This knowledge is critical to understand how crust-forming processes are related to metal accumulations at specific time and conditions of Earth evolution. To this end, high-precision absolute geochronology utilising the rhenium-osmium (Re-Os) radiometric system in specific sulphide minerals is becoming a method of choice. Here, we present a procedure to obtain mineral separates of individual sulphide species that may coexist within specific mineralized horizons in ore deposits. This protocol is based on preliminary petrographic and paragenetic investigations of sulphide and gangue minerals using reflected and transmitted light microscopy. Our approach emphasizes the key role of a stepwise use of a Frantz isodynamic separator to produce mineral separates of individual sulphide species that are subsequently processed for Re-Os and sulphur isotope geochemistry. Specifications TablePolished thin sections of the arsenopyrite-pyrite-mineralised samples were studied using transmitted and reflected light microscopy in order to establish the paragenetic relationships and constrain the workflow  for optiAll sulphide samples were cut into slabs that were thoroughly cleaned using silicon carbide grit, milli-Q water and ethanol to remove any metal traces potentially introduced through hammering or sawing . These clean sulphide-bearing samples were then crushed using a zirconia ceramic dish and puck and sieved through disposable home-made nylon sieves to produce 70‒200 mesh size fractions . Each 70An aliquot of each arsenopyrite and pyrite mineral separate was embedded in epoxy to operate a quality control of these mineral separates . The mounts were studied by reflected light microscopy. We recommend the use of a scanning electron microscope (SEM) operated in backscattered electron mode (SEM-BSE) if doubts persist regarding the quality of mineral separates. Qualitative observations may then be complemented by point wavelength-dispersive spectroscopy (WDS) quality control analyses of arsenopyrite and pyrite in the mounts using the following suite of elements: S, Fe, Ni, Cu, As.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.


The role of fibronectin (FN) in tumorigenesis and malignant progression has been highly controversial. Cancerous FN plays a tumor-suppressive role, whereas it is pro-metastatic and associated with poor prognosis. Interestingly, FN matrix deposited in the tumor microenvironments (TMEs) promotes tumor progression but is paradoxically related to a better prognosis. Here, we justify how FN impacts tumor transformation and subsequently metastatic progression. Next, we try to reconcile and rationalize the seemingly conflicting roles of FN in cancer and TMEs. Finally, we propose future perspectives for potential FN-based therapeutic strategies. Identification of a general and suitable target that is unambiguously oncogenic or tumor suppressive is a foundation on which cancer therapeutic strategies could be designed and developed. Fibronectin (FN) A has lonAccomplishment of cancer development, a rather slow and chronic process, temporally and spatially requires various cellular activities across different tissues. Tumor cells originate from healthy, often epithelial, cells that acquire hereditary mutations  or somatIn contrast to such intratumor heterogeneity, immune and stromal cells in the tumor microenvironments (TMEs) initially arise to eliminate pre-tumor abnormal cells and early transformed cells that encounter environmental stresses. Consequently, these stresses impose early transformed cells enormous selective pressures to force evolution, rendering tumor cells staying in the equilibrium stage for a long while before being able to escape immunosurveillance and make a malignant progression ,26,27. HOxygen delivery within the TMEs is inefficient mainly due to various abnormalities in the tumor vasculature . Indeed,The liberation and survival of circulating tumor cells (CTCs) is a requirement for the colonization of disseminated tumor cells (DTCs) in secondary organs and finally outgrowth and macrometastasis development ,34. Like+ bone marrow-derived cells (BMDCs) that have been driven by cytokines or exosomes secreted by the metastatic competent tumor cells in primary tissues long before extravasation of DTCs in distant tissues    formed ted data]  [unpubli435 DTCs . Uncouplt organs . Such pht organs ,350, likhigh CTCs colonize more and form more metastatic tumor nodules in distant organs, unless there are strategies to reverse FNhigh CTCs back to pro-epithelial phenotypes that tend to render CTCs suffer more from anoikis and mechanical stresses and injuries.Since how cancerous FN and ECM FN participate in tumor progression remains obscure and paradoxical, FN-based cancer therapies have so far only been focused on the functions of drug delivery. For example, EDA- and EDB-containing oncofetal variants have often been utilized for that purpose ,351,352.At the same stage of tumor patients, FN deposition in ECM of TMEs exacerbates tumor growth and subsequent progression. Therefore, approaches targeting such matrix-depositing FN may be ideal for effectively slowing down the tumor progression. FN secretion and deposition may due in part to tumor-infiltrating pro-tumor stromal cells including CAFs and TAMs . Ablatiohigh CTCs prior to extravasation in distant organs as DTCs. Blockade of the attachment of FNhigh CTCs to DPP IV-expressing endothelia can be an ideal strategy to prevent tumor metastasis and improve patients’ prognosis. Indeed, in experimental metastasis assays, polypeptides derived either from FN harboring DPP IV-binding sites [In later stages of tumor progression, tumor cells with the metastatic potential begin to intravasate into the circulation and become FNng sites  or from ng sites ,2 have bng sites . More imng sites . Intrigung sites .high CTCs become highly metastatic and capable of colonizing distant organs. The prevailing therapeutic strategies are to switch to a second line of tumor-killing drugs or combinatory therapies including immune checkpoint blockade, which may cause further genetic or epigenetic evolutions and eventually lead to another drug resistance. These problems may be avoided by finding a drug that by itself has no cytotoxic effect on tumor cells but is able to sensitize the resistant tumor cells to the original drugs. Efforts can be exerted to screening such drug from either small molecule library or a series of less harmful natural phytochemicals. By combining such drug with periFN/DPP IV binding blockade treatments, the drug-resistant tumor cells can be re-sensitized and controlled in the primary sites and FNhigh CTCs can simultaneously prevented from entering distant sites.In most cases, tumor patients receive either tradition chemo/radiotherapies or targeted anti-tumor therapies. As aforementioned, tumor patients often develop resistance to these anti-cancer drugs, driving tumor evolution, malignant progression, intravasation of tumor cells to become CTCs, and metastatic recurrence simultaneously with the upregulation of endogenous FN. Although therapy-elevated FN expression in resistant tumor cells slow down the tumor growth, the blood-borne FNIn summary, after extensively reviewing the bulk literature regarding the roles of FN in cancer progression, we provided intriguing possibilities that reasonably reconcile the seemingly paradoxical roles FN plays. We hypothesized that cancerous FN and FN mactrices in TMEs can coordinately regulate tumor transformation and malignant progression in temporal and spatial manners. Upon accomplished experimental proof of concept, FN can be carefully targeted at the right location and in the right time. We finally provided a few FN-based therapeutic strategies as future perspectives. Hopefully, this review article can attract more cancer researchers to be delved into concerted efforts in unveiling and validating what had been proposed here.


Despite the well-understood benefits of vaccination in older adults, national rates still fall below public health targets, especially among certain racial and ethnic groups. Recent scholarship examining healthcare use patterns in adults revealed that health care providers miss several opportunities to provide vaccination during regular healthcare encounters, including Medicare annual wellness visits. Several barriers to older adult vaccination have been identified, including lack of patient and provider understanding of the importance of vaccination, financial barriers to vaccines covered under Medicare Part D, and patient hesitancy about the safety and effectiveness of vaccines. Strategies to address these barriers will be discussed, including the use of national quality measures to strengthen incentives for adult vaccination. Part of a symposium sponsored by the Health Behavior Change Interest Group.


Individual sensory deficits have been associated with adverse outcomes, including dementia, in older adults. Using data from the Baltimore Longitudinal Study of Aging (BLSA) (N=259) and Atherosclerosis Risk in Communities Study (ARIC) (N=962), we examined the prevalence of one, two, or three sensory deficits  among older adults ≥70 years. Any hearing loss was the most prevalent sensory deficit , followed by vision loss and olfactory loss. Hearing and vision impairments were more prevalent than hearing and olfactory losses as well as vision and olfactory losses in both age groups and studies There were few people with deficits in all three senses . Further research should investigate the potential impact of multisensory impairments on older adults.


