The Role of Multiple Sclerosis as a Risk Factor for the Development of Osteoporosis

Background: Osteoporosis is the most common bone disease in the United States, and it is particularly common among women with multiple sclerosis (MS). However, despite this association, the temporal relationship between these two conditions has not been previously studied. Data from the Women’s Health Initiative provides a unique opportunity to examine the risk of developing osteoporosis over time in individuals diagnosed with MS. Objective: The purpose of this study is to refine the relationship between MS and osteoporosis, clarifying the impact of environmental and pharmacologic factors on each condition, as well as addressing treatment and preventative efforts for a patient population at a greater potential risk for osteoporosis. Methods: The study sample, derived from the Women’s Health Initiative, included 449 women who reported an MS diagnosis at baseline and 161,359 women without MS who comprised a control group. Baseline measures of self-reported osteoporosis, age, smoking status, steroid and anti-inflammatory use, and supplementary as well as dietary calcium and vitamin D were compared. MS patients reporting osteoporosis at baseline were removed, resulting in 355 women with MS to monitor for time to incident osteoporosis. Survival analyses were performed on follow-up data gathered annually between 1993 and 2005 to factor out significant associations of additional factors. Proportions of participants on osteoporosis-related medications as well as latency to use were compared between the multiple sclerosis and control cohorts. Results: At baseline, women with MS are nearly three times as likely to report osteoporosis (p Conclusions: A higher prevalence of osteoporosis at baseline suggests MS may significantly increase the risk of osteoporosis in premenopausal women. In contrast, environmental and pharmacologic variables appear to have a more significant role in the post-menopausal population. While osteoporosis was treated similarly between both groups, the point for intervention or prevention of osteoporosis in MS patients may be earlier in the disease course

Assessment of Parental Mental Disorders in the National Children’s Study (NCS)

Introduction: Parental mental disorders are powerful risk factors for children’s behavioral and mental disorders, making it critical to obtain estimates of parental mental disorders in NCS baseline assessments. These disorders are usually clinically assessed and diagnosed using lengthy interview instruments. This study will validate a brief set of mental health screens against the gold-standard Composite International Diagnostic Interview (CIDI). Methods: Sample: Up to 1200 English-speaking pregnant women and their male partners, aged \u3e17 with over-sampling of racial and ethnic minorities. Instruments: A brief 25-minute set of REDCap based screening scales will be administered. Probability sub-samples of 450-600 respondents with or without DSM-IV diagnoses will be selected for clinical reappraisal using the CIDI. Patients without DSM-IV diagnoses but with subsyndromal disorders will be used to optimize the sensitivity and specificity of screening scales. Diagnostic Assessment: Major depression, bipolar spectrum disorders, generalized anxiety, panic, post-traumatic stress, and substance abuse will be assessed. Analytic Methods: Kappa statistics, Receiver Operating Curve and regression methods will be used to evaluate concordance between diagnoses from screening scales and the CIDI at the aggregate and individual levels. Sensitivity and specificity will be reported for the cohort and separately for mothers and fathers as well as racial and ethnic minorities. Significance: This is the largest investigation of the epidemiology of mental disorders in a representative sample of community based pregnant mothers and their male partners. Information will be used to study the importance of parental psychopathology in the emergence of mental disorders in children over 21 years of follow-up of the parents and their children

