Do Viruses Require the Cytoskeleton?

Background: It is generally thought that viruses require the cytoskeleton during their replication cycle. However, recent experiments in our laboratory with rubella virus, a member of the family Togaviridae (genus rubivirus), revealed that replication proceeded in the presence of drugs that inhibit microtubules. This study was done to expand on this observation. Findings: The replication of three diverse viruses, Sindbis virus (SINV; family Togaviridae family), vesicular stomatitis virus (VSV; family Rhabdoviridae), and Herpes simplex virus (family Herpesviridae), was quantified by the titer (plaque forming units/ml; pfu/ml) produced in cells treated with one of three anti-microtubule drugs (colchicine, noscapine, or paclitaxel) or the anti-actin filament drug, cytochalasin D. None of these drugs affected the replication these viruses. Specific steps in the SINV infection cycle were examined during drug treatment to determine if alterations in specific steps in the virus replication cycle in the absence of a functional cytoskeletal system could be detected, i.e. redistribution of viral proteins and replication complexes or increases/decreases in their abundance. These investigations revealed that the observable impacts were a colchicine-mediated fragmentation of the Golgi apparatus and concomitant intracellular redistribution of the virion structural proteins, along with a reduction in viral genome and sub-genome RNA levels, but not double-stranded RNA or protein levels. Conclusions: The failure of poisons affecting the cytoskeleton to inhibit the replication of a diverse set of viruses strongly suggests that viruses do not require a functional cytoskeletal system for replication, either because they do not utilize it or are able to utilize alternate pathways when it is not available

A mobile phone text messaging intervention to manage fatigue for people with multiple sclerosis, spinal cord injury, and stroke: Development and usability testing

BACKGROUND: Fatigue significantly affects daily functioning in persons with disabilities. Fatigue management can be challenging, and the information provided during routine physician visits to manage fatigue can be overwhelming. One way to address fatigue is to increase knowledge, skills, and confidence for self-management (ie, patient activation). Self-management programs have shown promising effects in targeting fatigue in persons with disabilities. However, satisfaction with self-management programs is low for persons with disabilities, and tailoring interventions to personalized needs has been recommended. SMS text messaging is increasingly being used to implement health behavior change interventions in a person\u27s natural environment. Little has been done to link mobile health approaches with patient activation and self-management to address fatigue in persons with disabilities. OBJECTIVE: This study aimed to develop and test a mobile phone-based fatigue self-management SMS text messaging intervention targeting patient activation in 3 groups of persons with disabilities: persons with multiple sclerosis, persons who had a stroke, and persons with a spinal cord injury. METHODS: We used evidence-based resources and input from a consumer advisory board (CAB; composed of 2 participants from each of the 3 disability groups) and a neurologist to develop the intervention. The study was conducted using a 4-step process: development of the initial SMS text messaging library and categorization of the content into 9 content areas, review and modification of the SMS text messages by the neurologist and CAB, integration of the content library into a digital platform, and utility testing by CAB members. RESULTS: A total of 6 CAB participants rated SMS text messages covering 9 domain areas of fatigue self-management with good clarity (mean ratings=3.5-5.0 out of 5) and relevance (mean ratings=3.2-5.0 out of 5). Overall, SMS text messaging content was reported by CAB participants as helpful, clear, and well suited for a mobile health intervention. The CAB reached consensus on the time of day that SMS text messages should be sent (morning) and their frequency (once per day). This feedback led the research team to narrow down the program to deliver 48 SMS text messages, 1 per day, Monday through Thursday only, a total of 4 SMS text messages per week, over a 12-week period. The final set of SMS text messages was programmed into a digital platform with a predefined delivery schedule. The usability of the intervention was high, with 55 (83%) out of 66 responses endorsing the highest rating. CONCLUSIONS: This study demonstrates a step-by-step process for developing a fatigue self-management SMS text messaging intervention for persons with disabilities. For this population, whose access to health services is often limited, this intervention provides an alternative delivery model to increase access to fatigue information and deliver content that aligns with the person\u27s needs

Deletion in chromosome 6 spanning alpha-synuclein and multimerin1 loci in the Rab27a/b double knockout mouse