PLOS Genetics publications that exemplify recent progress in human genetic admixture studies, and we discuss potential areas for future work.Throughout human history, large-scale migrations have facilitated the formation of populations with ancestry from multiple previously separated populations. This process leads to subsequent shuffling of genetic ancestry through recombination, producing variation in ancestry between populations, among individuals in a population, and along the genome within an individual. Recent methodological and empirical developments have elucidated the genomic signatures of this admixture process, bringing previously understudied admixed populations to the forefront of population and medical genetics. Under this theme, we present a collection of recent  One of the major insights from the modern genomic era is the ubiquity of migration and admixture throughout human history –7. Admix—the population origins of material within a genome. This is related to, but distinct, from genetic similarity and from genealogical ancestry, with the relationship further discussed by Mathieson and Scally [Human population movement frequently lacks historical records. Many migration events have occurred through colonization or forced displacement, and ancient admixture often predates historical records. Therefore, genetic studies provide an opportunity to understand population history and the forces generating variation. Recent empirical work has shown that studying the genetics of a wider set of human populations can yield historical insights as well as medically relevant information about health and phenotypes. The mosaic ancestry patterns of admixed populations can also be used to elucidate the mechanisms and timescales of evolution in humans more generally. For example, ancestry patterns in admixed populations have been used to infer recombination rates –15 and td Scally .PLOS Genetics publications. This compilation is a limited selection of work that exemplifies recent key advances and stimulates discussion about priorities for the future.Here, we highlight recent progress and discuss future directions for the study of admixed human populations . The terBroader genetic sampling of populations worldwide is increasingly being combined with advances in theory and computational methods to elucidate human history.Genetic ancestry often varies along a chromosome within an individual and between individuals within an admixed population . SummariClassic statistical methods in population genetics typically rely on allele frequencies, patterns of linkage disequilibrium (LD), and interpopulation sequence differences. However, the admixture process may distort patterns of LD, break up runs of homozygosity, and combine allele frequency distributions from distinct parental populations –29. Yet,PLOS Genetics that improve our understanding of the demographic processes shaping genetic variation in admixed populations and human evolutionary history. Ragsdale and colleagues (2019) generalize 1- and 2-locus genetic summary statistics in a computationally efficient algorithm able to explore complex demographic models [A number of major theoretical and methodological advances have recently been published in c models . Other rc models . Methodoc models . Identifc models –38. Browc models –41. A rec models .Intricate sociocultural practices such as marriage customs, colonization events, and phenotypic preferences direct how parental populations interact to form admixed human populations. Whereas computational methods are increasingly considering these intricacies, empirical studies of admixed populations have already made substantial progress on fine-scale demography providing insight into how sociocultural practices shape the admixture process and within-region variation.Using these new methods, empirical studies have brought to the forefront within-continent variation, particularly for historically excluded and under-sampled populations. Analyses of genomic ancestry within the context of geography have revealed between and within continent population structure . For exaEmpirical studies such as these highlight the role social processes play in shaping genetic variation; for example, male and female demographic histories can differ. Considering population structure, sex-biased admixture, and effective population size changes, Font-Porterias and colleagues (2019) clarified the dynamic demographic history of European Roma groups, including showing that they share a common South Asian origin but have complex contributions from West Eurasian groups . AnotherSelective pressures, such as those from environments and pathogens, play an important role in genetic variation and disease risk. Admixture both obscures genetic signatures of selection in source populations and provides new genetic material upon which selection can rapidly act.Despite major progress on theory and methods to study demography in admixed human populations, methodological advances to study other processes such as adaptation and phenotypic variation remains an open area with substantial room for growth. Recent admixture may obscure genetic signatures of selection in the source populations by distorting linkage, rapidly changing allele frequencies, and breaking up homozygosity ,56. TherDARC locus is protective against malaria-causing Plasmodium vivax infection, which is estimated to be one of the strongest selective pressures in recent human history. The Duffy-null allele is nearly fixed in sub-Saharan African populations and mostly absent in non-African populations, producing a classic signal in which the DARC locus is an outlier in its proportion of local African ancestry in multiple admixed populations [DARC locus is not typical of human adaptation. These local ancestry outlier approaches likely miss many loci under weaker or polygenic selection or those not highly differentiated in the sources. Additionally, outlier approaches generate false positives due to drift or long-range LD and discard other genetic information along the genome. For example, in Western African rainforest hunter–gatherer populations, Jarvis and colleagues (2012) found reduced levels of switching between ancestry types in a genomic region that may contribute to adaptive phenotypes such as short stature [A common approach to identify candidate regions under selection post-admixture looks for outliers in local ancestry –21,59,60ulations . However stature . DespiteDespite the challenges of identifying phenotypically important loci and regions under selection in admixed populations, recent empirical studies have highlighted the importance of using admixed populations to understand how selective pressures shape genetic variation and disease risk. Discovering phenotypically important loci in admixed populations requires careful consideration of the data, including strategies to integrate genotypes, local ancestry, and information from source populations. Once phenotypically important loci are identified, admixed populations can provide insight into how these loci interact with different ancestral backgrounds and how characteristics of the source populations shape post-admixture selection.ApoE is the strongest known risk gene for late-onset Alzheimer disease; Rajabli and colleagues (2018) showed that variation in risk for Alzheimer disease across populations may be at least partially explained by the ancestral background interacting with the risk allele [In addition to looking for correlations between genotype and phenotype, phenotypically important loci in admixed populations can be identified by looking for correlation between local ancestry and phenotype when the phenotype differs in the source populations . A combik allele . The relk allele . In Latik allele . Going fNotably, these types of studies of quantitative variation and disease risk in admixed populations rely on careful consideration of the genotype and local ancestry calls, including reference-bias and characteristics of the source populations. Identifying phenotypically important loci in admixed populations is challenging in the absence of appropriate reference panels and knowledge of the source populations. The growing availability of genetic data from diverse groups shows that the unique LD structure of admixed groups and limited availability of suitable reference panels can particularly impair variant mapping and detection for novel or rare alleles. For example, Kowalski and colleagues (2019) recently analyzed a large cohort of phased genomes from African and Hispanic/Latino individuals (NHLBI TOPMed), revealing significant phenotypic associations for rare variants that were not detected with imputation using 1000 Genomes reference data .Contributing source populations also have their own distinct selective and demographic histories. Although recent admixture obscures genetic signatures of selection in the source populations, consideration of past selective pressures can help identify important loci and clarify the genetic basis of disease risk. For example, Yao and colleagues (2018) found that in African ancestral backgrounds, past selection for the Duffy-null allele may also contribute to population differences in plasma levels of chemokines involved in a variety immune processes and diseases . In IndiThe set of papers highlighted here exemplifies recent advances and important areas for future work in the study of genetic admixture and its roles in human evolution. Recent theoretical and methodological advances have improved our understanding of the dynamic and complex demographic histories of modern human populations. New empirical insights will continue to emerge with the development of approaches that consider complex sociocultural variables, account for within-population heterogeneity, and avoid reference bias. With increasing genomic and phenotypic data available from populations around the world, we are only beginning to characterize genetic underpinnings of traits, the importance of their genetic background, and mechanisms of adaptation. Importantly, as we move forward, the field must emphasize the inclusion of local communities, ensure that people maintain agency over their genomic information, prioritize infrastructure for science, and improve scientific theories by collaborating across disciplinary knowledge –75.


According to the World Health Organization, the global population is aging, but ageism may now be the most socially “normalized” of any prejudice, more pervasive than sexism or racism. Ageism produces avoidant and disrespectful treatment of older adults and contributes to a shortage of college students seeking careers with older adults. To foster positive intergenerational contact and combat ageism, we organized life-story sharing by older adult community members in four undergraduate psychology courses with lifespan themes . A panel visited each class; instructors and graduate students facilitated discussion between students and panelists. Students completed pre- and post-surveys of ageism and attitudes toward aging. A majority of students recommended integrating the activity into future semesters. In free-responses, students also frequently expressed surprise that panelists reported not feeling different than they had at age 20, and that this information challenged previously held stereotypes.


Nineteen percent (13 million) older adults have incomes below 150% of the Federal Poverty Level, leaving them with limited means to afford basic living expenses. Public benefits can help bridge the gap allowing older adults to afford food, home energy, and health expenses. There are studies demonstrating the positive health outcomes associated with public benefits in older adults. It remains unclear how benefits may also improve subjective measures of well-being in older adults. To examine this question, baseline measures of well-being including the CFPB Financial Well-Being Scale were administered to older adults before they enrolled in benefits and again six months after receiving benefits to examine changes in well-being as a result of accessing benefits to help ease some of their financial burdens. Results revealed that older adults experience subjective, psychological improvements from benefits. These findings have implications for the social and behavioral determinants of health in older adults.


Older adults in the deep south are living with high food insecurity rates; this is exacerbated by challenges with rural-living, like transportation limitations and no grocery stores. To address this, we must increase emergency food assistance offerings and adopt best practices for food pantries including choice food pantry approaches, which empowers clients with some autonomy in choosing the foods they receive as part of their pantry distribution. Coalitions in eight income-limited, aging, rural Mississippi Delta counties received support from a Centers for Disease Control and Prevention Grant to enhance the food-related infrastructure in their communities through technical assistance and economic investments. A detailed process evaluation was conducted on this effort. Each coalition adopted food pantry-related policies like adding new food pantries and adapting their existing food pantries with the choice model. Both aging volunteers and clients indicated positive outcomes from the process of adding pantries and adapting existing ones.


