Neur1 and Neur2 are required for hippocampus-dependent spatial memory and synaptic plasticity.

Neur1 and Neur2, mouse homologs of the Drosophila neur gene, consist of two neuralized homology repeat domains and a RING domain. Both Neur1 and Neur2 are expressed in the whole adult brain and encode E3 ubiquitin ligases, which play a crucial role in the Notch signaling pathways. A previous study reported that overexpression of Neur1 enhances hippocampus-dependent memory, whereas the role of Neur2 remains largely unknown. Here, we aimed to elucidate the respective roles of Neur1 and Neur2 in hippocampus-dependent memory using three lines of genetically modified mice: Neur1 knock-out, Neur2 knock-out, and Neur1 and Neur2 double knock-out (D-KO). Our results showed that spatial memory was impaired when both Neur1 and Neur2 were deleted, but not in the individual knock-out of either Neur1 or Neur2. In addition, basal synaptic properties estimated by input-output relationships and paired-pulse facilitation did not change, but a form of long-term potentiation that requires protein synthesis was specifically impaired in the D-KO mice. These results collectively suggest that Neur1 and Neur2 are crucially involved in hippocampus-dependent spatial memory and synaptic plasticity.

Current status of intestinal transplantation in East Asia.

PURPOSE OF REVIEW: Intestinal transplantation (ITx) activity remains low in East Asia. We conducted a multinational, retrospective study on patients who underwent ITx in Korea, Taiwan, and Japan, to provide an overview and to foresee future developments and collaborations in this region. RECENT FINDINGS: Total 71 ITx were performed in 67 patients. Living donor ITx was most commonly conducted in Japan (n = 13). Despite the low caseload, all three countries demonstrated acceptable patient survival rates of approximately 70% at 5 years. Over 70% of recipients with a functioning graft were free from total parenteral nutrition. SUMMARY: There is an urgent need to establish a nationwide and multinational registry of ITx recipients and patients with intestinal failure in East Asia. An efficient referral system to specialized intestinal rehabilitation and ITx centers and a multidisciplinary team approach is also warranted to provide state-of-the-art treatment for patients desperately waiting for a chance to survive.

Remote Memory and Cortical Synaptic Plasticity Require Neuronal CCCTC-Binding Factor (CTCF).

The molecular mechanism of long-term memory has been extensively studied in the context of the hippocampus-dependent recent memory examined within several days. However, months-old remote memory maintained in the cortex for long-term has not been investigated much at the molecular level yet. Various epigenetic mechanisms are known to be important for long-term memory, but how the 3D chromatin architecture and its regulator molecules contribute to neuronal plasticity and systems consolidation is still largely unknown. CCCTC-binding factor (CTCF) is an 11-zinc finger protein well known for its role as a genome architecture molecule. Male conditional knock-out mice in which CTCF is lost in excitatory neurons during adulthood showed normal recent memory in the contextual fear conditioning and spatial water maze tasks. However, they showed remarkable impairments in remote memory in both tasks. Underlying the remote memory-specific phenotypes, we observed that female CTCF conditional knock-out mice exhibit disrupted cortical LTP, but not hippocampal LTP. Similarly, we observed that CTCF deletion in inhibitory neurons caused partial impairment of remote memory. Through RNA sequencing, we observed that CTCF knockdown in cortical neuron culture caused altered expression of genes that are highly involved in cell adhesion, synaptic plasticity, and memory. These results suggest that remote memory storage in the cortex requires CTCF-mediated gene regulation in neurons, whereas recent memory formation in the hippocampus does not.SIGNIFICANCE STATEMENT CCCTC-binding factor (CTCF) is a well-known 3D genome architectural protein that regulates gene expression. Here, we use two different CTCF conditional knock-out mouse lines and reveal, for the first time, that CTCF is critically involved in the regulation of remote memory. We also show that CTCF is necessary for appropriate expression of genes, many of which we found to be involved in the learning- and memory-related processes. Our study provides behavioral and physiological evidence for the involvement of CTCF-mediated gene regulation in the remote long-term memory and elucidates our understanding of systems consolidation mechanisms.

