrotoxicity (P = 0.027 and 0.017, respectively). Conclusions : We conclude that the nephrotoxicity risk of high-dose vancomycin in Japanese patients is not excessively high when administered within the confines of a therapeutic drug-monitoring program. However, special care must be taken with patients who are older or on concurrent piperacillin/tazobactam therapy.

Geriatric considerations in older persons with end-stage kidney disease.

Decision-making in older persons with end-stagebkidney disease (ESKD) regarding dialysis initiation is highly complex. While some older persons improve with dialysis and maintain a good quality of life, others experience less benefit and multiple complications due to a high morbidity burden and (early) mortality. Geriatric impairments are highly prevalent among this population and these impairments may complicate the care of an older person with ESKD. Knowledge of these impairments can potentially help improve care and decision-making regarding dialysis initiation and advance care planning. Therefore, the aim of this review is to give healthcare providers an insight into the existing literature on geriatric impairments in older persons with ESKD. Furthermore, specific areas of concern will be discussed, in combination with some practical advice.

The prevalence and incidence of vertebral fractures in end-stage renal disease and the role of parathyroid hormone.

The risk of vertebral fracture is unclear in end-stage renal disease. We report a high vertebral fracture prevalence and incidence in transplantation-eligible patients on dialysis, suggesting that these patients may benefit from radiographic screening for vertebral fractures. Parathyroid hormone had a U-shaped association with vertebral fracture risk. INTRODUCTION: Vertebral fractures are often overlooked, but even undiagnosed vertebral fractures negatively impact physical functioning, quality of life, and mortality. The risk of vertebral fractures in end-stage renal disease (ESRD) patients is unclear, and parathyroid hormone (PTH) might play a role in the development of vertebral fractures. We therefore determined vertebral fracture prevalence and incidence in ESRD patients and assessed associations of vertebral trabecular bone mineral density (BMD) and PTH with vertebral fracture. METHODS: In 146 transplantation-eligible patients on dialysis, we determined vertebral fractures on lateral chest radiographs, which image the thoracic and upper lumbar spine. We determined incident vertebral fractures in 70 patients with follow-up radiographs (23 received a kidney transplant) after median 1.8 years. Vertebral trabecular BMD was measured with computed tomography, and PTH measured with 2-site immunoassays, categorized in tertiles with the middle tertile as reference. We used Poisson regression to assess associations of vertebral trabecular BMD and PTH with vertebral fracture. RESULTS: Mean age of the study population was 52 ± 13 years, and 98 (67%) were male. Median dialysis duration was 26 (IQR 13-55) months. Vertebral fractures were present in 50/146 patients (34%) and incident vertebral fractures occurred in 20/70 patients (29%). Vertebral trabecular BMD was not associated with vertebral fracture prevalence (relative risk 0.97, 95% CI 0.89 to 1.04). For the lowest PTH tertile (< 11 pmol/L), the relative risk of vertebral fracture was greater although not significant (2.28, 95% CI 0.97 to 5.97) and was significantly greater for the highest PTH tertile (≥ 30 pmol/L; 2.82, 95% CI 1.22 to 7.27) after adjustment for potential confounders. CONCLUSIONS: The prevalence and incidence of vertebral fractures is high even in relatively young and healthy ESRD patients. Vertebral trabecular BMD is not associated with vertebral fracture, and the association of PTH with vertebral fracture risk appears U-shaped. Nevertheless, our study did not measure vertebral BMD using DXA and assessed vertebral fractures using lateral chest radiographs and not spine radiographs.

The association between chronic kidney disease, falls, and fractures: a systematic review and meta-analysis.

