Something has Fallen: Pelvic Organ Prolapse or Vaginal Cuff Dehiscence and Evisceration? A Case Report.

SOMETHING HAS FALLEN: PELVIC ORGAN PROLAPSE OR VAGINAL CUFF DEHISCENCE AND EVISCERATION? A CASE REPORT.Learning Objectives: 1) Recognize late presenting complications of hysterectomy. 2) Include vaginal cuff dehiscence with evisceration (VCDE) in the differential diagnosis of women suspected of having acute pelvic organ prolapse (POP).3) Appreciate the relative rarity of VCDE in younger women.Case Summary: A 36 year old G0P0 female presented to the ED with a chief complaint of sudden onset excruciating epigastric pain, followed by diarrhea and visible vaginal bulge. Pertinent past medical and surgical history includes breast cancer diagnosed 15 months prior, status post bilateral mastectomy, radiation, chemotherapy, and robotic-assisted prophylactic hysterectomy and BSO 6 months prior. Relevant social history includes tobacco use and first postoperative coitus 2 days prior. CT abdomen/pelvis findings included microscopic pneumoperitoneum, pelvic organ prolapse, prolapse of bowel loops into the vaginal vault, and localized small bowel obstruction. In the ED she was diagnosed with POP, which was reduced, leading to a reduction in her pain. Subsequent examination revealed an abdomen tender to palpation. Speculum exam displayed no pelvic organ prolapse. Bowel was visible at the vaginal cuff with clear yellow fluid pooling in the vaginal vault. Vesicovaginal fistula was ruled out and VCDE was suspected. During exploratory laparoscopy, a 4 cm vaginal cuff defect was found and transvaginal cuff closure was performed. Post-operative course was uncomplicated, and the patient was discharged on POD #2

Expanding Paramedicine in the Community (EPIC): study protocol for a randomized controlled trial.

BackgroundThe incidence of chronic diseases, including diabetes mellitus (DM), heart failure (HF) and chronic obstructive pulmonary disease (COPD) is on the rise. The existing health care system must evolve to meet the growing needs of patients with these chronic diseases and reduce the strain on both acute care and hospital-based health care resources. Paramedics are an allied health care resource consisting of highly-trained practitioners who are comfortable working independently and in collaboration with other resources in the out-of-hospital setting. Expanding the paramedic's scope of practice to include community-based care may decrease the utilization of acute care and hospital-based health care resources by patients with chronic disease.Methods/designThis will be a pragmatic, randomized controlled trial comparing a community paramedic intervention to standard of care for patients with one of three chronic diseases. The objective of the trial is to determine whether community paramedics conducting regular home visits, including health assessments and evidence-based treatments, in partnership with primary care physicians and other community based resources, will decrease the rate of hospitalization and emergency department use for patients with DM, HF and COPD. The primary outcome measure will be the rate of hospitalization at one year. Secondary outcomes will include measures of health system utilization, overall health status, and cost-effectiveness of the intervention over the same time period. Outcome measures will be assessed using both Poisson regression and negative binomial regression analyses to assess the primary outcome.DiscussionThe results of this study will be used to inform decisions around the implementation of community paramedic programs. If successful in preventing hospitalizations, it has the ability to be scaled up to other regions, both nationally and internationally. The methods described in this paper will serve as a basis for future work related to this study.Trial registrationClinicalTrials.gov: NCT02034045. Date: 9 January 2014

Endosomal trafficking inhibitor EGA can control TLR7-mediated IFNα expression by human plasmacytoid dendritic cells

Plasmacytoid dendritic cells (pDC) are the major producer of type 1 IFN in response to TLR7 agonists. Aberrant TLR7 activation and type 1 IFN expression by pDCs are linked to the pathogenesis of certain types of autoimmune diseases, including systemic lupus erythematosus (SLE). This study investigated the underlying mechanisms for TLR7-mediated cytokine expression by pDCs using a late endosome trafficking inhibitor, EGA (4-bromobenzaldehyde N-(2,6-dimethylphenyl) semicarbazone). We found that EGA treatment decreased IFNα expression by pDCs stimulated with imiquimod (R837), single-stranded RNA40, and influenza virus. EGA also decreased TNFα expression and secretion by R837-stimulated pDCs. Mechanistically, EGA treatment decreased phosphorylation of IKKα/β, STAT1, and p38, and prolonged degradation of IκBα. Furthermore, EGA treatment decreased the colocalization of 3F, a substituted adenine TLR7 agonist, with LAMP1+ compartments in pDCs. EGA was also capable of diminishing IFNα expression by SLE pDCs treated with R837 or live PR8/A/34 influenza viruses. Therefore, we concluded that trafficking of TLR7 agonists to LAMP1+ compartments is important for IFNα expression by pDCs. Data from this study support additional examinations of the potential benefits of EGA in treating type 1 IFN-associated inflammatory diseases in the future