Venous Thromboembolism Following Abdominal Cancer Surgery in the Korean Population: Incidence and Validation of a Risk Assessment Model.

BACKGROUND: A cancer patient slated for abdominal surgery is considered to be at moderate to high risk for developing venous thromboembolism (VTE), but the incidence is quite low in Korean patients. Most risk assessment models and recommendations for VTE management are from Western reports, however they possibly overestimate the risk of VTE in the Korean population. METHODS: We retrospectively reviewed the medical records of 1966 patients who were diagnosed with abdominal organ cancer and required surgical treatment. RESULTS: Each patient was rated using the Caprini risk scoring model. The mean score was 7.5 ± 0.7 points; 98.4% of patients were classified as high risk for VTE. Symptomatic VTE occurred in eight patients, and the overall incidence was 0.4%. The mean Caprini score for VTE patients was 8.8 ± 1.9 points. In the group with scores between 5 and 9 points, the incidence was 0.3-0.5%, while in patients with scores > 10 points, the incidence of VTE was found to be 1.12%. CONCLUSIONS: The risk stratification system in the Caprini scoring model needs to be modified based on the actual incidence in the Korean population.

Coagulation profile in patients with chronic kidney disease before and after kidney transplantation: A retrospective cohort study.

BACKGROUND: Patients with chronic kidney disease (CKD) tend to experience both thrombotic and hemorrhagic complications; however, the pathophysiology remains unclear. This study aimed to identify the underlying mechanisms and characteristics of hemostatic problems in patients with CKD and to demonstrate the role of kidney transplantation (KT) in correcting these hemostatic abnormalities. METHODS: In this retrospective observational study, 557 KT recipients who did not receive perioperative plasmapheresis and who did not exhibit graft failure within 1 month after KT were included. RESULTS: KT recipients demonstrated increased levels of homocysteine and D-dimer. A total of 80.9% of patients exhibited ≥1 thrombophilic factor at pre-transplantation, and the proportion of these patients decreased to 47% at 28th post-operative day (P<.001). The renal function of patients with no thrombophilic factors was better than that of patients with ≥1 thrombophilic factor at all post-operative assessments (P<.001). The duration of pre-operative dialysis significantly correlated with the thrombotic tendency of patients with CKD before and after KT. CONCLUSION: Patients with CKD can exhibit hypercoagulability, which might be caused by reduced renal function per se. Both HD and PD can aggravate the prothrombotic tendency of patients with CKD via different mechanisms. Most thrombophilic factors in patients with CKD were corrected after KT.

Prediction of clinical outcomes after kidney transplantation from deceased donors with acute kidney injury: a comparison of the KDIGO and AKIN criteria.

BACKGROUND: Acute kidney injury (AKI) is frequently detected in deceased donors (DDs), and it could be associated with adverse clinical outcomes in corresponding kidney transplant recipients (KTRs). In this regard, we sought to identify which criteria is better between the KDIGO and AKIN criteria for the diagnosis of AKI in DDs in the prediction of clinical outcomes after kidney transplantation (KT). METHODS: Two hundred eighty-five cases of deceased donor kidney transplantation (DDKT) were included. We divided them into three groups; the non-AKI by both KDIGO and AKIN criteria group (n = 120), the AKI by KDIGO only group (n = 61), and the AKI by both criteria group (n = 104) according to the diagnosis of AKI using the KDIGO and AKIN criteria in the corresponding 205 DDs. We compared the development of delayed graft function (DGF), the change in allograft function, the allograft survival among the three groups. RESULTS: The incidence of DGF was significantly higher in the AKI by KDIGO only and the AKI by both criteria groups than in the non-AKI by both criteria group (P < 0.05 each). But no difference was detected between the AKI by KDIGO only group and the AKI by both criteria group (P > 0.05). Therefore, the KDIGO criteria had a better predictive value for DGF occurrence than the AKIN criteria (Area under the curve = 0.72 versus 0.63, P < 0.05) in Receiver Operation Characteristic analysis. On comparison of allograft function, the AKI by KDIGO only and the AKI by both criteria groups showed a significantly deteriorating pattern by 6 months after KT in comparison with the non-AKI by both criteria group (P < 0.05). However, the differences disappeared at 1 year from KT and long-term allograft survival did not differ among the three groups. AKI stage either by KDIGO or AKIN in DDs did not affect long-term allograft survival in corresponding KTRs as well. CONCLUSIONS: The KDIGO criteria may be more useful for predicting DGF than the AKIN criteria. However, AKI or AKI stage by either criteria in DDs failed to affect long-term allograft outcomes in KTRs.

