Three-dimensional dynamic MR-hysterosalpingography; a new, low invasive, radiation-free and less painful radiological approach to female infertility

BACKGROUND: The purpose of this study was to propose a new method for imaging the uterine cavity and Fallopian tube patency by three-dimensional dynamic magnetic resonance hysterosalpingography (3D dMR-HSG) and to analyse if, by using a higher viscosity contrast solution, direct visualization of the Fallopian tubes may be achieved by this new technique. METHODS: 10 consecutive infertile women underwent 3D dMR-HSG and conventional HSG as gold standard. 3D dMR-HSG consisted of injection of 20 ml of a gadolinium-polyvidone solution into the uterine cavity while acquiring five consecutive three-dimensional (3D) T1-weighted MR-sequences. RESULTS: In three patients the catheter became dislodged during 3D dMR-HSG. However, in one of these patients the examination was still partially diagnostic. Imaging findings of 3D dMR-HSG showed good correlation with conventional hysterosalpingography and allowed 3D imaging of the uterine cavity and of Fallopian tube patency in 8/10 patients and direct visualization of the Fallopian tubes in 5/7 patients. CONCLUSION: 3D dMR-HSG represents a new and promising imaging approach to female infertility causing less pain and avoiding exposure of the ovaries to ionizing radiation. By using a higher viscosity MR-contrast agent it allows not only visualization of uterine cavity and Fallopian tube patency but also direct visualization of Fallopian tube

Workplace experience of radiographers: impact of structural and interpersonal interventions

PURPOSE: Within the framework of organisational development, an assessment of the workplace experience of radiographers (RGs) was conducted. The aims of this study were to develop structural and interpersonal interventions and to prove their effectiveness and feasibility. METHODS: A questionnaire consisting of work-related factors, e.g. time management and communication, and two validated instruments (Workplace Analysis Questionnaire, Effort-Reward Imbalance Scale) was distributed to all RGs (n = 33) at baseline (T1). Interventions were implemented and a follow-up survey (T2) was performed 18 months after the initial assessment. RESULTS: At T1, areas with highest dissatisfaction were communication and time management for ambulant patients (bad/very bad, 57% each). The interventions addressed adaptation of work plans, coaching in developing interpersonal and team leadership skills, and regular team meetings. The follow-up survey (T2) showed significantly improved communication and cooperation within the team and improved qualification opportunities, whereas no significant changes could be identified in time management and in the workplace-related scales 'effort' expended at work and 'reward' received in return for the effort. CONCLUSION: Motivating workplace experience is important for high-level service quality and for attracting well-qualified radiographers to work at a place and to stay in the team for a longer period

Effects of bovine colostrum on performance, survival, and immunoglobulin status of suckling piglets during the first days of life

Supplementation of bovine colostrum (BC) has shown to improve growth performance, intestinal development, and immune response in early-weaned pigs. Little is known about whether BC may have similar effects in neonatal piglets. In the present study, the effect of BC supplementation on mortality, growth performance, and blood parameters (plasma proteins and white blood count) of suckling piglets in the first 10 days of life was investigated under practical conditions with special emphasis on low birth weight piglets. In total, 258 newborn piglets from 30 multiparous sows in a commercial breeding unit were randomly assigned to two different treatment groups. Piglets received either 1 ml of BC orally on days 1-3 of life (group BC, n = 128) or 1 ml of saline (0.9%) (control (CON) group; n = 130). Body weight was measured on days 1, 4, and 10 of life. Blood was collected on days 1 and 4 from 60 piglets per group. No differences in mortality, body weight, and average daily weight gain were observed between treatment groups in days 1-10. However, compared to CON, particularly in low birth weight piglets the administration of BC supported (P < 0.01) their survival. Group BC exhibited lower plasma total protein (P = 0.03) and beta-globulin (P = 0.02) concentrations compared to group CON. In conclusion, BC improved low and normal birth weight piglets' survival during their first 10 days of life. Further research is needed to clarify whether the survival rate is related to earlier gut closure indicated by lower plasma protein levels, which might be beneficial due to a lower uptake of potential antigenic substances

