Saturated and Unsaturated Bone Marrow Lipids Have Distinct Effects on Bone Density and Fracture Risk in Older Adults

Greater bone marrow adiposity (BMAT) is associated with lower bone mineral density (BMD) and vertebral fractures; less is known about BMAT composition and bone. We studied BMAT composition and bone outcomes in 465 participants from the Age Gene/Environment Susceptibility (AGES)-Reykjavik study. BMAT saturation and unsaturation, measured with magnetic resonance spectroscopy, were defined as the ratio of saturated (1.3 ppm peak) or unsaturated (5.3 ppm peak) lipid to total marrow contents, respectively. At baseline and follow-up visits, spine and hip BMD were assessed with quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA) and vertebral fractures were identified with DXA. Incident clinical fractures were identified through medical records for up to 8.8 years of follow-up. Associations between BMAT composition and BMD, bone loss, and fractures were evaluated in adjusted regression models. At baseline, mean ± standard deviation (SD) participant age was 81.7 ± 4.3 years, mean BMAT unsaturation was 3.5% ± 1.0%, and mean saturation was 46.3% ± 7.2% in the full cohort (47.7% women). Each SD increase in BMAT saturation was associated with lower trabecular BMD: −23.6% (spine) and −13.0% (total hip) (all p < 0.0001). Conversely, BMAT unsaturation (per SD increase) was associated with higher trabecular BMD: +17.5% (spine) and +11.5% (total hip) (all p < 0.001). BMAT saturation (per SD increase) was associated with greater risk for prevalent (odds ratio [OR] 1.46; 95% confidence interval [CI], 1.11–1.92) and incident (OR 1.55; 95% CI, 1.03–2.34) vertebral fracture. BMAT unsaturation (per SD increase) was associated with lower risk for incident vertebral fracture (OR 0.58; 95% CI, 0.38–0.89). In gender stratified analyses, BMAT saturation and unsaturation had opposite associations with incident clinical fracture among men. In general, saturated marrow lipids were associated with worse skeletal outcomes, whereas unsaturated lipids were associated with better outcomes. We recommend that future studies of marrow fat and skeletal health report measurements of saturated and unsaturated marrow lipids, rather than total marrow fat content alone. © 2022 American Society for Bone and Mineral Research (ASBMR).     

Mediation Analysis of Aortic Stiffness and Renal Microvascular Function

Aortic stiffening, assessed by carotid-femoral pulse wave velocity, is associated with CKD. Transmission of excessive flow pulsatility into the low-impedance renal microvasculature may mediate this association. However, direct analyses of macrovascular–microvascular relations in the kidney are limited. Using arterial tonometry, iohexol clearance, and magnetic resonance imaging, we related arterial stiffness, GFR, urinary albumin excretion, and potential mediators, including renal artery pulsatility index, renal vascular resistance, and arterial volume in the cortex, in 367 older adults (ages 72–92 years) participating in the Age, Gene/Environment Susceptibility-Reykjavik Study. In a model adjusted for age, sex, heart rate, and body size, aortic stiffness was related to GFR (Slope of regression B=−2.28±0.85 ml/min per SD, P=0.008) but not urine albumin (P=0.09). After accounting for pulsatility index, the relation between aortic stiffness and GFR was no longer significant (P=0.10). Mediation analysis showed that 34% of the relation between aortic stiffness and GFR was mediated by pulsatility index (95% confidence interval of indirect effect, −1.35 to −0.29). An additional 20% or 36% of the relation was mediated by lower arterial volume in the cortex or higher renal vascular resistance, respectively, when offered as mediators downstream from higher pulsatility index (95% confidence interval of indirect effect including arterial volume in the cortex, −2.22 to −0.40; 95% confidence interval of indirect effect including renal vascular resistance, −2.51 to −0.76). These analyses provide the first evidence that aortic stiffness may contribute to lower GFR by transferring excessive flow pulsatility into the susceptible renal microvasculature, leading to dynamic constriction or vessel loss.     

Effects of blood contamination on resin-resin bond strength.