The role of nuclear PKMζ in memory maintenance.

Recently, protein kinase M ζ (PKMζ) has emerged as an important player for maintaining memory. It has been reported that PKMζ regulates the trafficking of GluA2 in postsynaptic membranes to maintain memory. However, there has been no study on PKMζ outside the synaptic region regarding memory maintenance. Here, we found that PKMζ is transported to the nucleus in a neural activity-dependent manner. Moreover, we found that PKMζ phosphorylates CREB-binding protein (CBP) at serine residues and that PKMζ inhibition reduces the acetylation of histone H2B and H3. Finally, we showed that the amnesic effect of PKMζ inhibition can be rescued by enhancing histone acetylation level. These results suggest the possibility that nuclear PKMζ has a crucial role in memory maintenance.

Prevalence of the Factor XIII Val34Leu Polymorphism in Korean Patients with Deep Vein Thrombosis.

OBJECTIVE: According to recent reports, a common polymorphism resulting in Val to Leu substitution, located 3 amino acids (Val34Leu) upstream of the thrombin cleavage site of FXIII A, has been related to a lower incidence of deep vein thrombosis (DVT). And, a different expression pattern has been shown across nations and races. However, the frequency of FXIII polymorphism expression in Koreans has not been reported in normal individuals or DVT-patient groups. DESIGN: Case-control study in Korean population. METHODS: We investigated the distribution of factor XIII Val34Leu polymorphisms in Korean patients of DVT (50 cases) and Korean healthy controls (100 cases), using real-time polymerase chain reaction for single nucleotide polymorphism genotyping. RESULTS: With regard to the frequency of the FXIII polymorphism in DVT patients and in the general control group, all 50 cases in the patient group and 100 cases in the control group were found to be Val34 homozygotes. CONCLUSIONS: The Val34Leu polymorphism of FXIII was not found in Korean people, and compared with Caucasians, a noticeably low incidence of DVT was shown. Thus, the preventive effect of the Val34 allele of FXIII on the formation of thrombi was shown.

Efficacy of Retrievable Inferior Vena Cava Filter Placement in the Prevention of Pulmonary Embolism during Catheter-Directed Thrombectomy for Proximal Lower-Extremity Deep Vein Thrombosis.

