Coordination of Care by Primary Care Practices: Strategies, Lessons and Implications

Documents successful strategies for coordinating care within primary care settings, including family and caregivers; with specialists; with hospital settings; and with community-based services. Discusses challenges, lessons learned, and implications

Exile Vol. XLVI No. 1

44th Year Title Page 3 Epigraph by Ezra Pound 5 Statement of Policy 6 Table of Contents 7 Contributors Notes 37 Editorial Board 38 ART Incredible Lines by David Tulkin \u2701 8 Untitled by David Tulkin \u2701 12 Untitled by Patrick Yingling \u2703 18 Sculpted Body by David Tulkin \u2701 20 Untitled by Tanya Sheremeta \u2701 25 Untitled by David Tulkin \u2701 28 Untitled by Dena Behi \u2701 36 POETRY Wednesday by Mary Ann T. Davis \u2700 9 Music by Jessica Kramer \u2703 10-11 Worship During the Rainy Season by Allison Armbrister \u2701 19 Mercy by Mary Ann T. Davis \u2700 26-27 Albino Lizard by Matthew Martz \u2702 29 Filling of Lake Cumberland, 1951 by Allison Armbrister \u2701 35 PROSE Storm Drain by Matthew Martz \u2702 13-17 Creases by Stephanie M. Vaccaro \u2701 21-24 When It Rains by Matthew Martz \u2702 30-34 Statement of Policy This semester Exile instituted a new policy limiting submissions to those not involved in the production of the magazine. As always, all submissions are reviewed on an anonymous basis, and all editorial decisions are shared equally among the members of the Editorial Board. -6 Cover Art Untitled by Dena Behi \u2701 / Back Cover Art Untitled by Tanya Sheremeta \u2701 -38 Printed by Printing Arts Press -38 Matthew Martz, Albino Lizard, Storm Drain and When It Rains , redacted due to copyright restrictions

Treatment of symptoms of the menopause: an endocrine society clinical practice guideline

Objective: The objective of this document is to generate a practice guideline for the management and treatment of symptoms of the menopause. Participants: The Treatment of Symptoms of the Menopause Task Force included six experts, a methodologist, and a medical writer, all appointed by The Endocrine Society. Evidence: The Task Force developed this evidenced-based guideline using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and the quality of evidence. The Task Force commissioned three systematic reviews of published data and considered several other existing meta-analyses and trials. Consensus Process: Multiple e-mail communications, conference calls, and one face-to-face meeting determined consensus. Committees of The Endocrine Society, representatives from endorsing societies, and members of The Endocrine Society reviewed and commented on the drafts of the guidelines. The Australasian Menopause Society, the British Menopause Society, European Menopause and Andropause Society, the European Society of Endocrinology, and the International Menopause Society (co-sponsors of the guideline) reviewed and commented on the draft. Conclusions: Menopausal hormone therapy (MHT) is the most effective treatment for vasomotor symptoms and other symptoms of the climacteric. Benefits may exceed risks for the majority of symptomatic postmenopausal women who are under age 60 or under 10 years since the onset of menopause. Health care professionals should individualize therapy based on clinical factors and patient preference. They should screen women before initiating MHT for cardiovascular and breast cancer risk and recommend the most appropriate therapy depending on risk/benefit considerations. Current evidence does not justify the use of MHT to prevent coronary heart disease, breast cancer, or dementia. Other options are available for those with vasomotor symptoms who prefer not to use MHT or who have contraindications because these patients should not use MHT. Low-dose vaginal estrogen and ospemifene provide effective therapy for the genitourinary syndrome of menopause, and vaginal moisturizers and lubricants are available for those not choosing hormonal therapy. All postmenopausal women should embrace appropriate lifestyle measures

Characterisation of the carboxypeptidase G2 catalytic site and design of new inhibitors for cancer therapy

The enzyme carboxypeptidase G2 (CPG2) is used in antibody‐directed enzyme prodrug therapy (ADEPT) to catalyse the formation of an active drug from an inert prodrug. Free CPG2 in the bloodstream must be inhibited before administration of the prodrug in order to avoid a systemic reaction in the patient. Although a few small‐molecule CPG2 inhibitors have been reported, none has been taken forward thus far. This lack of progress is due in part to a lack of structural understanding of the CPG2 active site as well as the absence of small molecules that can block the active site whilst targeting the complex for clearance. The work described here aimed to address both areas. We report the structural/functional impact of extensive point mutation across the putative CPG2 catalytic site and adjacent regions for the first time, revealing that residues outside the catalytic region (K208A, S210A and T357A) are crucial to enzyme activity. We also describe novel molecules that inhibit CPG2 whilst maintaining the accessibility of galactosylated moieties aimed at targeting the enzyme for clearance. This work acts as a platform for the future development of high‐affinity CPG2 inhibitors that occupy new chemical space and will advance the safe application of ADEPT in cancer treatment