Military service during early life can result in exposure to traumatic events that can reverberate throughout life. Although much attention is focused on the negative effects of military service, many veterans report positive effects. These papers explore life course effects of military service on veterans’ health and well-being. Three used national US longitudinal cohorts ; two sampled veterans from Oregon or from Korea. Three compared veterans to non-veterans; two examined veterans only. Cheng and colleagues found that veterans in HRS are more likely to be risk-averse than non-veterans. Risk aversion matters because it determines how people make decisions and predicts a wide array of health and economic outcomes. Kurth and colleagues examined Oregon veterans from several wars, finding PTSD symptoms were highest among Vietnam combat veterans, the oldest cohort; there were no differences among non-combat veterans. Piazza and colleagues examined in MIDUS the impact of veteran status on cortisol, a stress biomarker, finding older veterans more likely had non-normative patterns than did younger or non-veterans. Lee and colleagues studied patterns of mental health among Korean Vietnam veterans, identifying two patterns as ‘normal’ and ‘resilient’ encompassing half the sample; these veterans demonstrated positive outcomes of military service. Frochen and colleagues compared depression trajectories between veterans and non-veterans in HRS, finding veterans had less depression than non-veterans, but among veterans, trajectories varied based on extent of service. in sum, these papers demonstrate that military service can have positive as well as negative effects on veterans’ health and well-being in later life. Aging Veterans: Effects of Military Service across the Life Course Interest Group Sponsored Symposium.


Person-centered caregiving approaches emphasize efforts to protect and maintain the personhood of people living with dementia (PLWD). The influence on person-centered caregiving approaches on PLWD have predominantly focused on deficit-oriented outcomes, such as absence or reduction of behavioral symptoms. While important to quality of life, the absence of measurable “positive” responses to person-centered caregiving approaches limit opportunities to specify sensitive and meaningful outcome measures that more holistically represent PLWD’s care experiences as more than the absence of a negative outcome. To address these gaps, we conducted a secondary analysis of video-observations of PLWD (N=9) surrounding mealtime cares using a descriptive ethnographic approach. Our objectives were to descriptively summarize specific responsive behaviors demonstrated by PLWD surrounding person-centered caregiving interactions, specifying observable features of these responses and consider their utility in future video-observational research. Findings indicate PLWD contribute both verbal and non-verbal communication surrounding person-centered approaches which can be characterized as conversational , expressing preferences , emotional responses , and reflexive (mirroring of caregiver’s actions), with overlap between categories. Findings suggest that PLWD not only contribute and respond in meaningful ways to person-centered interactions, but also initiate a significant number of these interactions. This study contributes to a growing body of research and advocacy that examines the personhood and abilities of PLWD and establishes the utility of observational data in studying PLWD contributions.


Almost a hundred and thirty years ago, Emil Kraepelin described important weight changes in patients diagnosed with dementia praecox during the acute state of psychosis outbreaks . KraepelTwenty years later Eugenie Bleuler in his seminal book “Dementia praecox oder Gruppe der Schizophrenien” described that body weight of patients underwent irregular and severe variations from which no cause had been identified (being sometimes as much as 25 Kg), suggesting that it could not be considered as a compensation mechanism after the stressful circumstances of a psychotic outbreak . He alsoNevertheless the link faded with the introduction of chlorpromazine in 1952 like other medical conditions . HoweveWith the reintroduction of clozapine in the market, new studies regarding this association in patients diagnosed with schizophrenia or schizoaffective disorder appeared in the literature. Lamberti, without aiming at it, showed an inverse correlation between clinical symptom severity change and weight gain in 36 inpatients evaluated for 6 months with the brief psychiatric rating scale (BPRS) . LeadbetThe same approach was taken with olanzapine in patients diagnosed with schizophrenia spectrum disorders. Czobor showed a significant correlation between weight gain and improvement in 38 patients  . GaryfalThe placebo effect found in some studies is remarkable regarding previous considerations. Ascher-Svanum described that patients under placebo treatment presented a significant association between greater weight gain and greater therapeutic improvement suggesting that weight gain may serve as an important indicator of improved clinical status among acutely ill patients with schizophrenia who do not receive antipsychotic medication , 24. AlsDespite the paradox that a secondary side effect of antipsychotics such as weight increase might underlie clinical improvement, these mechanisms are worth being discussed. Initially authors underlined this issue suggesting hospital diet, physical inactivity, and the psychological and physical shelter provided by hospitalization as the cause . Later sNevertheless, recent research suggests that the gut-brain axis (GBA), specifically its neurohormones, might behave as a potential pathway underlying both conditions and a key player in promoting weight gain and clinical improvement. The biological effect on the central nervous system of leptin, adiponectin, ghrelin, cholescytokinin (CCK), neuropeptide Y (NPY), glucagon like protein I (GLP-I), and insulin has accumulated further evidence . InitialGBA has been described as a pathophysiological mechanism implicated in antipsychotic-induced weight gain , 34, howConsidering specifically clozapine or olanzapine, the two pharmacological agents more related with weight gain, they seem to display a direct effect on the hormonal pathways of energy homeostasis (adiponectin and ghrelin) rather than on weight gain . Indeed Overall, previous literature suggests that GBA might be a necessary element in both conditions and so underlie the undeciphered association between weight gain and clinical improvement. However, this association lacks specific studies evaluating the issue and so further studies are required to prove its implication .The author confirms being the sole contributor of this work and has approved it for publication.CC-R has received honoraria/speaker fees/research and travel support/from Adamed, Alter, Angelini, Janssen-Cilag and Lundbeck.


The world’s population is aging at an alarming rate, and the incidence of osteoporosis is skyrocketing. One major consequence of the decline in skeletal health is increased fracture risk in patients 65 years and older. Osteoporosis-related fractures are predicted to result in more than $25 billion in annual health care costs by 2025. For elderly patients, who demonstrate poor capacity for regeneration and a limited physiologic reserve, surgery has increased complication rates and higher risk of failed healing outcome which is potentially devastating and can result in morbidity and mortality . CurrentStem cell therapy has emerged as a potent new strategy to repair and replace injured tissue. Readily available bone marrow aspirates and adipose tissue have been used as a source for the isolation, study, and transplantation of bone forming cell populations. Despite often being called ‘stem cells’ the isolation of these cells has been largely retrospective in nature and relying on inexact separation criteria such as plastic adherence which produces highly variable and heterogeneous cellular mixtures of multiple tissue types including bone, blood vessels, blood, fat, and fibroblast cells which makes treatment outcomes difficult to evaluate or predict . In contIn our recent study, we applied this methodology to isolate human fracture derived SSCs (hSSC) from a broad cohort of patients to test if changes in SSC function were associated with patient age . We prosWe analyzed genetic regulation of aged SSC traits such as fibrogenicity by performing gene expression analysis on purified hSSCs. We utilized microarray analysis to compare global gene expression in purified hSSCs from young versus aged patients along with corresponding functional evaluation in vitro. Consistent with age-related functional changes, we found downregulation of genes related to bone formation in aged hSSCs. Moreover, aged hSSCs upregulated genes that are related to fibroblast-like extracellular matrix secretion and cellular senescence. Curiously, we also observed that the histone deacetylase Sirtuin1 was significantly downregulated in geriatric hSSCs, which hints at epigenetic mechanisms underlying hSSC aging. We showed that specific blockade of Sirt1 in young hSSCs impairs osteogenic potential in vitro. Excitingly, Resveratrol and a Sirtuin1-specific small molecule restored mineralization capacity in impaired hSSCs thus providing a rationale for future translational strategies.In summary, our report of an association between patient age and hSSC function opens new possibilities to identify diagnostic, prognostic, and therapeutic strategies for poor fracture healing and potentially even the preservation of youthful bone health and prevention of skeletal injuries. Targeted molecular therapies that inhibit cellular senescence pathways may reverse age-related fracture phenotypes without broad off-target systemic side effects of current regimens. Continued investigation of larger groups of patients will reveal if simple in vitro assays of hSSCs, or antigens associated with aged hSSCs might serve as a prognostic tool to predict healing outcome of fractures. Furthermore, analyzing hSSCs isolated from nonunions will yield insights into the involvement of hSSCs in the etiology of failed fracture healing. A more comprehensive approach including the analysis of all cells present at the fracture site might also help to elucidate the role of the stem cell microenvironment or “niche” in facilitating proper bone regeneration .


Research shows regular physical activity (PA) is associated with better health and longevity; however, few studies consider contextual factors related to PA among African American (AA) older adults living in socioeconomically disadvantaged neighborhoods. The Physical and Cognitive Health Pilot Study (n=50) was used to examine associations between PA and level of neighborhood socioeconomic disadvantage among sedentary, AA older adults from four public housing communities in Durham, NC and Annapolis, MD . Participants were administered the Community Healthy Activities Model Program for Seniors (CHAMPS), a self-report questionnaire measuring weekly frequency and duration of PAs. Neighborhood socioeconomic disadvantage was defined by the Neighborhood Atlas Area Deprivation Index (ADI), which ranks neighborhoods according to Census block group/neighborhoods within each state and nationally. For the present sample, two of the Durham housing facilities were located in communities in the most disadvantaged block groups. Meanwhile, one Durham location and the Annapolis community were located in the least disadvantaged block groups. Bivariate correlations showed greater neighborhood socioeconomic disadvantage was associated with less participation in various PAs (p<.05). Next, ANOVA revealed the Annapolis group participated in statistically significantly more PAs, including visiting the senior center, church attendance, and light gardening (p<.05) compared to the most disadvantaged groups. The present findings suggest there are benefits to living in advantaged contexts despite lower-income status. These findings also suggest barriers within disadvantaged neighborhoods that limit access to recreational activities favorable to health status. Future research should address ways to overcome such barriers.


