The relationship between rumination, gender, age, and posttraumatic stress

The purpose of the present study was to assess the relationship between rumination and posttraumatic stress, and to determine the effects of gender and age on that relationship. Responses on brooding and reflective subscales of a rumination measure were compared across adult age groups, and evaluated in relationship to an individual\u27s gender and emotional response to trauma. Women demonstrated higher levels of rumination than men, and younger adults demonstrated higher levels of rumination than older adults. In a college sample, total rumination score was a positive indicator of whether an individual was emotionally bothered by a traumatic experience. In a community sample, age was a negative indicator of whether an individual was emotionally bothered by trauma

Expression of RUNX1 correlates with poor patient prognosis in triple negative breast cancer

The RUNX1 transcription factor is widely recognised for its tumour suppressor effects in leukaemia. Recently a putative link to breast cancer has started to emerge, however the function of RUNX1 in breast cancer is still unknown. To investigate if RUNX1 expression was important to clinical outcome in primary breast tumours a tissue microarray (TMA) containing biopsies from 483 patients with primary operable invasive ductal breast cancer was stained by immunohistochemistry. RUNX1 was associated with progesterone receptor (PR)-positive tumours (P<0.05), more tumour CD4+(P<0.05) and CD8+(P<0.01) T-lymphocytic infiltrate, increased tumour CD138+plasma cell (P<0.01) and more CD68+macrophage infiltrate (P<0.001). RUNX1 expression did not influence outcome of oestrogen receptor (ER)-positive or HER2-positive disease, however on univariate analysis a high RUNX1 protein was significantly associated with poorer cancer-specific survival in patients with ER-negative (P<0.05) and with triple negative (TN) invasive breast cancer (P<0.05). Furthermore, multivariate Cox regression analysis of cancer-specific survival showed a trend towards significance in ER-negative patients (P<0.1) and was significant in triple negative patients (P<0.05). Of relevance, triple negative breast cancer currently lacks good biomarkers and patients with this subtype do not benefit from the option of targeted therapy unlike patients with ER-positive or HER2-positive disease. Using multivariate analysis RUNX1 was identified as an independent prognostic marker in the triple negative subgroup. Overall, our study identifies RUNX1 as a new prognostic indicator correlating with poor prognosis specifically in the triple negative subtype of human breast cancer

Independent evolution of neurotoxin and flagellar genetic loci in proteolytic Clostridium botulinum

<p>Abstract</p> <p>Background</p> <p>Proteolytic <it>Clostridium botulinum </it>is the causative agent of botulism, a severe neuroparalytic illness. Given the severity of botulism, surprisingly little is known of the population structure, biology, phylogeny or evolution of <it>C. botulinum</it>. The recent determination of the genome sequence of <it>C. botulinum </it>has allowed comparative genomic indexing using a DNA microarray.</p> <p>Results</p> <p>Whole genome microarray analysis revealed that 63% of the coding sequences (CDSs) present in reference strain ATCC 3502 were common to all 61 widely-representative strains of proteolytic <it>C. botulinum </it>and the closely related <it>C. sporogenes </it>tested. This indicates a relatively stable genome. There was, however, evidence for recombination and genetic exchange, in particular within the neurotoxin gene and cluster (including transfer of neurotoxin genes to <it>C. sporogenes</it>), and the flagellar glycosylation island (FGI). These two loci appear to have evolved independently from each other, and from the remainder of the genetic complement. A number of strains were atypical; for example, while 10 out of 14 strains that formed type A1 toxin gave almost identical profiles in whole genome, neurotoxin cluster and FGI analyses, the other four strains showed divergent properties. Furthermore, a new neurotoxin sub-type (A5) has been discovered in strains from heroin-associated wound botulism cases. For the first time, differences in glycosylation profiles of the flagella could be linked to differences in the gene content of the FGI.</p> <p>Conclusion</p> <p>Proteolytic <it>C. botulinum </it>has a stable genome backbone containing specific regions of genetic heterogeneity. These include the neurotoxin gene cluster and the FGI, each having evolved independently of each other and the remainder of the genetic complement. Analysis of these genetic components provides a high degree of discrimination of strains of proteolytic <it>C. botulinum</it>, and is suitable for clinical and forensic investigations of botulism outbreaks.</p