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Pattanayak, R., Underwood, R., Crowley, M. R., Crossman, D. K., Morgan, J. R., & Yacoubian, T. A. Deletion in chromosome 6 spanning alpha-synuclein and multimerin1 loci in the Rab27a/b double knockout mouse. Scientific Reports, 12(1), (2022): 9837, https://doi.org/10.1038/s41598-022-13557-8.We report an incidental 358.5 kb deletion spanning the region encoding for alpha-synuclein (αsyn) and multimerin1 (Mmrn1) in the Rab27a/Rab27b double knockout (DKO) mouse line previously developed by Tolmachova and colleagues in 2007. Western blot and RT-PCR studies revealed lack of αsyn expression at either the mRNA or protein level in Rab27a/b DKO mice. PCR of genomic DNA from Rab27a/b DKO mice demonstrated at least partial deletion of the Snca locus using primers targeted to exon 4 and exon 6. Most genes located in proximity to the Snca locus, including Atoh1, Atoh2, Gm5570, Gm4410, Gm43894, and Grid2, were shown not to be deleted by PCR except for Mmrn1. Using whole genomic sequencing, the complete deletion was mapped to chromosome 6 (60,678,870–61,037,354), a slightly smaller deletion region than that previously reported in the C57BL/6J substrain maintained by Envigo. Electron microscopy of cortex from these mice demonstrates abnormally enlarged synaptic terminals with reduced synaptic vesicle density, suggesting potential interplay between Rab27 isoforms and αsyn, which are all highly expressed at the synaptic terminal. Given this deletion involving several genes, the Rab27a/b DKO mouse line should be used with caution or with appropriate back-crossing to other C57BL/6J mouse substrain lines without this deletion.This study was supported by NIH [R56NS115767 (TAY), RF1NS115767-01A1 (TAY), P50NS108675 (TAY), and NINDS/NIA RF1NS078165 (JRM)]

Six-Minute Walk Test Performance in Persons With Multiple Sclerosis While Using Passive or Powered Ankle-Foot Orthoses

Objective To determine whether a powered ankle-foot orthosis (AFO) that provides dorsiflexor and plantar flexor assistance at the ankle can improve walking endurance of persons with multiple sclerosis (MS). Design Short-term intervention. Setting University research laboratory. Participants Participants (N=16) with a neurologist-confirmed diagnosis of MS and daily use of a prescribed custom unilateral passive AFO. Interventions Three 6-minute walk tests (6MWTs), 1 per footwear condition: shoes (no AFO), prescribed passive AFO, and portable powered AFO (PPAFO). Assistive devices were worn on the impaired limb. Main Outcome Measures Distance walked and metabolic cost of transport were recorded during each 6MWT and compared between footwear conditions. Results Each participant completed all three 6MWTs within the experimental design. PPAFO use resulted in a shorter 6MWT distance than did a passive AFO or shoe use. No differences were observed in metabolic cost of transport between footwear conditions. Conclusions The current embodiment of this PPAFO did not improve endurance walking performance during the 6MWT in a sample of participants with gait impairment due to MS. Further research is required to determine whether expanded training or modified design of this powered orthosis can be effective in improving endurance walking performance in persons with gait impairment due to MS

Ghrelin is not Related to Hunger or Calories Consumed at Breakfast in Lean and Obese Women

poster abstractBackground: The mechanisms that result in greater caloric intake in obese individuals are incompletely understood. Ghrelin administration increases ad lib food intake in humans. We investigated the relationship of ghrelin to calorie consumption and hunger at breakfast on two separate occasions in lean and obese women. Methods: 23 lean (BMI 22.3±0.5 kg/m2, 26.5±1.0 yr) and 25 obese (BMI 36.9±0.7 kg/m2, 27.8±1.1 yr) women participated in a noncontiguous 2 day study. The minimum and maximum days between visits were 6 and 43 days. Participants were given the same breakfast on both days (turkey sausage, French toast with margarine/syrup, fruit cup, coffee, tea, diet soda, or water) with portions adjusted to provide 20% of the daily energy requirement for weight maintenance. Subjects were instructed to eat until full. Hunger was evaluated on a Satiety Labeled Intensity Magnitude Scale (SLIM) before and after the meal. Anchors were “greatest imaginable fullness” at 0 and “greatest imaginable hunger” at 100. Blood samples were collected over 120 minutes for measurement of active ghrelin. Results: Lean subjects consumed an equivalent number of calories on both days (380.0±14.6 vs 378.2±14.9 kcal), as did the obese (419.4±16.2 vs 428.8±15.4 kcal). On average for both days, obese consumed significantly more breakfast calories than lean (424.1±11.1 vs 379.1±10.3 kcal; P<0.01), but the same percentage of calories provided (85.7±1.8 vs 86.1±1.7 %kcal). Lean subjects rated hunger before breakfast the same on both days (69.2±1.6 vs 71.7±1.4), as did the obese (69.8±1.6 vs 69.6±1.8), and there was no difference between the groups. Lean subjects rated hunger after breakfast the same on both days (27.8±1.9 vs 30.3±2.4), as did the obese (25.0±1.7 vs 24.3±1.8). The reduction in hunger score following breakfast was significant for both groups (P<0.0001), with the obese reporting significantly less hunger/more fullness after breakfast than the lean (P=0.02). Fasting ghrelin was significantly greater in the lean than obese women (549.9±58.9 vs 231.0±29.1 pg/ml; P<0.0001). Ghrelin was significantly reduced at 60 min following breakfast in the lean (375.8±49.2 pg/ml; P=0.028) but not the obese (212.2±26.4 pg/ml). Ghrelin was not related to hunger score prior to breakfast, and there was no relationship between reduction in ghrelin and hunger score in the lean or obese. Conclusion: Caloric intake (as a percentage provided) and hunger scores before breakfast on two occasions were the same for both lean and obese women. Fasting ghrelin was significantly different between lean and obese women but did not predict hunger score or calories consumed. Our findings do not support a role for ghrelin in driving food intake at breakfast