Effects of bovine colostrum on performance, survival, and immunoglobulin status of suckling piglets during the first days of life

Supplementation of bovine colostrum (BC) has shown to improve growth performance, intestinal development, and immune response in early-weaned pigs. Little is known about whether BC may have similar effects in neonatal piglets. In the present study, the effect of BC supplementation on mortality, growth performance, and blood parameters (plasma proteins and white blood count) of suckling piglets in the first 10 days of life was investigated under practical conditions with special emphasis on low birth weight piglets. In total, 258 newborn piglets from 30 multiparous sows in a commercial breeding unit were randomly assigned to two different treatment groups. Piglets received either 1 ml of BC orally on days 1-3 of life (group BC, n = 128) or 1 ml of saline (0.9%) (control (CON) group; n = 130). Body weight was measured on days 1, 4, and 10 of life. Blood was collected on days 1 and 4 from 60 piglets per group. No differences in mortality, body weight, and average daily weight gain were observed between treatment groups in days 1-10. However, compared to CON, particularly in low birth weight piglets the administration of BC supported (P < 0.01) their survival. Group BC exhibited lower plasma total protein (P = 0.03) and beta-globulin (P = 0.02) concentrations compared to group CON. In conclusion, BC improved low and normal birth weight piglets' survival during their first 10 days of life. Further research is needed to clarify whether the survival rate is related to earlier gut closure indicated by lower plasma protein levels, which might be beneficial due to a lower uptake of potential antigenic substances

VgrG and PAAR Proteins Define Distinct Versions of a Functional Type VI Secretion System

The Type VI secretion system (T6SS) is widespread among bacterial pathogens and acts as an effective weapon against competitor bacteria and eukaryotic hosts by delivering toxic effector proteins directly into target cells. The T6SS utilises a bacteriophage-like contractile machinery to expel a puncturing device based on a tube of Hcp topped with a VgrG spike, which can be extended by a final tip from a PAAR domain-containing protein. Effector proteins are believed to be delivered by specifically associating with particular Hcp, VgrG or PAAR proteins, either covalently ('specialised') or non-covalently ('cargo' effectors). Here we used the T6SS of the opportunistic pathogen Serratia marcescens, together with integratecd genetic, proteomic and biochemical approaches, to elucidate the role of specific VgrG and PAAR homologues in T6SS function and effector specificity, revealing new aspects and unexpected subtleties in effector delivery by the T6SS. We identified effectors, both cargo and specialised, absolutely dependent on a particular VgrG for delivery to target cells, and discovered that other cargo effectors can show a preference for a particular VgrG. The presence of at least one PAAR protein was found to be essential for T6SS function, consistent with designation as a 'core' T6SS component. We showed that specific VgrG-PAAR combinations are required to assemble a functional T6SS and that the three distinct VgrG-PAAR assemblies in S. marcescens exhibit distinct effector specificity and efficiency. Unexpectedly, we discovered that two different PAAR-containing Rhs proteins can functionally pair with the same VgrG protein. Showing that accessory EagR proteins are involved in these interactions, native VgrG-Rhs-EagR complexes were isolated and specific interactions between EagR and cognate Rhs proteins identified. This study defines an essential yet flexible role for PAAR proteins in the T6SS and highlights the existence of distinct versions of the machinery with differential effector specificity and efficiency of target cell delivery

Bacteroides muris sp. nov. isolated from the cecum of wild-derived house mice

Two bacterial strains, KH365_2T and KH569_7, were isolated from the cecum contents of wild-derived house mice. The strains were characterized as Gram-negative, rod-shaped, strictly anaerobic, and non-motile. Phylogenetic analysis based on 16S rRNA gene sequences revealed that both strains were most closely related to Bacteroides uniformis ATCC 8492T. Whole genome sequences of KH365_2T and KH569_7 strains have a DNA G + C content of 46.02% and 46.03% mol, respectively. Most morphological and biochemical characteristics did not differ between the newly isolated strains and classified Bacteroides strains. However, the average nucleotide identity (ANI) and dDNA–DNA hybridization (dDDH) values clearly distinguished the two strains from described members of the genus Bacteroides. Here, we present the phylogeny, morphology, and physiology of a novel species of the genus Bacteroides and propose the name Bacteroides muris sp. nov., with KH365_2T (DSM 114231T = CCUG 76277T) as type strain