BACKGROUND: Inferior vena cava (IVC) filter placement is not indicated for thrombolytic interventional treatment for deep vein thrombosis (DVT). We analyzed the efficacy and feasibility of retrievable IVC filter placement for the preventive management of embolic shedding during catheter-directed thrombectomy (CDT) for DVT of lower extremity. METHODS: Seventy patients (35 males and 35 females) who underwent retrievable IVC filter placement to prevent thrombus dislodgement during CDT in all symptomatic DVT with thrombus age suspected within 4 weeks of the lower extremity between March 2008 and January 2014 were included in this study. All patients underwent laboratory blood study, duplex ultrasound and/or computed tomography for diagnosis, treatment, and follow-up in accordance with treatment policy of our Uijeongbu St. Mary's hospital. Two types of retrievable IVC filters (OptEase Filter, Cordis, Roden, The Netherlands; Gunther Tulip Filter, Cook, Bloomington, IN) were used to prevent thromboembolic events during CDT. After filter placement, subcutaneous low-molecular-weight heparin and overlapped to warfarin or new oral anticoagulant tried to achieve a target international normalized ratio (INR) of 2.0-3.0 in warfarin patients. RESULTS: The thrombus was dislodged through the IVC filter during catheter-directed thrombolytic therapy in 22 patients (31.4%). In 22 cases, the thromboses were trapped by the retrievable IVC filter, and follow-up images showed thrombus capture. Thirty-four patients (48.6%) received percutaneous transluminal angioplasty (PTA). Additional stents were inserted in 23 patients (32.8%). Pulmonary embolism (PE) was not observed in patients implanted with retrievable IVC filters. CONCLUSIONS: Our study findings suggest that retrieval IVC filter placement during interventional treatments of DVT of lower extremity such as thrombectomy of vein thrombus with or without stent insertion at compressed deep vein is favorable and effective for protecting against PE or lethal complications. We recommend carefully that before the management of DVT thrombus of lower extremity, retrieval IVC filter placement should be considered for preventing morbidity related with the PE.

Risk factors for postoperative bleeding in ABO-incompatible kidney transplantation.

INTRODUCTION: The outcome of ABO-incompatible kidney transplantation (ABOi KT) has improved and is now comparable to that of ABO-compatible kidney transplantation (ABOc KT). However, ABOi KT may be associated with a higher risk of postoperative bleeding than ABOc KT. METHODS: Seventy patients with ABOi KT were divided into a bleeding group (n = 9) and non-bleeding group (n = 61). General, immunologic, and hematological characteristics were compared to identify the risk factors for postoperative bleeding. RESULTS: Pre-emptive transplantation and a high pre-transplant blood urea nitrogen level were more common in the bleeding group (p = 0.0176 and 0.023, respectively). A high anti-ABO antibody titer after plasmapheresis (median, ≥16; p = 0.0226), a low platelet count of ≤100 000/mm(3) after plasmapheresis (p = 0.0289), a prolonged activated partial thromboplastin time (p = 0.0073), and impaired platelet function (p = 0.0274) were associated with an increased risk of bleeding after ABOi KT. CONCLUSION: Postoperative bleeding after ABOi KT was difficult to control and increased the risk of immediate graft loss (p = 0.015). Our results suggest that changes in coagulability associated with uremia and plasmapheresis may increase the risk of bleeding after ABOi KT.

Clinical Importance of Intraoperative Cephalic Vein Distensibility as a Predictor of Radiocephalic Arteriovenous Fistula Maturation.

Radiocephalic arteriovenous fistula (RCAVF) is the preferred vascular access, but the maturation failure rate is high. Poor vein distensibility is the main cause of maturation failure. There have been several studies regarding vein distensibility, but vein dilation protocol and the cut-off value predicting maturation failure were inconsistent. We were doubtful that the vein distensibility had been appropriately evaluated, and sought to determine a more clinically applicable parameter. The cephalic vein was dilated via intraluminal hydrostatic pressure during the surgery and the vein size was measured. Maturation failure occurred in 30 patients (22.4%) and was more common in females and in patients who had a previous history of arteriovenous access formation (p = 0.0095 and p = 0.014). The intraoperative postdilation diameter, and the difference between pre and postdilation diameters differed between the two groups (p = 0.0004 and p = 0.0004). The cut-off value of the postdilation diameter, which indicated a high probability of maturation success, was >4 mm, and the cut-off value which indicated a higher probability of maturation failure; that is, the difference between the pre and postdilation diameter, was ≤2.2 mm. The degree of distensibility of the cephalic vein may be an important determinant of RCAVF maturation.