Genetic basis of the very short life cycle of ‘Apogee’ wheat

Background: ‘Apogee’ has a very short life cycle among wheat cultivars (flowering 25 days after planting under a long day and without vernalization), and it is a unique genetic material that can be used to accelerate cycling breeding lines. However, little is known about the genetic basis of the super-short life of Apogee wheat. Results: In this study, Apogee was crossed with a strong winter wheat cultivar ‘Overland’, and 858 F2 plants were generated and tested in a greenhouse under constant warm temperature and long days. Apogee wheat was found to have the early alleles for four flowering time genes, which were ranked in the order of vrn-A1 \u3e VRN-B1 \u3e vrn- D3 \u3e PPD-D1 according to their effect intensity. All these Apogee alleles for early flowering showed complete or partial dominance effects in the F2 population. Surprisingly, Apogee was found to have the same alleles at vrn-A1a and vrn-D3a for early flowering as observed in winter wheat cultivar ‘Jagger.’ It was also found that the vrn-A1a gene was epistatic to VRN-B1 and vrn-D3. The dominant vrn-D3a alone was not sufficient to cause the transition from vegetative to reproductive development in winter plants without vernalization but was able to accelerate flowering in those plants that carry the vrn-A1a or Vrn-B1 alleles. The genetic effects of the vernalization and photoperiod genes were validated in Apogee x Overland F3 populations. Conclusion: VRN-A1, VRN-B1, VRN-D3, and PPD-D1 are the major genes that enabled Apogee to produce the very short life cycle. This study greatly advanced the molecular understanding of the multiple flowering genes under different genetic backgrounds and provided useful molecular tools that can be used to accelerate winter wheat breeding schemes

Genetic and environmental effects on crop development determining adaptation and yield

Slafer, Gustavo Ariel. ICREA - AGROTECNIO - Spain.Kantolic, Adriana Graciela. Universidad de Buenos Aires. Facultad de Agronomía. Buenos Aires, Argentina.Appendino, María Laura. Universidad de Buenos Aires. Facultad de Agronomía. Buenos Aires, Argentina.Tranquilli, Gabriela Edith. Instituto Nacional de Tecnología Agropecuaria (INTA). Recursos Naturales. Instituto de Recursos Biológicos. Buenos Aires, Argentina.Miralles, Daniel Julio. Universidad de Buenos Aires. Facultad de Agronomía. Buenos Aires, Argentina.Savin, Roxana. ICREA - AGROTECNIO - Spain.Crop development is a sequence of phenological events controlled by the genetic background and influenced by external factors, which determines changes in the morphology and/or function of organs (Landsberg, 1977). Although development is a continuous process, the ontogeny of a crop is frequently divided into discrete periods, for instance ‘vegetative’, ‘reproductive’ and ‘grain - filling’ phases (Slafer, 2012). Patterns of phenological development largely determine the adaptation of a crop to a certain range of environments. For example, genetic improvement in grain yield of wheat has been associated with shorter time from sowing to anthesis in Mediterranean environments of western Australia (Siddique et al., 1989), whereas no consistent trends in phenology were found where drought is present but not necessarily terminal, including environments of Argentina, Canada and the USA (Slafer and Andrade, 1989, 1993; Slafer et al., 1994a) (Fig. 12.1). Even in agricultural lands of the Mediterranean Basin where wheat has been grown for many centuries, breeding during the last century did not clearly change phenological patterns (Acreche et al., 2008). This chapter focuses on two major morphologically and hysiologically contrasting grain crops: wheat and soybean. For both species, we have an advanced understanding of development and physiology in general. Wheat is a determinate, long-day grass of temperate origin, which is responsive to vernalization. Soybean is a typically indeterminate (but with determinate intermediate variants), short-day grain legume of tropical origin, which is insensitive to vernalization. Comparisons with other species are used to highlight the similarities and differences. The aims of this chapter are to outline the developmental characteristics of grain crops and the links between phenology and yield, to revise the mechanisms of environmental and genetic control of development and to explore the possibilities of improving crop adaptation and yield potential through the fine-tuning of developmental patterns

A genome-wide association study of marginal zone lymphoma shows association to the HLA region

Marginal zone lymphoma (MZL) is the third most common subtype of B-cell non-Hodgkin lymphoma. Here we perform a two-stage GWAS of 1,281 MZL cases and 7,127 controls of European ancestry and identify two independent loci near BTNL2 (rs9461741, P - 3.95 x 10(-15)) and HLA-B (rs2922994, P - 2.43 x 10(-9)) in the HLA region significantly associated with MZL risk. This is the first evidence that genetic variation in the major histocompatibility complex influences MZL susceptibility

Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes

Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the number of telomere length-associated variant alleles an individual carries with the published change in kb of telomere length. The analysis of the telomere length GRS resulted in an association between longer telomere length and increased NHL risk [four B-cell histologic types combined; odds ratio (OR) = 1.49, 95% CI 1.22–1.82, P-value = 8.5 × 10−5]. Subtype-specific analyses indicated that chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) was the principal NHL subtype contributing to this association (OR = 2.60, 95% CI 1.93–3.51, P-value = 4.0 × 10−10). Significant interactions were observed across strata of sex for CLL/SLL and marginal zone lymphoma subtypes as well as age for the follicular lymphoma subtype. Our results indicate that a genetic background that favors longer telomere length may increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk