Integrins direct Src family kinases to regulate distinct phases of oligodendrocyte development

Specific integrins expressed on oligodendrocytes, the myelin-forming cells of the central nervous system, promote either differentiation and survival or proliferation by amplification of growth factor signaling. Here, we report that the Src family kinases (SFKs) Fyn and Lyn regulate each of these distinct integrin-driven behaviors. Fyn associates with α6β1 and is required to amplify platelet-derived growth factor survival signaling, to promote myelin membrane formation, and to switch neuregulin signaling from a phosphatidylinositol 3-kinase to a mitogen-activated protein kinase pathway (thereby changing the response from proliferation to differentiation). However, earlier in the lineage Lyn, not Fyn, is required to drive αVβ3-dependent progenitor proliferation. The two SFKs respond to integrin ligation by different mechanisms: Lyn, by increased autophosphorylation of a catalytic tyrosine; and Fyn, by reduced Csk phosphorylation of the inhibitory COOH-terminal tyrosine. These findings illustrate how different SFKs can act as effectors for specific cell responses during development within a single cell lineage, and, furthermore, provide a molecular mechanism to explain similar region-specific hypomyelination in laminin- and Fyn-deficient mice

“But I’ve always lived here”: Evidence Informed Analysis on Aging in Place

Purpose: The purpose of this poster/presentation is to provide an exploration and analysis of aging in place. To ensure the success of the older adult to remain in their home it is essential to determine and meet the changing needs of the aging population in a way that preserves lifelong health and wellness. Description: The global trend of population aging is on the continual rise due to longer life expectancy and lower fertility rates.1 It is predicted that by the year 2036 one in every four individuals will be a senior citizen. In some areas, the availability of long-term care facilities is not sufficient to meet the needs of the population, resulting in seniors living in hospitals up to 6 months awaiting a room. This problem is expected to continue to grow.1 While age related declines compromise an individual’s ability to maintain their personal wellbeing and household, maintaining independence is essential in the perception of successful aging.2 Aging in place is the primary goal in the aging population; US housing data suggests that this is accomplished by 80% of older adults.2 In addition to benefiting the emotional needs of seniors, aging in place has significant financial benefits on both the individual and the community at large, however the demands of the environment and the abilities of the person must align or a mal-adaptive situation occurs.2 Methods: Search USA: 2010-2019; Ag(e)ing in place, Ag(e)ing in place AND Challenges, Ag(e)ing in place AND quality of life, Ag(e)ing in place AND modification(s), Review of 7 articles Conclusion: Recent evidence is suggesting that in the next 10 years, middle income seniors will no longer be able to afford assisted living facilities so the need for maximizing aging in place will significantly increase. Summary of Use: This poster/presentation provides a summary of the benefits to aging in place, modifications and maintenance requirements for success and analyzes the factors contributing to decision making to ensure successful aging in place. Clinical Relevance: Therapists working in the home health setting are often required to provide appropriate information when asked by their clients if they should or could safely remain in the home, aging in place. This poster/presentation provides therapists with an analysis of the benefits and challenges for individuals desiring to age in place and provides the therapist suitable topics to introduce to the conversation to ensure that an appropriate and evidence-informed decision is made by the client and their family

A Review of Applications Evaluating Fisheries Management Scenarios through Marine Ecosystem Models.

Management Strategy Evaluation (MSE) is a framework to explore the tradeoffs amongst fishing strategies and assess the consequences for achieving management goals provided sources of uncertainty by means of simulation models (referred to as operating models). Single-species stock assessment often implements simulations for MSE, but the operating models often omit the dynamics of key biological interactions. This could be a disadvantage for the evaluation of tradeoffs as species interactions could have an impact on the performance of harvesting strategies. Tools for conducting ecosystem-based fisheries management (EBFM), such as integrated ecosystem assessments, include executing MSEs with ecosystem models, many of which explicitly include biological interactions. Although the support for EBFM has grown over the years, the amount of information provided by MSEs based on ecosystem models appears to be limited. A clear summary of such efforts would provide beneficial information for future efforts for EBFM. Herein, an inventory of applications simulating MSEs with ecosystem models that explicitly include biological interactions was developed based on findings from a literature review. First, the methodologies and foci across all identified applications are analyzed. Next, summaries of each application are provided. Lastly, general observations are provided along with recommendations for future applications.publishedVersio

Incidence, attributable mortality, and healthcare and out-of-pocket costs of Clostridioides difficile infection in US Medicare Advantage Enrollees

