Prevalence of Risk Factors for Adverse Spinopelvic Mobility Among Patients Undergoing Total Hip Arthroplasty

BackgroundPatients with adverse spinopelvic mobility have higher complication rates following total hip arthroplasty (THA). Risk factors include a stiff lumbar spine, standing posterior pelvic tilt ≤ ?10°, and a severe sagittal spinal deformity (pelvic incidence minus lumbar lordosis mismatch ≥20°). The purpose of this study is to define the spinopelvic risk factors and quantify the prevalence of risk factors for pathologic spinopelvic mobility.MethodsA retrospective cohort analysis from January 2014 to February 2020 was performed on a multicenter series of 9414 primary THAs by 168 surgeons, all with preoperative spinopelvic measurements in the supine, standing, and flex-seated positions. All patients were included. The prevalence of adverse spinopelvic mobility and frequency of each spinopelvic risk factor was calculated.ResultsThe cohort was 52% female, 48% male, with an average age of 65 years. Thirteen percent of patients exhibited adverse spinopelvic mobility and 17% had one or more of the 3 risk factors. Adverse mobility was found in 35% of patients with at least 1 risk factor, 47% with at least 2 risk factors, and 57% with all 3 risk factors.ConclusionForty-six percent of patients had spinopelvic pathology driven by one or more of the risk factors. Number of risk factors present and risk of adverse spinopelvic mobility were positively correlated, with 57% of patients with all 3 risk factors exhibiting adverse spinopelvic mobility. Although this study defines the prevalence of these risk factors in this highly selected cohort, it does not report incidence in a general THA population.Level of EvidencePrognostic Level IV.     

雷帕霉素抑制LPS诱导的RAW264.7细胞表达和释放HMGB1的机制

目的：探讨雷帕霉素抑制LPS诱导小鼠RAW264.7细胞表达和释放HMGB1的作用机制。方法:传代培养的小鼠RAW264.7细胞分5组接种于6孔板，即仅加培养液的对照组；加250 μg/L LPS的诱导组； 诱导组基础上加100 μg/L雷帕霉素的干预组；干预组基础上加rTNF-α 50 μg/L的抗干预组；及抗干预组基础上加抗鼠TNF-α 100 μg/L的抗体中和组。培养4 h后，ELISA法检测对照组、诱导组和干预组上清液中TNF-α水平；培养24 h后，RT-PCR和Western blotting法分别检测各组细胞内HMGB1 mRNA表达水平和上清液中HMGB1含量。结果:培养4 h，干预组上清液中TNF-α水平与对照组比无显著差异（P>0.05），但明显低于诱导组（P<0.05）；培养24 h, 与对照组比，诱导组细胞内HMGB1 mRNA表达明显增强（P<0.05），上清液中HMGB1含量也明显增多（P<0.05）；干预组明显减少了HMGB1 mRNA表达及上清液中HMGB1含量（P<0.05）； 与干预组比，抗干预组细胞HMGB1 mRNA表达及上清液中HMGB1含量明显增加（P<0.05）；抗体中和组细胞HMGB1 mRNA表达水平及上清液中HMGB1含量和干预组无显著差异（P>0.05）。 结论:雷帕霉素抑制LPS诱导RAW264.7细胞表达和释放HMGB1，可能部分地与其抑制TNF-α的表达有关。     

应用激光电泳技术对MA737小鼠乳腺癌细胞膜表面电荷特性的研究

本工作应用激光多普勒电泳技术对ＭＡ７３７小鼠乳腺癌细胞膜表面电荷特性及高温（４２．５℃）对癌细胞的热效应进行了深入的研究。结果发现，ＭＡ７３７癌细胞的电泳迁移率（ＥＰＭ）明显高于相应正常细胞的ＥＰＭ（约２０％），表明癌细胞表面负电荷增高；实验发现唾液酸可能是ＭＡ７３７癌细胞膜表主要负电基团的来源之一。研究还发现，ＭＡ７３７癌细胞的热敏性比相应的正常细胞强，随高温受热时间的延长，癌细胞的ＥＰＭ呈下降趋势。     

Lateral Mobility of the Cell Adhesion Molecule L1 Within the Surface Membrane of Morphologically Undifferentiated and Differentiated Neuroblastoma Cells

