Adult care providers' perspectives on the transition to adult care for emerging adults with Type 1 diabetes: a cross-sectional survey.

AIMS: To assess adult diabetes care providers' current transition practices, knowledge about transition care, and perceived barriers to implementation of best practices in transition care for emerging adults with Type 1 diabetes mellitus. METHODS: We administered a 38-item web-based survey to adult diabetes care providers identified through the Québec Endocrinologist Medical Association and Diabetes Québec. RESULTS: Fifty-three physicians responded (35%). Fewer than half of all respondents (46%) were familiar with the American Diabetes Association's transition care position statement. Approximately one-third of respondents reported a gap of >6 months between paediatric and adult diabetes care. Most (83%) believed communication with the paediatric team was adequate; however, only 56% reported receiving a medical summary and 2% a psychosocial summary from the paediatric provider. Respondents believed that the paediatric team should improve emerging adults' preparation for transition care by developing their self-management skills and improve teaching about the differences between paediatric and adult-oriented care. Only 31% had a system for identifying emerging adults lost to follow-up in adult care. Perceived barriers included difficulty accessing psychosocial services, emerging adults' lack of motivation, and inadequate transition preparation. Most (87%) were interested in having additional resources, including a self-care management tool and a registry to track those lost to follow-up. CONCLUSIONS: Our findings highlight the need to better engage adult care providers into transition care practices. Despite adult physicians' interest in transition care, implementation of transition care recommendations and resources in clinical care remains limited. Enhanced efforts are needed to improve access to mental health services within the adult healthcare setting.

[Multicentric evaluation of a self-screening questionnaire for occupational bladder cancer]. / Évaluation multicentrique d'un auto-questionnaire de dépistage des cancers de vessie d'origine professionnelle.

OBJECTIVE: Evaluate a self-screening questionnaire for bladder cancer of occupational origin and analyse an influence of exposure to a carcinogen bladder tumor on prognosis. PATIENTS AND METHODS: Five hundred and thirty-one patients followed, between 2005 and 2010, for bladder cancer in two university centers have received a self-screening questionnaire derived from questionnaire KVP 08. Patients who responded positively to at least one of the items were considered to have a self-screening questionnaire "positive". Patients were finally invited to take an appointment for consultation in occupational pathology. RESULTS: The response rate to self-screening questionnaire was 39.9% (212/531). It was "positive" in 82 cases (38.7%). Among the 82 patients with a self-screening questionnaire "positive", 46 patients consulted in occupational pathology (56%). Occupational exposure to a bladder carcinogen was documented in 91.3% of cases. Among the 22 patients who consulted in occupational pathology with a self-screening questionnaire "negative", an occupational exposure to a bladder carcinogen was documented in 13.6% of cases. The sensibility of the self-screening questionnaire was 91.3%, the specificity 86.4% and the accuracy 89.7%. The relative risk to have an occupational exposure if the self-screening questionnaire was "positive" was 6.69. The analysis of groups "positive" versus "negative" does not reveal any statistically significant difference in terms of tumor aggressiveness and disease-free survival. CONCLUSION: The self-screening questionnaire was considered relevant with good reliability for detection of occupational exposure to a bladder carcinogen.

[Prostatic Stromal Tumors of Uncertain Malignant Potential (STUMP): definition, pathology, prognosis and management]. / Tumeur stromale prostatique à potentiel malin incertain (STUMP) : définition, anatomopathologie, pronostic et prise en charge.

Prostatic Stromal Tumors of Uncertain Malignant Potential (STUMP) are rare tumor of the prostate of mesenchymal origin, accounting, with sarcoma for 0.1-0.2% of all malignant prostatic tumours. They however require to be individualized, to differentiate it from a benign prostatic hyperplasia or a sarcoma of the prostate. The therapeutic management should be made keeping in mind the risk of degeneration towards a malignant shape. Although the appropriate treatment is unknown, radical prostatectomy seem to be the treatment of reference, especially for young patient or for extensive lesion.

Developing a model of a patient-group pathway to accessing cancer clinical trials in Canada.