OBJECTIVE: Incremental placement and curing of resin composites has been recommended. However, this requires longer operating time, and therefore, increased risk of contamination. The purpose of this study was to evaluate the effects of blood contamination on microtensile bond strengths (microTBS) between resin interfaces and to determine the best decontamination method to re-establish the original resin-resin bond strength. MATERIALS: The top surfaces of 64, 4-mm composite blocks (Z-250, Renew, APX, Pertac II) were untreated as the control, or were treated as follows: blood applied and dried on the surface (Treatment 1), blood applied, rinsed, dried (Treatment 2), blood applied, rinsed, and an adhesive applied (Single Bond, One-Step, Clearfil SE, Prompt L-Pop) (Treatment 3). Fresh composite was applied and light-cured in 2-mm increments. After 24 h storage in water, the specimens were sectioned into 0.7-mm thick slabs, trimmed to a cross-sectional area of 1 mm(2), and loaded to failure at a crosshead speed of 1 mm/min using an Instron universal testing machine. Data were analyzed using two-way ANOVA and Fisher's PLSD test (p<0.05). RESULTS: Control values ranged from 45.1 MPa for Pertac II to 71.5 MPa for APX. Untreated blood contamination resulted in resin-resin bond strengths of only 1.0-13.1 MPa. Rinsing raised bond strengths to over 40 MPa for each material. Use of an adhesive further increased bond strengths except for Pertac II. SIGNIFICANCE: Rinsing blood from contaminated surfaces increases the resin-resin bond strength significantly and the application of an appropriate adhesive increases the bond strength to control levels.     

Guidelines for the management of traumatic dental injuries. III. Primary teeth

Abstract –  Trauma to the primary dentition present special problems and the management is often different as compared with permanent teeth. An appropriate emergency treatment plan is important for a good prognosis. Guidelines are useful for delivering the best care possible in an efficient manner. The International Association of Dental Traumatology (IADT) has developed a consensus statement after a review of the dental literature and group discussions. Experienced researchers and clinicians from various specialties were included in the group. In cases in which the data did not appear conclusive, recommendations were based on the consensus opinion of the IADT board members. The guidelines represent the current best evidence based on literature research and professional opinion. In this third article out of three, the IADT Guidelines for the management of traumatic injuries in the primary dentition, are presented.     

Shape matters in protein mobility within membranes

The lateral mobility of proteins within cell membranes is usually thought to be dependent on their size and modulated by local heterogeneities of the membrane. Experiments using single-particle tracking on reconstituted membranes demonstrate that protein diffusion is significantly influenced by the interplay of membrane curvature, membrane tension, and protein shape. We find that the curvature-coupled voltage-gated potassium channel (KvAP) undergoes a significant increase in protein mobility under tension, whereas the mobility of the curvature-neutral water channel aquaporin 0 (AQP0) is insensitive to it. Such observations are well explained in terms of an effective friction coefficient of the protein induced by the local membrane deformation.Brownian motion plays an essential role in biological processes. Since the pioneering experiments of Perrin (1), the observation of diffusing objects has emerged as a mean to extract the rheological properties of the surrounding medium or the probe particle size. The theoretical investigation of diffusion of proteins within membranes has been studied widely going back to P. G. Saffman and M. Delbrück (SD). They investigated the hydrodynamic drag acting on a membrane inclusion when the membrane is described as a 2D fluid sheet of viscosity embedded within a less viscous fluid of viscosity η (2). In this theory, the diffusion coefficient D₀ in the limit of a large viscosity contrast between the membrane and bulk fluid is given by:The length is the length scale over which flow is generated within the bilayer by the inclusion, k_BT is the thermal energy, and γ is Euler’s constant. This model predicts a logarithmic dependence of D₀ on the protein radius a_p, which has been confirmed for some in vitro experiments on membranes containing transmembrane proteins (see ref. 3 and references therein). In contrast, the experiments of Gambin et al. (4) showed significant deviations from the SD theory.A possible origin for the discrepancy observed by Gambin et al. (4) is the significant local membrane deformation due to the interaction between the inclusion and the lipid bilayer (5). Naji et al. suggested in ref. 6 that inclusions experience additional dissipation, either due to internal flows within the membrane or to additional fluid flows produced by the deformed membrane. This work triggered a number of theoretical studies investigating the coupling of inclusion proteins with the membrane that had been pioneered by the Seifert’s group (see ref. 7 and references therein). Such studies have systematically gone beyond the SD model by including additional effects (8–12). So far, a thorough verification of these ideas has not been attempted. To investigate the effect of the protein–lipid coupling on the protein mobility, we study its dependence on membrane tension, because this parameter affects the local membrane deformation.In this work, we compare the mobility of two transmembrane proteins with the same lateral size, aquaporin 0 (AQP0) and a voltage-gated potassium channel (KvAP), reconstituted in giant unilamellar vesicles (GUVs). Whereas AQP0 does not deform locally the bilayer, KvAP locally bends the membrane (13). Using single-particle tracking (SPT), we demonstrate that the curvature-coupled protein KvAP undergoes a significant increase in mobility under tension, whereas the mobility of the curvature-neutral water channel AQP0 is insensitive to it. This difference, which goes beyond the SD model, is explained by an approach that includes the interplay between membrane deformation and friction with the surrounding medium and within the bilayer. This is compelling evidence that the Brownian motion of a shaping-membrane protein is not simply dependent on the inclusion size but also related to the lateral extension of the deformed membrane patch, which depends on tension.     

