How can we effectively treat stress urinary incontinence without drugs or surgery?

Q. How can we effectively treat stress urinary incontinence without drugs or surgery? A. Pelvic floor muscle training (PFMT) and intravaginal electrical stimulation seem to be the best bets. PFMT increases urinary continence and improves symptoms of stress urinary incontinence (SUI) (strength of recommendation [SOR]: A, systematic review or randomized, controlled trials [RCTs]). PFMT also improves quality of life (QOL) (activity and psychological impact) (SOR: B, 1 RCT). Intravaginal electrical simulation increases urinary continence and improves SUI symptoms; percutaneous electrical simulation also improve SUI symptoms and likely improves QOL measures (SOR: a, systematic review). Magnetic simulation doesn't increase continence, has mixed effects on SUI symptoms, and produces no clinically meaningful improvement in QOL (SOR: B, heterogeneous RCTs with conflicting results). Vaginal cones don't increase continence or QOL (SOR: B, 2 RCTs with methodoligic flaws)

Which drugs work best for early Parkinson's disease?

Levodopa/carbidopa is the most effective medical therapy for Parkinson's disease, but it's associated with dyskinesia (strength of recommendation [SOR]: A, Cochrane reviews and randomized controlled trials [RCTs]). Treating early Parkinson's disease with dopamine agonists such as bromocriptine can improve symptoms (SOR: B, Cochrane reviews, RCTs with heterogeneity)

The Grizzly, November 5, 2009

Escape Velocity Performances are Timeless • Dr. William Keim Inspires with Humor • National Deficit May Favor Health Care Reform • Second Annual Greek Activities Fair Held in Wismer Parents Lounge • Sophomores Learn About the ILE • Behind the Scenes: Association for Computing Machinery • Educational Effect of the International Film Festival • Haunted Ursinus: Good ole\u27 Ghost Stories • Opinion: Where Did the Lounges Go? The Cramped UC Community; Texting and Facebook IM: Our Generation Conversation; Drop the Natural Light and Expand Your Beverage Horizons • UC Athletics Spotlight: Alyssa Thren of Field Hockeyhttps://digitalcommons.ursinus.edu/grizzlynews/1798/thumbnail.jp

The Grizzly, September 17, 2009

Recycling Team Takes Action Against Campus Waste • Annual Activities Fair Starts the Year Off • Campus Safety, Police Relations: Battle of Jurisdiction • Berman\u27s New Exhibit: Muriel\u27s Moores • Is the Power Plant Damaging More Than Our Eardrums? • Restaurant Review: Iron Hill Brewery • Club Spotlight: InterVarsity Christian Fellowship • Hidden Treasures in the Berman and Myrin • Opinion: Liberal Arts, Limited Choices?; Facebook Friends: How Far is Too Far?; Obama\u27s Administration and the Takeover of the Communist Czar Regime; Socialism is the New Word for Progress • UC Men\u27s Soccer Coach Adds Sustainability Coordinator to His Title • Positivity and Friendship Staples of the UC Women\u27s Volleyball Teamhttps://digitalcommons.ursinus.edu/grizzlynews/1791/thumbnail.jp

Identification of novel loci associated with hip shape:a meta-analysis of genome-wide association studies