A comparison of vaginal versus buccal misoprostol for cervical ripening in women for labor induction at term (the IMPROVE trial): a triple-masked randomized controlled trial

Background Cervical ripening is commonly needed for labor induction. Finding an optimal route of misoprostol dosing for efficacy, safety, and patient satisfaction is important and not well studied for the buccal route. Objective To compare the efficacy and safety of vaginal and buccal misoprostol for women undergoing labor induction at term. Study Design The IMPROVE trial was an institutional review board–approved, triple-masked, placebo-controlled randomized noninferiority trial for women undergoing labor induction at term with a Bishop score ≤6. Enrolled women received 25 mcg (first dose), then 50 mcg (subsequent doses) of misoprostol by assigned route (vaginal or buccal) and a matching placebo tablet by the opposite route. The primary outcomes were time to delivery and the rate of cesarean delivery performed urgently for fetal nonreassurance. A sample size of 300 was planned to test the noninferiority hypothesis. Results The trial enrolled 319 women, with 300 available for analysis, 152 in the vaginal misoprostol group and 148 in the buccal. Groups had similar baseline characteristics. We were unable to demonstrate noninferiority. The time to vaginal delivery was lower for the vaginal misoprostol group (median [95% confidence interval] in hours: vaginal: 20.1 [18.2, 22.8] vs buccal: 28.1 [24.1, 31.4], log-rank test P = .006, Pnoninferiority = .663). The rate of cesarean deliveries for nonreassuring fetal status was 3.3% for the vaginal misoprostol group and 9.5% for the buccal misoprostol group (P = .033). The rate of vaginal delivery in <24 hours was higher in the vaginal group (58.6% vs 39.2%, P = .001). Conclusion We were unable to demonstrate noninferiority. In leading to a higher rate of vaginal deliveries, more rapid vaginal delivery, and fewer cesareans for fetal issues, vaginal misoprostol may be superior to buccal misoprostol for cervical ripening at term

Beyond the Bandwagon: Curating Cultural Memory at Milner Library

Archival and manuscript materials record human experience; they document how people have lived, worked, interacted, and thought about the world. These unique or rare materials make visible the experience and impact of individuals and organizations within their respective cultural, geographical, historical, local, and educational milieu. By exploring such documents and objects, patrons can see and investigate these relationships firsthand. Primary sources form the bedrock of humanistic research, personal inquiry, and engaged teaching. With this volume, we invite you to explore the unique and rare materials housed in Milner Library’s Special Collections and Dr. Jo Ann Rayfield University Archives as well as the services that bring them to life for readers worldwide. Contributed essays from scholars and collection stewards highlight how a small sample of these rich collections facilitate teaching and learning within the Illinois State University community and beyond.https://ir.library.illinoisstate.edu/mlp/1032/thumbnail.jp

Who knows best? A Q methodology study to explore perspectives of professional stakeholders and community participants on health in low-income communities