Patients with chronic kidney disease (CKD) are more likely to experience falls and fractures due to renal osteodystrophy and the high prevalence of risk factors for falls. However, it is not well established how great the risk is for falls and fractures for the different stages of CKD compared to the general population. The objective of this systematic review and meta-analysis was to assess whether, and in which degree, CKD was associated with falls and fractures in adults. A systematic search in PubMed, Embase, CINAHL, and The Cochrane Library was performed on 7 September 2018. All retrospective, cross-sectional, and longitudinal studies of adults (18 years of older) that studied the association between CKD, fractures, and falls were included. Additional studies were identified by cross-referencing. A total of 39 publications were included, of which two publications assessed three types of outcome and four publications assessed two types of outcome. Ten studies focused on accidental falling; seventeen studies focused on hip, femur, and pelvis fractures; seven studies focused on vertebral fractures; and thirteen studies focused on any type of fracture without further specification. Generally, the risk of fractures increased when kidney function worsened, with the highest risks in the patients with stage 5 CKD or dialysis. This effect was most pronounced for hip fractures and any type of fractures. Furthermore, results on the association between CKD and accidental falling were contradictory. Compared to the general population, fractures are highly prevalent in patients with CKD. Besides more awareness of timely fracture risk assessment, there also should be more focus on fall prevention.

Thoracic vertebral fractures and hyperkyphosis in elderly patients with end-stage kidney disease; do these patients have different clinical outcomes?

BACKGROUND AND OBJECTIVES: Elderly patients with end-stage kidney disease (ESKD) are at high risk for fractures. However, the prevalence of vertebral fractures and hyperkyphosis is not studied well. This is relevant, because in the general population, both vertebral fractures and hyperkyphosis are associated with poor outcome. Therefore, the primary aim of our study was to assess the prevalence of vertebral fractures and hyperkyphosis in the ESKD population. The secondary aim was to assess if patients with vertebral fractures and/or hyperkyphosis more often have poor outcome after starting dialysis, such as accidental falling, functional decline and mortality compared to the patients without vertebral fractures and/or hyperkyphosis. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: This study included patients ≥65 years with ESKD who were enrolled in the Geriatric assessment in Older patients starting Dialysis (GOLD) study of whom a lateral chest radiograph was available. Chest radiographs were scored independently by two observers for vertebral fractures (Genant ≥1) and hyperkyphosis (≥50 degrees). The relation between vertebral fractures and hyperkyphosis with clinical outcomes (falls, decline in ADL and IADL, mortality) was studied using the Chi-square test. RESULTS: Of the 196 enrolled patients, chest radiographs were available for 160 patients. Mean age was 75.3 (SD ±6.9), and 35% were female. The prevalence of vertebral fractures was 43% and of hyperkyphosis 22%. Patients with hyperkyphosis had a higher one-year mortality compared to patients without hyperkyphosis (20% vs. 8%, p = 0.04). No differences were observed between patients with and without hyperkyphosis, vertebral fractures and the remaining outcomes after six months of follow-up. CONCLUSIONS: In patients ≥65 years old with ESKD starting dialysis, vertebral fractures are highly prevalent. In contrast to the general population, patients with vertebral fractures did experience poor outcome as often as patients without vertebral fractures. Remarkably, patients with hyperkyphosis did have a higher one-year mortality. However, these patients did not experience more functional decline or accidental falls.

Quality of life after the initiation of dialysis or maximal conservative management in elderly patients: a longitudinal analysis of the Geriatric assessment in OLder patients starting Dialysis (GOLD) study.

