Long-term potentiation decay and memory loss are mediated by AMPAR endocytosis

Long-term potentiation (LTP) of synaptic strength between hippocampal neurons is associated with learning and memory, and LTP dysfunction is thought to underlie memory loss. LTP can be temporally and mechanistically classified into decaying (early-phase) LTP and nondecaying (late-phase) LTP. While the nondecaying nature of LTP is thought to depend on protein synthesis and contribute to memory maintenance, little is known about the mechanisms and roles of decaying LTP. Here, we demonstrated that inhibiting endocytosis of postsynaptic α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptors (AMPARs) prevents LTP decay, thereby converting it into nondecaying LTP. Conversely, restoration of AMPAR endocytosis by inhibiting protein kinase Mζ (PKMζ) converted nondecaying LTP into decaying LTP. Similarly, inhibition of AMPAR endocytosis prolonged memory retention in normal animals and reduced memory loss in a murine model of Alzheimer’s disease. These results strongly suggest that an active process that involves AMPAR endocytosis mediates the decay of LTP and that inhibition of this process can prolong the longevity of LTP as well as memory under both physiological and pathological conditions.     

Kugel手术与腹腔镜完全腹膜外疝修补术的比较研究

目的比较Kugel疝修补术与腹腔镜完全腹膜外疝修补术(TEP)治疗腹股沟疝的临床效果。方法回顾性分析2009年8月至2013年7月,南方医科大学附属小榄医院收治的385例腹股沟疝患者的临床资料,根据腹膜外疝修补术方式分为Kugel组(163例)与TEP组(222例)。比较二组患者手术时间、住院时间、恢复正常活动时间、住院费用、术后腹股沟区疼痛情况、术后并发症等。结果二组患者手术时间、住院时间、切口感染、疝复发率比较,差异无统计学意义(t=0.018、5.563、χ2=0.647、0.048,P=0.057、0.206、0.421、0.826);术后腹股沟区疼痛发生率、恢复正常活动时间、血清肿发生率,TEP组明显少于Kugel组(χ2=5.958、t=24.545、χ2=4.438,P=0.015、0.000、0.035);住院费用Kugel组低于TEP组(t=8.072,P=0.000)。结论 TEP与Kugel 2种术式治疗腹股沟疝均可取得良好疗效,TEP具有术后疼痛轻、恢复快等优点,但住院费用较高,临床医师需根据患者的经济水平、意愿以及术者水平等综合选择最佳的手术方式。     

Screw-Home Movement of the Tibiofemoral Joint during Normal Gait: Three-Dimensional Analysis

Background

The purpose of this study was to evaluate the screw-home movement at the tibiofemoral joint during normal gait by utilizing the 3-dimensional motion capture technique.

Methods

Fifteen young males and fifteen young females (total 60 knee joints) who had no history of musculoskeletal disease or a particular gait problem were included in this study. Two more markers were attached to the subject in addition to the Helen-Hayes marker set. Thus, two virtual planes, femoral coronal plane (P_f) and tibial coronal plane (P_t), were created by Skeletal Builder software. This study measured the 3-dimensional knee joint movement in the sagittal, coronal, and transverse planes of these two virtual planes (P_f and P_t) during normal gait.

Results

With respect to kinematics and kinetics, both males and females showed normal adult gait patterns, and the mean difference in the temporal gait parameters was not statistically significant (p > 0.05). In the transverse plane, the screw-home movement occurred as expected during the pre-swing phase and the late-swing phase at an angle of about 17°. However, the tibia rotated externally with respect to the femur, rather than internally, while the knee joint started to flex during the loading response (paradoxical screw-home movement), and the angle was 6°.

Conclusions

Paradoxical screw-home movement may be an important mechanism that provides stability to the knee joint during the remaining stance phase. Obtaining the kinematic values of the knee joint during gait can be useful in diagnosing and treating the pathological knee joints.     

