In Vivo Kinematics of Functional Ankle Instability Patients and Lateral Ankle Sprain Copers During Stair Descent

Patients with mechanic ankle instability experience increased tibiotalar and subtalar joint laxity. However, in vivo joint kinematics in functional ankle instability (FAI) patients and lateral ankle sprain (LAS) copers, especially during dynamic activities, are poorly understood. Ten FAI patients, 10 LAS copers, and 10 healthy controls were included in this study. A dual fluoroscopic imaging system was used to analyze the tibiotalar and subtalar joint kinematics during stair descent. Five key poses of stair descent were analyzed. Kinematic data from six degrees of freedom were calculated utilizing a solid modeling software. The range of motion and joint positions in each degree of freedom were compared among the three groups. The tibiotalar joints of FAI patients and LAS copers were significantly more inverted than those of healthy controls during the foot strike (p = 0.016, = 0.264). The subtalar joints of FAI patients were significantly more anteriorly translated (pose 2, p = 0.003, = 0.352; pose 3, p < 0.001, = 0.454; pose 4, p = 0.004, = 0.334), inverted (pose 4, p = 0.027, = 0.234; pose 5,p = 0.034, = 0.221), and externally rotated (pose 4, p = 0.037, = 0.217; pose 5; p = 0.004, = 0.331) than those of healthy controls during the mid‐stance and the heel off. The FAI patients showed excessive tibiotalar inversion and subtalar joint hypermobility during stair descent. Meanwhile, the LAS copers maintained subtalar joint stability, and only showed excessive tibiotalar inversion in foot strike. These data provide insight into the mechanisms behind the development of FAI after initial LAS. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1860–1867, 2019     

Genetic variations of HSD11B2 in hypertensive patients and in the general population, six rare missense/frameshift mutations.

Mutations in the gene encoding 11beta-hydroxysteroid dehydrogenase type 2, HSD11B2, cause a rare monogenic juvenile hypertensive syndrome called apparent mineralocorticoid excess (AME). In AME, defective HSD11B2 enzyme activity results in overstimulation of the mineralocorticoid receptor (MR) by cortisol, causing sodium retention, hypokalemia, and salt-dependent hypertension. Here, we have studied whether genetic variations in HDS11B2 are implicated in essential hypertension in Japanese hypertensives and the general population. By sequencing the entire coding region and the promoter region of HDS11B2 in 953 Japanese hypertensives, we identified five missense mutations in 11 patients (L14F, n = 5; R74H, n = 1; R147H, n = 3; T156I, n = 1; R335H, n = 1) and one novel frameshift mutation (4884Gdel, n = 1) in a heterozygous state, in addition to 19 genetic variations. All genetic variations identified were rare, with minor allele frequencies less than 0.005. Four of 12 patients with the missense/frameshift mutations showed renal failure. Four missense mutations, L14F, R74H, R147H, and R335H, were successfully genotyped in the general population, with a sample size of 3,655 individuals (2,175 normotensives and 1,480 hypertensives). Mutations L14F, R74H, R147H, and R335H were identified in hypertensives (n = 6, 8, 3, and 0, respectively) and normotensives (n = 8, 12, 5, and 0, respectively) with a similar frequency, suggesting that these missense mutations may not strongly affect the etiology of essential hypertension. Since the allele frequency of all of the genetic variations identified in this study was rare, an association study was not conducted. Taken together, our results indicate that missense mutations in HSD11B2 do not substantially contribute to essential hypertension in Japanese.     

Implant wear induces inflammation, but not osteoclastic bone resorption, in RANK(-/-) mice.

Signaling of RANK (receptor activator of nuclear factor kappa B) through its ligand RANKL appears critical in osteolysis associated with aseptic loosening (AL). The purpose of this study was to investigate the role of RANK in a murine osteolysis model developed in RANK knockout (RANK(-/-)) mice. Ultra high molecular weight polyethylene (UHMWPE) debris was introduced into established air pouches on RANK(-/-) mice, followed by implantation of calvaria bone from syngeneic littermates. Wild type C57BL/6 (RANK(+/+)) mice injected with either UHMWPE or saline alone were included in this study. Pouch tissues were collected 14 days after UHMWPE inoculation for molecular and histology analysis. Results showed that UHMWPE stimulation induced strong pouch tissue inflammation in RANK(-/-) mice, as manifested by inflammatory cellular infiltration, pouch tissue proliferation, and increased gene expression of IL-1beta, TNFalpha, and RANKL. However, the UHMWPE-induced inflammation in RANK(-/-) mice was not associated with the osteoclastic bone resorption observed in RANK(+/+) mice. In RANK(+/+) mice subjected to UHMWPE stimulation, a large number of TRAP(+) cells were found on the implanted bone surface, where active osteoclastic bone resorption was observed. No TRAP(+) cells were found in UHMWPE-containing pouch tissues of RANK(-/-) mice. Consistent with the lack of osteoclastic activity shown by TRAP staining, no significant UHMWPE particle-induced bone resorption was found in RANK(-/-) mice. A well preserved bone collagen content (Van Gieson staining) and normal plateau surface contour [microcomputed tomography (microCT)] of implanted bone was observed in RANK(-/-) mice subjected to UHMWPE stimulation. In conclusion, this study provides the evidence that UHMWPE particles induce strong inflammatory responses, but not associated with osteoclastic bone resorption in RANK(-/-) mice. This indicates that RANK signaling is essential for UHMWPE particle-induced osteoclastic bone resorption, but does not participate in UHMWPE particle-induced inflammatory response.     

Reconstruction of the nasal tip including the columella and soft triangle using a mastoid composite graft.