Exposure to harmful substances and chemicals such as tobacco smoke, chemicals  and metal dust has been associated with increased risk of developing cancer, cardiovascular disease, and other diseases that contribute to shorter life expectancy. Associations with brain health in relation to these exposures are less well studied. We examined the relationship between brain health and prolonged exposure to different harmful substances in 498 male participants average age 68 (range 61 to 73) from the Vietnam Era Twin Study of Aging (VETSA). For self-reported tobacco smoke, herbicides/pesticides, and metal dust we created three groups reflecting recency of exposure (current/former/never). For Agent Orange we examined two exposure groups (ever/never). Brain health, defined as predicted brain age (PBAD), was evaluated by applying Brain-Age Regression Analysis and Computation Utility software (BARACUS) to magnetic resonance images collected at age 68. Tobacco smoking  was significantly correlated with PBAD and remained significant  in multivariate analyses adjusted for age, socioeconomic status (SES), age 20 general cognitive ability, and non-independence of twins within pairs. Never smokers had significantly younger brains than current or former smokers. PBAD did not differ for current versus former smokers. In other analyses, more advanced PBAD was associated with non-amnestic MCI. In this sample, tobacco smoking had the strongest relationship with overall brain health in late midlife compared with other types of environmental exposures, reinforcing its role in pathological aging and its importance as a public health priority.


Recent findings suggest that childhood exposures can lead to chronic inflammation decades later, but the mechanisms underlying this relationship are relatively unknown. We investigate how childhood exposures influence adult chronic inflammation (measured by C-reactive protein) and examine five potential mediators comprising two midlife domains: socioeconomic status (SES) and health lifestyles. Using a sample of 8,891 adults aged 51 and older from the Health and Retirement Study (HRS), the analysis tests whether these life course mediators operate differently for Black, White, and Hispanic Americans. Among the six childhood domains examined, low SES and risky parental behaviors predict adult chronic inflammation, but adult health lifestyles mediate the effects of childhood SES and parental behavior. Adult SES also mediates the effect of childhood SES. Smoking and wealth exert stronger direct and indirect effects on adult inflammation for White Americans compared to Black Americans whereas BMI and exercise exert stronger direct and indirect effects for White Americans compared to Hispanic Americans. Although education mediated the effect of childhood SES on adult chronic inflammation, its effects did not vary by race. These results demonstrate that the physiological consequences of childhood exposures are carried into late-life via adult lifestyle factors and SES. In addition, the life course antecedents of chronic inflammation are distinct for Black, White, and Hispanic Americans. Future research investigating the early origins of adult health should consider not only multiple midlife mechanisms but also how resource mediation varies by race and ethnicity.


The nonunion of distal phalangeal communized fracture is relatively rare in hand fractures. However, if it occurred, the surgical treatment is quite difficult because of small piece of fragmentations. We developed a new fixation method that involves the insertion of two wires and external wire compression fixation using a metal clamp. The aim of this technique was to increase the compression force between fragments and rigidity of conventional percutaneous Kirschner wire fixation. Here, we present a patient with the nonunion of distal phalangeal communized fracture who was satisfactorily treated with open reduction and percutaneous interfragmentary compression fixation with a linking external wire fixator (the Ichi-Fixator system). Such a treatment that enables compression fixation for communized distal phalangeal fracture of nonunion will clearly boost bone healing. Linked external wire-type compression fixator (the Ichi-Fixator system) enables enhanced security of fixation and facilitates the bone healing. Distal phalangeal fractures can be managed conservatively with good outcomes if diagnosed early. However, if the initial reduction is imperfect with total displacement between fragments such as communized fracture, then it may be necessary to use headless screw or Kirschner wire (K-wire) for fixation after closed or open reduction. Moreover, if conservative treatment failed, fracture site was occupied by soft tissue and fibrous connective tissues and finally become nonunion. Treatment of nonunion will need to firmly fix at fracture site after sufficient refreshment for increasing the bone union rate. The treatment options for nonunion of distal phalangeal fracture include conservative management with use of ultrasound , bone grrd distal phalangeal fracture was made based on radiographs and computed tomography scans. Anteroposterior, lateral, of the right middle finger showed dorsal displacement of the distal phalangeal fracture, with communized fracture  treatment of distal phalangeal nonunion. This system enables to increase the compression force at the nonunion site compared with conventional percutaneous K-wire fixation.


Cardiac regenerative therapy is expected to be a promising therapeutic option for the treatment of severe cardiovascular diseases. Artificial tissues or organoids made from cardiovascular cell lineages differentiated from human induced pluripotent stem cells (iPSCs) are expected to regenerate the damaged heart. Even though immune rejection rarely occurs when iPSC-derived graft and the recipient have the same HLA type, in some cases, such as tissue transplantation onto hearts, the HLA matching would not be sufficient to fully control immune rejection. The present review introduces recent immunomodulatory strategies in iPSC-based transplantation therapies other than MHC matching including the induction of immune tolerance through iPSC-derived antigen-presenting cells, simultaneous transplantation of syngeneic mesenchymal stem cells, and using the universal donor cells such as gene editing-based HLA modulation in iPSCs to regulate T cell compatibility. In addition, we present future perspectives for proper adjustment of immunosuppression therapy after iPSC-derived tissue/organoid-based cardiac regenerative therapies by identifying biomarkers monitoring immune rejection. Cardiovascular diseases are leading causes of death and medical expenditure worldwide even recent progresses in medical treatments . TherapeAn immunological privilege of iPSCs in regenerative medicine is that autologous iPSCs which are considered to be immunologically identical with the host can be established from the host somatic cells and used for transplantation therapies . HoweverMacaca fascicularis). iPSCs from MHC-homozygous animals were differentiated into cardiomyocytes (iPSC-CMs) and subsequently transplanted to MHC-matched monkeys by direct intramyocardial injection. The grafted cardiomyocytes showed electrically coupling to the host heart and survived without immune rejection in monkeys treated with clinically relevant doses of immunosuppressants, whereas the transplantation of iPSC-CMs to MHC-mismatched monkeys even treated with immunosuppressants exhibited immune rejection of grafted cardiomyocytes with severe infiltration of T lymphocytes [Several allogeneic transplant models have been tested to validate whether the use of HLA-homozygous iPSCs can mitigate immune rejection. The experiments using cynomolgus monkeys demonstrated that immune rejection is rarely detected in allograft transplantation differentiated from major histocompatibility complex (MHC) type-matched iPSC. In transplantation experiments of retinal pigment epithelial (RPE) cells derived from monkey MHC-homozygous iPSCs, fair engraftment of RPE cells transplanted to MHC-matched animal models was confirmed without the use of immunosuppressants . Anotherphocytes .On the other hand, the benefits of MHC-matching seem to be alleviated in transplantation of iPSC-derived bioengineered heart tissues which is a promising strategy in cardiac regenerative medicine to promote therapeutic efficiency –23. KawaIn this context, several attempts have been made to overcome immune rejection through strategies other than HLA-matching so far. One of the promising strategies is the induction of immune tolerance in iPSC-based transplantation. There are two pathways in immune tolerance: central pathway by selective elimination of self-antigenic immune cells in the thymus and bone marrow and peripheral pathway. An important mechanism for this peripheral pathway of immune tolerance is the immunosuppression mediated by regulatory T cells (Tregs) Fig. a. Tregs Therapeutic approaches for the establishment of immune tolerance are reported so far Table . Otsuka + cytotoxic T cells against the transplants which accordingly achieved the induction of immune torelance [In addition to the induction of immune tolerance by antigen-presenting cells of identical MHC type, tolerance induction using syngeneic mesenchymal stem cells (MSCs) has also been reported Fig. b. Yoshidorelance .+ cytotoxic T cells. The modulated iPSCs were also protected from immune responses from natural killer cells because HLA-C, HLA-E, HLA-F, and HLA-G were preserved. Differentiated cells from the modulated iPSCs would be considered as an immunologically ideal cell source for transplantation therapies with enhanced immunocompatibility suppressing immune rejection after transplantation. It is also estimated that only 12 strains of iPSCs with HLA modulation theoretically cover more than 90% of the population worldwide which encourages the establishment of clinical-grade human iPSC bank covering almost all mankind [Another intriguing approach is HLA modulation in iPSCs to regulate T cell compatibility which depends on HLA types Fig. c. Xu et  mankind . Even thCRISPR-Cas9 and other gene-editing systems have recently been used to create donor cells that escape interference from the immune system . As previously described, it is not only possible to genetically modify the expression patterns of HLA class I and class II, but also to apply the immune escape mechanisms that occur in nature, such as cancer cells and placentas, to prevent the expansion of T cells and NK cells and promote Treg cell responses. Recently, some groups reported the creation of universal donor cells expressing immunomodulatory transgenes that have improved viability in allogeneic transplants . On the Although aforementioned approaches may possibly solve the problems in iPSC-based transplantation immunity, it remains to be further investigated whether these approaches will sufficiently work in iPSC-based cardiac regenerative therapies considering possible severe immunological circumstances of the heart. Another immunological consideration in iPSC-based cardiac regenerative therapies is the possible transition of transplantation subjects from “cells” to “tissue/organoids” . This paIt also means that immune regulation strategies which would even work in organ transplantation would be required in future iPSC-based cardiac regenerative therapies based on iPSC-derived tissue/organoid transplantation. Given the long history of research on immune rejection in organ transplants , it woulA strategy for the alleviation of immunosuppressant-related complications is to establish a system that can detect immune rejection in daily clinical practices to precisely control the immunosuppression level Fig. . To consIn the present review, we introduced present status and possible immunological problems in iPSC-based transplantation therapies including ongoing research attempts for immune regulation such as production of “cells that control the immune system” and “cells that get past the immune system.” Further investigations on immune regulation are required for standardization of iPSC-derived cardiac regenerative therapy based on distinctive features of iPSC-based tissue/organoid transplantation of the heart.