Background: Colorectal Cancer Canada, in partnership with a Scientific Advisory Committee, is developing a Canadian Patient Group Pathway to Accessing Cancer Clinical Trials ("Pathway"). A central element of the Pathway is presented here-namely, a set of recommendations and tools aimed at each stakeholder group. Methods: A summary of the peer-reviewed and grey literature informed discussions at a meeting, held in June 2017, in which a cross-section of stakeholders reached consensus on the potential roles of patient groups in the cancer clinical trials process, barriers to accessing cancer clinical trials, best practice models for patient-group integration, and a process for developing the Pathway. Canadian recommendations and tools were subsequently developed by a small working group and reviewed by the Scientific Advisory Committee. Results: The major output of the consensus conference was agreement that the Clinical Trials Transformation Initiative (ctti) model, successfully applied in the United States, could be adapted to create a Canadian Pathway. Two main differences between the Canadian and American cancer clinical research environments were highlighted: the effects of global decision-making and systems of regulatory and funding approvals. The working group modified the ctti model to incorporate those aspects and to reflect Canadian stakeholder organizations and how they currently interact with patient groups. Conclusions: Developing and implementing a Canadian Pathway that incorporates the concepts of multi-stakeholder collaboration and the inclusion of patient groups as equal partners is expected to generate significant benefits for all stakeholders. The next steps to bring forward a proposed Pathway will involve engaging the broader cancer research community. Clinical trial sponsors will be encouraged to adopt a Charter recognizing the importance of including patient groups, and to support the training of patient groups through an independent body to ensure quality research partners. Integration of patient groups into the process of developing "real world" evidence will be advanced by a further consensus meeting being organized by Colorectal Cancer Canada for 6-7 November 2018.

Effect of equilibration time on the motility and functional integrity of canine spermatozoa frozen in three different extenders.

The present work aimed to assess the effect of equilibration time on post-thaw motility parameters of canine sperm frozen in three extenders: 6% low-density lipoproteins (LDL), 6% liposomes (LIPO), and 40% egg yolk plasma (EYP). A second experiment is aimed at evaluating the functional integrity of canine spermatozoa frozen in the three extenders at the best equilibration time found in the experiment one. In the first experiment, 20 ejaculates harvested from 7 dogs, were frozen in three extenders (LDL, LIPO, and EYP) after four equilibration times (30min, 1h, 3h, and 6h). The semen was evaluated after thawing using an image analyser (HT-IVOS 14.0). The 6h equilibration time gave better results of motility and progressive motility in the three studied extenders. (LDL: 58.9% vs. 42.7%; LIPO: 54.4% vs. 31.9%; EYP: 55.4% vs 40.5% for motility 6 vs. 1h). In the second experiment, 10 ejaculates taken from 6 dogs were frozen under the same conditions as the previous experiment, after 6h equilibration time. The integrity parameters of the spermatozoal membrane (hypo-osmotic swelling test, and SYBR14/propidium Iodide staining), acrosome (FITC-Pisium sativum Aglutinin staining), and DNA (acridine orange staining) were evaluated at three different stages: post-dilution (T0), post-equilibration, and post-thawing. Post-thaw results were as follows: membrane integrity (HOSt: 62;6% vs 58% vs 64.4%; SYBR14/IP: 63.6% vs 57.9% vs 64.8%); acrosome integrity (FITC-PSA: 79.4% vs 74% vs 76.2%) and DNA integrity (Acridine-orange: 98.9% vs 98.5% vs 98.7%) respectively for LDL vs. LIPO vs. EYP. No significant difference existed between the extenders tested; thus 6%LIPO and 40%EYP could be good candidates for replacement of 6%LDL in the protection of canine sperm during the freeze-thaw process without altering motility and integrity parameters.

Can Chlamydia abortus be transmitted by embryo transfer in goats?

