Electrocardiographic and echocardiographic evaluation in dogs with hypothyroidism before and after levothyroxine supplementation: A prospective controlled study.

Background: Improvement in cardiac function has been demonstrated after thyroxine treatment in humans with hypothyroidism using the myocardial performance index (MPI). Cardiac changes after thyroxine supplementation are poorly documented in dogs with spontaneous hypothyroidism and comparison with clinically healthy dogs is lacking. Objectives: To evaluate the electrical activity and mechanical function of the heart in dogs with primary hypothyroidism at baseline (T0) and after thyroxine supplementation (T60). Animals: Forty client-owned dogs with hypothyroidism and 20 clinically healthy dogs. Methods: Prospective cohort study. Selected electrocardiographic and echocardiographic variables, including the MPI, were measured in all dogs at T0 and in 30 hypothyroid dogs at T60. Results: Hypothyroid dogs had significantly decreased median or mean heart rate (HR), P wave amplitude, and R wave amplitude (P =.04, P =.002, and P =.003, respectively) and E-point-to-septal separation normalized to body weight (EPSSn) and trans-mitral E wave velocity (E max; P <.001 and P =.025, respectively) at T0 compared to control dogs. At T60, significantly increased median or mean HR, P wave amplitude, fractional shortening, and E max (P <.001, P =.004, P =.002, and P =.009, respectively) and significantly decreased left ventricular end-diastolic volume index, and normalized systolic diameter and EPSSn (P =.03, P =.03, and P =.001, respectively) were found. Conclusions and Clinical Importance: Hypothyroidism in dogs induces mild and reversible changes of electromechanical cardiac function. The MPI does not have clinical importance in identifying cardiac dysfunction in affected dogs

Electrocardiographic and echocardiographic evaluation in dogs with hypothyroidism before and after levothyroxine supplementation: A prospective controlled study

Background: Improvement in cardiac function has been demonstrated after thyroxine treatment in humans with hypothyroidism using the myocardial performance index (MPI). Cardiac changes after thyroxine supplementation are poorly documented in dogs with spontaneous hypothyroidism and comparison with clinically healthy dogs is lacking. Objectives: To evaluate the electrical activity and mechanical function of the heart in dogs with primary hypothyroidism at baseline (T0) and after thyroxine supplementation (T60). Animals: Forty client-owned dogs with hypothyroidism and 20 clinically healthy dogs. Methods: Prospective cohort study. Selected electrocardiographic and echocardiographic variables, including the MPI, were measured in all dogs at T0 and in 30 hypothyroid dogs at T60. Results: Hypothyroid dogs had significantly decreased median or mean heart rate (HR), P wave amplitude, and R wave amplitude (P =.04, P =.002, and P =.003, respectively) and E-point-to-septal separation normalized to body weight (EPSSn) and trans-mitral E wave velocity (E max; P <.001 and P =.025, respectively) at T0 compared to control dogs. At T60, significantly increased median or mean HR, P wave amplitude, fractional shortening, and E max (P <.001, P =.004, P =.002, and P =.009, respectively) and significantly decreased left ventricular end-diastolic volume index, and normalized systolic diameter and EPSSn (P =.03, P =.03, and P =.001, respectively) were found. Conclusions and Clinical Importance: Hypothyroidism in dogs induces mild and reversible changes of electromechanical cardiac function. The MPI does not have clinical importance in identifying cardiac dysfunction in affected dogs

When love hurts : A systematic review on the effects of endometriosis surgical and pharmacological treatments on female sexual functioning