自体干细胞移植治疗老年心肌梗死后心力衰竭

目的：实验以移植后3个月、6个月时间超声心动图客观指标评估了自体干细胞冠状动脉内移植治疗老龄心肌梗死后心力衰竭的效果和安全性。方法：选择2004—06／2006—06江苏省苏北人民医院心内科自愿接受干细胞移植的7例心肌梗死后心力衰竭患者，平均年龄69岁，心功能Ⅲ-Ⅳ级，左室射血分数〈50％。药物治疗基础上加用自体干细胞冠状动脉内移植治疗的方法，其中2例骨髓干细胞在体外扩增后获得，5例经粒细胞集落刺激因子皮下注射动员自体骨髓干细胞后分离外周血获得干细胞悬液。将采集的干细胞悬液经0ver-the-wire球囊导管中心腔注入梗死相关动脉。观察自体干细胞动员，培养，采集和回输过程中的不良反应。在移植前、移植后3月、6月应用超声心动图评价左室形态和心功能变化，室壁运动积分指数及6min步行距离。结果：7例患者均进入结果分析。移植3个月后，心功能得到改善，超声心动图检查左室收缩期内径及射血分数变化不大，6min步行距离有所提高，但差异无显著性（P〉0．05）。移植6个月后，患者心功能明显改善，超声心动图检查左室收缩期内径及射血分数和室壁运动积分均有明显提高（P〈0．05），6min步行距离也有明显提高（P〈0．05）。整个过程中未出现严重并发症。结论：自体干细胞冠状动脉内移植治疗老龄心肌梗死后心力衰竭，6个月时超声心动图客观指标评估能够改善患者心功能，且安全。     

ANTIDEPRESSANT THERAPY AND BEHAVIOURAL COMPETENCE

SUMMARY Major depression can impair an individual's motivation to perform routine daily activities and cause a deterioration in cognitive and psychomotor function. Some antidepressants add to pathological dysfunction through unwanted side-effects. Although most patients eventually recover as a simultaneous consequence of tolerance and therapeutic response, some may not. Where side-effects continue to retard normal recovery they can be called behaviourally toxic, which can be classified as disruptive, inhibitory or provocative. Disruptive behavioural toxic effects are measured using either psychometric tests or simulations of real-life activities (for example, a driving test). There are no widely-accepted tests for inhibitory or provocative behavioural toxicity, and assessments of antidepressants are made on the basis of case studies. This review summarises the results of psychometric and real-life simulation tests and compares the effects of antidepressants on behaviour competence. The purpose is to identify those drugs that seem to be the most and least likely to produce behavioural toxicity.     