With the emergence of affordable, clinical-orientated gait analysis techniques, clinicians may benefit from a general understanding of quantitative gait analysis procedures and their clinical applications. This article provides an overview of the potential of a quantitative gait analysis for decision support in three clinically relevant scenarios of early stage gait disorders: scenario I: gait ataxia and unsteadiness; scenario II: hypokinesia and slow gait; scenario III: apparently normal gait with a specific fall tendency in complex mobility situations. In a first part, we justify the advantages of standardized data collection and analysis procedures including data normalization and dimensionality reduction techniques that facilitate clinical interpretability of instrument-based gait profiles. We then outline typical patterns of pathological gait and their modulation during different walking conditions  and highlight key aspects that are particularly helpful to support and guide clinical decision-making. Gait instability is prevalent in patients with balance problems, vertigo, and dizziness, and is associated with adverse health outcomes. Depending on the underlying disease entity, the risk of falling and consequent injuries is markedly increased . Falls aIn this context, quantitative, instrument-based gait analysis is a promising tool to capture and accurately assess gait function. Clinical approaches with a justifiable trade-off between the clinical benefit and infrastructural resources have been recently established. Central for clinical implementation of these techniques is application of standardized protocols for the recording, the analysis, and the interpretation of clinical gait profiles. Clinical experience and evidence from several studies emphasize that clinical gait examination should in particular assess patients’ gait function during different walking conditions , 8, 15. This article provides an overview of typical alterations of spatial and temporal gait features related to three basic syndromic scenarios: (1) gait ataxia and unsteadiness of gait with fall risk; (2) hypokinesia and slow gait; (3) fall tendency in complex situations . A special emphasis is placed on the relevance of gait findings for supporting clinical differential diagnosis.®, CIR System, Franklin, NJ, USA). A multi-condition assessment protocol with walking at self-chosen walking speed (PWS), at slow speed (SS), at maximally fast speed (MS), with reclination of the head (HR), with eyes closed (EC), with performance of a serial seven dual task (DTC), with performance of a verbal fluency dual task (DTS), and while carrying an empty tray (DTM) was performed as described elsewhere [The clinical gait profiles, which are discussed in the subsequent paragraphs were recorded on a pressure-sensitive gait carpet . The healthy control group was collected by direct recruitment and covers the age spectrum from 18 to 99 years. The resulting data are arranged in a color-coded data matrix that at first glance provides a rapid overview on the individual patient’s gait performance under various challenging conditions in comparison to age- and gender-matched healthy reference performance  , gait paThe hallmarks of the gait impairments in patients with sensory deficits, cerebellar disorders, or functional ataxia comprise distinct alterations in variability and support domains of walking. Accordingly, the spatial and temporal variability of stepping is typically increased in these cohorts —a gait aWalking pace in patients with cerebellar and sensory ataxia  is typically preserved or only slightly decreased. This observation can be explained by the fact that sensory integration for gait stabilization is speed dependent and less essential during fast locomotion . AccordiThe characteristic modulation of ataxic gait impairments during multi-condition gait assessment can further support the differential diagnosis in the context of gait ataxia. Slow walking modes accentuate gait instability in patients with vestibular and cerebellar disorders, in particular in terms of a considerably increased gait variability . As mentHypokinetic gait patterns can be observed in patients with Parkinsonism, patients with subcortical vascular encephalopathy (SAE), and patients with normal pressure hydrocephalus (NPH). The general identification of hypokinetic gait is not challenging for experienced neurologists. Typical features of gait impairments related to this syndromic category include a reduction of stepping pace, a reduced stride length, and reduced foot clearance during swing phases. Variability measures can be increased, especially in the late course of disease or when freezing-of-gait episodes are present . PatientIn hypokinetic gait disorders, alterations of gait parameters typically persist during all examination conditions. Patients with SAE or NPH show a further decline of walking performance during cognitive dual task , 26, 30—Besides the interaction of sensory feedback with supraspinal and spinal locomotor regions, human postural control also relies on cognitive and attentional capacities. Patients with mild cognitive dysfunctions frequently consult clinical centers for balance problems due to apparent locomotion impairments. They typically report a slowing of gait during real-world mobility and the occurrence of falls in complex mobility situations. The clinical examination of sensory functions and simple motor tasks does not show any significant findings in these patients. Instrument-based gait analysis shows normal gait performance during single-task walking, but typically yields strikingly abnormal findings during cognitive dual-task conditions. Accordingly, walking pace and stride length become considerably decreased  and walkDisturbances of mobility and gait are major symptoms of patients with balance disorders, dizziness, or vertigo. They are related to deteriorations of the functional status and to severe health outcomes, such as falls and fall-related morbidity . The cli


Mild traumatic brain injury (mTBI) represents more than 80% of total TBI cases and is a robust environmental risk factor for neurodegenerative diseases including Alzheimer’s disease (AD). Besides direct neuronal injury and neuroinflammation, blood–brain barrier (BBB) dysfunction is also a hallmark event of the pathological cascades after mTBI. However, the vascular link between BBB impairment caused by mTBI and subsequent neurodegeneration remains undefined. In this review, we focus on the preclinical evidence from murine models of BBB dysfunction in mTBI and provide potential mechanistic links between BBB disruption and the development of neurodegenerative diseases. Traumatic brain injury (TBI) is a leading cause of death and long-term disability around the world . Based oThe BBB is a highly selective membrane that mainly encompasses endothelial cells, sealed by tight junctions, and fortified by pericytes and astrocytic endfeet . This coMore importantly, clinical data indicated that BBB impairment can persist for many years and is highly associated with long-term neurological deficits in mTBI patients . TherefoMurine models have helped us tremendously to understand the pathogenic events after mTBI, including cerebral microvascular injury and BBB dysfunction. We searched over 6,000 publications related to mTBI on PubMed and found 232 studies potentially covering cerebrovascular impairment and BBB dysfunction . Among tin vivo imaging techniques including magnetic resonance imaging (MRI) and multi-photon imaging; and (iii) additional methods such as brain water content calculation for cerebral edema (wet/dry weight ratio). Analysis of the protein and mRNA expression of tight junction protein was also reported.We surveyed the BBB dysfunction and relevant pathologic changes found in mouse or rat models, covering the acute and subacute stages that evolve within the first 2 weeks after mTBI and the chronic stage that usually takes place 2 weeks after mTBI. The methods commonly used for BBB functional analysis in murine models are (i) histological assessment using plasma proteins such as immunoglobulin G (IgG) and/or exogenous tracers such as Evans blue dye, horseradish peroxidase (HRP), or fluoresce labeled albumin; (ii) via the in vivo two-photon imaging of intravenously injected rhodamine B. They showed that BBB disruption in wild-type C57BL/6 mice occurred at a very early stage of mTBI (between 5 and 60 min), which was even exacerbated in Slit2-Tg mice  when compared with controls. Similar situations were also reported from patients diagnosed with concussion in adolescent sports  and military service, which can be exacerbated by repetitive mild trauma injury . There aMechanistically, impairment of BBB can initiate a series of adverse events, including the leakage of serum-derived circulating agents into the brain parenchyma and improper activation of signaling pathways . As someMild traumatic brain injury is considered a long-term risk for neurobehavioral changes, cognitive decline, and neurodegenerative disease including AD . CognitiIn this review, we focused on BBB dysfunction after mTBI in murine models and found that BBB breakdown and microvascular impairment are important pathological mechanisms for cognitive impairment after mTBI. Restoring vascular functions might be beneficial for patients with mTBI and reduce the risk of developing cognitive impairments post-insult.ZZ and YW designed the review outline, wrote and reviewed the review, did the literature search, and data extraction and interpretation. HW, XG, and BP provided critical reviews, revised the manuscript, and provided relevant insights and edits. All authors read and approved the final version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