This study was funded by Arthritis Research UK project grant 20244, which also provided salary funding for DB and CVG. LP works in the MRC Integrative Epidemiology Unit, a UK MRC‐funded unit (MC_ UU_ 12013/4 & MC_UU_12013/5). ALSPAC: We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. ALSPAC data collection was supported by the Wellcome Trust (grants WT092830M; WT088806; WT102215/2/13/2), UK Medical Research Council (G1001357), and University of Bristol. The UK Medical Research Council and the Wellcome Trust (102215/2/13/2) and the University of Bristol provide core support for ALSPAC. Framingham Heart Study: The Framingham Osteoporosis Study is supported by grants from the National Institute of Arthritis, Musculoskeletal, and Skin Diseases and the National Institute on Aging (R01 AR41398, R01 AR 061162, R01 AR050066, and R01 AR061445). The analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource project. The Framingham Heart Study of the National Heart, Lung, and Blood Institute of the National Institutes of Health and Boston University School of Medicine were supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (N01‐HC‐25195) and its contract with Affymetrix, Inc., for genotyping services (N02‐HL‐6‐4278). Analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. A portion of this research was conducted using the Linux Cluster for Genetic Analysis (LinGA‐II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. DK was also supported by Israel Science Foundation grant #1283/14. TDC and DR thank Dr Claire Reardon and the entire Harvard University Bauer Core facility for assistance with ATAC‐seq next generation sequencing. This work was funded in part by the Harvard University Milton Fund, NSF (BCS‐1518596), and NIH NIAMS (1R01AR070139‐01A1) to TDC. MrOS: The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute on Aging (NIA), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Center for Advancing Translational Sciences (NCATS), and NIH Roadmap for Medical Research under the following grant numbers: U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, and UL1 TR000128. The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) provides funding for the MrOS ancillary study “Replication of candidate gene associations and bone strength phenotype in MrOS” under the grant number R01 AR051124. The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) provides funding for the MrOS ancillary study “GWAS in MrOS and SOF” under the grant number RC2 AR058973. SOF: The Study of Osteoporotic Fractures (SOF) is supported by National Institutes of Health funding. The National Institute on Aging (NIA) provides support under the following grant numbers: R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, and R01 AG027576. TwinsUK: The study was funded by the Wellcome Trust; European Community's Seventh Framework Programme (FP7/2007‐2013). The study also receives support from the National Institute for Health Research (NIHR)‐funded BioResource, Clinical Research Facility, and Biomedical Research Centre based at Guy's and St Thomas’ NHS Foundation Trust in partnership with King's College London. SNP genotyping was performed by The Wellcome Trust Sanger Institute and National Eye Institute via NIH/CIDR. This study was also supported by the Australian National Health and Medical Research Council (project grants 1048216 and 1127156), the Sir Charles Gairdner Hospital RAC (SGW), and the iVEC/Pawsey Supercomputing Centre (project grants Pawsey0162 and Director2025 [SGW]). The salary of BHM was supported by a Raine Medical Research Foundation Priming Grant. The Umeå Fracture and Osteoporosis Study (UFO) is supported by the Swedish Research Council (K20006‐72X‐20155013), the Swedish Sports Research Council (87/06), the Swedish Society of Medicine, the Kempe‐Foundation (JCK‐1021), and by grants from the Medical Faculty of Umeå Unviersity (ALFVLL:968:22‐2005, ALFVL:‐937‐2006, ALFVLL:223:11‐2007, and ALFVLL:78151‐2009) and from the county council of Västerbotten (Spjutspetsanslag VLL:159:33‐2007). This publication is the work of the authors and does not necessarily reflect the views of any funders. None of the funders had any influence on data collection, analysis, interpretation of the results, or writing of the paper. DB will serve as the guarantor of the paper. Authors’ roles: Study conception and design: DAB, JSG, RMA, LP, DK, and JHT. Data collection: DJ, DPK, ESO, SRC, NEL, BHM, FMKW, JBR, SGW, TDC, BGF, DAL, CO, and UP‐L. Data analysis: DAB, DSE, FKK, JSG, FRS, CVG, RJB, RMA, SGW, EG, TDC, DR, and TB. Data interpretation: JSG, RMA, TDC, DR, DME, LP, DK, and JHT. Drafting manuscript: DAB and JHT. Revising manuscript content: JHT. All authors approved the final version of manuscript. DAB takes responsibility for the integrity of the data analysis.Peer reviewedPublisher PD

Creating Systems of Sustainability: Four Focus Areas for the Future of PK-12 Open Educational Resources

Over the past few years, state and school district education leaders have renewed their focus on the quality of learning materials available in our nation’s classrooms (Chiefs for Change, 2017; RAND Corp., 2016; RAND Corp., 2017). Many leaders have been dismayed to find that existing proprietary textbooks and supplementary resources often do not match their teachers’ and students’ needs (Ishmael, 2018a). Fortunately, there is a growing recognition of teachers and school leaders who are addressing this challenge head-on through open educational resources. Simply put, open educational resources, or OER, are “high quality teaching, learning, and research resources that are free for others to use and repurpose”(Hewlett Foundation, 2015). OER range from entire curricula and textbooks to smaller grain-size learning materials, including assessments, videos and images