The objectives of this study were to determine (i) whether Chlamydia abortus would adhere to or penetrate the intact zona pellucida (ZP-intact) of early in vivo-derived caprine embryos, after in vitro infection; and (ii) the efficacy of the International Embryo Transfer Society (IETS) washing protocol for bovine embryos. Fifty-two ZP-intact embryos (8-16 cells), obtained from 14 donors were used in this experiment. The embryos were randomly divided into 12 batches. Nine batches (ZP-intact) of five embryos were incubated in a medium containing 4 × 10(7)Chlamydia/mL of AB7 strain. After incubation for 18 hours at 37 °C in an atmosphere of 5% CO2, the embryos were washed in batches in 10 successive baths of a phosphate buffer saline and 5% fetal calf serum solution in accordance with IETS guidelines. In parallel, three batches of ZP-intact embryos were used as controls by being subjected to similar procedures but without exposure to C. abortus. The 10 wash baths were collected separately and centrifuged for 1 hour at 13,000 × g. The washed embryos and the pellets of the 10 centrifuged wash baths were frozen at -20 °C before examination for evidence of C. abortus using polymerase chain reaction. C. abortus DNA was found in all of the infected batches of ZP-intact embryos (9/9) after 10 successive washes. It was also detected in the 10th wash fluid for seven batches of embryos, whereas for the two other batches, the last positive wash bath was the eighth and the ninth, respectively. In contrast, none of the embryos or their washing fluids in the control batches were DNA positive. These results report that C. abortus adheres to and/or penetrates the ZP of in vivo caprine embryos after in vitro infection, and that the standard washing protocol recommended by the IETS for bovine embryos, failed to remove it. The persistence of these bacteria after washing makes the embryo a potential means of transmission of the bacterium during embryo transfer from infected donor goats to healthy recipients and/or their offspring. Nevertheless, the detection of C. abortus DNA by polymerase chain reaction does not prove that the bacteria found was infectious. Further studies are required to investigate whether enzymatic and/or antibiotic treatment of caprine embryos infected by C. abortus would eliminate the bacteria from the ZP.

Direct regulatory effect of fatty acids on macrophage lipoprotein lipase: potential role of PPARs.

Atherosclerosis is a major complication of type 2 diabetes. The pathogenesis of this complication is poorly understood, but it clearly involves production in the vascular wall of macrophage (Mo) lipoprotein lipase (LPL). Mo LPL is increased in human diabetes. Peripheral factors dysregulated in diabetes, including glucose and free fatty acids (FAs), may contribute to this alteration. We previously reported that high glucose stimulates LPL production in both J774 murine and human Mo. In the present study, we evaluated the direct effect of FAs on murine Mo LPL expression and examined the involvement of peroxisome proliferator-activated receptors (PPARs) in this effect. J774 Mo were cultured for 24 h with 0.2 mmol/l unsaturated FAs (arachidonic [AA], eicosapentaenoic [EPA], and linoleic acids [LA]) and monounsaturated (oleic acid [OA]) and saturated FAs (palmitic acid [PA] and stearic acid [SA]) bound to 2% bovine serum albumin. At the end of this incubation period, Mo LPL mRNA expression, immunoreactive mass, activity, and synthetic rate were measured. Incubation of J774 cells with LA, PA, and SA significantly increased Mo LPL mRNA expression. In contrast, exposure of these cells to AA and EPA dramatically decreased this parameter. All FAs, with the exception of EPA and OA, increased extra- and intracellular LPL immunoreactive mass and activity. Intracellular LPL mass and activity paralleled extracellular LPL mass and activity in all FA-treated cells. In Mo exposed to AA, LA, and PA, an increase in Mo LPL synthetic rate was observed. To evaluate the role of PPARs in the modulatory effect of FAs on Mo LPL gene expression, DNA binding assays were performed. Results of these experiments demonstrate an enhanced binding of nuclear proteins extracted from all FA-treated Mo to the peroxisome proliferator-response element (PPRE) consensus sequence of the LPL promoter. PA-, SA-, and OA-stimulated binding activity was effectively diminished by immunoprecipitation of the nuclear proteins with anti-PPAR-alpha antibodies. In contrast, anti-PPAR-gamma antibodies only significantly decreased AA-induced binding activity. Overall, these results provide the first evidence for a direct regulatory effect of FAs on Mo LPL and suggest a potential role of PPARs in the regulation of Mo LPL gene expression by FAs.

In vitro bovine embryo production in a synthetic medium: embryo development, cryosurvival, and establishment of pregnancy.