INTRODUCTION: Endometriosis is associated with an increased risk of dyspareunia, therefore this chronic gynaecologic disease should be considered as a major cause of sexual dysfunctions. The aims of this study were to review the literature on the effects of endometriosis surgical and pharmacological treatments on female sexual functioning, and to provide suggestions for future treatment strategies. MATERIAL AND METHODS: We followed the PRISMA guidelines to conduct this systematic review, which involved an electronic database search of studies on the association between endometriosis and sexuality published between 2000 and 2016. RESULTS: As a result of the screening process, 22 studies were included in this systematic review. The 22 studies included were divided in 2 categories: 1) surgical intervention studies (n = 17), examining postoperative sexual outcomes of surgery for endometriosis; 2) pharmacological intervention studies (n = 5), evaluating the effects of pharmacological endometriosis treatments on sexual functioning. The studies considered showed that overall surgical and pharmacological interventions for endometriosis can lead to medium-/long-term improvement, but not necessarily to a definitive resolution of female sexual dysfunctions due to endometriosis. CONCLUSIONS: Sexual functioning is a multidimensional phenomenon and the ideal treatment for endometriosis related sexual dysfunctions should be conducted by a multidisciplinary team that involves not only gynaecologists, but also sexologists and psychologists/psychotherapists. Improving global sexual functioning, and not just reducing pain at intercourse, should be considered as a major clinical goal of endometriosis treatment

Proliferative activity in human breast cancer: Ki-67 automated evaluation and the influence of different Ki-67 equivalent antibodies

<p>Abstract</p> <p>Background</p> <p>Ki67 labeling index (Ki67 LI), the percentage Ki67 immunoreactive cells, is a measure of tumor proliferation, with important clinical relevance in breast cancer, and it is extremely important to standardize its evaluation.</p> <p>Aim</p> <p>To test the efficacy of computer assisted image analysis (CAIA) applied to completely digitized slides and to assess its feasibility in routine practice and compare the results obtained using two different Ki67 monoclonal antibodies.</p> <p>Materials and methods</p> <p>315 consecutive breast cancer routinely immunostained for Ki-67 (223 with SP6 and 92 with MM1 antibodies previously examined by an experienced pathologist, have been re-evaluated using Aperio Scanscope Xs.</p> <p>Results</p> <p>Mean human Ki67 LI values were 36%± 14.% and 28% ± 18% respectively for SP6 and MM1 antibodies; mean CAM Ki67 LI values were 31%± 19% and 22% ± 18% respectively for SP6 and MM1. Human and CAIA evaluation are statistically highly correlated (Pearson: 0.859, p<0.0001), although human LI are systematically higher. An interobserver variation study on CAIA performed on 84 cases showed that the correlation between the two evaluations was linear to an excellent degree.</p> <p>Discussion</p> <p>Our study shows that a) CAIA can be easily adopted in routine practice, b) human and CAIA Ki67 LI are highly correlated, although human LI are systematically higher, c) Ki67 LI using different evaluation methods and different antibodies shows important differences in cut-off values.</p

Impact of endometriosis on obstetric outcome after natural conception: a multicenter Italian study

Purpose To evaluate obstetric outcome in women with endometriosis who conceive naturally and receive standard obstetric care in Italy. Methods Cases were consecutive women with endometriosis managed in eleven Italian referral centers. Controls were women in whom endometriosis was excluded. All women filled in a questionnaire addressing previous natural pregnancies. Marginal logistic regression models were fitted to evaluate the impact of endometriosis on obstetric outcome. A post hoc analysis was performed within the endometriosis group comparing women with severe adenomyosis versus women with absent or mild adenomyosis. Results Three hundred and fifty-five pregnancies in endometriosis group and 741 pregnancies in control group were included. Women with endometriosis had a higher risk of preterm delivery &lt; 34 weeks (6.4% vs 2.8%, OR 2.42, 95% CI 1.22–4.82), preterm delivery &lt; 37 weeks (17.8% vs 9.7%, OR 1.98, 95% CI 1.23–3.19), and neonatal admission to Intensive Care Unit (14.1% vs 7.0%, OR 2.04, 95% CI 1.23–3.36). At post hoc analysis, women with endometriosis and severe adenomyosis had an increased risk of placenta previa (23.1% vs 1.8%, OR 16.68, 95% CI 3.49–79.71), cesarean delivery (84.6% vs 38.9%, OR 8.03, 95% CI 1.69–38.25) and preterm delivery &lt; 34 weeks (23.1% vs 5.7%, OR 5.52, 95% CI 1.38–22.09). Conclusion Women with endometriosis who conceive naturally have increased risk of preterm delivery and neonatal admission to intensive care unit. When severe adenomyosis is coexistent with endometriosis, women may be at increased risk of placenta previa and cesarean delivery. Trial registration Clinical trial registration number: NCT03354793