BACKGROUND: US attributable Clostridioides difficile infection (CDI) mortality and cost data are primarily from Medicare fee-for-service populations, and little is known about Medicare Advantage Enrollees (MAEs). This study evaluated CDI incidence among MAEs from 2012 to 2019 and determined attributable mortality and costs by comparing MAEs with and without CDI occurring in 2018. METHODS: This retrospective cohort study assessed CDI incidence and associated mortality and costs for eligible MAEs ≥65 years of age using the de-identified Optum Clinformatics Data Mart database (Optum; Eden Prairie, Minnesota, USA). Outcomes included mortality, healthcare utilization, and costs, which were assessed via a propensity score-matched cohort using 2018 as the index year. Outcome analyses were stratified by infection acquisition and hospitalization status. RESULTS: From 2012 to 2019, overall annual CDI incidence declined from 609 to 442 per 100 000 person-years. Although the incidence of healthcare-associated CDI declined overall (2012, 53.2%; 2019, 47.2%), community-associated CDI increased (2012, 46.8%; 2019, 52.8%). The 1-year attributable mortality was 7.9% (CDI cases, 26.3%; non-CDI controls, 18.4%). At the 2-month follow-up, CDI-associated excess mean total healthcare and out-of-pocket costs were $13 476 and$396, respectively. Total excess mean healthcare costs were greater among hospitalized (healthcare-associated, $28 762; community-associated,$28 330) than nonhospitalized CDI patients ($5704 and$2320, respectively), whereas total excess mean out-of-pocket cost was highest among community-associated hospitalized CDI patients ($970). CONCLUSIONS: CDI represents an important public health burden in the MAE population. Preventive strategies and treatments are needed to improve outcomes and reduce costs for healthcare systems and this growing population of older US adults

Increased incidence and risk of septicemia and urinary tract infection after Clostridioides difficile infection

BACKGROUND: Although increased occurrence of septicemia in persons with METHODS: The first episode of CDI was identified using 2011-2017 MarketScan and CMS Medicare data and CDI cases categorized by standard surveillance definitions. Uninfected persons were frequency matched 4:1 to cases by the CDI case surveillance definition. Multivariable Cox proportional hazards models were used to identify risk factors for septicemia and UTI within 90 days of CDI onset, accounting for the competing risk of death in the Medicare population. RESULTS: The incidence of septicemia was highest after hospital-onset CDI in the Medicare, younger commercial, and younger Medicaid populations (25.5%, 15.7%, and 19.5%, respectively) and lowest in those with community-associated CDI (3.8%, 4.3%, and 8.3%, respectively). In contrast, the incidence of UTI was highest in those with other healthcare facility onset CDI in all 3 populations (32.1%, 24.2%, and 18.1%, respectively). Hospital-onset CDI was associated with highest risk of septicemia compared with uninfected controls in all 3 populations. In the younger populations, risk of septicemia was more uniform across the CDI surveillance definitions. The risk of UTI was significantly higher in all CDI surveillance categories compared to uninfected controls, and among CDI cases it was lowest in those with community-associated CDI. CONCLUSIONS: The incidence of septicemia is high after CDI, particularly after hospital-onset infection. Additional preventive measures are needed to reduce infectious complications of CDI

Healthcare costs of Clostridioides difficile infection in commercially insured younger adults

In a US adult population aged \u3c65 years, attributable costs due t

Ecological Effects and Ecosystem Shifts Caused by Mass Mortality Events on Early Life Stages of Fish

Mass mortality events (MMEs) are a key concern for the management of marine ecosystems. Specific stages and species are at risk and the causes may be single or cumulative pressure from a range of sources including pollutants, anthropogenic climate change or natural variability. Identifying risk and quantifying effects of plausible scenarios including MMEs are key to stakeholders and a quest for scientists. MMEs affect the whole ecosystem, but are traditionally only studied in relation to specific species, disregarding ecological feedbacks. Here we use an end-to-end ecosystem model adapted to the Nordic and Barents seas to evaluate the species-specific and ecological impacts for 50 years following an MME. MMEs were modeled as 10, 50, or 90% reduced recruitment for cod, herring and haddock, individually or in combination. The MME scenarios were compared to a base case model run that includes the current fishing mortality. All species showed declines in population biomass following an MME, increasing in duration and severity with increasing mortality. Cod biomass rebounded to the base case level within 3–13 years post the MME independent of scenario, while neither haddock nor herring fully rebounded to base case levels within the considered time horizon. Haddock responded much more variably to the mortality scenarios than cod or herring, with some scenarios yielding much higher levels of biomass than the base case. Herring responded negatively to all scenarios, leading to lower herring biomass and a steeper decline of the species than seen in the base case due to persistent harvest pressure. Corresponding responses showed that the demersal guild biomass increased substantially, while the pelagic guild biomass declined. Few effects were observed on the other guilds, including the top predators. Ecosystem effects as measured by ecological indicators were greatest after 5 years, but persisted through the entire model run. Fishery indicators showed the same features, but the responses were stronger than for the ecosystem indicators. Taken together this indicates long-term, ecological response to MMEs that can be described as regime shifts, highlighting the importance of using ecosystem models when evaluating effects of MMEs.publishedVersio

