Publications by authors named "Laura Wright"

59 Publications

Physical Activity Protects Against the Negative Impact of Coronavirus Fear on Adolescent Mental Health and Well-Being During the COVID-19 Pandemic.

Front Psychol 2021 11;12:580511. Epub 2021 Mar 11.

School of Sport, Exercise and Rehabilitation Sciences, College of Life and Environmental Sciences, University of Birmingham, Birmingham, United Kingdom.

The severity of the Coronavirus pandemic has led to lockdowns in different countries to reduce the spread of the infection. These lockdown restrictions are likely to be detrimental to mental health and well-being in adolescents. Physical activity can be beneficial for mental health and well-being; however, research has yet to examine associations between adolescent physical activity and mental health and well-being during lockdown. Examine the effects of adolescent perceived Coronavirus prevalence and fear on mental health and well-being and investigate the extent to which physical activity can be a protective factor against these concerns. During United Kingdom lockdown restrictions, 165 participants (100 female, aged 13-19) completed an online questionnaire assessing perceived Coronavirus prevalence and fear, physical activity, and indicators of mental health and well-being (stress, anxiety, depression, fatigue, vitality, and perceived health). Separate hierarchical multiple linear regression analyses (with age, gender, perceived Coronavirus prevalence, and fear entered in step 1, and physical activity in step 2) were run to predict each well-being outcome. Regression analyses indicated that in general, while Coronavirus fear was a negative predictor, physical activity was a positive and stronger predictor of enhanced mental health and well-being outcomes. Findings suggest that physical activity during the Coronavirus pandemic can counteract the negative effects of Coronavirus fear on adolescent mental health and well-being. Therefore, physical activity should be promoted during lockdown to support good mental health and well-being.
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http://dx.doi.org/10.3389/fpsyg.2021.580511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990778PMC
March 2021

The clinical and microbiological utility of inhaled aztreonam lysine for the treatment of acute pulmonary exacerbations of cystic fibrosis: An open-label randomised crossover study (AZTEC-CF).

J Cyst Fibros 2020 Dec 21. Epub 2020 Dec 21.

Adult CF Centre, Liverpool Heart & Chest Hospital, UK; Institute of Infection & Global Health, University of Liverpool, UK.

Background: The objective of this study was to explore the clinical and microbiological outcomes associated with substituting inhaled aztreonam lysine for an intravenous antibiotic in the treatment of acute pulmonary exacerbations of CF.

Methods: An open-label randomised crossover pilot trial was conducted at a UK CF centre among 16 adults with CF and P. aeruginosa infection. Median [IQR] age was 29.5 [24.5-32.5], mean ± SD forced expiratory volume in 1 second (FEV1) was 52.4 ± 14.7 % predicted. Over the course of two exacerbations, participants were randomised to sequentially receive 14 days of inhaled aztreonam lysine plus IV colistimethate (AZLI+IV), or dual IV antibiotics (IV+IV). Primary outcome was absolute change in % predicted FEV1. Other outcomes evaluated changes in quality of life, bacterial load and the lung microbiota.

Results: The difference between mean change in lung function at day 14 between AZLI+IV and IV+IV was +4.6% (95% CI 2.1-7.2, p=0.002). The minimum clinically important difference of the Cystic Fibrosis Revised Questionnaire (CFQ-R) was achieved more frequently with AZLI+IV (10/12, 83.3%) than IV+IV (7/16, 43.8%), p=0.05. No differences were observed for modulation of serum white cell count, C-reactive protein or sputum bacterial load. Microbiome compositional changes were observed with IV+IV (Bray-Curtis r=0.14, p=0.02), but not AZLI+IV (r=0.03, p=0.64).

Conclusion: In adults with CF and P. aeruginosa infection experiencing an acute pulmonary exacerbation, AZLI+IV improved lung function and quality of life compared to the current standard treatment. These findings support the need for larger definitive trials of inhaled antibiotics in the acute setting.

Clinical Trial Registration: EudraCT 2016-002832-34 ClinicalTrials.org NCT02894684.
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http://dx.doi.org/10.1016/j.jcf.2020.12.012DOI Listing
December 2020

Optimizing and Profiling Prostaglandin E2 as a Medical Countermeasure for the Hematopoietic Acute Radiation Syndrome.

Radiat Res 2021 02;195(2):115-127

Department of a Medicine, Division of Hematology/Oncology, Indiana University School of Medicine, Indianapolis, Indiana 46202.

Identification of medical countermeasures (MCM) to mitigate radiation damage and/or protect first responders is a compelling unmet medical need. The prostaglandin E2 (PGE2) analog, 16,16 dimethyl-PGE2 (dmPGE2), has shown efficacy as a radioprotectant and radiomitigator that can enhance hematopoiesis and ameliorate intestinal mucosal cell damage. In this study, we optimized the time of administration of dmPGE2 for protection and mitigation against mortality from the hematopoietic acute radiation syndrome (H-ARS) in young adult mice, evaluated its activity in pediatric and geriatric populations, and investigated potential mechanisms of action. Windows of 30-day survival efficacy for single administration of dmPGE2 were defined as within 3 h prior to and 6-30 h after total-body γ irradiation (TBI). Radioprotective and radio-mitigating efficacy was also observed in 2-year-old geriatric mice and 6-week-old pediatric mice. PGE2 receptor agonist studies suggest that signaling through EP4 is primarily responsible for the radioprotective effects. DmPGE2 administration prior to TBI attenuated the drop in red blood cells and platelets, accelerated recovery of all peripheral blood cell types, and resulted in higher hematopoietic and mesenchymal stem cells in survivor bone marrow. Multiplex analysis of bone marrow cytokines together with RNA sequencing of hematopoietic stem cells indicated a pro-hematopoiesis cytokine milieu induced by dmPGE2, with IL-6 and G-CSF strongly implicated in dmPGE2-mediated radioprotective activity. In summary, we have identified windows of administration for significant radio-mitigation and radioprotection by dmPGE2 in H-ARS, demonstrated survival efficacy in special populations, and gained insight into radioprotective mechanisms, information useful towards development of dmPGE2 as a MCM for first responders, military personnel, and civilians facing radiation threats.
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http://dx.doi.org/10.1667/RADE-20-00181.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929087PMC
February 2021

Mechanical suppression of breast cancer cell invasion and paracrine signaling to osteoclasts requires nucleo-cytoskeletal connectivity.

