MG-132, an inhibitor of proteasomes and calpains, induced inhibition of oocyte maturation and aneuploidy in mouse oocytes

BACKGROUND: Although chromosome missegregation during oocyte maturation (OM) is a significant contributor to human morbidity and mortality, very little is known about the causes and mechanisms of aneuploidy. Several investigators have proposed that temporal perturbations during OM predispose oocytes to aberrant chromosome segregation. One approach for testing this proposal is to temporarily inhibit the activity of protein proteolysis during OM. We used the reversible proteasome inhibitor MG-132 to transiently perturb the temporal sequence of events during OM and subsequently analyzed mouse metaphase II (MII) for cytogenetic abnormalities. The transient inhibition of proteasome activity by MG-132 resulted in elevated levels of oocytes containing extra chromatids and chromosomes. RESULTS: The transient inhibition of proteasome-mediated proteolysis during OM by MG-132 resulted in dose-response delays during OM and elevated levels of aneuploid MII oocytes. Oocytes exposed in vitro to MG-132 exhibited greater delays during metaphase I (MI) as demonstrated by significantly (p < 0.01) higher levels of MI arrested oocytes and lower frequencies of premature sister chromatid separation in MII oocytes. Furthermore, the proportions of MII oocytes containing single chromatids and extra chromosomes significantly (p < 0.01) increased with MG-132 dosage. CONCLUSIONS: These data suggest that the MG-132-induced transient delay of proteasomal activity during mouse OM in vitro predisposed oocytes to abnormal chromosome segregation. Although these findings support a relationship between disturbed proteasomal activity and chromosome segregation, considerable additional data are needed to further investigate the roles of proteasome-mediated proteolysis and other potential molecular mechanisms on chromosome segregation during OM

Quality of Life Improvement with Sublingual Immunotherapy: A Prospective Study of Efficacy

Due to its excellent safety profile, ease of administration, and economic considerations, sublingual immunotherapy (SLIT) is becoming a preferred form of allergen specific immunotherapy. The efficacy of SLIT is still debated. The purpose of this act of practice trial is to evaluate quality of life outcomes in patients treated with SLIT. Fifty one patients with allergic rhinoconjunctivitis demonstrated by skin testing completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) at initiation, at four months and at 10–12 months of SLIT. Significant improvement (P < 0.05) on six of seven domain categories of the RQLQ questionnaire was noted. Total RQLQ scores also showed significant improvement. This study supports SLIT as a modality effective in controlling allergic symptoms

The Use of Personal Projects Analysis to Enhance Occupational Therapy Goal Identification

Background: Client-centered occupational therapy begins with the identification of personally-relevant patient goals. This study aimed to determine whether the elicitation module of Personal Projects Analysis (PPA) could help patients in an acquired brain injury day hospital program identify more meaningful goals than those identified using the Canadian Occupational Performance Measure (COPM) alone. Method: Ten patients completed the COPM. They rated the importance of each goal and their confidence that they could attain each goal. During the next session, using the elicitation module of PPA, they identified personal projects just prior to their brain injuries, current personal projects, and future desired personal projects. They were then invited to revise their COPM goals and re-rate them for importance and confidence. Results: Following completion of the elicitation module of PPA, seven participants changed at least one goal. Of the goals that were changed, half were revised to include the mention of another person. There were no significant changes in average goal importance or perceived attainability. Occupational therapists reported that the elicitation module of PPA helped them get to know their patients better and identify potential therapeutic occupations. Discussion: The elicitation module of PPA may help people develop goals that are more embedded in their social contexts

Generalized and specific anxiety in adolescents following heart transplant

Mental health concerns are associated with worse outcomes after adult heart transplant. Illness‐specific anxiety is associated with worsened psychological well‐being after other solid organ transplants but has never been characterized after pediatric heart transplant. This single‐center cross‐sectional study aimed to evaluate illness‐specific and generalized anxiety after heart transplantation in adolescents. A novel 12‐item PHTF, GAD‐7, and the PedsQL were administered. Univariate associations of demographics, clinical features, and medication adherence as measured by immunosuppression standard deviation with the PHTF and GAD‐7 scores were evaluated. Internal consistency and validity of the PHTF were examined. In total, 30 patients participated. The most common illness‐specific fears were retransplantation, rejection, and more generally post‐transplant complications. The PHTF had good internal consistency (Cronbach α = .88). Construct validity was demonstrated between PHTF and GAD‐7 (r = .62) and PedsQL (r = −.54 to −.62). 23% endorsed moderate to severe generalized anxiety symptoms. More severe symptoms were associated with older age at survey (P = .03), older age at listing (P = .01) and having post‐transplant complications (P = .004). Patients with moderate or severe symptoms were more likely to report late immunosuppression doses (P = .004). Illness‐specific and generalized anxiety may be prevalent after pediatric heart transplant. Screening for anxiety in adolescents post‐transplant may identify those at risk for adverse outcomes including non‐adherence. The PHTF is a brief, valid, and reliable instrument identifying illness‐specific anxiety in this population.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153669/1/petr13647.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153669/2/petr13647_am.pd

Understanding the Relationship between Health PACs and Health Lobbying in the American States