Constitutive Type VI Secretion System Expression Gives Vibrio cholerae Intra- and Interspecific Competitive Advantages

The type VI secretion system (T6SS) mediates protein translocation across the cell membrane of Gram-negative bacteria, including Vibrio cholerae – the causative agent of cholera. All V. cholerae strains examined to date harbor gene clusters encoding a T6SS. Structural similarity and sequence homology between components of the T6SS and the T4 bacteriophage cell-puncturing device suggest that the T6SS functions as a contractile molecular syringe to inject effector molecules into prokaryotic and eukaryotic target cells. Regulation of the T6SS is critical. A subset of V. cholerae strains, including the clinical O37 serogroup strain V52, express T6SS constitutively. In contrast, pandemic strains impose tight control that can be genetically disrupted: mutations in the quorum sensing gene luxO and the newly described regulator gene tsrA lead to constitutive T6SS expression in the El Tor strain C6706. In this report, we examined environmental V. cholerae isolates from the Rio Grande with regard to T6SS regulation. Rough V. cholerae lacking O-antigen carried a nonsense mutation in the gene encoding the global T6SS regulator VasH and did not display virulent behavior towards Escherichia coli and other environmental bacteria. In contrast, smooth V. cholerae strains engaged constitutively in type VI-mediated secretion and displayed virulence towards prokaryotes (E. coli and other environmental bacteria) and a eukaryote (the social amoeba Dictyostelium discoideum). Furthermore, smooth V. cholerae strains were able to outcompete each other in a T6SS-dependent manner. The work presented here suggests that constitutive T6SS expression provides V. cholerae with an advantage in intraspecific and interspecific competition.Canadian Institutes of Health Research (Operating Grant MOP-84473)Alberta Heritage Foundation for Medical Research (Alberta Innovates-Health Solutions, Endowment Fund)National Institutes of Health (U.S.) (grant MD001091-01)National Institutes of Health (U.S.) (grant GM068855-02)Olegario V. Rana FellowshipAlberta Heritage Foundation for Medical Research (Alberta Innovates-Health Solutions Graduate Studentships

Monitoring physical and psychosocial symptom trajectories in ovarian cancer patients receiving chemotherapy

<p>Abstract</p> <p>Background</p> <p>Diagnosis and treatment of ovarian cancer (OC) entail severe symptom burden and a significant loss of quality of life (QOL). Somatic and psychological impairments may persist well beyond active therapy. Although essential for optimal symptom management as well as for the interpretation of treatment outcomes, knowledge on the course of QOL-related issues is scarce. This study aimed at assessing the course of depressive symptoms, anxiety, fatigue and QOL in patients with OC over the course of chemotherapy until early after-care.</p> <p>Methods</p> <p>23 patients were assessed longitudinally (eight time points) with regard to symptom burden (depression, anxiety, fatigue, and QOL) by means of patient-reported outcome instruments (HADS, MFI-20, EORTC QLQ-C30/-OV28) and clinician ratings (HAMA/D) at each chemotherapy cycle and at the first two aftercare visits.</p> <p>Results</p> <p>Statistically significant decrease over time was found for depressive symptoms and anxiety as well as for all fatigue scales. With regard to QOL, results indicated significant increase for 11 of 15 QOL scales, best for Social (effect size = 1.95; <it>p </it>< 0.001), Emotional (e.s. = 1.62; <it>p </it>< 0.001) and Physical Functioning (e.s. = 1.47; <it>p </it>< 0.001). Abdominal Symptoms (e.s. = 1.01; <it>p </it>= 0.009) decreased, Attitudes towards Disease and Treatment (e.s. = 1.80; <it>p </it>< 0.001) improved significantly over time. Analysis of Sexual Functioning was not possible due to a high percentage of missing responses (61.9%).</p> <p>Conclusions</p> <p>The present study underlines the importance of longitudinal assessment of QOL in order to facilitate the identification of symptom burden in OC patients. We found that patients show high levels of fatigue, anxiety and depressive symptoms and severely impaired QOL post-surgery (i.e. at start of chemotherapy) but condition improves considerably throughout chemotherapy reaching nearly general population symptoms levels until aftercare.</p