Bone Res 2020 Nov 17;8(1):40. Epub 2020 Nov 17.

Department of Physical Therapy, School of Health and Rehabilitation Sciences, Indiana University, Indianapolis, IN, 46202, USA.

Exercise benefits the musculoskeletal system and reduces the effects of cancer. The effects of exercise are multifactorial, where metabolic changes and tissue adaptation influence outcomes. Mechanical signals, a principal component of exercise, are anabolic to the musculoskeletal system and restrict cancer progression. We examined the mechanisms through which cancer cells sense and respond to low-magnitude mechanical signals introduced in the form of vibration. Low-magnitude, high-frequency vibration was applied to human breast cancer cells in the form of low-intensity vibration (LIV). LIV decreased matrix invasion and impaired secretion of osteolytic factors PTHLH, IL-11, and RANKL. Furthermore, paracrine signals from mechanically stimulated cancer cells, reduced osteoclast differentiation and resorptive capacity. Disconnecting the nucleus by knockdown of SUN1 and SUN2 impaired LIV-mediated suppression of invasion and osteolytic factor secretion. LIV increased cell stiffness; an effect dependent on the LINC complex. These data show that mechanical vibration reduces the metastatic potential of human breast cancer cells, where the nucleus serves as a mechanosensory apparatus to alter cell structure and intercellular signaling.
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http://dx.doi.org/10.1038/s41413-020-00111-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673025PMC
November 2020

Clinical and Demographic Characteristics of Upper Limb Dystonia.

Mov Disord 2020 11 26;35(11):2086-2090. Epub 2020 Aug 26.

Departments of Neurology and Radiology, Washington University School of Medicine, St. Louis, Missouri, USA.

Background: Knowledge of characteristics in upper limb dystonia remains limited, derived primarily from small, single-site studies.

Objective: The objective of this study was to characterize demographic and clinical characteristics of upper limb dystonia from the Dystonia Coalition data set, a large, international, multicenter resource.

Methods: We evaluated clinical and demographic characteristics of 367 participants with upper limb dystonia from onset, comparing across subcategories of focal (with and without dystonia spread) versus nonfocal onset.

Results: Focal onset occurred in 80%; 67% remained focal without spread. Task specificity was most frequent in this subgroup, most often writer's cramp and affecting the dominant limb (83%). Focal onset with spread was more frequent in young onset (<21 years). Focal onset occurred equally in women and men; nonfocal onset affected women disproportionately.

Conclusions: Upper limb dystonia distribution, focality, and task specificity relate to onset age and likelihood of regional spread. Observations may inform clinical counseling and design, execution, and interpretation of future studies. © 2020 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28223DOI Listing
November 2020

A megaplasmid family driving dissemination of multidrug resistance in Pseudomonas.

Nat Commun 2020 03 13;11(1):1370. Epub 2020 Mar 13.

Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.

Multidrug resistance (MDR) represents a global threat to health. Here, we used whole genome sequencing to characterise Pseudomonas aeruginosa MDR clinical isolates from a hospital in Thailand. Using long-read sequence data we obtained complete sequences of two closely related megaplasmids (>420 kb) carrying large arrays of antibiotic resistance genes located in discrete, complex and dynamic resistance regions, and revealing evidence of extensive duplication and recombination events. A comprehensive pangenomic and phylogenomic analysis indicates that: 1) these large plasmids comprise an emerging family present in different members of the Pseudomonas genus, and associated with multiple sources (geographical, clinical or environmental); 2) the megaplasmids encode diverse niche-adaptive accessory traits, including multidrug resistance; 3) the accessory genome of the megaplasmid family is highly flexible and diverse. The history of the megaplasmid family, inferred from our analysis of the available database, suggests that members carrying multiple resistance genes date back to at least the 1970s.
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http://dx.doi.org/10.1038/s41467-020-15081-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070040PMC
March 2020

Re-drawing the Maps for Endemic Mycoses.

Mycopathologia 2020 Oct 10;185(5):843-865. Epub 2020 Feb 10.

Division of Infectious Diseases, Department of Internal Medicine, University of Kansas, Kansas City, KS, USA.

Endemic mycoses such as histoplasmosis, coccidioidomycosis, blastomycosis, paracoccidioidomycosis, and talaromycosis are well-known causes of focal and systemic disease within specific geographic areas of known endemicity. However, over the past few decades, there have been increasingly frequent reports of infections due to endemic fungi in areas previously thought to be "non-endemic." There are numerous potential reasons for this shift such as increased use of immune suppressive medications, improved diagnostic tests, increased disease recognition, and global factors such as migration, increased travel, and climate change. Regardless of the causes, it has become evident that our previous understanding of endemic regions for these fungal diseases needs to evolve. The epidemiology of the newly described Emergomyces is incomplete; our understanding of it continues to evolve. This review will focus on the evidence underlying the established areas of endemicity for these mycoses as well as new data and reports from medical literature that support the re-thinking these geographic boundaries. Updating the endemic fungi maps would inform clinical practice and global surveillance of these diseases.
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http://dx.doi.org/10.1007/s11046-020-00431-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416457PMC
October 2020

Pain is Associated With Increased Physical and Psychosocial Impairment in Youth With a History of Burn Injuries.