We examine whether and how health PAC activity in the states is connected to lobbying. Is the political money that health interest organizations bring to the policy process a powerful, independent means of influence or is it better understood more narrowly as a lobbing tactic used to support lobbying? We examine a range of conjectures on the relationship between campaign contributions and lobby activity and the limited work that has been conducted on them and raise a number of questions about the process by which they are connected. We test these hypotheses with 1998 data on state lobbying and PAC activity. We conclude that PAC activity is best viewed as an adjunct of lobbying rather than an independent form of political activity

The effects of high dose interferon-β1a on plasma microparticles: Correlation with MRI parameters

<p>Abstract</p> <p>Objectives</p> <p>We previously reported a correlation between levels of microparticles carrying CD31 (PMP ^CD31+) and disease activity in MS. However, the effects of long term (12 month) treatment with high dose, high frequency interferon-β1a (Rebif™) on plasma levels of PMP^CD31+, PMP^CD146+, and PMP^CD54+and MRI measures of disease activity have not yet been assessed.</p> <p>Methods</p> <p>During this prospective 1-year study, we used flow cytometry to measure changes in plasma microparticles (PMP) bearing CD31 (PMP^CD31+), CD146 (PMP^CD146+), and CD54/ICAM-1 (PMP^CD54+) in 16 consecutive patients with relapsing-remitting MS (RRMS) before and after 3, 6, and 12 months of subcutaneous therapy with interferon-beta1a (44 micrograms, 3X weekly). At each visit, clinical exams and expanded disability status scale (EDSS) scores were recorded.</p> <p>Results</p> <p>Plasma levels of PMP^CD31+, and PMP^CD54+were significantly reduced by treatment with IFN-β1a. PMP^CD146+appeared to decrease only at 3 months and did not persist at 6 and 12 months (p = 0.0511). In addition, the decrease in plasma levels of PMP^CD31+and PMP^CD54+levels at 12 months were associated with a significant decrease in the number and volume of contrast enhancing T1-weigthed lesions.</p> <p>Conclusion</p> <p>Our data suggest that serial measurement of plasma microparticles (PMP), particularly in the initial stages of MS (when neuro-inflammatory cascades are more intense), may serve as reliable and reproducible surrogate markers of response to IFN-β1a therapy for MS. In addition, the progressive decline in plasma levels of PMP^CD31+and PMP^CD54+further supports the concept that IFN-β1a exerts stabilizing effect on the cerebral endothelial cells during pathogenesis of MS.</p

11 C-Metomidate PET/CT is a useful adjunct for lateralization of primary aldosteronism in routine clinical practice.

OBJECTIVE: To describe clinical practice experience of 11 C-Metomidate PET/CT as an adjunct to adrenal vein sampling (AVS) in the lateralization of aldosterone-producing adenomas (APA) in primary aldosteronism (PA). CONTEXT: Accurate lateralization of APA in the setting of PA offers the potential for surgical cure and improved long-term cardiovascular outcomes. Challenges associated with AVS, the current gold standard lateralization modality, mean that only a small proportion of potentially eligible patients currently make it through to surgery. This has prompted consideration of alternative strategies for lateralization, including the application of novel molecular PET tracers such as 11 C-Metomidate. DESIGN: Clinical Service Evaluation/Retrospective audit. PATIENTS: Fifteen individuals with a confirmed diagnosis of PA, undergoing lateralization with 11 C-Metomidate PET/CT prior to final clinical decision on surgical vs medical management. MEASUREMENTS: All patients underwent screening aldosterone renin ratio (ARR), followed by confirmatory testing with the seated saline infusion test, according to Endocrine Society Clinical Practice Guidelines. Adrenal glands were imaged using dedicated adrenal CT. 11 C-Metomidate PET/CT was undertaken due to equivocal or failed AVS. Management outcomes were assessed by longitudinal measurement of blood pressure, ARR, number of hypertensive medications following adrenalectomy or institution of medical therapy. RESULTS: We describe the individual lateralization and clinical outcomes for 15 patients with PA. CONCLUSION: 11 C-Metomidate PET/CT in conjunction with adrenal CT and AVS provided useful information which aided clinical decision-making for PA within a multidisciplinary hypertension clinic

The use of telehealth for diabetes management: a qualitative study of telehealth provider perceptions

BACKGROUND: Monitoring and Messaging Devices (MMDs) are telehealth systems used by patients in their homes, and are designed to promote patient self-management, patient education, and clinical monitoring and follow-up activities. Although these systems have been widely promoted by health care systems, including the Veterans Health Administration, very little information is available on factors that facilitate use of the MMD system, or on barriers to use. METHODS: We conducted in-depth qualitative interviews with clinicians using MMD-based telehealth programs at two Veterans Affairs Medical Centers in the Midwestern United States. RESULTS: Findings suggest that MMD program enrollment is limited by both clinical and non-clinical factors, and that patients have varying levels of program participation and system use. Telehealth providers see MMDs as a useful tool for monitoring patients who are interested in working on management of their disease, but are concerned with technical challenges and the time commitment required to use MMDs. CONCLUSION: Telehealth includes a rapidly evolving and potentially promising range of technologies for meeting the growing number of patients and clinicians who face the challenges of diabetes care, and future research should explore the most effective means of ensuring successful program implementation