Different disease profiles for women and men with abdominal aortic aneurysms.

OBJECTIVE: The overall aim with this study was to investigate causes of death and mortality rates for women and men treated for abdominal aortic aneurysm (AAA) in Sweden. MATERIALS AND METHOD: All patients treated for ruptured and non-ruptured AAA 1987-2002 in Sweden were identified in national registries (n=12917). Age, sex, diagnosis, surgical procedure and mortality were analysed on a patient specific level. Logistic regression and analysis of standardised mortality rates (SMR) were performed. RESULTS: Post operative mortality was similar between the sexes. Age (p<0.0001), and surgery for rupture (p=0.0005), but not gender (p=0.65) were significant risk factor for poor long term survival. SMR revealed increased risk for both sexes compared to the population with significantly higher values for women than men (2.26, CI 2.10-2.43 vs. 1.63, CI 1.57-1.68, p<0.0001). The higher risk for women could be explained by the higher risk for aneurysm related death (ie.thoracic or abdominal aorta) compared to men (Hazard ratio 1.57 vs. 1.0, p<0.0001). CONCLUSION: Women do not have an increased surgical risk compared to men, but treated women have an increased risk of premature death compared to men and women in the population. They also have a higher risk for aneurysm related death compared to men with AAA.     

Outcome of Staphylococcus aureus-triggered sepsis and arthritis in IL-4-deficient mice depends on the genetic background of the host.

Disruption of the IL-4 gene in two inbred mouse strains revealed a dual role of IL-4 in Staphylococcus aureus sepsis and arthritis depending on the host's genetic background. IL-4 was protective in 129SV mice, since 5 days after S. aureus inoculation IL-4(-/-) mice displayed 70% mortality as compared to survival of all 129SV wild-type counterparts. On the other hand, IL-4 was detrimental in C57BL/6 mice, since survival of IL-4(-/-) C57BL/6 mice was increased, as compared to wild-type controls, due to decreased staphylococcal growth. Altogether, our results show the dual role of IL-4 in S. aureus sepsis and arthritis, depending on the genetic background of the host.     

Antibodies to the hepatitis B e antigen (HBeAg) can be induced in HBeAg-transgenic mice by adoptive transfer of a specific T-helper 2 cell clone.

Production of antibody to hepatitis B e antigen (HBeAg); i.e., anti-HBe antibody,) in HBeAg-transgenic mice is believed to be mediated by T-helper 2 (Th2) cells. Injection of an HBeAg-specific Th2 clone into HBeAg-transgenic H-2k mice induced anti-HBe antibody production, confirming the function of Th2 cells in this model system.     