Maternal and infant outcomes associated with lithium use in pregnancy

Background Concerns about teratogenicity and offspring complications limit use of lithium in pregnancy. We aimed to investigate the association between in-utero lithium exposure and risk of pregnancy complications, delivery outcomes, neonatal morbidity and congenital malformations. Methods Meta-analysis of primary data analyzed using a shared protocol. Six study sites participated: Denmark, Canada, Netherlands, Sweden, UK, and US, totaling 727 lithium-exposed pregnancies compared to 21,397 reference pregnancies in mothers with a mood disorder, but unexposed to lithium. Main outcome measures included: (1) pregnancy complications, (2) delivery outcomes, (3) neonatal readmission to hospital within 28 days of birth, and (4) congenital malformations (major malformations and cardiac malformations). Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were generated using logistic regression models. Site-specific prevalence rates and ORs were pooled using random-effects meta-analytic models. Findings Lithium exposure was not associated with any of the pre-defined pregnancy complications or delivery outcomes. There was an increased risk for neonatal readmission in lithium exposed (27·5%) versus reference group (14·3%) (Pooled aOR1·62; 95% CI: 1·12–2·33). Lithium exposure during first trimester was associated with increased risk of major malformations (7·4% versus 4·3%; pooled aOR 1·71, 95% CI: 1·07–2·72). Similarly, more lithium exposed children had major cardiac malformations, albeit not stasticially significant (2·1% versus 1·6%; pooled aOR 1·54, 95% CI: 0·64–3·70). Limitations in our study include: Serum lithium 5 levels were not available, hence no analyses related to dose-response effects could be performed, and residual confounding from e.g. substance abuse cannot be ruled out. Interpretation Treatment decisions must weigh the potential for increased risks, considering both effct sizes and the precision of the estimates, in particular associated with first-trimester lithium use against its effectiveness at reducing relapse

Information-sharing with respite care services for older adults:a qualitative exploration of carers’ experiences

This study was financially supported by the Queen’s Nursing Institute Scotland (QNIS Project ELCRI01), Edinburgh, Scotland.Respite services play an important role in supporting older adults and their carers. When an older person is unable to fully represent themselves, provision of respite care relies on effective information-sharing between carers and respite staff. This study aimed to explore, from carers’ perspectives, the scope, quality and fit of information-sharing between carers, older people and respite services. An explorative, cross-sectional qualitative study involving a purposive sample of 24 carers, recruited via carer support groups and community groups in voluntary organisations, was undertaken in North East Scotland. Data were collected from August 2013 to September 2014, with participants taking part in a focus group or individual interview. Data were analysed systematically using the Framework Approach. The multiple accounts elicited from carers identified how barriers and facilitators to information-sharing with respite services changed over time across three temporal phases: ‘Reaching a point’, ‘Trying it out’ and ‘Settled in’. Proactive information-sharing about accessibility and eligibility for respite care, and assessment of carers’ needs in their own right, were initially important; as carers and older people moved on to try services out, time and space to develop mutual understandings and negotiate care arrangements came to the fore; then, once shared expectations had been established, carers’ chief concerns were around continuity of care and maintaining good interpersonal relationships. The three temporal phases also impacted on which modes of information-sharing were available to, and worked best for, carers as well as on carers’ perceptions of how information and communication technologies should be utilised. This study highlights the need for respite staff to take proactive, flexible approaches to working with carers and to make ongoing efforts to engage with carers, and older people, throughout the months and years of them utilising respite services. Information and communication technologies have potential to enhance information-sharing but traditional approaches will remain important.PostprintPeer reviewe

The influence of oblique-angle forced exercise in surgically destabilized stifle joints is synergistic with bone, but antagonistic with cartilage in an ovine model of osteoarthritis

Large animal models of osteoarthritis are a necessary testing ground for FDA approval of human medicine applications. Sheep models have advantages over other available large animals, but development and progression of osteoarthritis in sheep is exceedingly slow, which handicaps progress in development of potential treatments. We combined oblique angle forced exercise to increase stress on the stifle, with surgical destabilization to hasten the development of osteoarthritis in ewes. Methods for early detection of clinical signs included radiography, urine, and serum biomarker assays and gait analysis and ex vivo we used microcomputed tomography and macroscopic joint analysis. Our model was able to produce clinically detectable signs of osteoarthritis in a relatively short period (14 weeks). Changes in bone were highly correlated between microcomputed tomography and radiographic analysis and changes in cartilage correlated well between urinary glycosaminoglycan levels and serum aggrecanase analyses. Exercise improved the negative effects of destabilization in bone but exacerbated the negative effects of destabilization in cartilage. These observations suggest that we may need to consider treatments for bone and cartilage separately. These results represent an improved large animal model of osteoarthritis with rapid onset of disease and superior detection of bone and soft tissue changes