BACKGROUND: Maximal conservative management (MCM) may be an appropriate alternative option for dialysis in some elderly patients with end-stage kidney disease (ESKD). Evidence about the impact of dialysis or MCM on quality of life (QoL) in older patients is sparse. In the GOLD (Geriatric assessment in OLder patients starting Dialysis) Study the trajectory of QoL was assessed in patients starting dialysis or MCM. METHODS: Patients ≥65 years old were included just prior to dialysis initiation or after decision for MCM. Baseline data included demographics, frailty as measured with a geriatric assessment, comorbidity (CIRS-G) and QoL, measured with the EQ-5D-3 L (EQ-5D Index and overall self-rated health). Six months follow-up data included QoL, hospitalizations and mortality. Change of QoL was assed with paired t-tests. Cox-regression was used to assess survival of MCM and dialysis patients. RESULTS: The cohort comprised 192 dialysis and 89 MCM patients. The MCM patients were older (mean age 82 ± 6 vs. 75 ± 7 years, p <  0.01) and mean kidney function was better (eGFR 11.5 ± 4.0 vs. 8.0 ± 2.9 ml/min/1.73m2, p <  0.01). Baseline QoL did not differ significantly between the groups. After six months, EQ-5D Index did not improve significantly in the dialysis group with mean ± standard error (SE) 0.026 ± 0.014 (p = 0.10; not clinically relevant), but a small but clinically relevant decline was seen in the conservative group: 0.047 ± 0.022 (p < 0.01; between group difference p < 0.01). Hospitalization occurred in 50% of dialysis patients vs. 24% of conservative patients (p < 0.01). In patients over 80 years old, no survival benefit could be found for dialysis patients starting dialysis vs. MCM. CONCLUSION: A small decline of QoL was found for conservative patients, while QoL did not change in dialysis patients. However, hospitalization rate was higher in patients starting dialysis. In patients over 80 years, no survival benefit was found.

Serum αKlotho as a Predictor of Graft Dysfunction After Kidney Transplantation.

OBJECTIVE: To improve the long-term survival rate after kidney transplantation (KTx), allograft injury should be identified as soon as possible. Regardless of aggressive immunosuppressive therapies, recipients of kidney transplants still have a significant risk of graft failure. No specific predictor for the progression of chronic kidney disease (CKD) after KTx has yet been found. Aberrant molecular mechanisms involving the αKlotho-fibroblast growth factor (FGF) 23 axis may be a useful determinant of renal impairment and graft failure over time. METHODS: Plasma and spot urine samples were collected from 47 patients 1 year after KTx. Evaluation of renal function after KTx was performed using levels of biomarkers including serum intact FGF23, soluble αKlotho, 25(OH) vitamin D (25(OH)D), and the difference in the estimated glomerular filtration rate (eGFR) between the first and third year after KTx (ΔeGFR). RESULTS: The median serum αKlotho, intact FGF23, and 25(OH)D were 516.3 pg/mL, 58.7 pg/mL, and 5.7 ng/mL, respectively. No marked changes in the standard biomarkers that regulate phosphate homeostasis were found. Serum αKlotho levels were associated with ΔeGFR. Multivariate regression analysis revealed that serum αKlotho levels significantly predicted a decrease in eGFR in the graft kidney 2 years after KTx, but serum 25(OH)D and FGF23 levels were not significant. Serum αKlotho levels showed an inverse correlation with fractional excretion of magnesium, which reflects tubular injury in the early stage of CKD. CONCLUSION: Measurement of serum αKlotho may serve as a useful predictor of KTx patients who require initiation of pre-emptive medication.

Efficacy of Eculizumab Therapy for Atypical Hemolytic Uremic Syndrome Recurrence and Antibody-Mediated Rejection Progress After Renal Transplantation With Preformed Donor-Specific Antibodies: Case Report.