Performance of Fasting Plasma Glucose and Postprandial Urine Glucose in Screening for Diabetes in Chinese High-risk Population

Background:

The conventional approaches to diabetes screening are potentially limited by poor compliance and laboratory demand. This study aimed to evaluate the performance of fasting plasma glucose (FPG) and postprandial urine glucose (PUG) in screening for diabetes in Chinese high-risk population.

Methods:

Nine hundred and nine subjects with high-risk factors of diabetes underwent oral glucose tolerance test after an overnight fast. FPG, hemoglobin A1c, 2-h plasma glucose (2 h-PG), and 2 h-PUG were evaluated. Diabetes and prediabetes were defined by the American Diabetes Association criteria. The area under the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic accuracy of 2 h-PUG, and the optimal cut-off determined to provide the largest Youden index. Spearman correlation was used for relationship analysis.

Results:

Among 909 subjects, 33.4% (304/909) of subjects had prediabetes, and 17.2% (156/909) had diabetes. The 2 h-PUG was positively related to FPG and 2 h-PG (r = 0.428 and 0.551, respectively, both P < 0.001). For estimation of 2 h-PG ≥ 7.8 mmol/L and 2 h-PG ≥ 11.1 mmol/L using 2 h-PUG, the area under the ROC curve were 0.772 (95% confidence interval [CI ]: 0.738–0.806) and 0.885 (95% CI: 0.850–0.921), respectively. The corresponding optimal cut-offs for 2 h-PUG were 5.6 mmol/L and 7.5 mmol/L, respectively. Compared with FPG alone, FPG combined with 2 h-PUG had a higher sensitivity for detecting glucose abnormalities (84.1% vs. 73.7%, P < 0.001) and diabetes (82.7% vs. 48.1%, P < 0.001).

Conclusion:

FPG combined with 2 h-PUG substantially improves the sensitivity in detecting prediabetes and diabetes relative to FPG alone, and may represent an efficient layperson-oriented diabetes screening method.     

Plantar Pressure Changes and Correlating Risk Factors in Chinese Patients with Type 2 Diabetes: Preliminary 2-year Results of a Prospective Study

Background:

Plantar pressure serves as a key factor for predicting ulceration in the feet of diabetes patients. We designed this study to analyze plantar pressure changes and correlating risk factors in Chinese patients with type 2 diabetes.

Methods:

We recruited 65 patients with type 2 diabetes. They were invited to participate in the second wave 2 years later. The patients completed identical examinations at the baseline point and 2 years later. We obtained maximum force, maximum pressure, impulse, pressure-time integral, and loading rate values from 10 foot regions. We collected data on six history-based variables, six anthropometric variables, and four metabolic variables of the patients.

Results:

Over the course of the study, significant plantar pressure increases in some forefoot portions were identified (P < 0.05), especially in the second to forth metatarsal heads. Decreases in heel impulse and pressure-time integral levels were also found (P < 0.05). Plantar pressure parameters increased with body mass index (BMI) levels. Hemoglobin A1c (HbA1c) changes were positively correlated with maximum force (β = 0.364, P = 0.001) and maximum pressure (β = 0.366, P = 0.002) changes in the first metatarsal head. Cholesterol changes were positively correlated with impulse changes in the lateral portion of the heel (β = 0.179, P = 0.072) and pressure-time integral changes in the second metatarsal head (β = 0.236, P = 0.020). Ankle-brachial index (ABI) changes were positively correlated with maximum force changes in the first metatarsal head (β = 0.137, P = 0.048). Neuropathy symptom score (NSS) and common peroneal nerve sensory nerve conduction velocity (SCV) changes were positively correlated with some plantar pressure changes. In addition, plantar pressure changes had a correlation with the appearance of infections, blisters (β = 0.244, P = 0.014), and calluses over the course of the study.

Conclusions:

We should pay attention to the BMI, HbA1c, cholesterol, ABI, SCV, and NSS changes in the process of preventing high plantar pressure and ulceration. Some associated precautions may be taken with the appearance of infections, blisters, and calluses.     