Optimal prophylactic method of venous thromboembolism for gastrectomy in Korean patients: an interim analysis of prospective randomized trial.

BACKGROUND: Whereas routine prophylaxis for venous thromboembolism (VTE) is frequently utilized in the West, Asian physicians employ it much less often, based on its recorded rarity amongst their patients. This study was designed to examine the incidence of VTE and to determine the optimal method of thromboembolic prophylaxis following gastrectomy for cancer. METHODS: In this prospective, randomized trial, patients were assigned to either an intermittent pneumatic compression (IPC) only or an IPC plus enoxaparin. The primary end point of this study was to determine the VTE incidence rate within 30 days of surgery. A history with physical examinations for VTE and a serum d-dimer test was scheduled on postoperative days (POD) 0, 1, 4, and 7. Duplex ultrasonography (DUS) was performed as an objective test for deep vein thrombosis at POD 4. An interim analysis was performed to determine if it was ethical to continue the study. This clinical trial was registered at www.clinicaltrials.gov (NCT01448746). RESULTS: Among the 220 patients, 3 (all from the IPC group) were diagnosed with VTE; these cases were asymptomatic, having been detected only on DUS 4 days after surgery. Postoperative bleeding occurred in 12 cases, among which 11 patients were in the IPC plus enoxaparin group. CONCLUSIONS: This interim analysis showed a higher incidence of VTE in the IPC group but a higher bleeding rate in the IPC plus enoxaparin group. We expect that this study, once completed, will provide information key to the determination of the optimal method for preventing VTE in Korean gastric cancer patients.

Clinical impact of the baseline donor-specific anti-human leukocyte antigen antibody measured by Luminex single antigen assay in living donor kidney transplant recipients after desensitization therapy.

The aim of this study is to investigate the clinical impact of donor-specific anti-HLA-antibody (HLA-DSA) baseline levels, measured using the Luminex single antigen assay (LSA), in living donor kidney transplantation (LDKT). Total 129 cases of LDKT were divided into four groups according to baseline mean fluorescence intensity (MFI) HLA-DSA values: Strong (n = 6), >10,000; Moderate (n = 8), 5,000-10,000; Weak (n = 11), 1,000-5,000, Negative (n = 104), <1,000. Pretransplant desensitization (DSZ) was performed to decrease the MFI to weak or negative values before KT. Clinical outcomes in the four groups were compared. After DSZ, HLA-DSA decreased to weak or negative levels in all patients; Acute rejections developed more frequently in strong group [5/6 (83.3%)] compared with other three groups (P < 0.05), and especially acute antibody-mediated rejection (AAMR) developed almost exclusively in strong group [4/6 (66.7%)]. Strong HLA-DSA levels at baseline were more predictive of AAMR than either type of XM (complement-dependent lymphocytotoxicity or flow cytometry) in ROC analysis. Allograft function in this group showed significant deterioration during follow-up compared with the other groups. In conclusion, strong HLA-DSA levels at baseline are associated with worse allograft outcome even after successful desensitization; therefore, strict monitoring and strong maintenance immunosuppression may be required in such patients.

Comparative analysis of post-transplant lymphoproliferative disorder after kidney transplantation versus hematopoietic stem cell transplantation.