J Pain 2020 Mar - Apr;21(3-4):355-363. Epub 2019 Aug 8.

Division of Pain Medicine, Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.

Burn injuries are significantly painful and associated with physical and psychological impairment. However, little research to-date has examined the potential role of the subjective experience of pain in either physical or psychological impairment in this population. This may be particularly important to examine, given that the pain experience can often be a significant barrier to recovery in other pediatric populations. The current study examined the cross-sectional and predictive relationships between patient-reported experience of pain (operationalized as PROMIS pain interference and self-reported pain intensity) and physical and psychosocial outcomes. Data were gathered as part of the Burn Model System National Database (1994-2018) with the data request inclusive of pediatric self-report PROMIS measures, child PTSD, and post-traumatic growth symptoms assessed at 6- and 12-month postdischarge following initial injury. A total of 65 youth between the ages of 6 and 16 years at the time of their injury were included in the dataset. Correlational and regression analyses indicated that pain interference was cross-sectionally and longitudinally associated with decreased physical functioning, depressive symptoms, and peer relationships. Pain intensity was significantly associated with and predictive of physical functioning and pain interference. Results of the current study are an important first step in understanding the pain experience and associated outcomes in youth with a history of burn injuries. Future research is needed to further examine these relationships. PERSPECTIVE: This study presents preliminary findings from a national database on pain-related outcomes both cross-sectionally and longitudinally in youth with a history of burn injury. To-date, pain-related outcomes are poorly understood in this population and the results of this study serve to inform future research and treatment-related efforts.
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http://dx.doi.org/10.1016/j.jpain.2019.08.002DOI Listing
August 2019

Adding Value by Working with Sponsored Projects.

Med Ref Serv Q 2019 Jul-Sep;38(3):211-217

a Rudolph Matas Library of the Health Sciences, Tulane University , New Orleans , Louisiana , USA.

This case study describes how librarians at Rudolph Matas Library of the Health Sciences at Tulane University have partnered and worked with several departments that fall under the Vice President of Research. Examples include detailed literature searches, cooperative purchasing, and clinical trial registration. Some upcoming activities and opportunities for collaboration will also be discussed. Finally, the authors will share some valuable lessons learned through the process of collaboration with the research infrastructure of the university.
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http://dx.doi.org/10.1080/02763869.2019.1623603DOI Listing
January 2020

Reservoirs of resistance: polymyxin resistance in veterinary-associated companion animal isolates of .

Vet Rec 2019 08 25;185(7):206. Epub 2019 Jun 25.

Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.

Background: is an opportunistic pathogen and a major cause of infections. Widespread resistance in human infections are increasing the use of last resort antimicrobials such as polymyxins. However, these have been used for decades in veterinary medicine. Companion animals are an understudied source of antimicrobial resistant isolates. This study evaluated the susceptibility of veterinary isolates to polymyxins to determine whether the veterinary niche represents a potential reservoir of resistance genes for pathogenic bacteria in both animals and humans.

Methods And Results: Clinical isolates (n=24) from UK companion animals were compared for antimicrobial susceptibility to a panel of human-associated isolates (n=37). Minimum inhibitory concentration (MIC) values for polymyxin B and colistin in the companion animals was significantly higher than in human isolates (P=0.033 and P=0.013, respectively). Genotyping revealed that the veterinary isolates were spread throughout the population, with shared array types from human infections such as keratitis and respiratory infections, suggesting the potential for zoonotic transmission. Whole genome sequencing revealed mutations in genes associated with polymyxin resistance and other antimicrobial resistance-related genes.

Conclusion: The high levels of resistance to polymyxin shown here, along with genetic similarities between some human and animal isolates, together suggest a need for sustained surveillance of this veterinary niche as a potential reservoir for resistant, clinically relevant bacteria in both animals and humans.
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http://dx.doi.org/10.1136/vr.105075DOI Listing
August 2019

Combating osteoporosis and obesity with exercise: leveraging cell mechanosensitivity.

Nat Rev Endocrinol 2019 06;15(6):339-355

Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA.

Osteoporosis, a condition of skeletal decline that undermines quality of life, is treated with pharmacological interventions that are associated with poor adherence and adverse effects. Complicating efforts to improve clinical outcomes, the incidence of obesity is increasing, predisposing the population to a range of musculoskeletal complications and metabolic disorders. Pharmacological management of obesity has yet to deliver notable reductions in weight and debilitating complications are rarely avoided. By contrast, exercise shows promise as a non-invasive and non-pharmacological method of regulating both osteoporosis and obesity. The principal components of exercise - mechanical signals - promote bone and muscle anabolism while limiting formation and expansion of fat mass. Mechanical regulation of bone and marrow fat might be achieved by regulating functions of differentiated cells in the skeletal tissue while biasing lineage selection of their common progenitors - mesenchymal stem cells. An inverse relationship between adipocyte versus osteoblast fate selection from stem cells is implicated in clinical conditions such as childhood obesity and increased marrow adiposity in type 2 diabetes mellitus, as well as contributing to skeletal frailty. Understanding how exercise-induced mechanical signals can be used to improve bone quality while decreasing fat mass and metabolic dysfunction should lead to new strategies to treat chronic diseases such as osteoporosis and obesity.
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http://dx.doi.org/10.1038/s41574-019-0170-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520125PMC
June 2019

UP1306: A Composition Containing Standardized Extracts of and for Arthritis Management.

