Cerebral cavernous malformations (CCMs) are common inherited and sporadic vascular malformations that cause stroke and seizures in younger individuals1. CCMs arise from endothelial cell loss of KRIT1, CCM2, or PDCD10, non-homologous proteins that form an adaptor complex2. How disruption of the CCM complex results in disease remains controversial, with numerous signaling pathways (including Rho3,4, SMAD5 and Wnt/β-catenin6) and processes such as endothelial-mesenchymal transition (EndMT)5 proposed to play causal roles. CCM2 binds MEKK37–11, and we have recently demonstrated that CCM complex regulation of MEKK3 is essential during vertebrate heart development12. Here, we investigate this mechanism in CCM disease pathogenesis. Using a neonatal mouse model of CCM disease, we find that expression of the MEKK3 target genes KLF2 and KLF4, as well as Rho and ADAMTS protease activity, are increased in the endothelial cells of early CCM lesions. In contrast, we find no evidence of EndMT or increased SMAD or Wnt signaling during early CCM formation. Endothelial-specific loss of Mekk3, Klf2, or Klf4 dramatically prevents lesion formation, reverses the increase in Rho activity, and rescues lethality. Consistent with these findings in mice, we demonstrate that endothelial expression of KLF2 and KLF4 is elevated in human familial and sporadic CCM lesions, and that a disease-causing human CCM2 mutation abrogates MEKK3 interaction without affecting CCM complex formation. These studies identify gain of MEKK3 signaling and KLF2/4 function as causal mechanisms for CCM pathogenesis that may be targeted to develop new CCM therapeutics.

In an effort at theoretical clarification, the authors reviewed 45 recent articles reporting empirical research employing the concept of ‘social capital’. The literature is roughly equally divided between those who treat social capital as an independent variable and those who consider it as a dependent variable, and between those who operationalize the concept principally in terms of norms, values and attitudes and those who choose a more social structural operationalization, invoking social networks, organizations and linkages. Work on social capital as a mainly normative variable is dominated by political scientists and economists, while sociologists and a wide range of applied social scientists utilize more social structural understandings of the term. We find little to recommend in the use of ‘social capital’ to represent the norms, values and attitudes of the civic culture argument. We present empirical, methodological and theoretical arguments for the irrelevance of ‘generalized social trust’, in particular, as a significant factor in the health of democracies or economic development. Social structural interpretations of social capital, on the other hand, have demonstrated considerable capacity to draw attention to, and illuminate, the many ways in which social resources are made available to individuals and groups for individual or group benefit, which we take to be the prime focus and central attraction of the social capital concept. The paper concludes by elaborating a context-dependent conceptualization of social capital as access plus resources, and cautions against ‘over-networked’ conceptualizations that equate social capital with access alone.

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Both civil society and social capital have proven useful heuristics for drawing attention to neglected nonmarket aspects of social reality and constitute a needed corrective to narrowly economistic models. However, both break down, although in different ways, when treated as the basis for elaborating testable hypotheses and further theory. Civil society is most useful in polemical or normative contexts, but attempts to distinguish it from other sectors of society typically break down in unresolvable boundary disputes over just what constitutes civil society and what differentiates it from “state” and “market.” Work by Robert Putnam and others has assimilated social capital to the civic culture model, using it as just another label for the norms and values of the empirical democratic theory of the 1950s. This strategy undermines the empirical value of James Coleman and Pierre Bourdieu's useful social relational concept.

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Background: The introduction of texture to the outer shell of breast implants was aimed at increasing tissue incorporation and reducing capsular contracture. It has also been shown that textured surfaces promote a higher growth of bacteria and are linked to the development of breast implant–associated anaplastic large cell lymphoma. Methods: The authors aimed to measure the surface area and surface roughness of 11 available implants. In addition, the authors aimed to subject these implant shells to an in vitro bacterial attachment assay with four bacterial pathogens (Staphylococcus epidermidis, S. aureus, Pseudomonas aeruginosa, and Ralstonia pickettii) and study the relationship among surface area, surface roughness, and bacterial growth. Results: Surface area measurement showed grouping of implants into high, intermediate, low, and minimal. Surface roughness showed a correlation with surface area. The in vitro assay showed a significant linear relationship between surface area and bacterial attachment/growth. The high surface area/roughness implant texture grew significantly more bacteria at 24 hours, whereas the minimal surface area/roughness implant textures grew significantly fewer bacteria of all types at 24 hours. For implants with intermediate and low surface areas, some species differences were observed, indicating possible affinity of specific bacterial species to surface morphology. Conclusions: Implant shells should be reclassified using surface area/roughness into four categories (high, intermediate, low, and minimal). This classification is superior to the use of descriptive terms such as macrotexture, microtexture, and nanotexture, which are not well correlated with objective measurement and/or functional outcomes.

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