Post-transplant lymphoproliferative disorder (PTLD) is a major complication caused by immune-suppression after transplantation. Survival outcome is known to be poor and the characteristics are not fully understood because of its rare incidence. This single center retrospective study enrolled 41 adult PTLD patients after kidney-transplantation (KT, n = 28) and hematopoietic stem cell transplantation (HSCT, n = 13) from 1992 to 2012. We compared the characteristics and estimated the survival outcomes according to several factors [age-adjusted-IPI (aaIPI), pathologic subtype, viral status, extranodal manifestation] and added some significant parameters to aaIPI scoring system. Post-HSCT-PTLD patients were younger and showed earlier onset, and viral status was more frequently identified. Ten-year OS of the entire group was 44% but the 10-year OS was not significantly different between post-KT-PTLD and post-HSCT-PTLD (39% vs. 56%, P = 0.860). The time onset of PTLD and viral statuses were not meaningful, however, aaIPI, age > 50, extranodal manifestation and monomorphic subtype were predictive for OS. We used those factors for PTLD-specific scoring which showed intermediate-risk (HR = 7.1, P = 0.019) and high-risk (HR = 16.5, P = 0.001) presented worse OS compared to low-risk subgroup. Although the treatment strategies were heterogenous, this study showed comprehensive PTLD data between KT versus HSCT, and our PTLD-specific scoring might be validated by another larger studies.

Mechanical thrombectomy with Trerotola compared with catheter-directed thrombolysis for treatment of acute iliofemoral deep vein thrombosis.

BACKGROUND: Mechanical thrombectomy (MT) of acute deep vein thrombosis (DVT) is safe and effective in reducing thrombus burden. MT utilizing a percutaneous thrombectomy device confers a great advantage because it may reduce both the dose of the thrombolytic agent and the overall procedure time compared with a conventional catheter-directed thrombolysis (CDT). We examined the results of MT using the Trerotola device and evaluated factors affecting patient outcome. METHODS: This retrospective study was performed using data from a database of patients who had undergone treatment for an acute iliofemoral DVT from January 2005 to December 2011, at 2 institutions. The patients' clinical characteristics and procedures were compared, and the outcomes of treatment with the Trerotola in the MT group were compared with those obtained with CDT. RESULTS: There were a total of 98 DVTs (left 76; right 22) in 90 patients (34 men); 53 DVTs were treated with MT and 45 with CDT. There were no statistical differences in the clinical characteristics among the MT with CDT, MT only and CDT group. Inferior vena cava filters were placed in 93 DVTs (95%), and iliac vein stenting was used in 64 (65%). Symptom improvement was seen in 78% (18 limbs) of the MT group, 80% (24 limbs) of the MT with CDT group, and 71% (32 limbs) of the CDT group (P = 0.498). The procedure time was shorter in the MT with CDT group (18.2 ± 8.2 hr) or in the MT only group (2.7 ± 2.0 hr) compared with the CDT group (29.3 ± 9.4 hr; P < 0.001). Urokinase dose was lower in MT only (0 million units) or in the MT with CDT group (5.13 ± 3.72 million units) than in the CDT group (7.51 ± 4.54 million units; P < 0.001). There was no difference in complications during the procedures or in primary patency rate during the follow-up period (mean 16.0 ± 19.1 months; range: 0-78 months). CONCLUSIONS: MT with the Trerotola device for acute iliofemoral DVT required shorter procedure times and lower urokinase doses than conventional CDT, while providing the same results.

Use of bortezomib as anti-humoral therapy in kidney transplantation.

This study aimed to investigate the effect of bortezomib in the desensitization and treatment of acute antibody mediated rejection (AAMR) in kidney transplantation. Nine patients who received bortezomib therapy for desensitization (DSZ group, n = 3) or treatment of AAMR (AAMR group, n = 6) were included in this study. In the DSZ group, 2 patients required DSZ owing to positive cross match and 1 owing to ABO mismatch with high baseline anti-ABO antibody titer (1:1,024). Bortezomib was used at 1, 3, 8, and 11 days from the start of the treatment. In the AAMR group, 3 patients showed full recovery of allograft function after bortezomib use and decrease in donor specific anti-HLA antibody (HLA-DSA). However, 3 patients did not respond to bortezomib and experienced allograft failure. In the DSZ group, negative conversion of T-CDC (complement-dependent cytotoxicity) was achieved, and HLA-DSA was decreased to lower than a weak level (median fluorescence intensity [MFI] < 5,000) in 2 patients. In the case of ABO mismatch kidney transplantation, the anti-A/B antibody titer decreased to below the target (≤ 1:16) after bortezomib therapy. Therefore, bortezomib could be an alternative therapeutic option for desensitization and treatment of AAMR that is unresponsive to conventional therapies.