α-Tocopherols modify the membrane dipole potential leading to modulation of ligand binding by P-glycoprotein

Journal ArticleThis is the author accepted manuscript. The final version is available from ASBMB via the DOI in this record.α-Tocopherol (vitamin E) has attracted considerable attention as a potential protective or palliative agent. In vitro, its free radical-scavenging antioxidant action has been widely demonstrated. In vivo, however, vitamin E treatment exhibits negligible benefits against oxidative stress. α-Tocopherol influences lipid ordering within biological membranes and its derivatives have been suggested to inhibit the multi-drug efflux pump, P-glycoprotein (P-gp). This study employs the fluorescent membrane probe, 1-(3-sulfonatopropyl)-4-[β[2-(di-n-octylamino)-6-naphthyl]vinyl] pyridinium betaine, to investigate whether these effects are connected via influences on the membrane dipole potential (MDP), an intrinsic property of biological membranes previously demonstrated to modulate P-gp activity. α-Tocopherol and its non-free radical-scavenging succinate analog induced similar decreases in the MDP of phosphatidylcholine vesicles. α-Tocopherol succinate also reduced the MDP of T-lymphocytes, subsequently decreasing the binding affinity of saquinavir for P-gp. Additionally, α-tocopherol succinate demonstrated a preference for cholesterol-treated (membrane microdomain enriched) cells over membrane cholesterol-depleted cells. Microdomain disruption via cholesterol depletion decreased saquinavir's affinity for P-gp, potentially implicating these structures in the influence of α-tocopherol succinate on P-gp. This study provides evidence of a microdomain dipole potential-dependent mechanism by which α-tocopherol analogs influence P-gp activity. These findings have implications for the use of α-tocopherol derivatives for drug delivery across biological barriers

Challenges, Opportunities, and Adaptations of a College Preparatory 4-H Youth Development Program during COVID-19

SARS-CoV-2 (COVID-19) has proliferated across the United States, and in the process, it has disrupted all sense of normalcy. Because adolescents are in a critical period for growth and development, youth are particularly susceptible to negative impacts of disruption from COVID-19. Therefore, sustaining youth development programs is essential to ensuring positive youth development occurs despite significant challenges. Unfortunately, the implementation of programs that maintain safety precautions can be challenging. Many programs have been forced to either cancel all activities or to transition program elements to a virtual format. Rural Medical and Science Scholars (RMSS) program administrative staff made the decision to transition to a virtual delivery. Despite only having a few weeks to reshape the program, RMSS administrative staff were able to innovatively adapt to new challenges in order to deliver a successful program. The success of the program extends beyond its participants. By understanding potential program barriers and successful adaptation methods, other youth development programs will be better equipped to sustain program activities and youth outreach during the COVID-19 pandemic

Behavioural abnormalities in a novel mouse model for Silver Russell Syndrome

Silver Russell Syndrome (SRS) syndrome is an imprinting disorder involving low birth weight with complex genetics and diagnostics. Some rare SRS patients carry maternally inherited microduplications spanning the imprinted genes CDKN1C, PHLDA2, SLC22A18 and KCNQ1, suggesting that overexpression of one of more of these genes contributes to the SRS phenotype. While this molecular alteration is very rare, feeding difficulties are a very common feature of this condition. Given that SRS children also have very low body mass index, understanding the underpinning biology of the eating disorder is important, as well as potential co-occurring behavioural alterations. Here, we report that a mouse model of this microduplication exhibits a number of behavioural deficits. The mice had a blunted perception of the palatability of a given foodstuff. This perception may underpin the fussiness with food. We additionally report hypoactivity, unrelated to anxiety or motoric function, and a deficit in appropriate integration of incoming sensory information. Importantly, using a second genetic model, we were able to attribute all altered behaviours to elevated expression of a single gene, Cdkn1c. This is the first report linking elevated Cdkn1c to altered behaviour in mice. Importantly, the findings from our study may have relevance for SRS and highlight a potentially underreported aspect of this disorder