Nutrients 2019 Jan 26;11(2). Epub 2019 Jan 26.

Unigen Inc., 2121 South State Street, Suite 400, Tacoma, WA 98405, USA.

Osteoarthritis (OA) is characterized by progressive articular cartilage degradation. Although there have been significant advances in OA management, to date, there are no effective treatment options to modify progression of the disease. We believe these unmet needs could be bridged by nutrients from natural products. Collagen induced arthritis in rats was developed and utilized to evaluate anti-inflammatory and cartilage protection activity of orally administered botanical composition, UP1306 (50 mg/kg) and Methotrexate (75 µg/kg) daily for three weeks. Objective arthritis severity markers, urine, synovial lavage, and serum were collected. At necropsy, the hock joint from each rat was collected for histopathology analysis. Urinary cartilage degradation marker (CTX-II), pro-inflammatory cytokines (tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6), and proteases (Matrix Metallopeptidase 3 (MMP3) and 13) were measured. Rats treated with UP1306 showed statistically significant improvements in arthritis severity markers, including uCTX-II (91.4% vs. collagen-induced arthritis (CIA)), serum IL-1β, TNF-α, and IL-6 levels as well as synovial MMP-13. The histopathology data were also well aligned with the severity score of arthritis for both UP1306 and Methotrexate. UP1306, a botanical composition that contains a standardized blend of extracts from the heartwood of and the root bark of , could potentially be considered as a dietary supplement product for the management of arthritis.
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http://dx.doi.org/10.3390/nu11020272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413154PMC
January 2019

Union Transitions and Fertility Within First Premarital Cohabitations in Canada: Diverging Patterns by Education?

Authors:
Laura Wright

Demography 2019 02;56(1):151-167

Department of Sociology, University of Saskatchewan, 1019 Arts Building, 9 Campus Drive, Saskatoon, Saskatchewan, S7N 5A5, Canada.

Cohabitation has become increasingly accepted and normalized as part of the family system in Canada and has become the most common way to form a first union. The changing role of cohabitation in the family system is often understood as being driven by the ideational changes associated with the second demographic transition, but increasing international evidence indicates that this explanation is incomplete. Using nationally representative retrospective data from Canadians born between 1940 and 1979 from the 2011 General Social Survey, this study examines transitions out of first premarital cohabitation and fertility within these unions as two measures of the changing role of cohabitation. Across birth cohorts, Canadians are increasingly likely to use cohabitation as an alternative to marriage and less likely to use cohabitation as a short-lived prelude to marriage. These overall trends support the second demographic transition perspective. However, this study also finds that Canadians without a bachelor's degree are far more likely to experience a birth within cohabitation and that their likelihood of transitioning to marriage has declined steeply across birth cohorts. This educational gradient in childbearing in cohabitation and the increasing educational differences in union transitions over time provide support for the diverging destinies thesis in Canada.
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http://dx.doi.org/10.1007/s13524-018-0741-0DOI Listing
February 2019

Improving Patient Safety Through Video Monitoring.

Rehabil Nurs 2018 Mar/Apr;43(2):111-115

Sunnyview Rehabilitation Hospital, Schenectady, NY, USA.

Purpose: Falls are a major safety issue in rehabilitation settings. Patients receive mixed messages-try to be as independent as possible, but don't do anything in your room without calling for assistance. Despite the use of multiple falls interventions at this facility, the fall rate remained high. To impact this rate, the facility implemented a video monitoring system. This system allows for patients at risk for falling to be monitored from a remote location. The monitor technician is able to speak to the patient directly and/or contact staff members to respond to the room, preventing a fall.

Design: Sequential cohort design.

Method: Fifteen video monitoring units were installed on high-risk units in a 115-bed inpatient rehabilitation facility. Total falls and falls rates were tracked and reported pre- and postimplementation.

Findings: Over a 21-month period prior to implementing the video monitoring system, the average hospital-wide rate of falls was 6.34 per 1,000 patient-days (SD = 1.7488). After a year of usage, that average has decreased to 5.099 falls per 1,000 patient-days (SD = 1.524). The reduction in falls was statistically significant. In addition, there have been significant cost savings by reducing sitter usage.

Conclusions: Video monitoring can improve patient safety by decreasing falls; decreasing sitter usage and cost; and improving patient, family, and staff satisfaction.

Clinical Relevance: Falls are a significant issue in rehabilitation settings, and current fall prevention strategies fall short of reducing fall rates. Implementation of new video monitoring technology can help reduce fall rates in inpatient rehabilitation settings.
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http://dx.doi.org/10.1097/RNJ.0000000000000089DOI Listing
June 2018

Implementing Integrated Mental Health and Chaplain Care in a National Quality Improvement Initiative.

Psychiatr Serv 2017 Dec;68(12):1213-1215

Dr. Nieuwsma, Dr. King, Dr. Jackson, Dr. Bidassie, Ms. Wright, Rev. Cantrell, Ms. White, and Dr. Meador are with the U.S. Department of Veterans Affairs (VA). Dr. Nieuwsma, Dr. King, and Dr. Jackson are also with Duke University Medical Center, Durham, North Carolina, and Dr. Meador is also with Vanderbilt University, Nashville, Tennessee. Dr. Bates, Dr. Rhodes, and Ms. Gatewood are with the Department of Defense (DoD), Arlington, Virginia.