Atypical hemolytic uremic syndrome (aHUS) develops as the result of unregulated complement progression and precipitates de novo thrombotic microangiopathy. Plasma therapy is used to control the progression of the complement cascade, but that therapy is not effective in all patients and is accompanied by risk of infection and/or allergy. Eculizumab has been reported as an efficient therapy for aHUS. We report the case of a 35-year old woman who underwent effective eculizumab therapy for aHUS recurrence and antibody-mediated rejection (AMR) progress after renal transplantation with preformed donor-specific antibodies (DSA). She developed end-stage renal disease due to suspicious IgA nephropathy at age 33 years. Kidney transplantation was performed at age 35 years, and aHUS recurred 2 weeks later, leading to the progressive hemolytic anemia and renal dysfunction. Therefore, she underwent plasma therapy several times. Because it was difficult to continue to plasma therapy for severe allergy, eculizumab was proposed as an alternate therapy. Treatment with eculizumab was initiated 36 days after renal transplantation. After 3 years of eculizumab treatment, and without plasma therapy, schistocytes decreased, haptoglobin increased to within normal limits, creatinine levels stabilized, and no further episodes of diarrhea were reported. At protocol biopsy 1 year after transplantation, she was diagnosed with C4d-negative subclinical AMR. However, her pathologic findings at follow-up biopsy 3 years after transplantation were recovered. We conclude that eculizumab alone, without plasma therapy, is sufficient to treat recurrence of aHUS and AMR due to DSA after renal transplantation and to maintain long-term graft function.

[Autoimmune encephalitis due to mantle cell lymphoma]. / Auto-immune encefalitis door een mantelcellymfoom.

BACKGROUND: Autoimmune encephalitis is a rare condition characterized by subacute development of cognitive and psychiatric symptoms. A paraneoplastic syndrome involves autoimmune encephalitis caused by classic antibodies. Although this condition is often associated with cancer, no malignancy has yet been found in 70-90% of patients at the time of diagnosis. CASE DESCRIPTION: We saw a 58-year-old male patient with fatigue, diarrhoea and weight loss. He was also experiencing hyperekplexia, personality changes and an instable gait. PET-CT revealed generalised lymphadenopathy. Histopathological analysis of a lymph node showed mantle cell lymphoma. Further investigation of the fluid revealed anti-DPPX IgG antibodies. We treated the patient's mantle cell lymphoma with R-CHOP; he achieved complete remission and his neurological symptoms resolved almost completely. CONCLUSION: The presence of anti-DPPX IgG antibodies is rare. Although it has not been proven that these antibodies are related to malignancies, this is the third of 30 known cases in which anti-DPPX IgG antibodies and a lymphatic malignancy were found.

Encephalitis caused by human herpesvirus-6B in pancreas-after-kidney transplantation.

Human herpesvirus-6 (HHV-6) is a common pathogen among children, classically presenting with fever and rash that resolves without specific therapy. HHV-6 can be reactivated in the immunosuppressed patient. After bone marrow and solid organ transplantation, HHV-6 has been linked to various clinical syndromes, including undifferentiated febrile illness, encephalitis, myelitis, hepatitis, pneumonitis, and bone marrow suppression. However, HHV-6 encephalitis after pancreatic transplant has rarely been reported. Early diagnosis and treatment of HHV-6 encephalitis may be important for affected patients. We report the case of a 53-year-old pancreas-after-kidney transplant recipient who initially presented with high fever and confusion 3 weeks after operation. We managed to save the patient's life and preserve the pancreas graft function. We also review previously reported cases of HHV-6B encephalitis in solid organ transplant recipients.

Pharmacokinetics of everolimus when combined with cyclosporine in Japanese de novo renal transplant recipients.