Lateral mobility and localization in the surface membrane of the adhesion molecule L1 was studied in morphologically undifferentiated and differentiated neuroblastoma cells to gain insight into its possible association with the different molecular forms of N-CAM. In undifferentiated cells, the fraction of mobile L1 molecules is high and similar to that of N-CAM 140. Upon long-term morphological differentiation, the fraction of mobile L1 molecules is reduced by a factor of three and is similar to that of N-CAM 180, the predominant molecular form of N-CAM in differentiated neuroblastoma cells. Comparable to N-CAM 180, L1 is also preferentially accumulated at contact sites between these cells as seen by indirect immunofluorescence. These observations raise the question of whether at least part of the L1 molecules may be directly or indirectly (e.g. via N-CAM 180) linked to the cytoskeleton, thus stabilizing cell contacts between differentiated cells.     

Dependence of the Molecular Mobility and Protein Stability of Freeze-Dried γ-Globulin Formulations on the Molecular Weight of Dextran

Purpose. The effect of the molecular weight of dextran on the molecular mobility and protein stability of freeze-dried serum -globulin (BGG) formulations was studied. The stabilizing effect of higher molecular weight dextran is discussed in relation to the molecular mobility of the formulations. Methods. The molecular mobility of freeze-dried BGG formulations containing dextrans of various molecular weights was determined based on the free induction decay of dextran and water protons measured by proton NMR. The protein stability of the formulations was determined at temperatures ranging from 20 to 70°C by size exclusion chromatography. Results. Changes in the molecular mobility of freeze-dried formulations that occurred at temperatures below the glass transition temperature could be detected as the molecular mobility-changing temperature (T_mc), at which dextran protons started to exhibit a Lorentzian relaxation decay due to higher mobility in addition to a Gaussian relaxation decay. T_mc increased as the molecular weight of dextran increased. The proportion of dextran protons which exhibited the higher mobility relaxation process (P_hm) at temperatures above T_mc decreased as the molecular weight of dextran increased. Protein stability was closely related to molecular mobility. The temperature dependence of the denaturation rate changed at around T_mc, and denaturation in the microscopically liquidized state decreased as P_hm decreased with increasing molecular weight of dextran. Conclusions. The effect of the molecular weight of dextran on the protein stability of freeze-dried BGG formulations could be explained in terms of the parameters obtained by ¹H-NMR such as T_mc and P_hm. These parameters appear to be useful in preformulation and stability prediction of freeze-dried formulations.     

The Relationship Between Protein Aggregation and Molecular Mobility Below the Glass Transition Temperature of Lyophilized Formulations Containing a Monoclonal Antibody

Purpose. To find out if the physical instability of a lyophilized dosage form is related to molecular mobility below the glass transition temperature. Further, to explore if the stability data generated at temperatures below the glass transition temperature can be used to predict the stability of a lyophilized solid under recommended storage conditions. Methods. The temperature dependence of relaxation time constant, , was obtained for sucrose and trehalose formulations of the monoclonal antibody (5 mg protein/vial) from enthalpy relaxation studies using differential scanning calorimetry. The non-exponentiality parameter, , in the relaxation behavior was also obtained using dielectric relaxation spectroscopy. Results. For both sucrose and trehalose formulations, the variation in with temperature could be fitted Vogel-Tammann-Fulcher (VTF) equation. The two formulations exhibited difference sensitivities to temperature. Sucrose formulation was more fragile and exhibited a stronger non-Arrhenius behavior compared to trehalose formulation below glass transition. Both formulations exhibited <2% aggregation at t values <10, where t is the time of storage. Conclusions. Since the relaxation times for sucrose and trehalose formulations at 5°C are on the order of 10⁸ and 10⁶ hrs, it is likely that both formulations would undergo very little (<2%) aggregation in a practical time scale under refrigerated conditions.     

Measurements of preferred walking speed in subjects with central and peripheral vision loss

BACKGROUND: Previous mobility studies have used Preferred Walking Speed (PWS) in order to determine the walking efficiency in terms of the Percent Preferred Walking Speed (PPWS) of visually impaired adults. PWS has been measured in previous studies using the sighted guide (SG) and non-sighted guide (NSG) techniques. This study compared the NSG, SG and string (ST) (subjects walked by holding on lightly to a cardboard tube attached to a piece of string) techniques of measuring PWS in visually impaired subjects. METHODS: Forty visually impaired subjects with central and peripheral vision loss were recruited. PWS was measured using the NSG, SG and ST techniques. For each technique, PWS was determined by recording the time taken for a subject to walk an unobstructed, straight 20-m corridor. RESULTS: There were no significant differences in PWS using the SG, NSG and ST techniques. CONCLUSION: For assessing walking efficiency, either the SG, NSG or ST technique could be employed when measuring PWS in visually impaired subjects.     