This column describes the development, implementation, and outcomes of a quality improvement learning collaborative that aimed to better integrate chaplaincy with mental health care services at 14 participating health care facilities evenly distributed across the U.S. Department of Veterans Affairs and Department of Defense. Teams of health care chaplains and mental health professionals from participating sites sought to improve cross-disciplinary service integration in six key domains: screening, referrals, assessment, communication and documentation, cross-disciplinary training, and role clarification. Chaplains and mental health providers across all facilities at participating sites were significantly more likely post-collaboration to report having a clear understanding of how to collaborate and to report using a routine process for screening patients who could benefit from seeing a professional from the other discipline. Foundational efforts to enhance cross-disciplinary awareness and screening practices between chaplains and mental health professionals appear particularly promising.
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http://dx.doi.org/10.1176/appi.ps.201700397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5726535PMC
December 2017

Healthy Grandparenthood: How Long Is It, and How Has It Changed?

Demography 2017 12;54(6):2073-2099

Department of Sociology, University of Saskatchewan, 1106-9 Campus Drive, Saskatoon, Saskatchewan, S7N 5A5, Canada.

Healthy grandparenthood represents the period of overlap during which grandparents and grandchildren can build relationships, and grandparents can make intergenerational transfers to younger kin. The health of grandparents has important implications for upward and downward intergenerational transfers within kinship networks in aging societies. Although the length of grandparenthood is determined by fertility and mortality patterns, the amount of time spent as a healthy grandparent is also affected by morbidity. In this study, we estimate the length of healthy grandparenthood for the first time. Using U.S. and Canadian data, we examine changes in the length of healthy grandparenthood during years when grandparenthood was postponed, health improved, and mortality declined. We also examine variation in healthy grandparenthood by education and race/ethnicity within the United States. Our findings show that the period of healthy grandparenthood is becoming longer because of improvements in health and mortality, which more than offset delays in grandparenthood. Important variation exists within the United States by race/ethnicity and education, which has important implications for family relationships and transfers.
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http://dx.doi.org/10.1007/s13524-017-0620-0DOI Listing
December 2017

Cartilage Protection and Analgesic Activity of a Botanical Composition Comprised of , , and .

Evid Based Complement Alternat Med 2017 20;2017:7059068. Epub 2017 Aug 20.

Unigen Inc., 3005 1st Ave., Seattle, WA 98121, USA.

Although there have been augmented advances in drug discovery, current OA management is inadequate due to the lack of successful therapies proven to be effective in modifying disease progression. For some, the risk outweighs the benefit. As a result, there is a desperate need for safe and efficacious natural alternatives. Here we evaluated a composition from , , and in maintaining joint structural integrity and alleviating OA associated symptoms in monoiodoacetate- (MIA-) induced rat OA disease model. Study lasted for 6 weeks. 59.6%, 64.6%, 70.7%, 69.9%, and 70.3% reductions in pain sensitivity were observed for rats treated with the composition from week 1 to week 5, respectively. Statistically significant improvements in articular cartilage matrix integrity (maintained at 57.1% versus MIA + vehicle treated rats) were shown from the modified total Mankin score for animals treated with the composition. The composition showed a statistically significant reduction in uCTX-II level (54.1% reductions). The merit of combining these botanicals was also demonstrated in their synergistic analgesic activity. Therefore, the standardized blend of , , and could potentially be considered as an alternative remedy from natural sources for the management of OA and/or its associated symptoms.
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http://dx.doi.org/10.1155/2017/7059068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5585569PMC
August 2017

Emerging Adulthood, Emergent Health Lifestyles: Sociodemographic Determinants of Trajectories of Smoking, Binge Drinking, Obesity, and Sedentary Behavior.

J Health Soc Behav 2017 06 17;58(2):181-197. Epub 2017 Apr 17.

3 University of Saskatchewan, Saskatoon, SK, Canada.

During the transition to adulthood, many unhealthy behaviors are developed that in turn shape behaviors, health, and mortality in later life. However, research on unhealthy behaviors and risky transitions has mostly focused on one health problem at a time. In this article, we examine variation in health behavior trajectories, how trajectories cluster together, and how the likelihood of experiencing different behavior trajectories varies by sociodemographic characteristics. We use the National Longitudinal Study of Adolescent Health (Add Health) Waves I to IV to chart the most common health behavior trajectories over the transition to adulthood for cigarette smoking, alcohol consumption, obesity, and sedentary behavior. We find that health behavior trajectories cluster together in seven joint classes and that sociodemographic factors (including gender, parental education, and race-ethnicity) significantly predict membership in these joint trajectories.
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http://dx.doi.org/10.1177/0022146517702421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5894852PMC
June 2017

A Botanical Composition Mitigates Cartilage Degradations and Pain Sensitivity in Osteoarthritis Disease Model.

J Med Food 2017 Jun 31;20(6):568-576. Epub 2017 Mar 31.

1 Unigen, Inc. , Seattle, Washington, USA.

Osteoarthritis (OA) is a degenerative joint disease characterized by a progressive articular cartilage degradation manifested with significant functional impairment in consort with signs and symptoms of inflammation, stiffness, and loss of mobility. Current OA management is inadequate due to the lack of nominal therapies proven to be effective in hampering disease progression where symptomatic therapy focused intervention masks the primary etiology leading to irreversible structural damage. In this study, we describe the effect of UP1306, a composition containing a proprietary blend of two standardized extracts from the heartwood of Acacia catechu and the root bark of Morus alba, in maintaining joint structural integrity and alleviating OA associated symptoms in monosodium-iodoacetate (MIA)-induced rat OA disease model. Data from pain sensitivity, histopathology, and glycosaminoglycan (GAG) level were analyzed. Diclofenac at 10 mg/kg was used as a reference compound. Ex vivo proteoglycan protection model demonstrated 31.5%, 50.0%, and 54.8% inhibitions of proteoglycan degradations from UP1306 at concentrations of 50, 100, and 200 μg/mL, respectively. The merit of combining two bioflavonoid standardized extracts from A. catechu and M. alba was demonstrated in their Ex vivo synergistic proteoglycan protection activity. In the MIA in vivo OA model, administered orally at 500 mg/kg, UP1306 resulted in reductions of 17.5%, 29.0%, 34.4%, 33.5%, and 40.9% through week 1-5 in pain sensitivity, statistically significant improvements in articular cartilage matrix integrity, and minimal subchondral bone damage. Therefore, UP1306 could potentially be considered as an alternative remedy from natural sources for the management of OA and/or its associated symptoms.
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http://dx.doi.org/10.1089/jmf.2016.0167DOI Listing
June 2017

Spectral Shearing of Quantum Light Pulses by Electro-Optic Phase Modulation.

