The medical value of examining tissue from therapeutic abortions: an analysis of 13,477 cases

In 1983 the United States Supreme Court ruled that therapeutic abortion tissue must be examined by a pathologist. A review of 13,477 specimens indicated that 98.7% had routine confirmation of the intrauterine pregnancy. Of the remainder, 60% had a deciduoid appearance, suggestive of but not diagnostic of pregnancy, 39% were not diagnostic of pregnancy, and 1% showed hydatidiform mole. In a subgroup of patients with non-routine reports, 28% had a problem warranting further care for ectopic pregnancy or trophoblastic disease or intrauterine retained placental tissue. It is concluded that a small percentage of patients receive benefit from this additional study because real or potential complications are identified early in the post-abortion period.     

Pohl's track screw for the surgical treatment of femoral neck fracture. Reliable surgical principle or obsolete method?

Pohl's hip screw--the classic form of a dynamic osteosynthesis--is an approved method in the treatment of the fracture of the femoral neck (lateral and pertrochanteric fractures). Between 1963 and 1983 over 200 patients were treated with Pohl's hip screw. At an averaged stay of 29 days in hospital half of them were rehabilitated. The mortality rate was 9.3%. More recent methods--e.g. the dynamic hip screw, propagated by AO--present more technical improvements but they are only variations of an old therapeutic principle proved over a generation.     

Is Outpatient Unicompartmental Knee Arthroplasty Safe to Perform at an Ambulatory Surgery Center? A Comparative Study of Early Post-Operative Complications

Background

Unicompartmental knee arthroplasty (UKA) lends itself to the outpatient surgical setting. Prior literature has established a low rate of readmission and post-operative complications when performed in a hospital outpatient setting (HOP). To our knowledge, there have been no studies comparing complications of UKA performed at an ambulatory surgery center (ASC) and those in a HOP.

Health care utilization and functional status in the aged following a fall

Falls in the aged may lead to increases in health care utilization and declines in functional status. The Longitudinal Study of Aging was analyzed to test the hypotheses that use of the health care system is greater in elderly persons subsequent to a fall in the preceding year than in those who have not fallen and that fallers are more likely to decline in function than are nonfallers. One-time fallers and, especially repeated fallers, (2 or more falls in the preceding year) were at greater risk of subsequent hospitalization, nursing home admission, and frequent physician contact than were nonfallers, after controlling for age, sex, self-perceived health status, and difficulties with activities of daily living. Similarly, one-time fallers, and especially repeated fallers, were at greater risk of reporting subsequent difficulties with activities of daily living, instrumental activities of daily living, and more physically demanding activities. These findings highlight the significant impact that falls have on the health care system and on the individual.     

Inflammatory bowel disease and the X chromosome

A review of documented cases demonstrates a significant association of Turner's syndrome with Crohn's disease and ulcerative colitis; this association relates particularly to genetic constitutions comprising an abnormal rather than an absent X chromosome. The karyotype 46XiXq, in pure or mosaic form, appears to be a significant susceptibility factor for inflammatory bowel disease. This karyotype often gives rise to relatively weak phenotypic characteristics of Turner's syndrome, which may be overlooked in short females with inflammatory bowel disease. The association of inflammatory bowel disease with Turner's syndrome may reflect the presence on the X chromosome of genes involved in disease pathogenesis. Linkage analysis studies, involving microsatellite markers on the X chromosome, are being performed.      

Allostatic and environmental load in toddlers predicts anxiety in preschool and kindergarten

Psychobiological models of allostatic load have delineated the effects of multiple processes that contribute to risk for psychopathology. This approach has been fruitful, but the interactive contributions of allostatic and environmental load remain understudied in early childhood. Because this developmental period encompasses the emergence of internalizing problems and biological sensitivity to early experiences, this is an important time to examine this process. In two studies, we examined allostatic and environmental load and links to subsequent internalizing and externalizing problems. Study 1 examined relations between load indices and maladjustment, concurrently and at multiple times between age 2 and kindergarten; Study 2 added more comprehensive risk indices in a sample following a group of highly fearful toddlers from 2 to 3 years of age. Results from both studies showed that increased allostatic load related to internalizing problems as environmental risk also increased. Study 2, in addition, showed that fearfulness interacted with allostatic and environmental load indices to predict greater anxiety among the fearful children who had high levels of allostatic and environmental load. Taken together, the findings support a model of risk for internalizing characterized by the interaction of biological and environmental stressors, and demonstrate the importance of considering individual differences and environmental context in applying models of allostatic load to developmental change in early childhood.     