Abstract Background Health inequalities in the UK have proved to be stubborn, and health gaps between best and worst-off are widening. While there is growing understanding of how the main causes of poor health are perceived among different stakeholders, similar insight is lacking regarding what solutions should be prioritised. Furthermore, we do not know the relationship between perceived causes and solutions to health inequalities, whether there is agreement between professional stakeholders and people living in low-income communities or agreement within these groups. Methods Q methodology was used to identify and describe the shared perspectives (‘subjectivities’) that exist on i) why health is worse in low-income communities (‘Causes’) and ii) the ways that health could be improved in these same communities (‘Solutions’). Purposively selected individuals (n = 53) from low-income communities (n = 25) and professional stakeholder groups (n = 28) ranked ordered sets of statements – 34 ‘Causes’ and 39 ‘Solutions’ – onto quasi-normal shaped grids according to their point of view. Factor analysis was used to identify shared points of view. ‘Causes’ and ‘Solutions’ were analysed independently, before examining correlations between perspectives on causes and perspectives on solutions. Results Analysis produced three factor solutions for both the ‘Causes’ and ‘Solutions’. Broadly summarised these accounts for ‘Causes’ are: i) ‘Unfair Society’, ii) ‘Dependent, workless and lazy’, iii) ‘Intergenerational hardships’ and for ‘Solutions’: i) ‘Empower communities’, ii) ‘Paternalism’, iii) ‘Redistribution’. No professionals defined (i.e. had a significant association with one factor only) the ‘Causes’ factor ‘Dependent, workless and lazy’ and the ‘Solutions’ factor ‘Paternalism’. No community participants defined the ‘Solutions’ factor ‘Redistribution’. The direction of correlations between the two sets of factor solutions – ‘Causes’ and ‘Solutions’ – appear to be intuitive, given the accounts identified. Conclusions Despite the plurality of views there was broad agreement across accounts about issues relating to money. This is important as it points a way forward for tackling health inequalities, highlighting areas for policy and future research to focus on

The Contact Structure of Great Britain's Salmon and Trout Aquaculture Industry

We analyse the network structure of the British salmonid aquaculture industry from the perspective of infectious disease control. We combine for the first time live fish transport (or movement) data covering England and Wales with data covering Scotland and include network layers representing potential transmission by rivers, sea water and local transmission via human or animal vectors in the immediate vicinity of each farm or fishery site. We find that 7.2% of all live fish transports cross the England-Scotland border and network analysis shows that 87% of English and Welsh sites and 72% of Scottish sites are reachable from cross-border connections via live fish transports alone. Consequently, from a disease-control perspective, the contact structures of England and Wales and of Scotland should not be considered in isolation. We also show that large epidemics require the live fish movement network and so control strategies targeting movements can be very effective. While there is relatively low risk of widespread epidemics on the live fish transport network alone, the potential risk is substantially amplified by the combined interaction of multiple network layers

Inflammatory properties of inhibitor of DNA binding 1 secreted by synovial fibroblasts in rheumatoid arthritis

Abstract Background Inhibitor of DNA binding 1 (Id1) is a nuclear protein containing a basic helix-loop-helix (bHLH) domain that regulates cell growth by selective binding and prevention of gene transcription. Sources of Id1 production in rheumatoid arthritis synovial tissue (RA ST) and its range of functional effects in RA remain to be clarified. Methods We analyzed Id1 produced from synovial fibroblasts and endothelial cells (ECs) with histology and real-time polymerase chain reaction (RT-PCR). Fibroblast supernatants subjected to differential centrifugation to isolate and purify exosomes were measured for Id1 by enzyme-linked immunosorbent assay (ELISA). Western blotting of Id1-stimulated ECs was performed to determine the kinetics of intracellular protein phosphorylation. EC intracellular signaling pathways induced by Id1 were subsequently targeted with silencing RNA (siRNA) for angiogenesis inhibition. Results By PCR and histologic analysis, we found that the primary source of Id1 in STs is from activated fibroblasts that correlate with inflammatory scores in human RA ST and in joints from K/BxN serum-induced mice. Normal (NL) and RA synovial fibroblasts increase Id1 production with stimulation by transforming growth factor beta (TGF-β). Most of the Id1 released by RA synovial fibroblasts is contained within exosomes. Endothelial progenitor cells (EPCs) and human dermal microvascular ECs (HMVECs) activate the Jnk signaling pathway in response to Id1, and Jnk siRNA reverses Id1-induced HMVEC vessel formation in Matrigel plugs in vivo. Conclusions Id1 is a pleotropic molecule affecting angiogenesis, vasculogenesis, and fibrosis. Our data shows that Id1 is not only an important nuclear protein, but also can be released from fibroblasts via exosomes. The ability of extracellular Id1 to activate signaling pathways expands the role of Id1 in the orchestration of tissue inflammation.http://deepblue.lib.umich.edu/bitstream/2027.42/134552/1/13075_2016_Article_984.pd