Smoking Alters Inflammation and Skeletal Stem and Progenitor Cell Activity During Fracture Healing in Different Murine Strains

Smokers are at a higher risk of delayed union or nonunion after fracture repair. Few specific interventions are available for prevention because the molecular mechanisms that result in these negative sequelae are poorly understood. Murine models that mimic fracture healing in smokers are crucial in further understanding the local cellular and molecular alterations during fracture healing caused by smoking. We exposed three murine strains, C57BL/6J, 129X1/SvJ, and BALB/cJ, to cigarette smoke for 3 months before the induction of a midshaft transverse femoral osteotomy. We evaluated fracture healing 4 weeks after the osteotomy using radiography, micro-computed tomography (μCT), and biomechanical testing. Radiographic analysis demonstrated a significant decrease in the fracture healing capacity of smoking 129X1/SvJ mice. μCT results showed delayed remodeling of fracture calluses in all three strains after cigarette smoke exposure. Biomechanical testing indicated the most significant impairment in the functional properties of 129X1/SvJ in comparison with C57BL/6J and BALB/cJ mice after cigarette smoke exposure. Thus, the 129X1/SvJ strain is most suitable in simulating smoking-induced impaired fracture healing. Furthermore, in smoking 129X1/SvJ murine models, we investigated the molecular and cellular alterations in fracture healing caused by cigarette smoking using histology, flow cytometry, and multiplex cytokine/chemokine analysis. Histological analysis showed impaired chondrogenesis in cigarette smoking. In addition, the important reparative cell populations, including skeletal stem cells and their downstream progenitors, demonstrated decreased expansion after injury as a result of cigarette smoking. Moreover, significantly increased pro-inflammatory mediators and the recruitment of immune cells in fracture hematomas were demonstrated in smoking mice. Collectively, our findings demonstrate the significant cellular and molecular alterations during fracture healing impaired by smoking, including disrupted chondrogenesis, aberrant skeletal stem and progenitor cell activity, and a pronounced initial inflammatory response. © 2020 American Society for Bone and Mineral Research (ASBMR).     

How Do Medical Students Perceive Diversity in Orthopaedic Surgery,and How Do Their Perceptions Change After an Orthopaedic Clinical Rotation?

BackgroundA diverse physician workforce improves the quality of care for all patients, and there is a need for greater diversity in orthopaedic surgery. It is important that medical students of diverse backgrounds be encouraged to pursue the specialty, but to do so, we must understand students’ perceptions of diversity and inclusion in orthopaedics. We also currently lack knowledge about how participation in an orthopaedic clinical rotation might influence these perceptions.Questions/purposes(1) How do the perceptions of diversity and inclusion in orthopaedic surgery compare among medical students of different gender identities, races or ethnicities, and sexual orientations? (2) How do perceptions change after an orthopaedic clinical rotation among members of demographic groups who are not the majority in orthopaedics (that is, cis-gender women, underrepresented racial minorities, other racial minorities, and nonheterosexual people)?MethodsWe surveyed students from 27 US medical schools who had completed orthopaedic rotations. We asked about their demographic characteristics, rotation experience, perceptions of diversity and inclusion in orthopaedics, and personal views on specialty choice. Questions were derived from diversity, equity, and inclusion climate surveys used at major academic institutions. Cis-gender men and cis-gender women were defined as those who self-identified their gender as men or women, respectively, and were not transgender. Forty-five percent (59 of 131) of respondents were cis-men and 53% (70 of 131) were cis-women; 49% (64 of 131) were white, 20% (26 of 131) were of underrepresented racial minorities, and 31% (41 of 131) were of other races. Eighty-five percent (112 of 131) of respondents were heterosexual and 15% (19 of 131) reported having another sexual orientation. We compared prerotation and postrotation perceptions of diversity and inclusion between majority and nonmajority demographic groups for each demographic domain (for example, cis-men versus cis-women). We also compared prerotation to postrotation perceptions within each nonmajority demographic group. To identify potential confounding variables, we performed univariate analysis to compare student and rotation characteristics across the demographic groups, assessed using an alpha of 0.05. No potential confounders were identified. Statistical significance was assessed at a Bonferroni-adjusted alpha of 0.0125. Our estimated response percentage was 26%. To determine limitations of nonresponse bias, we compared all early versus late responders and found that for three survey questions, late responders had a more favorable perception of diversity in orthopaedic surgery, whereas for most questions, there was no difference.ResultsBefore rotation, cis-women had lower agreement that diversity and inclusion are part of orthopaedic culture (mean score 0.96 ± 0.75) compared with cis-men (1.4 ± 1.1) (mean difference 0.48 [95% confidence interval 0.16 to 0.81]; p = 0.004), viewed orthopaedic surgery as less diverse (cis-women 0.71 ± 0.73 versus cis-men 1.2 ± 0.92; mean difference 0.49 [95% CI 0.20 to 0.78]; p = 0.001) and more sexist (cis-women 1.3 ± 0.92 versus cis-men 1.9 ± 1.2; mean difference 0.61 [95% CI 0.23 to 0.99]; p = 0.002), believed they would have to work harder than others to be valued equally (cis-women 2.8 ± 1.0 versus cis-men 1.9 ± 1.3; mean difference 0.87 [95% CI 0.45 to 1.3]; p < 0.001), and were less likely to pursue orthopaedic surgery (cis-women 1.4 ± 1.4 versus cis-men 2.6 ± 1.1; mean difference 1.2 [95% CI 0.76 to 1.6]; p < 0.001). Before rotation, underrepresented minorities had less agreement that diversity and inclusion are part of orthopaedic surgery culture (0.73 ± 0.72) compared with white students (1.5 ± 0.97) (mean difference 0.72 [95% CI 0.35 to 1.1]; p < 0.001). Many of these differences between nonmajority and majority demographic groups ceased to exist after rotation. Compared with their own prerotation beliefs, after rotation, cis-women believed more that diversity and inclusion are part of orthopaedic surgery culture (prerotation mean score 0.96 ± 0.75 versus postrotation mean score 1.2 ± 0.96; mean difference 0.60 [95% CI 0.22 to 0.98]; p = 0.002) and that orthopaedic surgery is friendlier (prerotation 2.3 ± 1.2 versus postrotation 2.6 ± 1.1; mean difference 0.41 [95% CI 0.14 to 0.69]; p = 0.004), more diverse (prerotation 0.71 ± 0.73 versus postrotation 1.0 ± 0.89; mean difference 0.28 [95% CI 0.08 to 0.49]; p = 0.007), less sexist (prerotation 1.3 ± 0.92 versus postrotation 1.9 ± 1.0; mean difference 0.63 [95% CI 0.40 to 0.85]; p < 0.001), less homophobic (prerotation 2.1 ± 1.0 versus postrotation 2.4 ± 0.97; mean difference 0.27 [95% CI 0.062 to 0.47]; p = 0.011), and less racist (prerotation 2.3 ± 1.1 versus postrotation 2.5 ± 1.1; mean difference 0.28 [95% CI 0.099 to 0.47]; p = 0.003). Compared with before rotation, after rotation cis-women believed less that they would have to work harder than others to be valued equally on the rotation (prerotation 2.8 ± 1.0 versus postrotation 2.5 ± 1.0; mean difference 0.31 [95% CI 0.12 to 0.50]; p = 0.002), as did nonheterosexual students (prerotation 2.4 ± 1.4 versus postrotation 1.8 ± 1.3; mean difference 0.56 [95% 0.21 to 0.91]; p = 0.004). Underrepresented minority students saw orthopaedic surgery as less sexist after rotation compared with before rotation (prerotation 1.5 ± 1.1 versus postrotation 2.0 ± 1.1; mean difference 0.52 [95% CI 0.16 to 0.89]; p = 0.007).ConclusionEven with an estimated 26% response percentage, we found that medical students of demographic backgrounds who are not the majority in orthopaedics generally perceived that orthopaedic surgery is less diverse and inclusive than do their counterparts in majority groups, but these views often change after a clinical orthopaedic rotation.Clinical RelevanceThese perceptions may be a barrier to diversification of the pool of medical student applicants to orthopaedics. However, participation in an orthopaedic surgery rotation is associated with mitigation of many of these negative perceptions among diverse students. Medical schools have a responsibility to develop a diverse workforce, and given our findings, schools should promote participation in a clinical orthopaedic rotation. Residency programs and orthopaedic organizations can also increase exposure to the field through the rotation and other means. Doing so may ultimately diversify the orthopaedic surgeon workforce and improve care for all orthopaedic patients.     

