Prospective analysis of psychosocial outcomes in breast reconstruction: one-year postoperative results from the Michigan Breast Reconstruction Outcome Study

In the past decade, changing attitudes toward breast reconstruction among both patients and providers have led a growing number of women to seek breast reconstruction after mastectomy. Although investigators have documented the psychological, social, emotional, and functional benefits of breast reconstruction, little research has evaluated the effects of procedure choice on these outcomes. The current study prospectively evaluated and compared psychosocial outcomes for three common options for mastectomy reconstruction: tissue expander/implant, pedicle TRAM, and free TRAM techniques. In a prospective cohort design, patients undergoing postmastectomy reconstruction for the first time with expander/implant, pedicle TRAM, or free TRAM procedures were recruited from 12 centers and 23 plastic surgeons in the United States and Canada. Before reconstruction and at 1 year after reconstruction, patients were evaluated by a battery of questionnaires consisting of both generic and condition-specific surveys. Outcomes assessed included emotional well-being, vitality, general mental health, social functioning, functional well-being, social well-being, and body image. Baseline (preoperative) scores and the change in scores (the difference between postoperative and preoperative scores) were compared across procedure types using t tests and analysis of covariance. Preoperative and 1-year postoperative surveys were obtained from 273 patients. Procedure type was reported in 250 patients, of whom 56 received implant reconstructions, 128 pedicle TRAM flaps, and 66 free TRAM flaps. A total of 161 immediate and 89 delayed reconstructions were performed. Among women receiving immediate reconstruction, significant improvements were observed in all psychosocial variables except body image. However, no significant effects of procedure type on these changes over time existed. Similarly, delayed reconstruction patients had significant increases in emotional well-being, vitality, general mental health, functional well-being, and body image. Although the choice of reconstructive technique did not significantly impact most of these outcomes, significant differences existed among procedure types for three psychosocial subscales. Patients undergoing delayed expander/implant reconstructions reported greater improvements in vitality and social well-being relative to women receiving delayed TRAM procedures. By contrast, delayed TRAM patients noted significantly greater gains in body image compared with women choosing delayed expander-implant reconstruction. The authors conclude that both immediate and delayed breast reconstructions provide substantial psychosocial benefits for mastectomy patients. Although the choice of reconstructive procedure does not seem to significantly affect improvements in psychosocial status with immediate reconstruction, our data suggest that procedure type does have a significant effect on gains in vitality and body image for women undergoing delayed reconstruction.     

Iron-rich particles in embryos of seeds from the family Pinaceae

Summary Iron-rich particles, previously reported in seeds of members of the genus Pinus, were found in radicle-hypocotyl tissues of dry embryos from eight other genera in the family Pinaceae. Thus, these Fe-rich particles are of common occurrence in seeds of this conifer family. These particles were most difficult to locate inPseudolarix amabilis, which has green embryos. Energy-dispersive X-ray analysis was used to determine the elements present in conifer Fe-rich particles and phytoferritin deposits in pea embryo axes. Ferich particles from all species studied contained mainly Fe and P but also contained considerable K and Mg. Abietoideae group I (genera Cedrus andAbies) had lower Fe P ratios compared to all the other combined subfamilies within the Pinaceae. Pea phytoferritin deposits contained markedly lower amounts of P relative to Fe based on peakto-background ratios and quantitative values calculated by using a ferric phosphate standard. We also found, for the first time, that pea phytoferritin contained considerable K. A strong similarity was found between the energy-dispersive X-ray analysis spectra from Ferich particles and portions of a laboratory-synthesized Fe, K, Mg phytate salt. Phytate is a common mineral-nutrient storage compound in seeds. The possibility of these Fe-rich particles being phytoferritin cannot be ruled out, but if they are phytoferritin, they have lower Fe P ratios than almost all other ferritins reported to date.Abbreviations EDX energy-dispersive X-ray     

In vitro rearing of Edovum puttleri, an egg parasitoid of the Colorado potato beetle – development from egg through the pupal stage

A variety of semi-defined artificial diets were developed and tested for their ability to support the in vitro development of Edovum puttleri. In the most effective diet, 2.6% of E. puttleri pupated. This diet contained high levels of hen egg yolk combined with Manduca sexta larval hemolymph, or with a mixture of M. sexta egg homogenate and larval hemolymph. Egg homogenate alone (without the addition of hemolymph) was not capable of supporting the parasitoid's development. Thus, hemolymph appears to contain unidentified factor(s) important for inducing pupation of the wasp. Addition of M. sexta pupal fat body tissue extract (in place of hemolymph) also promoted pupation of E. puttleri. Gypsy moth (Lymantria dispar) larval hemolymph could not replace M. sexta larval hemolymph. Fractionation irreversibly reduced the growth-promoting effects of M. sexta larval hemolymph. However, the most effective fraction contained components whose molecular weights were 1000 kd. In diets that were devoid of insect materials, the best results were achieved when hen egg yolk, FreAmine, yeast extract, lactalbumin, trehalose, fetal bovine serum and bovine milk were included. This is the first report of an artificial diet for in vitro rearing an eulophid parasitoid from the egg through the pupal stage.     