Phys Rev Lett 2017 Jan 9;118(2):023601. Epub 2017 Jan 9.

Clarendon Laboratory, University of Oxford, Parks Road, Oxford OX1 3PU, United Kingdom.

Frequency conversion of nonclassical light enables robust encoding of quantum information based upon spectral multiplexing that is particularly well-suited to integrated-optics platforms. Here we present an intrinsically deterministic linear-optics approach to spectral shearing of quantum light pulses and show it preserves the wave-packet coherence and quantum nature of light. The technique is based upon an electro-optic Doppler shift to implement frequency shear of heralded single-photon wave packets by ±200  GHz, which can be scaled to an arbitrary shift. These results demonstrate a reconfigurable method to controlling the spectral-temporal mode structure of quantum light that could achieve unitary operation.
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http://dx.doi.org/10.1103/PhysRevLett.118.023601DOI Listing
January 2017

Aromatase inhibitor-induced bone loss increases the progression of estrogen receptor-negative breast cancer in bone and exacerbates muscle weakness in vivo.

Oncotarget 2017 Jan;8(5):8406-8419

Department of Medicine, Division of Endocrinology, Indiana University, Indianapolis, IN, USA.

Aromatase inhibitors (AIs) cause muscle weakness, bone loss, and joint pain in up to half of cancer patients. Preclinical studies have demonstrated that increased osteoclastic bone resorption can impair muscle contractility and prime the bone microenvironment to accelerate metastatic growth. We hypothesized that AI-induced bone loss could increase breast cancer progression in bone and exacerbate muscle weakness associated with bone metastases. Female athymic nude mice underwent ovariectomy (OVX) or sham surgery and were treated with vehicle or AI (letrozole; Let). An OVX-Let group was then further treated with bisphosphonate (zoledronic acid; Zol). At week three, trabecular bone volume was measured and mice were inoculated with MDA-MB-231 cells into the cardiac ventricle and followed for progression of bone metastases. Five weeks after tumor cell inoculation, tumor-induced osteolytic lesion area was increased in OVX-Let mice and reduced in OVX-Let-Zol mice compared to sham-vehicle. Tumor burden in bone was increased in OVX-Let mice relative to sham-vehicle and OVX-Let-Zol mice. At the termination of the study, muscle-specific force of the extensor digitorum longus muscle was reduced in OVX-Let mice compared to sham-vehicle mice, however, the addition of Zol improved muscle function. In summary, AI treatment induced bone loss and skeletal muscle weakness, recapitulating effects observed in cancer patients. Prevention of AI-induced osteoclastic bone resorption using a bisphosphonate attenuated the development of breast cancer bone metastases and improved muscle function in mice. These findings highlight the bone microenvironment as a modulator of tumor growth locally and muscle function systemically.
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http://dx.doi.org/10.18632/oncotarget.14139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352410PMC
January 2017

Murine models of breast cancer bone metastasis.

Bonekey Rep 2016 11;5:804. Epub 2016 May 11.

Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN, USA; Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN, USA.

Bone metastases cause significant morbidity and mortality in late-stage breast cancer patients and are currently considered incurable. Investigators rely on translational models to better understand the pathogenesis of skeletal complications of malignancy in order to identify therapeutic targets that may ultimately prevent and treat solid tumor metastasis to bone. Many experimental models of breast cancer bone metastases are in use today, each with its own caveats. In this methods review, we characterize the bone phenotype of commonly utilized human- and murine-derived breast cell lines that elicit osteoblastic and/or osteolytic destruction of bone in mice and report methods for optimizing tumor-take in murine models of bone metastasis. We then provide protocols for four of the most common xenograft and syngeneic inoculation routes for modeling breast cancer metastasis to the skeleton in mice, including the intra-cardiac, intra-arterial, orthotopic and intra-tibial methods of tumor cell injection. Recommendations for and assessment of tumor progression and bone destruction are provided, followed by discussion of the strengths and limitations of the available tools and translational models that aid investigators in the study of breast cancer metastasis to bone.
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http://dx.doi.org/10.1038/bonekey.2016.31DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5108088PMC
May 2016

Clinical and demographic characteristics related to onset site and spread of cervical dystonia.

Mov Disord 2016 12 18;31(12):1874-1882. Epub 2016 Oct 18.

Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.

Background: Clinical characteristics of isolated idiopathic cervical dystonia such as onset site and spread to and from additional body regions have been addressed in single-site studies with limited data and incomplete or variable dissociation of focal and segmental subtypes. The objectives of this study were to characterize the clinical characteristics and demographics of isolated idiopathic cervical dystonia in the largest standardized multicenter cohort.

Methods: The Dystonia Coalition, through a consortium of 37 recruiting sites in North America, Europe, and Australia, recruited 1477 participants with focal (60.7%) or segmental (39.3%) cervical dystonia on examination. Clinical and demographic characteristics were evaluated in terms of the body region of dystonia onset and spread.