New developments in canine hepatozoonosis in North America: a review

Canine hepatozoonosis is caused by Hepatozoon canis and Hepatozoon americanum, apicomplexan parasites transmitted to dogs by ingestion of infectious stages. Although the two agents are phylogenetically related, specific aspects, including characteristics of clinical disease and the natural history of the parasites themselves, differ between the two species. Until recently, H. canis infections had not been clearly documented in North America, and autochthonous infection with H. americanum has yet to be reported outside of the southern United States. However, recent reports demonstrate H. canis is present in areas of North America where its vector tick, Rhipicephalus sanguineus, has long been endemic, and that the range of H. americanum is likely expanding along with that of its vector tick, Amblyomma maculatum; co-infections with the two organisms have also been identified. Significant intraspecific variation has been reported in the 18S rRNA gene sequence of both Hepatozoon spp.-infecting dogs, suggesting that each species may represent a complex of related genogroups rather than well-defined species. Transmission of H. americanum to dogs via ingestion of cystozoites in muscle of infected vertebrates was recently demonstrated, supporting the concept of predation as a means of natural transmission. Although several exciting advances have occurred in recent years, much remains to be learned about patterns of infection and the nature of clinical disease caused by the agents of canine hepatozoonosis in North America

Bidirectional associations between body dissatisfaction and depressive symptoms from adolescence through early adulthood

Body dissatisfaction and depressive symptoms are commonly experienced during adolescence and increase the risk of adverse health outcomes, especially eating disorders. However, the dominant temporal associations between these two experiences (i.e., whether one is a risk factor for the other or the two are mutually reinforcing) has yet to be fully explored. We examined the associations between body dissatisfaction and depressive symptoms assessed at baseline and 5- and 10-year follow-up in younger (M age = 12.9 years at baseline, 56% female, n = 577) and older (M age = 15.9 years at baseline, 57% female, n = 1,325) adolescent cohorts assessed as part of Project Eating Among Teens and Young Adults. Associations between body dissatisfaction and depressive symptoms were examined using cross-lagged models. For females, the dominant directionality was for body dissatisfaction predicting later depressive symptoms. For males, the picture was more complex, with developmentally sensitive associations in which depressive symptoms predicted later body dissatisfaction in early adolescence and early adulthood, but the reverse association was dominant during middle adolescence. These findings suggest that interventions should be tailored to dynamic risk profiles that shift over adolescence and early adulthood, and that targeting body dissatisfaction at key periods during development may have downstream impacts on depressive symptoms

Segregation and preterm birth: The effects of neighborhood racial composition in North Carolina

Epidemiologic research suggests that racial segregation is associated with poor health among blacks in the United States (US). We used geocoded birth records and US census data to investigate whether neighborhood-level percent black is associated with preterm birth (PTB) for black and white women in two counties in the southern US, whether area-level deprivation modifies this association, and whether the association is influenced by the choice of geographic unit used to approximate a neighborhood. A 20%-point increase in tract-level percent black was found to be associated with increased PTB odds in white (OR=1.09, 95% CI: 1.01, 1.18) and black (OR=1.05, 95% CI: 0.99, 1.11) women. These small associations were similar to those observed in other US regions. Effects were robust to choice of neighborhood proxy and were not modified by area-level deprivation