High Yield Production Process for Shigella Outer Membrane Particles

Gram-negative bacteria naturally shed particles that consist of outer membrane lipids, outer membrane proteins, and soluble periplasmic components. These particles have been proposed for use as vaccines but the yield has been problematic. We developed a high yielding production process of genetically derived outer membrane particles from the human pathogen Shigella sonnei. Yields of approximately 100 milligrams of membrane-associated proteins per liter of fermentation were obtained from cultures of S. sonnei ΔtolR ΔgalU at optical densities of 30–45 in a 5 L fermenter. Proteomic analysis of the purified particles showed the preparation to primarily contain predicted outer membrane and periplasmic proteins. These were highly immunogenic in mice. The production of these outer membrane particles from high density cultivation of bacteria supports the feasibility of scaling up this approach as an affordable manufacturing process. Furthermore, we demonstrate the feasibility of using this process with other genetic manipulations e.g. abolition of O antigen synthesis and modification of the lipopolysaccharide structure in order to modify the immunogenicity or reactogenicity of the particles. This work provides the basis for a large scale manufacturing process of Generalized Modules of Membrane Antigens (GMMA) for production of vaccines from Gram-negative bacteria

Acinetobacter baumannii Secretes Cytotoxic Outer Membrane Protein A via Outer Membrane Vesicles

Acinetobacter baumannii is an important nosocomial pathogen that causes a high morbidity and mortality rate in infected patients, but pathogenic mechanisms of this microorganism regarding the secretion and delivery of virulence factors to host cells have not been characterized. Gram-negative bacteria naturally secrete outer membrane vesicles (OMVs) that play a role in the delivery of virulence factors to host cells. A. baumannii has been shown to secrete OMVs when cultured in vitro, but the role of OMVs in A. baumannii pathogenesis is not well elucidated. In the present study, we evaluated the secretion and delivery of virulence factors of A. baumannii to host cells via the OMVs and assessed the cytotoxic activity of outer membrane protein A (AbOmpA) packaged in the OMVs. A. baumannii ATCC 19606T secreted OMVs during in vivo infection as well as in vitro cultures. Potential virulence factors, including AbOmpA and tissue-degrading enzymes, were associated with A. baumannii OMVs. A. baumannii OMVs interacted with lipid rafts in the plasma membranes and then delivered virulence factors to host cells. The OMVs from A. baumannii ATCC 19606T induced apoptosis of host cells, whereas this effect was not detected in the OMVs from the ΔompA mutant, thereby reflecting AbOmpA-dependent host cell death. The N-terminal region of AbOmpA22-170 was responsible for host cell death. In conclusion, the OMV-mediated delivery of virulence factors to host cells may well contribute to pathogenesis during A. baumannii infection

Allorecognition in the Tasmanian Devil (Sarcophilus harrisii), an Endangered Marsupial Species with Limited Genetic Diversity

Tasmanian devils (Sarcophilus harrisii) are on the verge of extinction due to a transmissible cancer, devil facial tumour disease (DFTD). This tumour is an allograft that is transmitted between individuals without immune recognition of the tumour cells. The mechanism to explain this lack of immune recognition and acceptance is not well understood. It has been hypothesized that lack of genetic diversity at the Major Histocompatibility Complex (MHC) allowed the tumour cells to grow in genetically similar hosts without evoking an immune response to alloantigens. We conducted mixed lymphocyte reactions and skin grafts to measure functional MHC diversity in the Tasmanian devil population. The limited MHC diversity was sufficient to produce measurable mixed lymphocyte reactions. There was a wide range of responses, from low or no reaction to relatively strong responses. The highest responses occurred when lymphocytes from devils from the east of Tasmania were mixed with lymphocytes from devils from the west of Tasmania. All of the five successful skin allografts were rejected within 14 days after surgery, even though little or no MHC I and II mismatches were found. Extensive T-cell infiltration characterised the immune rejection. We conclude that Tasmanian devils are capable of allogeneic rejection. Consequently, a lack of functional allorecognition mechanisms in the devil population does not explain the transmission of a contagious cancer