The aim of this study was to develop an in vitro embryo culture medium without either fetal calf serum or BSA, using various growth factors and cytokines (GFs-CYKs; IGF-I, IGF-II, bFGF, LIF, GM-CSF, TGF-ß1, and PDGF-BB), and other molecules with surfactant and embryotrophic properties, such as recombinant albumin (RA) and hyaluronan (HA). The first part of the study was dedicated to define the best combination of GFs-CYKs + RA + HA for optimal embryonic development. Next, we compared development rates and embryo quality (inner cell mass [ICM]-to-total cell number [TCN] ratio), and postthaw survival and hatching rates using this synthetic medium (T1) and a control medium: synthetic oviduct fluid + BSA + ITS (insulin, transferrin, and selenium). The blastocyst rates were significantly higher with T1 than those with the control at 7 and 8 days after fertilization. There was no significant difference in TCN or the ICM/TCN ratio between the two treatments. Survival and hatching rates 48 hours after thawing were similar for both treatments. Finally, nine embryo transfers were conducted using fresh and previously frozen Day-7 blastocysts to evaluate the in vivo viability of embryos produced in this synthetic medium; four gestations were obtained from six fresh embryos and one gestation from three frozen embryos. In conclusion, the fetal calf serum and BSA-free medium, supplemented with GFs-CYKs + RA + HA, improved embryo development and gave comparable ICM/TCN ratios and postthaw survival rates to the control with BSA. Fresh and frozen embryos produced in this medium are viable for embryo transfer. This fully synthetic method of embryo culture is a useful means of reducing the risk of disease transmission via embryo transfer.

Suppression of Toll-like receptor-mediated innate immune responses at the ocular surface by the membrane-associated mucins MUC1 and MUC16.

Membrane-associated mucins (MAMs) expressed on the ocular surface epithelium form a dense glycocalyx that is hypothesized to protect the cornea and conjunctiva from external insult. In this study, the hypothesis that the MAMs MUC1 and MUC16, expressed on the apical surface of the corneal epithelium, suppress Toll-like receptor (TLR)-mediated innate immune responses was tested. Using an in vitro model of corneal epithelial cells that are cultured to express MAMs, we show that reduced expression of either MUC1 or MUC16 correlates with increased message and secreted protein levels of the proinflammatory cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) following exposure of cells to the TLR2 and TLR5 agonists, heat-killed Listeria monocytogenes and flagellin, respectively. As mice express Muc1 (but not Muc16) in the corneal epithelium, a Muc1(-/-) mouse model was used to extend in vitro findings. Indeed, IL-6 and TNF-α message levels were increased in the corneal epithelium of Muc1(-/-) mice, in comparison with wild-type mice, following exposure of enucleated eyes to the TLR2 and TLR5 agonists. Our results suggest that the MAMs MUC1 and MUC16 contribute to the maintenance of immune homeostasis at the ocular surface by limiting TLR-mediated innate immune responses.

The Amount of MUC5B mucin in cervical mucus peaks at midcycle.

The physical character and amount of mucus secreted by the endocervix changes dramatically during the menstrual cycle to facilitate sperm migration at the time of midcycle ovulation. Mucins are highly glycosylated, high-molecular-weight proteins, which are the major structural components of the protective mucus gel covering all wet-surfaced epithelia, including that of the endocervix. We have previously demonstrated that the endocervical epithelium expresses messenger RNA (mRNA) of three of the large gel-forming mucins, designated MUC5AC, MUC5B, and MUC6, with mRNA of MUC5B predominating. Because mucin protein levels may be regulated posttranscriptionally, measurement of MUC5B protein levels with cycle are needed for correlation to mRNA levels. Measurement of specific mucin gene products within mucus secretions has been limited by availability of specific, well-characterized antibodies and by volume requirements of the isolation protocols for mucins, which include CsCl density centrifugation and fraction isolation. To measure MUC5B protein within the cervical mucus through the hormone cycle, we developed a polyclonal antibody specific to the mucin. The antibody, designated no. 799, is to a synthetic peptide mimicking a 19-amino-acid segment of an intercysteine-rich region within the D4 domain in the 3' region of the MUC5B protein. It recognizes native as well as denatured MUC5B on immunoblot, is preadsorbable with its peptide, and binds to apical secretory vesicles of epithelia expressing MUC5B. We used the MUC5B antibody along with a cervical mucin standard cervical mucin isolate in enzyme-linked immunosorbent assay to determine the relative amount of MUC5B mucin in samples of human cervical mucus taken through the menstrual cycle. We demonstrate a peak of MUC5B mucin in human cervical mucus collected at midcycle, compared with mucus from early or late in the cycle. This peak in MUC5B content coincides with the change in mucus character that occurs at midcycle, suggesting that this large mucin species may be important to sperm transit to the uterus.