A Cyclic-di-AMP Adjuvanted CPAF Protein Vaccine Is Immunogenic in Swine, but It Fails to Reduce Genital Chlamydia trachomatis Burden

Background/Objectives: Chlamydia trachomatis (Ct) is the leading bacterial cause of sexually transmitted infection globally. If undiagnosed or left untreated, these infections can lead to serious complications such as infertility, ectopic pregnancies, and chronic pelvic pain. Despite the high prevalence and potential for serious health complications, no vaccine has been licensed. Pigs offer a valuable biomedical model for chlamydia research: they have an overall high degree of similarity to humans and serve as natural hosts for Chlamydia suis (Cs), a close relative of Ct. Thus, in this study, the pig model was used to evaluate a vaccine candidate against Ct. Methods: The vaccine candidate consists of chlamydial-protease-like activity factor (CPAF) protein adjuvanted with STING (Stimulator of Interferon Genes) pathway agonist cyclic-di-AMP (c-di-AMP). Pigs received two doses intramuscularly followed by two intranasal doses. Each week, the systemic T cell response was assessed via IFN-γ and IL-17 ELISpots, as well as multi-parameter flow cytometry on 0, 14, and 28 days post vaccination (dpv). The humoral immune response was analyzed by measuring CPAF-specific antibody levels and avidity via ELISAs. Results: Vaccination with c-di-AMP adjuvanted CPAF triggered low-level systemic IFN-γ and multifunctional IFN-γ+TNF-α+ CD4 T cell responses. Despite the rather low systemic effector cytokine production, robust anti-CPAF IgG responses were detected in serum, vaginal swab eluates, and oviduct flushes. Genital Ct challenge 42 dpv resulted in only transient infection, precluding a confident assessment of vaccine efficacy of the tested CPAF/c-di-AMP vaccine candidate. However, after challenge, vaccinated pigs exhibited boosted systemic anti-CPAF IFN-γ and mucosal IgG responses compared to unvaccinated pigs. Conclusions: Thus, while vaccine efficacy remains elusive, the CPAF/c-di-AMP vaccine candidate was immunogenic: it elicited a low-level systemic cell-mediated response and robust humoral immune responses. Future studies will incorporate a STING agonist directly conjugated to CPAF as well as addition of other Th1-inducing adjuvants to enhance cellular immunity

Evolution of E. coli in a mouse model of inflammatory bowel disease leads to a disease-specific bacterial genotype and trade-offs with clinical relevance

Objective: Inflammatory bowel disease (IBD) is a persistent inflammatory condition affecting the gastrointestinal tract, presenting significant challenges in its management and treatment. Despite the knowledge that within-host bacterial evolution occurs in the intestine, the disease has so far rarely been studied from an evolutionary perspective. In this study, we aimed to investigate resident bacterial evolution during intestinal inflammation, and whether- and how disease-related bacterial genetic changes may present trade-offs with potential therapeutic importance. Design: Here, we perform an in vivo evolution experiment of E. coli in a gnotobiotic mouse model of IBD, followed by multiomic analyses to identify disease-specific genetic and phenotypic changes in bacteria evolved in an inflamed versus non-inflamed control environment. Results: Our results demonstrate distinct evolutionary changes in E. coli specific to inflammation, including a single nucleotide variant that independently reached high frequency in all inflamed mice. Using ex vivo fitness assays, we find that these changes are associated with a higher fitness in an inflamed environment compared to isolates derived from non-inflamed mice. Further, using large-scale phenotypic assays, we show that bacterial adaptation to inflammation results in clinically relevant phenotypes, which intriguingly include collateral sensitivity towards antibiotics. Conclusions: Bacterial evolution in an inflamed gut yields specific genetic and phenotypic signatures. These results may serve as a basis for developing novel, evolution-informed treatment approaches for patients with intestinal inflammation.<br