Expression capable library for studies of Neisseria gonorrhoeae, version 1.0

Background The sexually transmitted disease, gonorrhea, is a serious health problem in developed as well as in developing countries, for which treatment continues to be a challenge. The recent completion of the genome sequence of the causative agent, Neisseria gonorrhoeae, opens up an entirely new set of approaches for studying this organism and the diseases it causes. Here, we describe the initial phases of the construction of an expression-capable clone set representing the protein-coding ORFs of the gonococcal genome using a recombination-based cloning system. Results The clone set thus far includes 1672 of the 2250 predicted ORFs of the N. gonorrhoeae genome, of which 1393 (83%) are sequence-validated. Included in this set are 48 of the 61 ORFs of the gonococcal genetic island of strain MS11, not present in the sequenced genome of strain FA1090. L-arabinose-inducible glutathione-S-transferase (GST)-fusions were constructed from random clones and each was shown to express a fusion protein of the predicted size following induction, demonstrating the use of the recombination cloning system. PCR amplicons of each ORF used in the cloning reactions were spotted onto glass slides to produce DNA microarrays representing 2035 genes of the gonococcal genome. Pilot experiments indicate that these arrays are suitable for the analysis of global gene expression in gonococci. Conclusion This archived set of Gateway® entry clones will facilitate high-throughput genomic and proteomic studies of gonococcal genes using a variety of expression and analysis systems. In addition, the DNA arrays produced will allow us to generate gene expression profiles of gonococci grown in a wide variety of conditions. Together, the resources produced in this work will facilitate experiments to dissect the molecular mechanisms of gonococcal pathogenesis on a global scale, and ultimately lead to the determination of the functions of unknown genes in the genome

Autoimmune disease and risk of postpartum venous thromboembolism

Background - The risk of pregnancy-related mortality in the United States has nearly doubled since 1990, with venous thromboembolism (VTE) accounting for approximately 10% of these deaths. Objectives - The objective of this study was to assess whether preexisting autoimmune disease is a risk factor for postpartum VTE. Methods - Using the MarketScan Commercial and Medicare Supplemental administrative databases, a retrospective cohort study analyzed whether postpartum persons with autoimmune disease had a higher risk of postpartum VTE incidence than postpartum persons without autoimmune disease. Using International Classification of Diseases codes, we identified 757,303 individuals of childbearing age who had a valid delivery date with at least 12 weeks of follow-up. Results - Individuals were, on average, 30.7 years old (SD, 5.4), and 3.7% (N = 27,997 of 757,303) of them had evidence of preexisting autoimmune disease. In covariate-adjusted models, postpartum persons with preexisting autoimmune disease had higher rates of postpartum VTE than postpartum persons without autoimmune disease (hazard ratio [HR], 1.33; 95% CI, 1.07-1.64). When analyzed by individual autoimmune disease, those with systemic lupus erythematosus (HR, 2.49; 95% CI, 1.47-4.21) and Crohn’s disease (HR, 2.49; 95% CI, 1.34-4.64) were at an elevated risk of postpartum VTE compared with those without autoimmune disease. Conclusion - Autoimmune disease was associated with a higher rate of postpartum VTE, with evidence that the association was most pronounced among individuals with systemic lupus erythematosus and Crohn’s disease. These findings suggest that postpartum persons of childbearing age with autoimmune disease may require more monitoring and prophylactic care after delivery to prevent potentially fatal VTE events

Mitotic stress is an integral part of the oncogene-induced senescence program that promotes multinucleation and cell cycle arrest

Oncogene-induced senescence (OIS) is a tumor suppression mechanism that blocks cell proliferation in response to oncogenic signaling. OIS is frequently accompanied by multinucleation; however, the origin of this is unknown. Here, we show that multinucleate OIS cells originate mostly from failed mitosis. Prior to senescence, mutant H-RasV12 activation in primary human fibroblasts compromised mitosis, concordant with abnormal expression of mitotic genes functionally linked to the observed mitotic spindle and chromatin defects. Simultaneously, H-RasV12 activation enhanced survival of cells with damaged mitoses, culminating in extended mitotic arrest and aberrant exit from mitosis via mitotic slippage. ERK-dependent transcriptional upregulation of Mcl1 was, at least in part, responsible for enhanced survival and slippage of cells with mitotic defects. Importantly, mitotic slippage and oncogene signaling cooperatively induced senescence and key senescence effectors p21 and p16. In summary, activated Ras coordinately triggers mitotic disruption and enhanced cell survival to promote formation of multinucleate senescent cells