Molecular basis of usher pore gating in Escherichia coli pilus biogenesis

Extracellular fibers called chaperone-usher pathway pili are critical virulence factors in a wide range of Gram-negative pathogenic bacteria that facilitate binding and invasion into host tissues and mediate biofilm formation. Chaperone-usher pathway ushers, which catalyze pilus assembly, contain five functional domains: a 24-stranded transmembrane β-barrel translocation domain (TD), a β-sandwich plug domain (PLUG), an N-terminal periplasmic domain, and two C-terminal periplasmic domains (CTD1 and 2). Pore gating occurs by a mechanism whereby the PLUG resides stably within the TD pore when the usher is inactive and then upon activation is translocated into the periplasmic space, where it functions in pilus assembly. Using antibiotic sensitivity and electrophysiology experiments, a single salt bridge was shown to function in maintaining the PLUG in the TD channel of the P pilus usher PapC, and a loop between the 12th and 13th beta strands of the TD (β12–13 loop) was found to facilitate pore opening. Mutation of the β12–13 loop resulted in a closed PapC pore, which was unable to efficiently mediate pilus assembly. Deletion of the PapH terminator/anchor resulted in increased OM permeability, suggesting a role for the proper anchoring of pili in retaining OM integrity. Further, we introduced cysteine residues in the PLUG and N-terminal periplasmic domains that resulted in a FimD usher with a greater propensity to exist in an open conformation, resulting in increased OM permeability but no loss in type 1 pilus assembly. These studies provide insights into the molecular basis of usher pore gating and its roles in pilus biogenesis and OM permeability.The β-barrel membrane proteins of Gram-negative bacteria participate in a variety of outer membrane (OM) functions, including physiological maintenance, protein folding, transport, and organelle assembly (1–5). Some OM pore proteins are involved in protein secretion and assembly of virulence-associated surface-exposed appendages required for adherence to host surfaces (3, 5, 6). One such class of proteins is the ushers of the chaperone-usher pathway (CUP) found in various phyla of bacteria ranging from Proteobacteria to Cyanobacteria to Deinococcus-Thermus (7). Ushers are gated OM channels that function as molecular machines that convert subunit binding and folding energy into work to assemble highly stable macromolecular CUP fibers and facilitate their extrusion to the bacterial surface in Gram-negative bacteria. In uropathogenic Escherichia coli (UPEC), type 1 pili are critical in causing bladder infection (8), whereas P pili are important in pyelonephritis (9, 10). Type 1 and P pili are encoded by the fim and pap operons, respectively, and have been extensively used as model systems to elucidate the structural basis of chaperone-usher pilus assembly. We used both the type 1 and P pilus ushers in this study to elucidate fundamental insights into the gating mechanism of OM ushers.P pilus assembly requires the function of a dedicated chaperone (PapD) (11, 12) and the usher (PapC) (3, 13). The P pilus comprises a flexible-tip fibrillum made up of minor pilins with the two-domain adhesin PapG at the distal end where it can recognize Galα1–4Gal disaccharide-containing glycolipids found in the human kidney (14, 15). The P pilus tip is joined to a right-handed, helical pilus rod made up of PapA pilins (16, 17) and is anchored in the OM via the terminator/anchoring subunit PapH (18). Type 1 pili are composed of FimA subunits making up the pilus rod joined to the tip fibrillum, which contains the FimH tip adhesin joined to FimG and adapted to the FimA rod by FimF. FimC and FimD are the chaperone and usher, respectively.CUP pilus subunits are incomplete Ig-like folds missing their C-terminal β-strand. Through a process called donor strand complementation, the chaperone transiently completes the Ig fold of a subunit in the periplasm to form a binary complex, which facilitates the subunit’s proper folding and stability and results in a subunit primed for assembly into a pilus fiber (19–21). Chaperone-subunit complexes are targeted to the OM usher, which catalyzes donor strand exchange (DSE), whereby the chaperone is displaced and the Ig fold of the polymerizing subunit is completed by its neighbor via an N-terminal extension in an ATP-independent manner (19, 22). The usher has five domains: an N-terminal periplasmic domain (NTD), a transmembrane β-barrel domain (TD), a β-sandwich plug domain (PLUG), and two periplasmic, β-sandwich C-terminal domains (CTD1 and 2) (3, 5). During the initiation of pilus assembly, a chaperone-adhesin is initially targeted to the usher NTD and then transferred from the NTD to the CTDs via catalytic dissociation by CTD2 (23).X-ray crystal structures of the PapC and FimD ushers showed that the apo PapC and FimD pores are kidney-shaped β-barrels of 24 strands, the largest number of strands identified for a single OM polypeptide (3, 5, 24). The inner dimensions of the apo ushers are large enough to allow transport of folded protein domains (25 Å × 45 Å diameter) (3). Thus, a precise usher gating mechanism is needed to facilitate the extrusion of polymerized pilus fibers across the OM while maintaining OM integrity. In the apo usher, in the absence of a polymerizing and/or anchored pilus, the β-sandwich PLUG occupies the inactive pore. The PLUG seems to be kept stable in the pore via its interactions with residues of the β-barrel interior wall as well as the β5–6-hairpin loop and an α-helix of the TD that caps the β5–6-hairpin loop (3, 25). In the active form, as seen in the FimDCH structure, the FimD pore rearranges to a nearly circular pore of 32 Å diameter (5, 24) and the PLUG is relocated to the periplasm, where it forms a high-affinity, stable interaction with the NTD (23). The NTD/PLUG complex serves to further recruit chaperone-subunit complexes for repeated rounds of DSE pilus assembly (23).We delineated the channel activities of the usher by focusing on two different ushers, the PapC usher of the P pilus system and the FimD usher of the type 1 pilus system. Using erythromycin (Erm) sensitivity assays, we identified a salt bridge interaction between R305 of the PLUG and E467 of the TD α-helix that functions to stabilize the PLUG in the PapC pore. Electrophysiology studies confirmed the destabilization of the PLUG in the R305A mutant. Pore gating and assembly functions of the usher were further decoupled by a pair of cysteine mutants, one in each of the NTD and PLUG domains of the FimD usher, which resulted in an open pore as assessed by Erm sensitivity in the absence of subunits while retaining pilus assembly function when the chaperone and subunits were coexpressed. We also discovered that a periplasmic loop between usher barrel β-strands 12 and 13 facilitates the removal of the PLUG, which is necessary for usher-catalyzed pilus biogenesis. Further, we demonstrated that proper anchoring of the mature pilus is necessary to retain the OM integrity. These results emphasize the importance of the coordinated, regulated expression and assembly of CUP pili. Collectively, these results demonstrate the cooperative roles that the usher plays in regulating pilus biogenesis and OM permeability.     