A Central Role for Foxp3+ Regulatory T Cells in K-Ras-Driven Lung Tumorigenesis

BACKGROUND: K-Ras mutations are characteristic of human lung adenocarcinomas and occur almost exclusively in smokers. In preclinical models, K-Ras mutations are necessary for tobacco carcinogen-driven lung tumorigenesis and are sufficient to cause lung adenocarcinomas in transgenic mice. Because these mutations confer resistance to commonly used cytotoxic chemotherapies and targeted agents, effective therapies that target K-Ras are needed. Inhibitors of mTOR such as rapamycin can prevent K-Ras-driven lung tumorigenesis and alter the proportion of cytotoxic and Foxp3+ regulatory T cells, suggesting that lung-associated T cells might be important for tumorigenesis. METHODS: Lung tumorigenesis was studied in three murine models that depend on mutant K-Ras; a tobacco carcinogen-driven model, a syngeneic inoculation model, and a transgenic model. Splenic and lung-associated T cells were studied using flow cytometry and immunohistochemistry. Foxp3+ cells were depleted using rapamycin, an antibody, or genetic ablation. RESULTS: Exposure of A/J mice to a tobacco carcinogen tripled lung-associated Foxp3+ cells prior to tumor development. At clinically relevant concentrations, rapamycin prevented this induction and reduced lung tumors by 90%. In A/J mice inoculated with lung adenocarcinoma cells resistant to rapamycin, antibody-mediated depletion of Foxp3+ cells reduced lung tumorigenesis by 80%. Likewise, mutant K-Ras transgenic mice lacking Foxp3+ cells developed 75% fewer lung tumors than littermates with Foxp3+ cells. CONCLUSIONS: Foxp3+ regulatory T cells are required for K-Ras-mediated lung tumorigenesis in mice. These studies support clinical testing of rapamycin or other agents that target Treg in K-Ras driven human lung cancer

Domestic Violence and Health Care: Opening Pandora¿s Box ¿ Challenges and Dilemmas

In this article we take a critical stance toward the rational progressive narrative surrounding the integration of domestic violence within health care. Whilst changes in recent UK policy and practice have resulted in several tangible benefits, it is argued that there may be hidden dilemmas and challenges. We suggest that the medical model of care and its discursive practices position women as individually accountable for domestic violence-related symptoms and injuries. This may not only be ineffective in terms of service provision but could also have the potential to reduce the political significance of domestic violence as an issue of concern for all women. Furthermore, it is argued that the use of specific metaphors enables practitioners to distance themselves from interactions that may prove to be less comfortable and provide less than certain outcomes. Our analysis explores the possibilities for change that might currently be available. This would appear to involve a consideration of alternative discourses and the reformulation of power relations and subject positions in health care

The Lantern, 2021-2022

No More Buses through El Paso • A Woman\u27s World • The Angel of Tragedy • A Victim of Circumstance • Ace of Hearts • Ghost Light • Missing Diamonds • The Upside-Down House: A Dialogue with the Self • What is Chronic Pain? • A Sunny Day in Sinkhole • Extra Marshmallows • Fourth Wall Broken • Hemlock • In the Comfort of Others • Lasting Impressions • Let\u27s Do the Time Warp Again • One Last Afternoon • Space Invaders • The Dogwood Tree • An Ode to Poppies • Charlotte\u27s Web • Crab • Crossing • Dandelions • Dandelion Sandwich • Grizzly Hood • Help Wanted • I Gave Way • I\u27m not who you wanted but maybe one day I can be • Kneeling • Lemon Cookies • Lies • Method Acting • Moment of Tranquility • Our Home • Overthinking • Sea Glass • Seasonal • Thirty-Two (No Spares) • The Autumn Beast • The Miller\u27s Daughter • Theodore • To the Earring I Left Behind in Your Carpet • Virginia • Waltzing • Yellow House • 1/25 British Monarch • Cracked • In the Shadows • Jewelwing • Life on the Wing • O\u27 Captain my Captain • Stars Above the Bay • The Common Fall • Tom • Cats + Crowshttps://digitalcommons.ursinus.edu/lantern/1190/thumbnail.jp

Stress biology:Complexity and multifariousness in health and disease

Preserving and regulating cellular homeostasis in the light of changing environmental conditions or developmental processes is of pivotal importance for single cellular and multicellular organisms alike. To counteract an imbalance in cellular homeostasis transcriptional programs evolved, called the heat shock response, unfolded protein response, and integrated stress response, that act cell-autonomously in most cells but in multicellular organisms are subjected to cell-nonautonomous regulation. These transcriptional programs downregulate the expression of most genes but increase the expression of heat shock genes, including genes encoding molecular chaperones and proteases, proteins involved in the repair of stress-induced damage to macromolecules and cellular structures. Sixty-one years after the discovery of the heat shock response by Ferruccio Ritossa, many aspects of stress biology are still enigmatic. Recent progress in the understanding of stress responses and molecular chaperones was reported at the 12th International Symposium on Heat Shock Proteins in Biology, Medicine and the Environment in the Old Town Alexandria, VA, USA from 28th to 31st of October 2023.</p