Results: Site of dystonia onset was: (1) focal neck only (78.5%), (2) focal onset elsewhere with later segmental spread to neck (13.3%), and (3) segmental onset with initial neck involvement (8.2%). Frequency of spread from focal cervical to segmental dystonia (22.8%) was consistent with prior reports, but frequency of segmental onset with initial neck involvement was substantially higher than the 3% previously reported. Cervical dystonia with focal neck onset, more than other subtypes, was associated with spread and tremor of any type. Sensory tricks were less frequent in cervical dystonia with segmental components, and segmental cervical onset occurred at an older age.

Conclusions: Subgroups had modest but significant differences in the clinical characteristics that may represent different clinical entities or pathophysiologic subtypes. These findings are critical for design and implementation of studies to describe, treat, or modify disease progression in idiopathic isolated cervical dystonia. © 2016 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.26817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5154862PMC
December 2016

Enhanced Surveillance for Fatal Dengue-Like Acute Febrile Illness in Puerto Rico, 2010-2012.

PLoS Negl Trop Dis 2016 Oct 11;10(10):e0005025. Epub 2016 Oct 11.

Dengue Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention (CDC), San Juan, Puerto Rico.

Background: Dengue is a leading cause of morbidity throughout the tropics; however, accurate population-based estimates of mortality rates are not available.

Methods/principal Findings: We established the Enhanced Fatal Acute Febrile Illness Surveillance System (EFASS) to estimate dengue mortality rates in Puerto Rico. Healthcare professionals submitted serum and tissue specimens from patients who died from a dengue-like acute febrile illness, and death certificates were reviewed to identify additional cases. Specimens were tested for markers of dengue virus (DENV) infection by molecular, immunologic, and immunohistochemical methods, and were also tested for West Nile virus, Leptospira spp., and other pathogens based on histopathologic findings. Medical records were reviewed and clinical data abstracted. A total of 311 deaths were identified, of which 58 (19%) were DENV laboratory-positive. Dengue mortality rates were 1.05 per 100,000 population in 2010, 0.16 in 2011 and 0.36 in 2012. Dengue mortality was highest among adults 19-64 years and seniors ≥65 years (1.17 and 1.66 deaths per 100,000, respectively). Other pathogens identified included 34 Leptospira spp. cases and one case of Burkholderia pseudomallei and Neisseria meningitidis.

Conclusions/significance: EFASS showed that dengue mortality rates among adults were higher than reported for influenza, and identified a leptospirosis outbreak and index cases of melioidosis and meningitis.
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http://dx.doi.org/10.1371/journal.pntd.0005025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5058557PMC
October 2016

Incidence, Treatment Intensity, and Incremental Annual Expenditures for Patients Experiencing a Cardiac Implantable Electronic Device Infection: Evidence From a Large US Payer Database 1-Year Post Implantation.

Circ Arrhythm Electrophysiol 2016 08;9(8)

From the Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN (M.R.S.); CRHF HEOR, Reimbursement and Evidence, Medtronic, Plc, Mounds View, MN (E.L.E.); Health Economics and Outcomes Research (M.P.R., C.G.) and Regulatory & Scientific Affairs (L.A.W.), CTI Clinical Trial and Consulting Services, Inc, Cincinnati, OH; and Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA (A.J.G.).

Background: Because of the increasing use of cardiac implantable electronic devices (CIEDs), it is important to estimate the incidence and annual healthcare expenditures associated with CIED infections.

Methods And Results: Patients with a record of an initial or replacement (full implant or generator only) CIED implant during the calendar years 2009 to 2012 in MarketScan Commercial Claims and Medicare Supplemental database were identified. CIED infections were classified into 4 categories: (1) infection not managed by inpatient admission nor implant removal, (2) infection managed by inpatient admission but no implant removal, (3) infection managed by an implant removal either in an inpatient or in an outpatient setting, and (4) infection with severe sepsis and managed in an inpatient setting with implant removal. Using separate models for initial and replacement cohorts, annualized incidence of infection and incremental annual expenditures by treatment intensity were estimated. Cumulative incidence of infection at 1 year post implant was 1.18% for initial CIED implants and 2.37% for replacement. Median time to infection was 35 days for initial and 23 days for replacement. Incremental healthcare expenditures by treatment intensity categories for initial implant patients at 1 year were $16 651, $104 077, $45 291, and $279 744. For replacement patients, incremental expenditures at 1 year by treatment intensity categories were $26 857, $43 541, $48 759, and $362 606.

Conclusions: The management of CIED infections results in a substantial healthcare burden with a significant increase in annual expenditures the year after implant when device infection occurs.
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http://dx.doi.org/10.1161/CIRCEP.116.003929DOI Listing
August 2016

SPM-1 metallo-β-lactamase-producing Pseudomonas aeruginosa ST277 in the UK.

J Med Microbiol 2016 Jul 27;65(7):696-697. Epub 2016 Apr 27.

Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, National Infection Service, Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK.

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http://dx.doi.org/10.1099/jmm.0.000269DOI Listing
July 2016

Clinical and genetic features of cervical dystonia in a large multicenter cohort.

Neurol Genet 2016 Jun 11;2(3):e69. Epub 2016 Apr 11.