The intergenerational sources of the U-turn in gender segregation

In the early 1970s, the balkanization of the US labor market into “men’s occupations” and “women’s occupations” began to unravel, as women entered the professions and other male-typed sectors in record numbers. This decline in gender segregation continued on for several decades but then suddenly stalled at the turn of the century and shows no signs of resuming. Although the stall is itself undisputed, its sources remain unclear. Using nearly a half-century of data from the General Social Survey, we show that a resurgence in segregation-inducing forms of intergenerational transmission stands behind the recent stall. Far from serving as impartial conduits, fathers are now disproportionately conveying male-typed occupations to their sons, whereas mothers are effectively gender-neutral in their transmission outcomes. This segregative turn among fathers accounts for 47% of the stall in the gender segregation trend (between 2000 and 2018), while the earlier integrative turn among fathers accounts for 34% of the initial downturn in segregation (between 1972 and 1999). It follows that a U-turn in intergenerational processes lies behind the U-turn in gender segregation.

In all late-industrial countries, women and men continue to occupy very different types of jobs, with women concentrated in service and nurturing occupations (e.g., sales clerk and nurse) and men concentrated in manual and analytic occupations (e.g., laborer and computer scientists). The standard sociological account of such segregation treats it as a premodern relic that should gradually disappear as educational opportunities are equalized, egalitarian gender attitudes diffuse, overt and covert forms of employer discrimination are rooted out, and family-friendly workplaces and related labor market reforms are instituted (1, 2). Between 1970 and 1990, these types of institutional reforms indeed seemed to be bearing fruit, with most late-industrial countries experiencing sharp declines in segregation (3).This egalitarian turn proved to be short-lived. By the end of the 20th century, the decline in gender segregation had stalled in many late-industrial countries, including the United States (4–7). In Fig. 1, we present the US trend using the General Social Survey (GSS), the main data source for our analyses (8). The trend lines in Fig. 1 reveal that the downturn stalled well before integration was achieved (and Fig. 1B additionally suggests a resegregative uptick off this already high baseline). To completely eliminate segregation, ∼60% of US workers would have to shift to a different occupation, a stark result given the stated commitment to gender equality and equal opportunity in the United States. This hypersegregation translates into profound gender gaps in pay, authority, working conditions, and much more (9–12). Because occupational segregation generates such a wide range of unequal outcomes, it has become a conventional policy target among those who seek to reduce gender inequality.Open in a separate windowFig. 1.The U-turn in occupational gender segregation shown by (A) the index of dissimilarity and (B) a margin-free measure of the gender-by-occupation association. Analysis is based on the 1972 to 2018 GSS using women and men in the labor force, ages 25 to 64 (inclusive), with nonmissing data on age, gender, and occupation. n = 44,640. Occupations are coded with 1970 Census Occupational Classification (see SI Appendix, Appendixes B and D, for details). Trend is smoothed with locally smoothed regression (LOESS) with the span set at 0.75. For the definition of D and A, see Materials and Methods.The long line of research on the sources of the stall proceeds in part from this widely shared (albeit not universal) commitment to reduce gender inequality. Although far from conclusive or exhaustive, the available research suggests that 1) the persisting double burden of domestic work erodes the willingness or capacity of women to hold jobs that entail long hours or overwork (12–14); 2) the persistence of norms against women outearning their partners (in marriages between women and men) leads to settling and underachievement (15); 3) the persistence of essentialist beliefs about the types of occupations that women and men are qualified to undertake locks in a conventional division of labor (1, 16, 17); and 4) the continuing tendency of employers to discriminate against mothers (18) and those who participate intermittently in the labor force (19, 20) makes it difficult for women to break into male-typed occupations.^* Across these assorted supply-side and demand-side accounts, a common theme is that the easy desegregative gains have been creamed off, that a new equilibrium or natural rate (22) has been reached, and that puncturing this equilibrium may require different or more aggressive countermeasures.This interpretation rests on a distinction between 1) overt and easy-to-attack inequalities and 2) covert and difficult-to-attack inequalities. It is often argued, for example, that overt forms of hiring discrimination against women can be reduced through antidiscrimination law and open hiring practices, whereas subtler or covert forms are not as easy to address, at least with legal remedies. Likewise, the extreme essentialist view that women are utterly lacking in rational faculties was an early casualty of the gender revolution, whereas it has proven more difficult to root out a subtler form of essentialism that presumes that