BACKGROUND: Currently, there are no published data on pharmacokinetics (PK) of everolimus in combination with cyclosporine in Japanese renal transplant patients. We evaluated the PK of everolimus in Japanese de novo renal transplant patients who received everolimus in combination with cyclosporine. METHODS: In this phase 3, multicenter, randomized, open-label study, patients were randomized (1:1) to 1 of the 2 groups: everolimus 1.5 mg (targeted C0 of 3-8 ng/mL) plus reduced-dose cyclosporine or mycophenolate mofetil 2 g/d plus standard-dose cyclosporine. PK assessments for everolimus were performed on day 28 (month 1) in the PK subpopulation. RESULTS: A total of 11 patients (7 men), mean age 47.5 ± 11.21 years, were enrolled for PK analysis of everolimus. Starting at 1.5 mg (0.75 mg twice a day), the mean dose over a period of 28 days was 0.705 ± 0.1011 mg. Everolimus mean trough concentration was 4.307 ± 1.2459 ng/mL and mean peak concentration was 13.539 ± 3.5330 ng/mL, which peaked at 1 to 2 hours postdose. The average concentration was 7.558 ± 1.4723 ng/mL, area under the concentration-time curve was 90.70 ± 17.667 ng·h/mL, and peak-trough fluctuation was 122.6%. The PK parameters of everolimus were comparable to those in the earlier phase 3 studies (A2306 and A2307). The mean everolimus trough levels were within the target ranges at all time points ranging from 3.4 to 5.5 ng/mL (everolimus 0.75 mg twice a day, safety population). The majority of patients (>85% from day 7 onward) were maintained within the targeted everolimus trough blood levels (safety population). These data were similar to a non-Japanese study (A2309). CONCLUSIONS: The pharmacokinetic characteristics of everolimus in Japanese de novo renal transplant patients did not differ from those previously observed in non-Japanese patients, hence the same dosage of everolimus may be acceptable in Japanese patients.

Acute antibody-mediated rejection possibly due to anti-human leukocyte antigen DQB1 antibodies after renal transplantation - case report.

A 61-year-old Japanese woman, who had undergone hemodialysis because of chronic glomerulonephritis, received a living renal transplant from her ABO blood type-compatible spouse. HLA typing of A, B and DRB showed 3/6 mismatches. Complement-dependent cytotoxicity crossmatches, HLA antibody screening with the use of flow panel reactive antibody (PRA), and flow cytometry crossmatches (FCXM) were all negative. Tacrolimus, mycophenolate mofetil, methylprednisolone (MP), and basiliximab induction were used as the standard immunosuppressive therapy. After renal transplantation, her serum creatinine level favorably decreased, but urine output was not sufficiently obtained, contrary to our expectations. Doppler sonography revealed disappearance of diastolic arterial flow on postoperative day 2. The episode biopsy showed acute antibody-mediated rejection (AMR) based on the current Banff classification, although FCXM and flow PRA were still negative. To determine the cause of acute AMR, we expanded the HLA typing at high resolution levels to Cw, DQB1, and DPB1. Retrospective analysis of perioperative sera demonstrated the presence of low levels of donor-specific HLA IgG and moderate levels of IgM antibody against DQB1 before transplantation. There was an elevation of IgM antibody at the time of rejection, whereas IgG antibody showed no remarkable change. AMR was successfully treated with plasma exchange, low-dose intravenous immunoglobulin, high-dose intravenous MP pulse, and rituximab.

Genetic characterization and conservation priorities of chicken lines.

Molecular markers are a useful tool for evaluating genetic diversity of chicken genetic resources. Seven chicken lines derived from the Plymouth Rock breed were genotyped using 40 microsatellite markers to quantify genetic differentiation and assess conservation priorities for the lines. Genetic differentiation between pairs of the lines (pairwise FST) ranged from 0.201 to 0.422. A neighbor-joining tree of individuals, based on the proportion of shared alleles, formed clearly defined clusters corresponding to the origins of the lines. In Bayesian model-based clustering, most individuals were clearly assigned to single clusters according to line origin and showed no admixture. These results indicated that a substantial degree of genetic differentiation exists among the lines. To decide priorities for conservation, the contribution of each line to the genetic diversity was estimated. The result indicated that a loss of 4 of the 7 lines would lead to a loss from 1.14 to 3.44% of total genetic diversity. The most preferred line for conservation purposes was identified based on multilocus microsatellite analysis. Our results confirmed that characterization by means of molecular markers is helpful for establishing a plan for conservation of chicken genetic resources.

Impairment of fear-conditioning responses and changes of brain neurotrophic factors in diet-induced obese mice.