Characterizing the Relationship Between Neutralization Sensitivity and

Although antiretroviral therapy (ART) successfully suppresses HIV-1 replication, ART-treated individuals must maintain therapy to avoid rebound from an integrated viral reservoir. Strategies to limit or clear this reservoir are urgently needed. Individuals infected for longer periods prior to ART appear to harbor more genetically diverse virus, but the roles of duration of infection and viral diversity in the humoral immune response remain to be studied. We aim to clarify a role, if any, for autologous and heterologous antibodies in multi-pronged approaches to clearing infection. To that end, we have characterized the breadths and potencies of antibody responses in individuals with varying durations of infection and HIV-1 envelope (env) gene diversity as well as the sensitivity of their inducible virus reservoir to broadly neutralizing antibodies (bNAbs). Plasma was collected from 8 well-characterized HIV-1(+) males on ART with varied durations of active infection. HIV envs from reservoir-derived outgrowth viruses were amplified and single genome sequenced in order to measure genetic diversity in each participant. IgG from plasma was analyzed for binding titers against gp41 and gp120 proteins, and for neutralizing titers against a global HIV-1 reference panel as well as autologous outgrowth viruses. The sensitivity to bNAbs of these same autologous viruses was measured. Overall, we observed that greater env diversity was associated with higher neutralizing titers against the global panel and also increased resistance to certain bNAbs. Despite the presence of robust anti-HIV-1 antibody titers, we did not observe potent neutralization against autologous viruses. In fact, 3 of 8 participants harbored viruses that were completely resistant to the highest tested concentration of autologous IgG. That this lack of neutralization was observed regardless of ART duration or viral diversity suggests that the inducible reservoir harbors ‘escaped’ viruses (that co-evolved with autologous antibody responses), rather than proviruses archived from earlier in infection. Finally, we observed that viruses resistant to autologous neutralization remained sensitive to bNAbs, especially CD4bs and MPER bNAbs. Overall, our data suggest that the inducible reservoir is relatively resistant to autologous antibodies and that individuals with limited virus variation in the env gene, such as those who start ART early in infection, are more likely to be sensitive to bNAb treatment

Establishment of A Novel Humanized Mouse Model To Investigate In Vivo Activation and Depletion of Patient-Derived HIV Latent Reservoirs.

Curing HIV infection has been thwarted by the persistent reservoir of latently infected CD4+ T cells, which reinitiate systemic infection after antiretroviral therapy (ART) interruption. To evaluate reservoir depletion strategies, we developed a novel preclinical in vivo model consisting of immunodeficient mice intrasplenically injected with peripheral blood mononuclear cells (PBMC) from long-term ART-suppressed HIV-infected donors. In the absence of ART, these mice developed rebound viremia which, 2 weeks after PBMC injection, was 1,000-fold higher (mean = 9,229,281 HIV copies/ml) in mice injected intrasplenically than in mice injected intraperitoneally (mean = 6,838 HIV copies/ml) or intravenously (mean = 591 HIV copies/ml). One week after intrasplenic PBMC injection, in situ hybridization of the spleen demonstrated extensive disseminated HIV infection, likely initiated from in vivo-reactivated primary latently infected cells. The time to viremia was delayed significantly by treatment with a broadly neutralizing antibody, 10-1074, compared to treatment with 10-1074-FcRnull, suggesting that 10-1074 mobilized Fc-mediated effector mechanisms to deplete the replication-competent reservoir. This was supported by phylogenetic analysis of Env sequences from viral-outgrowth cultures and untreated, 10-1074-treated, or 10-1074-FcRnull-treated mice. The predominant sequence cluster detected in viral-outgrowth cultures and untreated mouse plasma was significantly reduced in the plasma of 10-1074-treated mice, whereas two new clusters emerged that were not detected in viral-outgrowth cultures or plasma from untreated mice. These new clusters lacked mutations associated with 10-1074 resistance. Taken together, these data indicated that 10-1074 treatment depletes the reservoir of latently infected cells harboring replication competent HIV. Furthermore, this mouse model represents a new in vivo approach for the preclinical evaluation of new HIV cure strategies.IMPORTANCE Sustained remission of HIV infection is prevented by a persistent reservoir of latently infected cells capable of reinitiating systemic infection and viremia. To evaluate strategies to reactivate and deplete this reservoir, we developed and characterized a new humanized mouse model consisting of highly immunodeficient mice intrasplenically injected with peripheral blood mononuclear cells from long-term ART-suppressed HIV-infected donors. Reactivation and dissemination of HIV infection was visualized in the mouse spleens in parallel with the onset of viremia. The applicability of this model for evaluating reservoir depletion treatments was demonstrated by establishing, through delayed time to viremia and phylogenetic analysis of plasma virus, that treatment of these humanized mice with a broadly neutralizing antibody, 10-1074, depleted the patient-derived population of latently infected cells. This mouse model represents a new in vivo approach for the preclinical evaluation of new HIV cure strategies.status: Published onlin