TwoDay Method: a quick-start approach

Background

Requiring that women wait until the onset of menses to initiate a family planning method is a medical barrier that can result in unintended pregnancies. In the efficacy study of the TwoDay Method, a new fertility awareness-based method of family planning, women were taught the method in the first seven days of their cycles. This study tested a quick-start approach (providing the method at any time in the cycle) to TwoDay Method delivery.

Study Design

In Peru, 167 women were counseled in TwoDay Method use (regardless of cycle day) and followed for up to 7 months. They were interviewed periodically to assess their use of and satisfaction with the method. Simulated clients gauged providers' ability to correctly counsel in method use at different times of the cycle.

Results

No significant differences were observed in correct use, continuation rates, and acceptability of the method among women who were counseled at different points in the cycle; quality of counseling was not undermined by the quick-start approach.

Conclusions

There is no need to limit delivery of the TwoDay Method to the first seven days of the menstrual cycle.     

e-Ana and e-Mia: A Content Analysis of Pro–Eating Disorder Web Sites

Objectives. The Internet offers Web sites that describe, endorse, and support eating disorders. We examined the features of pro–eating disorder Web sites and the messages to which users may be exposed.Methods. We conducted a systematic content analysis of 180 active Web sites, noting site logistics, site accessories, “thinspiration” material (images and prose intended to inspire weight loss), tips and tricks, recovery, themes, and perceived harm.Results. Practically all (91%) of the Web sites were open to the public, and most (79%) had interactive features. A large majority (84%) offered pro-anorexia content, and 64% provided pro-bulimia content. Few sites focused on eating disorders as a lifestyle choice. Thinspiration material appeared on 85% of the sites, and 83% provided overt suggestions on how to engage in eating-disordered behaviors. Thirty-eight percent of the sites included recovery-oriented information or links. Common themes were success, control, perfection, and solidarity.Conclusions. Pro–eating disorder Web sites present graphic material to encourage, support, and motivate site users to continue their efforts with anorexia and bulimia. Continued monitoring will offer a valuable foundation to build a better understanding of the effects of these sites on their users.While health professionals investigate causes of and prevention strategies and treatments for eating disorders and their poor health consequences,¹ pro–eating disorder Web sites and communities have emerged wherein users can find material to support the progression and maintenance of eating disorders.^2–4 Similar to Web sites that promote other equally unhealthy behaviors such as self-injury and suicide,⁵ pro–eating disorder Web sites (also identified as pro-Ana and pro-Mia Web sites) are of great concern. A pro–eating disorder Web site is a collection of Internet pages, all accessed through a domain name or IP address, that deliver content about eating disorder such as anorexia and bulimia. This content can be conveyed through text, images, audio, or video, and it encourages knowledge, attitudes, and behaviors to achieve terribly low body weights.A distinction must be made; unlike Web sites that encourage healthy weights, moderate exercise, and recognized nutrition and diets, many pro–eating disorder sites recommend that their users try intense practices, such as vomiting and fasting, with an emphasis on achieving extremely thin or skeletal appearances. Adolescents exposed to pro–eating disorder Web sites have been shown to have higher levels of body dissatisfaction than adolescents not exposed to these sites, as well as decreased quality of life and longer durations of eating disorders.^4,6,7 In addition, increased use of pro–eating disorder sites has been positively correlated with disordered eating behaviors and negatively correlated with disease-specific quality of life among adults (R. Peebles et al., unpublished data, 2010).Behavior change and communication theories justify concern about pro–eating disorder Web sites. Bandura''s social cognitive theory proposes that modeled behaviors are more likely to be imitated when message receivers can relate to the model and perceive rewards with the communicated behavior.⁸ Vulnerable users may adopt conveyed behaviors not only when they admire online peers but also if they are repeatedly exposed to images of successful models, celebrities, and even real people with life-threatening and dangerously low body weights.Cultivation theory, a theory developed by communication scholar George Gerbner,^9,10 posits that when messages are pervasive and repeated, individuals with higher exposure levels are more likely to accept the conveyed messages as normative. Therefore, frequent visitors to pro–eating disorder Web sites may perceive extreme dieting and exercise as normal rather than symptomatic of a dangerous disease. Given the potential deleterious influence of pro–eating disorder sites, researchers must monitor these online sources to better understand the available messages and resources. The content analysis methodology allows such a systematic review.^11,12We conducted an in-depth examination of pro–eating disorder websites and the messages to which users may be exposed. To date, only a handful of studies have explored pro–eating disorder sites,^13–21 and these content analyses have considered fewer than a dozen sites.^3,22 These studies seem inadequate in that each reviewed only 12 Web sites and none of the assessments involved more than 1 coder. By contrast, we used extensive first- and second-generation sampling, a well-developed and detailed coding manual (created by the research team), and interrater reliability techniques. As a result, we are able to present a more valid depiction of what visitors to pro–eating disorder Web sites may encounter in this digital space.