Overlapping obesity-related glomerulopathy and immunoglobulin A nephropathy: clinical and pathologic characteristics and prognosis

Clinical and Experimental Nephrology - In this study, we investigated the clinical and pathologic characteristics and prognosis of overlapping obesity-related glomerulopathy (ORG) and...     

Osteoporosis following injury to the semilunar cartilage

In 54 cases of ruptured medial semilunar cartilages of the knee joint the bone mineral mass in the distal end of the femur was measured 0–5 years following removal of the injured cartilage. The bone mineral mass was significantly decreased. There was no tendency of restoration of the bone mass with time.Financial support was obtained from the Swedish Medical Research Council No: K69-23X-2737-01 and from the Gustav V 80: th Anniversary Foundation.     

恒力法测量运动对动物肌腱,韧带横截面积的影响

本文介绍一种方便，适用的肌腱，韧带横截面积的测量工具－软组织横截面积测微计。通过对兔屈趾肌腱反复测量，其重复性精密度在０．０４４ｍｍ以内，变异系数在１．４％以下，用该测微计对大强度训练一段时间后的兔屈趾肌腱，跟腱和膝内侧副韧带的测量发现，训练训练后ＦＤＰ，ＡＣ的横截面积减小，ＭＣＬ有增大的趋势，据此，作用认为肌腱的变化与长期大强度训练后试件的“疲劳蠕变”有关，ＭＣＬ的变化则与在体内的负荷形式有关。     

五种免疫相关性心血管疾病的免疫学研究

对扩张型心肌病、风湿性心脏病，原发性高血压，冠心病及肥厚型心肌病进行外周血清可溶性白细胞介素２受体，Ｔ淋巴细胞亚群及自然杀伤细胞活性的检测，并与健康对照组比较，结果显示：ＤＣＭ组，ＲＨＤ组及ＥＨＴ组的ｓＩＬ－２Ｒ明显高于ＮＣ组，而ＤＣＭ、ＲＨＤ风湿活动组的ＮＫ活性低于ＮＣ组，ＥＨＴ组ＮＫ活性高于ＮＣ组。     

艾滋病发病机制中的细胞凋亡理论

有关HIV感染引起CD4’T淋巴细胞耗竭最终导致艾滋病的确切机制尚不清楚。目前研究最多的仍是细胞凋亡理论,本文就细胞凋亡在艾滋病发病中的作用,凋亡的可能机制两方面进行概述。