men are more likely than women to be “brilliant” or “geniuses” (23). By this logic, the gender revolution will only be reenergized by developing new interventions that are fine-tuned for the subtler, albeit still very consequential, mechanisms that lie behind gender inequality.This conclusion may well be warranted. It would, however, be premature to adopt this interpretation without a fuller understanding of the institutional sources of the stalling out. It is striking in this regard that none of the foregoing accounts directly features the role of intergenerational processes. To be sure, conventional accounts routinely invoke the segregative effects of gender-biased training, norms, and culture, but the social processes through which gender-biased training is delivered or gender-biased norms and culture are instilled are left unclear and thus may or may not have intergenerational sources. This is an unfortunate omission because it undermines our capacity to remediate well. As it stands, most currently popular interventions do not target intergenerational processes (24), an understandable state of affairs given that relatively little is now known about their role in the stalling out.There is, then, a worrying omission in our research on the gender U-turn. Although this omission might seem surprising, it has to be remembered that the contemporary family is often seen as a prime carrier of new forms of gender egalitarianism and accordingly an unlikely source of the stalling out. The new gender-egalitarian family features mothers who are increasingly likely to work, to commit to bona fide careers, and to espouse liberal attitudes (25). In this conventional characterization of familial change, it is notable that mothers are represented as a main force for change, whereas fathers remain in the background largely carrying on. This raises the possibility that fathers may not always be unfettered agents of egalitarian change and may, to the contrary, be implicated in the stalling out. The purpose of our paper is to explore this segregative-father hypothesis by melding models of segregation and intergenerational transmission.The results will show that the U-turn in the segregation trend is indeed linked to a U-turn in intergenerational processes. As we will discuss, a variety of mechanisms may lie behind the rise of segregative reproduction, yet most of them involve familial processes in some fashion. It follows that insofar as desegregation is a policy objective, it may be strategic to build interventions that address contemporary family processes.The two streams of mobility research upon which our analysis will capitalize are those examining 1) the net effects of mothers and fathers on outcomes and 2) the effects of intragenerational mobility on segregation. The first of these two streams is of course especially relevant when examining the intergenerational sources of segregation (26, 27). In recent decades, there has been a backlash against treating the father’s or “family head’s” occupation as a satisfactory measure of class origins (28), a long-overdue development given that a rising share of children are now growing up in more complicated families with many potential role models (29, 30). This newer line of multiple-parent mobility research has, however, focused mainly on examining the relative size of the effects of mothers and fathers, a type of “horse race” analysis that comes naturally when one seeks to rectify decades of scholarship that ignored mothers altogether. As important and influential as this research is, it cannot directly answer the research question that we are taking on, given that the implications of this horse race for occupational segregation depend on the extent to which class and gender-typing reproduction come together. To understand how intergenerational transmission contributes to gender segregation, we need to know 1) whether mothers are passing on female-typed occupations disproportionately to daughters and 2) whether fathers are passing on male-typed occupations disproportionately to sons. Although the intergenerational transmission of gender-typed aspirations is well understood (31, 32), our research takes the next step of building gendered mobility models that uncover whether actual reproductive practices are affected by the gender of the parent, the gender typing of the occupation, and the gender of the offspring (33).The second stream of mobility research relevant to our analysis examines the effects of intragenerational mobility on gender segregation (34). This line of research, which has a long history (35), examines how women and men move in and out of the labor force over their career, how women and men move in and out of gender-typed occupations over their career, and how such mobility has gendered sources (e.g., sexual harassment, gender discrimination, and the “second shift”). Within this literature, many scholars (36) have examined whether the gender of managers affects hiring and promotion decisions (and hence downstream segregation), a line of questioning that is formally similar to our own interest in whether the gender of the parent affects occupational outcomes. Because parents are engaged in ongoing socialization, aspiration development, human capital investment, and network provisioning, their effects on segregation may well be more consequential than the pinpoint hiring and firing decisions of managers. This is the core rationale for building intergenerational processes into a segregation trend analysis.