During recent years, Graduate Medical Education (GME) leaders in the United States of America have witnessed many substantive changes, including movement to a single accreditation system under the Accreditation Council for Graduate Medical Education. Both MD- and DO-trained residents and faculty must now meet an increasingly stringent set of accreditation standards outlined in Next Accreditation System standards. Specifically, updated scholarly activity standards emphasize a consistent volume and quantity of quality improvement/research projects and dissemination products. The GME literature to date has frequently provided general commentaries regarding individual project strategies or oriented to settings with greater project-related resources. There have also been few articles offering scholarly activity planning strategies for community-based GME officials striving to increase scholarly activity levels.The authors propose a customizable assessment-planning framework, largely derived from their combined decades of consultation experiences with hundreds of community-based resident and faculty projects. The authors will first describe the primary elements of their proposed scholarly activity planning approach for GME leaders so often subject to worsening resource constraints. They will describe six ongoing developmental strategies with several exemplars described. Such a framework will likely require ongoing reassessments and modification.The authors hope that this proposed planning framework will offer GME administrators, faculty and residents with a pragmatic set of strategies to develop scholarly activity projects and supports. Ideally, GME leaders can use this approach to inform their design of a sustainable system-customized infrastructure of scholarly activity supports. Next Accreditation System (NAS) standards.During recent years, the nation’s graduate medical education (GME) leaders in the United States have witnessed substantive changes, including movement to a single accreditation system under the Accreditation Council for Graduate Medical Education (ACGME). Both MD and DO-trained resident and faculty physicians must now meet an increasingly stringent set of accreditation standards outlined in scholarly activity (SA) projects.SA to refer to both research and systems-oriented QIPS designs. Although both academic and community-based GME physicians contend with increasing resource constraints, a growing number of authors have contended that these types of challenges may be greater (or certainly different) in community-based GME settings.One particular standard that many GME authors have struggled to address relates to the enhanced requirements for Unfortunately, GME officials still lack a uniform definition of what comprises a minimal level of SA.More GME experts have concluded that community-based physicians may typically experience greater difficulty planning and conducting SA projects due to fewer available resources .Some GME authors have implemented SA resident teams, generally comprised of residents from multiple programs with complementary SA project interests.GME administrators have appointed later-year residents to chief research/QIPS resident positions to coordinate SA projects in some settings.Many authors have argued that any such mechanisms need to be modified due to system or program-specific influences, and that a standardized rollout approach is unlikely to work across diverse GME settings.Numerous experts have already shown that customized SA planning tools  can help facilitate SA project development.non-sequential and ongoing strategies to enable community-based GME leaders to facilitate increased SA levels. The authors will also describe several exemplary settings with ongoing SA infrastructure developments.The SCS authors have developed this comprehensive planning approach from their 2016-2017 experiences consulting on over 210  community-based SA projects. Resident and faculty project leaders have requested SA consultations from many of the 190+ SCS-affiliated residency programs based at 37 healthcare systems. This paper will: a) describe the key elements of the authors’ suggested SA developmental planning approach, and b) discuss six The first goal of this proposed SA planning framework is to provide community-based GME leaders with a specific set of criteria to assess their current in-house project resources and complexities. The authors propose that this approach will prove especially important for GME officials striving to first develop or improve their SA project supports. The authors have repeatedly seen that many community-based leaders’ success in increasing their SA levels have required a broader perspective than simply completing a series of individual projects and dissemination products. In this paper, they assert that the longer-term development of a sustainable SA infrastructure of project supports will prove integral for maintaining SA productivity in lesser-resourced GME settings.lessons learned from earlier SA projects in their healthcare system. GME experts have increasingly supported this broader type of ongoing self-learning model of SA development that entails ongoing reassessments and modification efforts.stop and start approach to SA will impede the development of a sustainable SA project support infrastructure so later project leaders may feel as if they are starting from scratch.The key elements of this planning framework  are largely derived from the authors’ successful workshop, online module and individual consultation experiences with community-based GME leaders. They have concluded that many faculty and residents develop idealized  projects without capitalizing on on-site resources, and/or conduct projects without the cultural realities: Faculty and resident SA attitudes and beliefs, varied specialty perspectives, perceived availability of project supports and mentoring.Referring to the upper-left of Figure 1, an effective SA support infrastructure should be oriented toward first developing projects that specifically capitalize on available specific resources, such as institutional review board (IRB) guidance, health library and data-capable personnel,Referring to the middle of Figure 1, certainly each SA project will need to be developed within the context of each project team’s competing role demands .Referring to the right of Figure 1, over time, both the volume and quality of SA projects and dissemination products  can be expected to increase and GME leaders may be able to realistically expect that improved SA levels will eventually impact patient care processes and outcomes.The following ongoing developmental strategies are encouraged for community-based GME leaders striving to attain an organized SA project support infrastructure:Periodically assess your project planners’ SA learning needs and preferences by promoting available resources in an ongoing manner.It is also been shown to be necessary to periodically gauge the key learning needs of faculty and residents concerning SA projects.The SCS authors have generally concluded that many primary care physicians tend to prefer GME or QIPS project designs than surgical/procedure-oriented clinicians more oriented to complex research designs .Plan-Do-Check-Act planning sheets, pertinent articles, project conduction checklists, etc.) can prove key for first meeting the needs and preferences of lesser experienced project learners.GME leaders can certainly improve perceptions of available SA project resources by purposefully disseminating information concerning library, electronic health record and QIPS department materials and resources.non-human subjects, exempt, expedited, full review).GME officials should also periodically consider how their respective IRB have been distinguishing different types of SA projects by perceived level of research risks or types of suggested IRB applications  program.One exemplar Te4Q learner was an emergency medicine physician who completed the program in 2016 after testing a QIPS curriculum with his senior chief resident.He had subsequently delivered this curriculum to two cohorts of residents with little SCS support. His curriculum-related projects have subsequently contributed at least a dozen regional/national resident poster presentations and two SA publications to date.Systematically embed SA planning activities into your pre-existing GME processes/groups.The GME literature contains a growing number of examples of how SA experts have incorporated project planning/evaluation activities into their current GME program/staff meetings.regular part of doing business in the minds of more residents and faculty.This approach may help SA activities become perceived as a Conduct a postmortem evaluation of every SA project and attempt to derive pragmatic system-specific knowledge for future projects.football coach analogy to GME officials striving to strengthen their SA team over several years by evaluating SA project successes and lessons. This routine practice of informing project novices about earlier project successes/failures may be integral for them to develop system-compatible projects. It is also unrealistic to expect a subset of residency programs or personnel to conduct most ongoing SA projects.writing mentor mechanisms since the responsibility of project leaders to report their community-based results in the GME literature remains increasingly important.GME officials may underestimate the impetus for future projects potentially derived from completed SA projects.The growing complexities of publishing one’s final project results in many GME journals due to increased article processing fees and greater publication competition certainly needs to be acknowledged.Consider how to attain maximal SA efficiencies in your GME environment.Desire To Learn online course management software. QIPS in Healthcare: Origins and Principles, b) Research and QIPS: Differences and Similarities, c) Feasible Project Design Strategies, d) Preparing your IRB Application, and e) Building a Program of Scholarly Activity as a GME Leader. Between January 2016 and March 2018, 87 users have been enrolled and made over 280 group/individual module hits.Since many community-based GME leaders continue to experience worsening resource constraints, it may only be realistic to offer workshop/training content through coordinated asynchronous and online mechanisms.A growing number of GME experts have also indicated that it may become increasingly impractical for individual settings or programs to achieve sustainable SA progress without some type of intuitional/consortium coordination.There will never likely be any standardized solutions for development of sustainable project support SA infrastructures across our nation’s diverse GME settings.This paper presents a non-sequential developmental planning approach comprised of strategies for community-based GME officials striving to address emerging accreditation standards. As GME setting conditions change, leaders’ implemented SA project supports may require ongoing trial and error adjustments.The authors declare no conflict of interest.


Studies using data from longitudinal health survey of older adults usually assumed the data were missing completely at random (MCAR) or missing at random (MAR). Thus subsequent analyses used multiple imputation or likelihood-based method to handle missing data. However, little existing research actually examines whether the data met the MCAR/MAR assumptions before performing data analyses. This study first summarized the commonly used statistical methods to test missing mechanism and discussed their application conditions. Then using two-wave longitudinal data from the Health and Retirement Study , this study applied different approaches to test the missing mechanism of several demographic and health variables. These approaches included Little’s test, logistic regression method, nonparametric tests, false discovery rate, and others. Results indicated the data did not meet the MCAR assumption even though they had a very low rate of missing values. Demographic variables provided good auxiliary information for health variables. Health measures  met the MAR assumptions. Older respondents could drop out and die in the longitudinal survey, but attrition did not significantly affect the MAR assumption. Our findings supported the MAR assumptions for the demographic and health variables in HRS, and therefore provided statistical justification to HRS researchers about using imputation or likelihood-based methods to deal with missing data. However, researchers are strongly encouraged to test the missing mechanism of the specific variables/data they choose when using a new dataset.