Dengue virus infection induces broadly cross-reactive human IgM antibodies that recognize intact virions in humanized BLT-NSG mice

The development of small animal models that elicit human immune responses to dengue virus (DENV) is important since prior immunity is a major risk factor for developing severe dengue disease. This study evaluated anti-DENV human antibody (hAb) responses generated from immortalized B cells after DENV-2 infection in NOD-scid IL2rγ^null mice that were co-transplanted with human fetal thymus and liver tissues (BLT-NSG mice). DENV-specific human antibodies predominantly of the IgM isotype were isolated during acute infection and in convalescence. We found that while a few hAbs recognized the envelope protein produced as a soluble recombinant, a number of hAbs only recognized epitopes on intact virions. The majority of the hAbs isolated during acute infection and in immune mice were serotype-cross-reactive and poorly neutralizing. Viral titers in immune BLT-NSG mice were significantly decreased after challenge with a clinical strain of dengue. DENV-specific hAbs generated in BLT-NSG mice share some of the characteristics of Abs isolated in humans with natural infection. Humanized BLT-NSG mice provide an attractive preclinical platform to assess the immunogenicity of candidate dengue vaccines.     

Shigella Effector OspB Activates mTORC1 in a Manner That Depends on IQGAP1 and Promotes Cell Proliferation

The intracellular bacterial pathogen Shigella infects and spreads through the human intestinal epithelium. Effector proteins delivered by Shigella into cells promote infection by modulating diverse host functions. We demonstrate that the effector protein OspB interacts directly with the scaffolding protein IQGAP1, and that the absence of either OspB or IQGAP1 during infection leads to larger areas of S. flexneri spread through cell monolayers. We show that the effect on the area of bacterial spread is due to OspB triggering increased cell proliferation at the periphery of infected foci, thereby replacing some of the cells that die within infected foci and restricting the area of bacterial spread. We demonstrate that OspB enhancement of cell proliferation results from activation of mTORC1, a master regulator of cell growth, and is blocked by the mTORC1-specific inhibitor rapamycin. OspB activation of mTORC1, and its effects on cell proliferation and bacterial spread, depends on IQGAP1. Our results identify OspB as a regulator of mTORC1 and mTORC1-dependent cell proliferation early during S. flexneri infection and establish a role for IQGAP1 in mTORC1 signaling. They also raise the possibility that IQGAP1 serves as a scaffold for the assembly of an OspB-mTORC1 signaling complex.     

Outer Hair Cell Lateral Wall Structure Constrains the Mobility of Plasma Membrane Proteins

Nature’s fastest motors are the cochlear outer hair cells (OHCs). These sensory cells use a membrane protein, Slc26a5 (prestin), to generate mechanical force at high frequencies, which is essential for explaining the exquisite hearing sensitivity of mammalian ears. Previous studies suggest that Slc26a5 continuously diffuses within the membrane, but how can a freely moving motor protein effectively convey forces critical for hearing? To provide direct evidence in OHCs for freely moving Slc26a5 molecules, we created a knockin mouse where Slc26a5 is fused with YFP. These mice and four other strains expressing fluorescently labeled membrane proteins were used to examine their lateral diffusion in the OHC lateral wall. All five proteins showed minimal diffusion, but did move after pharmacological disruption of membrane-associated structures with a cholesterol-depleting agent and salicylate. Thus, our results demonstrate that OHC lateral wall structure constrains the mobility of plasma membrane proteins and that the integrity of such membrane-associated structures are critical for Slc26a5’s active and structural roles. The structural constraint of membrane proteins may exemplify convergent evolution of cellular motors across species. Our findings also suggest a possible mechanism for disorders of cholesterol metabolism with hearing loss such as Niemann-Pick Type C diseases.     

Everything in Moderation - Dietary Diversity and Quality,Central Obesity and Risk of Diabetes

Diet guidelines recommend increasing dietary diversity. Yet, metrics for dietary diversity have neither been well-defined nor evaluated for impact on metabolic health. Also, whether diversity has effects independent of diet quality is unknown. We characterized and evaluated associations of diet diversity and quality with abdominal obesity and type II diabetes (T2D) in the Multi-Ethnic Study of Atherosclerosis. At baseline (2000–02), diet was assessed among 5,160 Whites, Hispanic, Blacks, and Chinese age 45–84 y and free of T2D, using a validated questionnaire. Three different aspects of diet diversity were characterized including count (number of different food items eaten more than once/week, a broad measure of diversity), evenness (Berry index, a measure of the spread of the diversity), and dissimilarity (Jaccard distance, a measure of the diversity of the attributes of the foods consumed). Diet quality was characterized using aHEI, DASH, and a priori pattern. Count and evenness were weakly positively correlated with diet quality (r with AHEI: 0.20, 0.04), while dissimilarity was moderately inversely correlated (r = -0.34). In multivariate models, neither count nor evenness was associated with change in waist circumference (WC) or incident T2D. Greater food dissimilarity was associated with higher gain in WC (p-trend<0.01), with 120% higher gain in participants in the highest quintile of dissimilarity scores. Diet diversity was not associated with incident T2D. Also, none of the diversity metrics were associated with change in WC or incident T2D when restricted to only healthier or less healthy foods. Higher diet quality was associated with lower risk of T2D. Our findings provide little evidence for benefits of diet diversity for either abdominal obesity or diabetes. Greater dissimilarity among foods was actually associated with gain in WC. These results do not support the notion that “eating everything in moderation” leads to greater diet quality or better metabolic health.