Analysis of the human E2 ubiquitin conjugating enzyme protein interaction network

In eukaryotic cells the stability and function of many proteins are regulated by the addition of ubiquitin or ubiquitin-like peptides. This process is dependent upon the sequential action of an E1-activating enzyme, an E2-conjugating enzyme, and an E3 ligase. Different combinations of these proteins confer substrate specificity and the form of protein modification. However, combinatorial preferences within ubiquitination networks remain unclear. In this study, yeast two-hybrid (Y2H) screens were combined with true homology modeling methods to generate a high-density map of human E2/E3-RING interactions. These data include 535 experimentally defined novel E2/E3-RING interactions and >1300 E2/E3-RING pairs with more favorable predicted free-energy values than the canonical UBE2L3–CBL complex. The significance of Y2H predictions was assessed by both mutagenesis and functional assays. Significantly, 74/80 (>92%) of Y2H predicted complexes were disrupted by point mutations that inhibit verified E2/E3-RING interactions, and a ∼93% correlation was observed between Y2H data and the functional activity of E2/E3-RING complexes in vitro. Analysis of the high-density human E2/E3-RING network reveals complex combinatorial interactions and a strong potential for functional redundancy, especially within E2 families that have undergone evolutionary expansion. Finally, a one-step extended human E2/E3-RING network, containing 2644 proteins and 5087 edges, was assembled to provide a resource for future functional investigations.Protein ubiquitination is mediated by the sequential action of an E1 activating enzyme, an E2 conjugating enzyme, and a range of E3 proteins, which are thought to confer substrate specificity (Hershko and Ciechanover 1998). Two main forms of E3 proteins have been characterized: HECT domain ligases, which act as enzymatic intermediates in protein ubiquitination and E3-RING proteins, which appear to be nonenzymatic recognition factors, although their exact role in catalysis remains to be established (Ozkan et al. 2005; Petroski et al. 2006). Although the sequence of events that facilitate the addition of ubiquitin (Ub) or ubiquitin-like (Ubl) proteins is conserved in all eukaryotic cells, the extent and form of Ub and Ubl modification can be diverse, ranging from the addition of single Ub or Ubl residues at one or more sites within a target protein (mono- and multi-ubiquitination), to the assembly of a range of structurally distinct polyubiquitin chains (Peng et al. 2003), which may confer different functional properties (Welchman et al. 2005; Ikeda and Dikic 2008).Although E2 and E3 proteins are thought to work in a combinatorial manner to generate different forms of substrate modification (Weissman 2001; Christensen et al. 2007), very little is known about the specificity or combinatorial nature of human E2/E3-RING interactions. As such, the potential for redundancy or antagonism within the human ubiquitome remains unclear, as does the degree of connectivity between different network components. As Ub and Ubl proteins are known to play a key role in the regulation of both physiological and pathological processes, there is a growing need to develop a better understanding of the complex ways in which E2 and E3 proteins work together in human cells.While isolated biochemical studies and unbiased global interactome projects continue to provide invaluable and exciting data, coverage of the human ubiquitome, and, in particular, E2/E3 interactions, remains limited. To provide new insights into partner preferences and the degree of redundancy within this combinatorial process, the density of network coverage must be significantly increased using techniques that define or predict binary interactions. Analysis of data contained within the MINT, IntAct, BioGRID, and HPRD databases revealed 60 human E2/E3-RING interactions (Fig. 1A; Supplemental Files 3 and 4), including data from both binary and co-complex isolation studies. This lack of experimental data is compounded by the expansion in E2- and E3-RING protein numbers, which has occurred during eukaryotic evolution. Searches performed using data from the Inparanoid and Homologene databases show that 34 of the 39 human E2-related proteins have clearly identifiable orthologs in yeast, fly, or worm. However, 48% (146 out of 304) of E3-RING proteins do not (Supplemental File 1). Consequently, methods developed to predict interactions between orthologous proteins in different species (Interolog interactions) (Matthews et al. 2001; Lehner and Fraser 2004) cannot be used to assign combinatorial preferences for all human E2/E3-RING complexes.Open in a separate windowFigure 1.Binary human E2/E3-RING protein interaction networks. (A) Previously known interactions derived from the MINT, IntAct, BioGRID, and HPRD databases at the time of this study. (B) Predicted human E2/E3-RING interactions including Interologs (purple edges) or non-Interolog predicted interactions from Hi-map and IntNet databases (orange edges). (C) Increased coverage within the human E2/E3-RING interaction space as a result of this study. Novel interactions are shown as red edges. Bold edges represent interactions confirmed by our data. Blue nodes represent E2 ubiquitin conjugating enzymes, while yellow nodes represent E3-RING proteins. To aid network analysis and node identification, all networks are provided as ready-to-view Cytoscape files (Supplemental File 3).To address these problems we have assembled a high-density binary protein interaction map containing >1810 human E2- or E3-RING interactions. Initially, two stringent Y2H methods were used to investigate the spectrum of human E2 protein interactions and the combinatorial nature of human E2/E3-RING complexes. In addition, a structure-based true homology modeling method was also used to provide an independent prediction of interactions between 3180 human E2/E3-RING pairs. Finally, experimental data from this study were combined with known human E2- or E3-RING interactions and available Interolog data to generate a one-step extended map, which provides an initial insight into the gross topology and modular organization within the highly combinatorial human E2/E3-RING network.