Infections induce dramatic rearrangements in host macro- and micronutrient processes  and like“Antagonistic” interactions between a host and a microbe involve host defense mechanisms that maintain the host’s fitness status while having a negative impact on microbial fitness. By contrast, “cooperation” between a host and a microbe involves host mechanisms that promote host fitness while having a neutral to positive influence on microbial fitness . These mThe role of iron regulatory pathways in immunity against pathogens has been well studied (reviewed in ). HoweveSiderophores are molecules that chelate external iron with high affinity and transport iron into microorganisms through dedicated transport systems . Thus, sCaenorhabditis elegans physiological development [Fig 1A). Microbe-derived Ent was found to bind to the alpha subunit of the host mitochondrial ATP synthase, thereby increasing mitochondrial iron levels and host development under both low and high iron conditions. We propose that this work exemplifies iron-mediating cooperative host–microbe interactions because development of the host facilitates replication, nutrient acquisition, and transmission of enterobacteria. Given that other canonical virulence factors for acquiring host iron are present in commensal or beneficial microbes, future work should reassess the role of these systems with the perspective of cooperative host–microbe interactions.In addition to the role of siderophores in antagonistic host–microbe coevolution, siderophores are also critical for interspecies competition between members of the microbiota . These ielopment  Escherichia coli and Vibrio vulnificus, suggesting that transient hypoferremia is an effective metabolic defense to restrict certain extracellular pathogens [Salmonella enterica, Burkholderia pseudomallei, Chlamydia spp., and Legionella pneumophila [During acute infections, individuals experience inflammation-dependent hypoferremia . Hepcidiathogens , 21. Intumophila –24.Fig 1B). Regulation of iron levels was necessary for proper microbiome composition and mucosal repair because cDC-specific hepcidin-deficient mice were slower to recover following intestinal damage [In addition to hepatocytes, myeloid cell types are also a source of hepcidin production . In respl damage . TherefoDuring infections, microbial and host-derived toxic compounds can be generated that cause tissue damage. Detoxification mechanisms serve as antivirulence mechanisms to promote cooperative defenses by preventing damage to the host without affecting pathogen burdens . During Plasmodium or subjected to intestinal perforation leading to systemic bacterial infection [Plasmodium infection [Research into heme recycling and detoxification demonstrates the importance of these pathways for cooperative defenses . Heme denfection , 30. Thinfection , therebynfection . The HO-nfection . Given tFig 1C). Weis and colleagues established that the ferritin, the intracellular iron storage protein, regulates hepatic gluconeogenesis and is critical for host survival during polymicrobial sepsis [Recent dietary and metabolic studies in animals and humans link iron metabolism to glucose homeostasis at many levels (l sepsis . Knockoul sepsis . These sCitrobacter rodentium [C. rodentium infection caused increased tissue iron levels in the WAT and insulin resistance. The insulin resistance caused a reduction in the amount of glucose absorbed from the intestine into the bloodstream, increasing the amount of glucose available to the pathogen to metabolize, which suppressed the virulence program of C. rodentium [Sanchez and colleagues found that administration of dietary iron and transient insulin resistance promotes survival of mice given oral doses of the diarrheal pathogen odentium . Dietaryodentium . Consistodentium . The worodentium . TogetheAn entire field, called nutritional immunity, has focused on iron and other micronutrients in antagonism between host and invading microorganisms . Some in


Background: An estimated 25% of older adults with diabetes (DM) may have co-occurring Alzheimer’s Disease and Related Dementias (ADRD), complicated by multiple treatment plans and providers. Assessing treatment burden has been limited to patients’ perspectives; little is known about caregiver perceptions of treatment burden despite their important role in personal care and treatment adherence. The purpose of this qualitative study was to describe caregiver perceptions of treatment burden for older adults with DM-ADRD. Methods: This qualitative study was conducted in the formative phase of “Enhanced Quality in Primary care for Elders with DM-ADRD (EQUIPED-ADRD) a pragmatic randomized controlled trial in a large, diverse healthcare system. A diverse sample of caregivers (n=15) of patients enrolled in the RCT participated in interviews about their caregiver role and perceptions of treatment burden of DM-ADRD clinical management. Qualitative data were analyzed using content analysis and themes about treatment burden were compared to domains on the Treatment Burden Questionnaire (TBQ). Results: Caregivers reported high levels of burden related to treatment plans for patients with DM-ADRD. Themes related to complexity and burden of medication management, monitoring , dietary and physical activity regimens, navigating healthcare providers and financial burden were reported. Caregivers also described high levels of emotional burden that was associated with patient’s cognitive decline and family functioning stress. Conclusions: Interventions to reduce treatment burden for patients and caregiver should include activating social/nursing services, respite care and care coordination that may support caregivers especially as patient treatment increases in complexity over time.


Chronic condition discordance  has adverse mental health implications but little is known about mechanisms accounting for these links. We considered how chronic condition discordance at the individual level and the couple level  was associated with perceived control among 2,676 couples from three waves  of the Health and Retirement Study. Dyadic growth curve models revealed that when wives had greater individual-level discordance, they reported lower initial health-related control and personal mastery and steeper reductions in personal mastery. When husbands had greater individual-level discordance, they reported lower initial health-related control and faster declines in health-related control and personal mastery, and wives had faster declines in personal mastery. When there was greater couple-level discordance, wives reported lower initial health-related control. Targeting increases in perceived control among older couples managing complex conditions may be beneficial. Part of a symposium sponsored by Dyadic Research on Health and Illness Across the Adult Lifespan Interest Group.


A standardized approach to annotating computational biomedical models and their associated files can facilitate model reuse and reproducibility among research groups, enhance search and retrieval of models and data, and enable semantic comparisons between models. Motivated by these potential benefits and guided by consensus across the COmputational Modeling in BIology NEtwork (COMBINE) community, we have developed a specification for encoding annotations in Open Modeling and EXchange (OMEX)-formatted archives. Distributing modeling projects within these archives is a best practice established by COMBINE, and the OMEX metadata specification presented here provides a harmonized, community-driven approach for annotating a variety of standardized model and data representation formats within an archive. The specification primarily includes technical guidelines for encoding archive metadata, so that software tools can more easily utilize and exchange it, thereby spurring broad advancements in model reuse, discovery, and semantic analyses.


Over one in four older adults (65 years and older) in the US reports falling annually with estimated medical costs of $50 billion. Evidence-based strategies exist that can reduce falls with one of the most promising being multifactorial, clinically-based initiatives such as the Centers for Disease Control and Prevention’s STEADI  Initiative. STEADI includes three core components for health care providers: screen for risk factors, assess modifiable factors, and intervene to reduce falls with evidence-based strategies. Barriers to implementation include competing patient demands and limited time during patient visits. Efficient, effective implementation of clinical fall prevention is important to increase the use of multifactorial interventions. In addition, understanding older adult attitudes about the preventability of falls is needed to increase patient adherence to prescribed interventions. This symposium will cover:1. Background data on older adult falls over time,2. Description of an initial implementation of STEADI in an outpatient, Southeastern clinical practice including lessons learned,3. Attitudes of older adults toward fall prevention with implications for health promotion,4. Process evaluation of an ongoing implementation of STEADI in New York State with lessons learned. Understanding practical methods of implementing the three core components of fall prevention into practice supports wider dissemination of evidence-based fall prevention, while understanding patient attitudes toward falls informs the design of health promotion approaches to increase patient uptake of prescribed interventions. Wider dissemination and increased patient adherence in combination can reduce older adult falls and their associated medical costs.


Late-life suicide is a complex public health issue, and older adults have a higher risk threshold than the national average . Most late-life suicide research focuses on elevated risk of older white males, and less is known about risk factors among Black older adults . Although fewer Black older adults die by suicide than White older adults, forms of suicidality do not differ between Black and White older adults . Suicide risk factors, such as psychological distress  and chronic pain , are prevalent among Black older adults. According to the Interpersonal Theory of Suicide , thwarted belongingness and perceived burdensomeness inform the development of suicidal desire. These findings have been corroborated among older adult samples, though lacking racial diversity. To better understand how the IPTS functions for older adults, and probe whether suicide risk pathways operate differently depending on race, we used data from over 400 homebound older adults residing in a U.S. metropolitan area to clarify if this suicide risk pathway is similar for Black and White older adults. Race moderated the relationship between physical and psychological pain and thwarted belongingness and perceived burdensomeness, with pain among Black older adults having a greater impact on their sense of belonging and burdensomeness. Findings illuminate the need for culturally nuanced understandings of suicidality in older adulthood. The presenters will demonstrate these results and discuss implications for cross-cultural suicide prevention frameworks.