Departments of Neurology and Anatomy & Neurobiology (M.S.L., S.R.V., J.X., M.M.T.), University of Tennessee Health Science Center, Memphis, TN; Department of Neurology (J.S.P., L.J.W.), Washington University School of Medicine, St. Louis, MO; Departments of Neurology (A.R.R.), Human Genetics, and Pediatrics (H.A.J.), School of Medicine, Emory University, Atlanta, GA; Department of Neurology (P.H.), Vanderbilt University, Nashville, TN; Department of Neurological Sciences (C.L.C.), Rush University, Chicago, IL; Institute of Neurogenetics (A.W., J. Junker), University of Lübeck, Germany; Department of Neurology (J. Jankovic), Baylor College of Medicine, Houston, TX; Department of Neurology (R.L.B.), University of Rochester, NY; Department of Neurology (S.G.R.), University of Maryland, Baltimore, MD; Department of Neurology (R.L.R.), University of Florida, Gainesville, FL; Department of Neurology (B.D.B.), University of Colorado Denver School of Medicine, Aurora, CO; Center of Excellence in Neuroscience (S.C.), University of Montreal, QC, Canada; Mirken Department of Neurology (L.S.), Mt. Sinai Beth Israel Medical Center, New York, NY; Booth Gardner Parkinson's Care Center (P.A.), Kirkland, WA; and Department of Neurology (N.P.S.), University of Alabama at Birmingham, AL.

Objective: To characterize the clinical and genetic features of cervical dystonia (CD).

Methods: Participants enrolled in the Dystonia Coalition biorepository (NCT01373424) with initial manifestation as CD were included in this study (n = 1,000). Data intake included demographics, family history, and the Global Dystonia Rating Scale. Participants were screened for sequence variants (SVs) in GNAL, THAP1, and Exon 5 of TOR1A.

Results: The majority of participants were Caucasian (95%) and female (75%). The mean age at onset and disease duration were 45.5 ± 13.6 and 14.6 ± 11.8 years, respectively. At the time of assessment, 68.5% had involvement limited to the neck, shoulder(s), and proximal arm(s), whereas 47.4% had dystonia limited to the neck. The remaining 31.5% of the individuals exhibited more extensive anatomical spread. A head tremor was noted in 62% of the patients. Head tremor and laryngeal dystonia were more common in females. Psychiatric comorbidities, mainly depression and anxiety, were reported by 32% of the participants and were more common in females. Family histories of dystonia, parkinsonian disorder, and tremor were present in 14%, 11%, and 29% of the patients, respectively. Pathogenic or likely pathogenic SVs in THAP1, TOR1A, and GNAL were identified in 8 participants (0.8%). Two individuals harbored novel missense SVs in Exon 5 of TOR1A. Synonymous and noncoding SVs in THAP1 and GNAL were identified in 4% of the cohort.

Conclusions: Head tremor, laryngeal dystonia, and psychiatric comorbidities are more common in female participants with CD. Coding and noncoding variants in GNAL, THAP1, and TOR1A make small contributions to the pathogenesis of CD.
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http://dx.doi.org/10.1212/NXG.0000000000000069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4830199PMC
June 2016

Development of the Comprehensive Cervical Dystonia Rating Scale: Methodology.

Mov Disord Clin Pract 2015 Jun 6;2(2):135-141. Epub 2015 Apr 6.

Rush Medical School, Chicago, Illinois, USA.

We present the methodology utilized for development and clinimetric testing of the Comprehensive Cervical Dystonia (CD) Rating scale, or CCDRS. The CCDRS includes a revision of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS-2), a newly developed psychiatric screening tool (TWSTRS-PSYCH), and the previously validated Cervical Dystonia Impact Profile (CDIP-58). For the revision of the TWSTRS, the original TWSTRS was examined by a committee of dystonia experts at a dystonia rating scales workshop organized by the Dystonia Medical Research Foundation. During this workshop, deficiencies in the standard TWSTRS were identified and recommendations for revision of the severity and pain subscales were incorporated into the TWSTRS-2. Given that no scale currently evaluates the psychiatric features of cervical dystonia (CD), we used a modified Delphi methodology and a reiterative process of item selection to develop the TWSTRS-PSYCH. We also included the CDIP-58 to capture the impact of CD on quality of life. The three scales (TWSTRS2, TWSTRS-PSYCH, and CDIP-58) were combined to construct the CCDRS. Clinimetric testing of reliability and validity of the CCDRS are described. The CCDRS was designed to be used in a modular fashion that can measure the full spectrum of CD. This scale will provide rigorous assessment for studies of natural history as well as novel symptom-based or disease-modifying therapies.
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http://dx.doi.org/10.1002/mdc3.12131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4827152PMC
June 2015

Carbapenem resistance mediated by blaOXA-181 in Pseudomonas aeruginosa.

J Antimicrob Chemother 2016 07 23;71(7):2056-7. Epub 2016 Mar 23.

Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, National Infection Service, Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK

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http://dx.doi.org/10.1093/jac/dkw087DOI Listing
July 2016

Older Adults With Three Generations of Kin: Prevalence, Correlates, and Transfers.

J Gerontol B Psychol Sci Soc Sci 2017 Oct;72(6):1067-1072

Department of Sociology, University of Alberta, Edmonton, Canada.

Objectives: We document the prevalence and sociodemographic correlates of older adults with three generations of living kin and examine the patterns of transfers among this group compared with those with fewer generations of kin available.

Method: We use the Health and Retirement Study (1998-2010) to estimate kin availability and intergenerational transfers among respondents in their 50s, 60s, and 70s.

Results: It is far more common for older adults to have aging parents, children, and grandchildren than to have just two generations of kin (parents and children). Forty percent of adults in their 50s, 30% of those in their 60s, and 7.5% of those in their 70s have three generations of kin available. Hispanics and the least educated are more likely to have this generational configuration. The vast majority provides financial or in-kind transfers to at least one generation, and a large minority provides support to both older and younger generations.

Discussion: Although there has been much concern about the strains among those sandwiched between parents and children, it is far more common among older adults to also have grandchildren, and many of these adults are transferring resources both upward and downward to multiple generations.
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http://dx.doi.org/10.1093/geronb/gbv158DOI Listing
October 2017