This paper describes the use of a composite graft from the mastoid area consisting of full-thickness skin peripherally and selectively localised fascia-fat tissue underneath the skin centrally for immediate reconstruction of moderate defects of the nasal tip including the columella and soft triangle. Mastoid composite grafting is a simple and safe procedure that avoids partial graft loss and provides adequate augmentation of soft tissue, easy reshaping of the new nostril rim, minimal post-operative shrinkage, and no donor-site morbidity. Then, it results in a satisfactory nasal appearance with adequate tip projection and symmetry. This procedure may represent a preferred method of nasal tip reconstruction.     

The effect of MS-818, a pyrimidine compound,on the regeneration of peripheral nerve fibers of mice after a crush injury

One of the pyrimidine compounds, 2-piperadino-6-methyl-5-oxo-5,6-dihydro(7H)pyrrolo[3,4-d]pyrimidine (MS-818), has neurotropic effects in vitro. Therefore, we studied the effect of MS-818 on the regeneration of the peroneal nerve in C57BL/6J mice after a crush injury. Two test groups, which received a daily intraperitoneal injection of 5 mg/kg or 10 mg/kg MS-818, respectively, were compared with controls, which received daily intraperitoneal injections of physiological saline, over a 14-day period. The maximum foot-width ratio (crushed side/uncrushed side) was obtained on days 1, 8 and 14 after the crush injury, and the various morphometric parameters were evaluated at both 5 and 10 mm distal to the proximal portion of the crush site. The significant effects of MS-818 included a larger maximum foot width (P<0.04) and a greater number of unmyelinated axons per nerve at both levels (P<0.003) in both test groups than in controls. MS-818 had no significant effects on body weight, the increase of total transverse fascicular area after the crush injury, the total number of myelinated fibers with their size distributions, or the number of nuclei of Schwann cells and macrophages. Therefore, we conclude that MS-818 promotes axonal sprouting and elongation after a crush injury in mice.     

Kindergarten children's representation and understanding of written number symbols

Two samples of kindergarten children's representation and understanding of written number symbols were examined in two time points in one academic year. About 85% of Chinese five year olds (mean = 5 years 10 months) were able to use conventional number symbols to represent the quantity of 30 or larger. At the end of the kindergarten year, 94% of Chinese six year olds (mean = 6 years 4 months) were able to use conventional number symbols to represent the quantity of 100 or larger. Some Chinese six year olds had problems in representing written addition and subtraction tasks. Children's ability to represent written number symbols, ability to represent written addition and subtraction formula and their performance on written addition and subtraction were closely related. The performance of children in a university-affiliated childcare center was better than that of the center serving working-class families in Time 1, but the performance reversed at the end of the kindergarten year.     

现代医学200词——138．黏附分子

所谓黏附分子是指存在于细胞表面，参与细胞间或细胞与细胞外基质的粘附的分子群的总称。广义来说，纤维连结蛋白、层粘连蛋白、透明质酸等细胞外基质的构成成分也是由细胞分泌并存在于细胞表面，也可归入黏附分子的范畴。但狭义所指的黏附分子是指贯通细胞膜的糖蛋白或构成细胞膜的糖脂质。膜贯通型糖蛋白黏附分子按其构造特征可分为若干家族。在免疫系统中的黏附分子主要分为整合素家族、免疫球蛋白超家族、选择素家族、钙粘素家族、连接蛋白家族以及唾液粘蛋白家族等。     

Reversal of vascular 18F-FDG uptake with plasma high-density lipoprotein elevation by atherogenic risk reduction

Vascular 18F-FDG uptake marker represents inflammation in atherosclerotic lesions, but whether inflammation can be reversed by risk-modifying interventions has not, to our knowledge, been demonstrated. In this study, we evaluated the change of vascular 18F-FDG uptake in response to lifestyle intervention on serial PET/CT scans and further assessed how the findings relate to atherogenic risk reduction. METHODS: A total of 60 healthy adults underwent 18F-FDG PET/CT scans and atherogenic risk-factor assessment at baseline and again after 17.1 +/- 8.3 mo of practicing lifestyle modification. The PET/CT images were evaluated for the presence of vascular 18F-FDG lesions, and vessel-to-blood-pool 18F-FDG ratios were measured. Indices from summed ratios of positive lesions were compared and correlated to atherogenic risk factors. RESULTS: At follow-up, significant reductions in diastolic blood pressure (P < 0.05), total cholesterol (P < 0.05), and low-density lipoprotein level (P < 0.05) and an increase in high-density lipoprotein (HDL) level (P < 0.0001) were demonstrated. On the initial PET/CT scan, 50 of 60 subjects showed 1 or more 18F-FDG-positive lesions (5.9 +/- 5.0/subject), leading to a total of 352 vascular sites. On follow-up, 18F-FDG-positive lesions were significantly reduced to 2.1 +/- 2.2 sites per subject (P < 0.0001) and a total of 124 sites (64.8% reduction). Follow-up 18F-FDG-positive rates were significantly reduced for the aorta and iliac arteries. In addition, significant reductions in the whole-body 18F-FDG index from 1.39 +/- 1.23 to 0.53 +/- 0.59 (P < 0.0001) and carotid 18F-FDG index from 0.08 +/- 0.16 to 0.03 +/- 0.06 (P = 0.01) were shown. The whole-body 18F-FDG index correlated with total cholesterol (P < 0.05) and HDL level (P < 0.05), and the magnitude of reduction in the 18F-FDG index closely correlated to the amount of increase in plasma HDL level (P = 0.005). CONCLUSION: Our study demonstrated that vascular 18F-FDG uptake is reversed in response to atherogenic risk reduction by lifestyle intervention and that the magnitude of improvement correlates to increases in plasma HDL levels. Thus, serial 18F-FDG PET/CT may be useful for monitoring improvements in the inflammatory component of atherosclerotic lesions in response to risk modification.