脑出血大鼠脑组织膜型基质金属蛋白酶、基质金属蛋白酶2和基质金属蛋白酶9表达及益气活血中药的干预效应

目的:观察益气活血中药对脑出血大鼠脑组织中膜型基质金属蛋白酶、基质金属蛋白酶2和基质金属蛋白酶9表达量的影响,从脑出血损伤区微血管系统重建的角度,探讨益气活血中药治疗脑出血的作用机制。方法:实验于2006-03/10在中南大学湘雅医院中西医结合研究所实验室完成。实验材料:补阳还五汤全方(黄芪,当归,赤芍,红花,川芎,地龙,桃仁按20∶3∶3∶3∶2∶3∶3的比例);补阳还五汤益气成分(黄芪按上述比例);补阳还五汤活血成分(当归,赤芍,地龙,川芎,桃仁,红花按3∶3∶3∶2∶3∶3的比例)。用蒸馏水两次水煎,分别浓缩为1.54,0.81和0.73g/mL。实验分组:155只SD大鼠随机分为正常对照组、假手术组、模型组、益气活血组、益气组、活血组。正常对照组5只大鼠,其余每组30只,再随机分为术后灌胃2,4,7,14,21,28d6个观察时间点,各个时间点5只大鼠。实验干预:造模:采用立体定位技术将胶原酶Ⅶ注入大鼠大脑右苍白球制成脑出血大鼠模型。假手术组大鼠仅注入2μL生理盐水,其余手术过程相同。给药:正常对照组:普通饲养,自由饮水;假手术组和模型组术后予蒸馏水灌胃2次/d,2mL/次;益气活血组、益气组、活血组分别给予补阳还五汤全方、补阳还五汤益气成分、补阳还五汤活血成分30.80,16.20,14.60g/(kg·d)(按体表面积计算为临床70kg成人剂量的3倍)灌胃,2次/d,2mL/次。各组大鼠分别于灌胃2,4,7,14,21,28d麻醉下取脑,制备切片;正常组动物于28d处死。实验评估:免疫组织化学染色方法检测各组灌胃不同时间脑组织基质金属蛋白酶2、基质金属蛋白酶9和膜型基质金属蛋白酶的阳性微血管数。结果:155只大鼠均进入结果分析。①正常组、假手术组皮质偶见膜型基质金属蛋白酶、基质金属蛋白酶2和基质金属蛋白酶9表达。②模型组膜型基质金属蛋白酶、基质金属蛋白酶2呈双峰表达,4d为最高峰,至14～21d再有小高峰出现。③益气活血组给药4d时,膜型基质金属蛋白酶、基质金属蛋白酶2为表达低谷,低于模型组(P<0.01)、益气组和活血组(P<0.05);在中后期,益气活血组膜型基质金属蛋白酶表达高峰为7～14d,较模型组提前出现,21d后与模型组比,各治疗组膜型基质金属蛋白酶已表达极少(P<0.01);益气活血组基质金属蛋白酶2在7d后一直呈高水平维持,高于其他各组(P<0.05),28d后开始逐渐下降。④模型组基质金属蛋白酶9在造模后4d达最高峰(P<0.01),两周后几乎无表达。益气活血组基质金属蛋白酶9高峰推迟至7d出现(P<0.05),之后逐渐下降。结论:益气活血中药可通过调节脑出血后膜型基质金属蛋白酶、基质金属蛋白酶2和基质金属蛋白酶9表达,改善出血后脑组织的微环境,有利于微血管系统重建,促进组织修复。     

Push enteroscopy in the investigation of small-intestinal disease

We report our experience with small-bowel push enteroscopy in 50 patients. The indications for push enteroscopy were: anaemia/occult gastrointestinal bleeding (22 patients); overt gastrointestinal bleeding (17 patients); abnormal small-bowel radiology (8 patients) and miscellaneous (3 patients). In those with undiagnosed gastrointestinal bleeding/anaemia, abnormalities were detected in 24/39 patients (62%): small bowel arteriovenous malformations (AVMs) were detected in 19 (49%), and five (13%) had lesions in the upper gastrointestinal tract. Seventeen patients had heater-probe ablation therapy of vascular lesions: nine patients had small-intestinal lesions, four patients gastric lesions, and four patients combined gastric and small- intestinal lesions. In those with abnormal small-bowel radiology, abnormalities were detected in 6/8 patients. We conclude that (i) push enteroscopy can establish a diagnosis in a high proportion of patients with gastrointestinal bleeding; (ii) heater-probe ablation therapy of vascular lesions can be performed routinely at the time of enteroscopy; (iii) a significant proportion of patients (9/50) referred for enteroscopy with undiagnosed gastrointestinal bleeding have lesions in the stomach/proximal duodenum missed at diagnostic endoscopy. Push enteroscopy is a valuable diagnostic and therapeutic endoscopic procedure.