Human assembloid model of the ascending neural sensory pathway.

The ascending somatosensory pathways convey crucial information about pain, touch, itch, and body part movement from peripheral organs to the central nervous system. Despite a significant need for effective therapeutics modulating pain and other somatosensory modalities, clinical translation remains challenging, which is likely related to species-specific features and the lack of in vitro models to directly probe and manipulate this polysynaptic pathway. Here, we established human ascending somatosensory assembloids (hASA)- a four-part assembloid completely generated from human pluripotent stem cells that integrates somatosensory, spinal, diencephalic, and cortical organoids to model the human ascending spinothalamic pathway. Transcriptomic profiling confirmed the presence of key cell types in this circuit. Rabies tracing and calcium imaging showed that sensory neurons connected with dorsal spinal cord projection neurons, which ascending axons further connected to thalamic neurons. Following noxious chemical stimulation, single neuron calcium imaging of intact hASA demonstrated coordinated response, while four-part concomitant extracellular recordings and calcium imaging revealed synchronized activity across the assembloid. Loss of the sodium channel SCN9A, which causes pain insensitivity in humans, disrupted synchrony across the four-part hASA. Taken together, these experiments demonstrate the ability to functionally assemble the essential components of the human sensory pathway. These findings could both accelerate our understanding of human sensory circuits and facilitate therapeutic development.

Impact of the baseline anti-A/B antibody titer on the clinical outcome in ABO-incompatible kidney transplantation.

BACKGROUND/AIMS: We investigated the impact of the baseline anti-A/B antibody titer on the clinical outcome in ABO-incompatible kidney transplantation (IKT). METHODS: We included 183 patients who had undergone KT (40 ABO IKT and 143 ABO-compatible KT). Eight patients with a baseline titer of ≥1:512 were assigned to the high-titer group and 32 patients with a baseline titer of ≤1:256 were assigned to the low-titer group. Patients who underwent ABO-compatible KT were used as the control group. We compared the clinical outcomes of the three groups. RESULTS: Before transplantation, the high-titer group displayed more frequent antibody rebound, as shown in a lower titer reduction rate, and more difficulty reaching the target titer (1:16) than the low-titer group. During the postoperative period and out-clinic follow-up, antibody rebound was more frequent, and the rate of acute rejection and infection were significantly higher and allograft function was lower in the high-titer group than in the low-titer and control groups. Multivariate analysis showed that high baseline antibody titer was an independent risk factor for acute rejection. CONCLUSION: ABO IKT in the high-titer group (baseline titer ≥1:512) required greater caution compared to the low-titer group because of the higher tendency of antibody rebound and the risk for acute rejection.

Hippocampal engram networks for fear memory recruit new synapses and modify pre-existing synapses in vivo.

As basic units of neural networks, ensembles of synapses underlie cognitive functions such as learning and memory. These synaptic engrams show elevated synaptic density among engram cells following contextual fear memory formation. Subsequent analysis of the CA3-CA1 engram synapse revealed larger spine sizes, as the synaptic connectivity correlated with the memory strength. Here, we elucidate the synapse dynamics between CA3 and CA1 by tracking identical synapses at multiple time points by adapting two-photon microscopy and dual-eGRASP technique in vivo. After memory formation, synaptic connections between engram populations are enhanced in conjunction with synaptogenesis within the hippocampal network. However, extinction learning specifically correlated with the disappearance of CA3 engram to CA1 engram (E-E) synapses. We observed "newly formed" synapses near pre-existing synapses, which clustered CA3-CA1 engram synapses after fear memory formation. Overall, we conclude that dynamics at CA3 to CA1 E-E synapses are key sites for modification during fear memory states.