Differences in Liver Injury and Trophoblastic Mitochondrial Damage in Different Preeclampsia-like Mouse Models

Background:

Preeclampsia is a multifactorial disease during pregnancy. Dysregulated lipid metabolism may be related to some preeclampsia. We investigated the relationship between triglycerides (TGs) and liver injury in different preeclampsia-like mouse models and their potential common pathways.

Methods:

Preeclampsia-like models (Nw-nitro-L-arginine-methyl ester [L-NAME], lipopolysaccharide [LPS], apolipoprotein C-III [Apo] transgnic mice + L-NAME, β2 glycoprotein I [βGPI]) were used in four experimental groups: L-NAME (LN), LPS, Apo-LN and βGPI, respectively, and controls received saline (LN-C, LPS-C, Apo-C, βGPI-C). The first three models were established in preimplantation (PI), early-, mid- and late-gestation (EG, MG and LG). βGPI and controls were injected before implantation. Mean arterial pressure (MAP), 24-hour urine protein, placental and fetal weight, serum TGs, total cholesterol (TC) and pathologic liver and trophocyte changes were assessed.

Results:

MAP and proteinuria were significantly increased in the experimental groups. Placenta and fetal weight in PI, EP and MP subgroups were significantly lower than LP. Serum TGs significantly increased in most groups but controls. TC was not different between experimental and control groups. Spotty hepatic cell necrosis was observed in PI, EG, MG in LN, Apo-LN and βGPI, but no morphologic changes were observed in the LPS group. Similar trophoblastic mitochondrial damage was observed in every experimental group.

Conclusions:

Earlier preeclampsia onset causes a higher MAP and urine protein level, and more severe placental and fetal damage. Preeclampsia-like models generated by varied means lead to different changes in lipid metabolism and associated with liver injury. Trophoblastic mitochondrial damage may be the common terminal pathway in different preeclampsia-like models.     

Short-term Rosuvastatin Treatment for the Prevention of Contrast-induced Acute Kidney Injury in Patients Receiving Moderate or High Volumes of Contrast Media: A Sub-analysis of the TRACK-D Study

Background:

Current randomized trials have demonstrated the effects of short-term rosuvastatin therapy in preventing contrast-induced acute kidney injury (CIAKI). However, the consistency of these effects on patients administered different volumes of contrast media is unknown.

Methods:

In the TRACK-D trial, 2998 patients with type 2 diabetes and concomitant chronic kidney disease (CKD) who underwent coronary/peripheral arterial angiography with or without percutaneous intervention were randomized to short-term (2 days before and 3 days after procedure) rosuvastatin therapy or standard-of-care. This prespecified analysis compared the effects of rosuvastatin versus standard therapy in patients exposed to (moderate contrast volume [MCV], 200–300 ml, n = 712) or (high contrast volume [HCV], ≥300 ml, n = 220). The primary outcome was the incidence of CIAKI. The secondary outcome was a composite of death, dialysis/hemofiltration or worsened heart failure at 30 days.

Results:

Rosuvastatin treatment was associated with a significant reduction in CIAKI compared with the controls (2.1% vs. 4.4%, P = 0.050) in the overall cohort and in patients with MCV (1.7% vs. 4.5%, P = 0.029), whereas no benefit was observed in patients with HCV (3.4% vs. 3.9%, P = 0.834). The incidence of secondary outcomes was significantly lower in the rosuvastatin group compared with control group (2.7% vs. 5.3%, P = 0.049) in the overall cohort, but it was similar between the patients with MCV (2.0% vs. 4.2%, P = 0.081) or HCV (5.1% vs. 8.8%, P = 0.273).

Conclusions:

Periprocedural short-term rosuvastatin treatment is effective in reducing CIAKI and adverse clinical events for patients with diabetes and CKD after their exposure to a moderate volume of contrast medium.