Analysis of the Neurotoxin Complex Genes in Clostridium botulinum A1-A4 and B1 Strains: BoNT/A3, /Ba4 and /B1 Clusters Are Located within Plasmids

BACKGROUND: Clostridium botulinum and related clostridial species express extremely potent neurotoxins known as botulinum neurotoxins (BoNTs) that cause long-lasting, potentially fatal intoxications in humans and other mammals. The amino acid variation within the BoNT is used to categorize the species into seven immunologically distinct BoNT serotypes (A-G) which are further divided into subtypes. The BoNTs are located within two generally conserved gene arrangements known as botulinum progenitor complexes which encode toxin-associated proteins involved in toxin stability and expression. METHODOLOGY/PRINCIPAL FINDINGS: Because serotype A and B strains are responsible for the vast majority of human botulism cases worldwide, the location, arrangement and sequences of genes from eight different toxin complexes representing four different BoNT/A subtypes (BoNT/A1-Ba4) and one BoNT/B1 strain were examined. The bivalent Ba4 strain contained both the BoNT/A4 and BoNT/bvB toxin clusters. The arrangements of the BoNT/A3 and BoNT/A4 subtypes differed from the BoNT/A1 strains and were similar to those of BoNT/A2. However, unlike the BoNT/A2 subtype, the toxin complex genes of BoNT/A3 and BoNT/A4 were found within large plasmids and not within the chromosome. In the Ba4 strain, both BoNT toxin clusters (A4 and bivalent B) were located within the same 270 kb plasmid, separated by 97 kb. Complete genomic sequencing of the BoNT/B1 strain also revealed that its toxin complex genes were located within a 149 kb plasmid and the BoNT/A3 complex is within a 267 kb plasmid. CONCLUSIONS/SIGNIFICANCE: Despite their size differences and the BoNT genes they contain, the three plasmids containing these toxin cluster genes share significant sequence identity. The presence of partial insertion sequence (IS) elements, evidence of recombination/gene duplication events, and the discovery of the BoNT/A3, BoNT/Ba4 and BoNT/B1 toxin complex genes within plasmids illustrate the different mechanisms by which these genes move among diverse genetic backgrounds of C. botulinum

Numerical experiments using deflation with the HISQ action

8 pages. Poster presented at the lattice 2017 conferenceWe report on numerical experiments using deflation to compute quark propagators for the highly improved staggered quark (HISQ) action. The method is tested on HISQ gauge configurations, generated by the MILC collaboration, with lattice spacings of 0.15 fm, with a range of volumes, and sea quark masses down to the physical quark mass

Sensory Communication

Contains table of contents for Section 2, an introduction and reports on fifteen research projects.National Institutes of Health Grant RO1 DC00117National Institutes of Health Grant RO1 DC02032National Institutes of Health Contract P01-DC00361National Institutes of Health Contract N01-DC22402National Institutes of Health/National Institute on Deafness and Other Communication Disorders Grant 2 R01 DC00126National Institutes of Health Grant 2 R01 DC00270National Institutes of Health Contract N01 DC-5-2107National Institutes of Health Grant 2 R01 DC00100U.S. Navy - Office of Naval Research/Naval Air Warfare Center Contract N61339-94-C-0087U.S. Navy - Office of Naval Research/Naval Air Warfare Center Contract N61339-95-K-0014U.S. Navy - Office of Naval Research/Naval Air Warfare Center Grant N00014-93-1-1399U.S. Navy - Office of Naval Research/Naval Air Warfare Center Grant N00014-94-1-1079U.S. Navy - Office of Naval Research Subcontract 40167U.S. Navy - Office of Naval Research Grant N00014-92-J-1814National Institutes of Health Grant R01-NS33778U.S. Navy - Office of Naval Research Grant N00014-88-K-0604National Aeronautics and Space Administration Grant NCC 2-771U.S. Air Force - Office of Scientific Research Grant F49620-94-1-0236U.S. Air Force - Office of Scientific Research Agreement with Brandeis Universit