Assisted living (AL) communities are increasingly home to frail, chronically ill older adults who remain until death. State laws mandate that AL facilities request copies of any advance care planning documents residents have and make forms available upon request. Using secondary data from a larger study funded by the National Institute on Aging (R01AG047408) that focuses on end-of-life (EOL) care in AL, this project investigated barriers and facilitators to conducting advance care planning in AL. Data included in-depth interviews (of 86 minute average length) with 20 administrators from 7 facilities around the Atlanta metropolitan area and aggregate data collected from each facility regarding facility, staff, and resident characteristics. Findings from thematic analysis of qualitative data showed that key barriers to planning in AL included lack of staff training and reluctance among administrators and families to discuss advance care planning and EOL care. Important facilitators included periodic follow-up discussions of residents’ wishes, often during care plan meetings, educating families about the importance of planning, and external support for staff training and family education from agencies such as hospice and home health. Three study facilities exceeded state requirements to request and store documents by systematically encouraging residents to complete documentation. These facilities, whose administrators discuss advance care planning and residents’ EOL wishes with residents and families during regular care plan meetings, were more likely to have planning documents on file, demonstrating the potential of long-term care communities, such as AL, to successfully promote advance care planning among residents and their family members.


Adenosarcoma is an extremely rare malignancy of the female genital tract composed of stromal sarcoma with a benign epithelial component. Current treatment recommendations include total hysterectomy with bilateral salpingo-oophorectomy, precluding future fertility. Although most frequently diagnosed in postmenopausal women, it is occasionally present in younger women of reproductive age with desire for future fertility. In 2015, we reported the case of a 23-year-old patient diagnosed with uterine adenosarcoma, who having strong desire of future fertility, opted for fertility sparing surgery. At a follow-up five years later, we can now report her case of spontaneous pregnancy and livebirth. A review of the literature concerning fertility outcomes in patients with uterine adenosarcoma undergoing fertility sparing therapeutic options is presented. Uterine adenosarcoma (UA) is a rare gynaecological malignancy composed of sarcomatous stroma and a benign epithelial component . While tLee et al.  describeA proposed fertility sparing treatment protocol includes fertility sparing surgery (FSS) consisting of a complete resection of the lesion followed by medical treatment with megestrol acetate 160 mg/day for at least 6 months. Once the desire for fertility is fulfilled, hysterectomy with bilateral salpingo-oophorectomy is recommended. A fertility sparing treatment protocol must be performed only in low-risk cases  and close longterm follow-up is needed . PatientIn 2015, a nulliparous 23-year-old woman referred to our institution was diagnosed with UA stage IA according to FIGO 2009 criteria. Due to her strong desire of future fertility, after extensive counselling she opted for FSS. Hysteroscopic complete resection of the tumour was performed, followed by oral megestrol acetate 160 mg/d as adjuvant therapy . This waMullerian adenosarcoma is a rare gynaecological cancer composed of a benign epithelial component with sarcomatous stroma . Total hAdenosarcoma is an extremely rare gynaecological malignancy with only a few cases reported in patients of reproductive age. The current recommended treatment is hysterectomy with bilateral salpingo- oophorectomy, however, fertility sparing treatment options are feasible in selected patients.In cases of focal tumours without sarcomatous overgrowth and without sign of infiltration or metastasis, a fertility sparing approach may be proposed to young women diagnosed with UA and who strongly wish to preserve their fertility. There is currently insufficient evidence regarding the ideal follow up protocol for patients diagnosed with UA who are managed with FSS.


Diversity and inclusion are essential perspectives on university campuses. In recent years, there has been a nationwide decline in admissions resulting in changes to traditionally FTIAC driven college campuses. An environmental scan was completed at a mid-sized midwestern university to explore age-inclusive barriers and opportunities for change. In-depth interviews were held with 28 EMU stakeholders representing a wide variety of ages in leadership positions across campus. Students aged 40 and above (N=248) were also surveyed about their experiences on campus. Qualitative analysis revealed ageist attitudes about older adults and older students from at all levels of the university. Results demonstrate that initial responses to ‘age-friendly’ focused on stereotypes of older adults, but attitudes adjusted when reframed as older learners and further refined when older learners were defined as 40 and above. Additionally, there was a distinct disconnect between ageist perceptions towards older adults and older students which highlights the importance of intergenerational opportunities as an approach to combat ageist attitudes on campus. While these barriers require long-term and complicated solutions, participants described the many benefits that older learners bring to enrich the campus. Results of this research revealed opportunities to reframe aging in the context of diversity and inclusion efforts on campus. Adopting diversity efforts to include age can benefit universities in not only admissions, classroom experiences, and connections to surrounding communities.


Tachycineta bicolor). We address two questions: (1) do the cloacal bacterial communities differ between female and male tree swallows within a population? and (2) do pair-bonded social partners exhibit more similar cloacal bacterial communities than expected by chance? To answer these questions, we sampled the cloacal microbiome of adults during the breeding season and then used culture-independent, 16S rRNA gene amplicon sequencing to assess bacterial communities. Overall, we found that the cloacal bacterial communities of females and males were similar, and that the communities of pair-bonded social partners were not more similar than expected by chance. Our results suggest that social monogamy does not correlate with an increased similarity in cloacal bacterial community diversity or structure. As social partners were not assessed at the same time, it is possible that breeding stage differences masked social effects on bacterial community diversity and structure. Further, given that tree swallows exhibit high variation in rates of extra-pair activity, considering extra-pair activity when assessing cloacal microbial communities may be important for understanding how these bacterial communities are shaped. Further insight into how bacterial communities are shaped will ultimately shed light on potential tradeoffs associated with alternative behavioral strategies and socially-transmitted microbes.Host-associated microbial communities can influence the overall health of their animal hosts, and many factors, including behavior and physiology, can impact the formation of these complex communities. Bacteria within these communities can be transmitted socially between individuals via indirect  or direct  pathways. Limited research has been done to investigate how social interactions that occur in the context of mating shape host-associated microbial communities. To gain a better understanding of these interactions and, more specifically, to assess how mating behavior shapes an animal’s microbiome, we studied the cloacal bacterial communities of a socially monogamous yet genetically polygynous songbird, the North American tree swallow ( Host-associated microbial communities can contribute to the overall health of their animal hosts –4, and mTachycineta bicolor) and house sparrows (Passer domesticus). More recent work using culture-independent methods has revealed that pair-bonded social partners experimentally blocked from making cloacal contact have significantly less similar cloacal bacterial communities compared to control pairs in black-legged kittiwakes (Rissa tridactyla) )munities . Given tStaphylococcus spp., Campylobacter spp., Salmonella spp., and Shigella spp. In our study, we used culture-independent, next-generation sequencing. We did not find that any of the cloacal bacteria they cultured were members of the core bacterial communities of birds within our study population. While Staphylococcus spp. and Lactobacilli were detected, their relative abundances were <0.001%. This suggests that culturing of cloacal bacteria may not consistently result in isolation of the most dominant bacteria in the system. It is also possible that the bacteria cultured by Lombardo et al. [Previous work examining the similarity of the cloacal bacteria of social partners in tree swallows used culture-dependent methods . The isoo et al.  are rareIn conclusion, our results suggest that the cloacal bacterial communities of female and male tree swallows are similar within our study population and that pair-bonded social partners do not share more similar cloacal bacterial communities than expected by chance. Given that tree swallows exhibit high variation in rates of extra-pair activity, we argue that considering rates of extra-pair activity or the number of sexual partners per bird when assessing cloacal bacterial communities may be important for understanding how cloacal bacterial communities are structured. Also, since cloacal bacterial communities comprise bacteria derived from both the reproductive and digestive tract, diet should also be considered when assessing cloacal bacterial communities. Lastly, we suggest that pair-bonded social partners should be sampled simultaneously to control for any temporal shifts in individual behavior and physiology that may influence shifts in cloacal bacterial community structure across breeding stages.


The Tailored Activity Program (TAP) is a proven program delivered primarily by occupational therapists addressing dementia-related clinical symptoms including caregiver well-being. Although used in 9 countries including the United States, scaling and widespread dissemination is challenging. We discuss key revisions to TAP to facilitate dissemination including matching assessments to those used in different practice settings, translation of materials into different languages, providing worksheets to help trainees adapt TAP to local contexts and a training/certification online experience using story board, an interactive media integrated onto the Blackboard learn management system, to provide on-demand training modules. The learning platform allows learners to engage with others, preview modules and share experiences. Revisions enable greater flexibility for program adaptation yet adherence to its core principles. With over 150 trainees, we use REAIM to evaluate effectiveness of modifications and to understand implications for its reach. Part of a symposium sponsored by the Behavioral Interventions for Older Adults Interest Group.