Recent epidemiological studies demonstrate that obesity is related to a high incidence of cognitive impairment. In the present study, cognitive behaviours in diet-induced obese (DIO) mice fed 60% high-fat diet for 16 weeks were compared with those in mice fed a control diet (CD) in fear-conditioning tests including both contextual and cued elements that preferentially depend on the hippocampus and amygdala, respectively. Furthermore, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) content in the brain areas was examined in both CD and DIO mice. In fear-conditioning tests, the freezing percentages of both contextual fear and cued fear responses in DIO mice were significantly lower than in CD mice. BDNF content in the cerebral cortex and hippocampus of DIO mice was significantly lower than that in CD mice. Its receptor, full-length TrkB, in the amygdala of DIO mice was significantly decreased compared to that in CD mice, although not in the cerebral cortex, hippocampus and hypothalamus. By contrast, NT-3 content in the hippocampus, amygdala and hypothalamus of DIO mice was significantly higher than that in CD mice. Its receptor, full-length TrkC, was not significantly different between CD and DIO mice. The present study demonstrates that DIO mice show impairment of both hippocampus-dependent contextual and amygdala-dependent cued responses in the fear-conditioning tests, as well as an imbalance in the interaction between the BDNF and NT-3 systems in the cerebral cortex, hippocampus and amygdala related to cognition and fear.

Potent immunosuppression for ABO-incompatible renal transplantation may not be a risk factor for malignancy.

ABO-incompatible (ABOi) renal transplantation has been increasing, but malignant tumor is a troubling complication of kidney transplantation due to potent immunosuppression. Few previous studies, however, have demonstrated that potent immunosuppression for ABOi living-donor renal transplantation (LDRT) is a risk factor for malignancy. In the present research, data on 252 LDRT patients ftom 2003 to 2008 were retrospectively analyzed to clarify whether ABOi LDRT was associated with malignancy. A potent immunosuppressive regimen for ABOiLDRT consisted of splenectomy, cyclophosphamide, and double-filtration plasmapheresis to minimize the risk of antibody-mediated rejection, in addition to conventional immunosuppresssants including calcineurin inhibitor, prednisolone, and anti-CD25 monoclonal antibody. A total of 11 incidences of malignancy were observed during a median follow-up of 48 months. The incidence rates in ABO-compatible (ABOc; n = 189) and ABOi (n = 63) LDRT groups were 4.2 % (8/189) and 4.8 % (3/63), respectively. Kaplan-Meier survival analysis showed no statistical difference in event-free survival for malignancy between ABOc and ABOiLDRT groups (log-rank P = .73). Multivariable Cox regression analyses identified no associations of malignancy with ABOi LDRT or any immunosuppressant use. In conclusion, our investigation suggested that potent immunosuppression with splenectomy and cyclophosphamide for ABOi LDRT may not be a risk factor for malignancy.

Clinical characteristics and outcomes of renal transplantation in elderly recipients.

BACKGROUND: Elderly renal transplant candidates constitute one the fastest-growing populations among end-stage renal disease patients. Since the impacts of advanced recipient age have not yet been fully defined, we evaluated the clinical characteristics and outcomes of elderly renal transplant recipients. METHODS: Among 564 adult renal transplant recipients, at our center between 2000 and 2009, 64 were at least 60 years of age (Elderly group), and 500 were younger than 60 years (Young group) at the time of the procedure. We compared their clinical features and surgical management. RESULTS: There were significant differences in mean donor age (55.6 years vs. 53.2 years, P = .030) and gender mismatch (77.0% vs. 63.4%, P = .035). However, there were no significant differences between the two groups in patient and graft survivals (P = .177 and P = .365, respectively). Malignancy after transplantation was a significant risk factor upon univariate evaluation but only ABO incompatibility upon multivariate analysis of patient and graft survival. The main cause of graft loss among the Elderly group was death with a functioning graft due to heart failure. CONCLUSIONS: Renal transplantation is a feasible, safe option for the elderly and should be actively implemented. However, screening for cancer and heart disease should be mandatory to improve outcomes.