Collectivism refers to the social practice of investing in and relying on one’s social network, rather than formal institutions, to ensure personal security. Using the re-engineered 2014 Survey of Income and Pension Participation (SIPP), we investigate how collectivist practices affect life course health disparities at older ages in the US. Indicators of Collectivism include measures of caregiving, inter and intrahousehold financial and material support and help from charities, friends and family members. Regression results indicate that increased collectivist interactions are associated with improved self-reported health status outcomes. Government support for collectivist behaviors can thus yield a low cost means of improving health outcomes among the elderly.


Falls are common, costly, and the leading cause of fatal and nonfatal injuries for older Americans. Reports show that fall death rates are increasing. Healthcare providers play an important role in fall prevention but few talk to their patients about falls. This lack of communication demonstrates the need for more physician-initiated fall prevention. The Centers for Disease Control and Prevention (CDC) created the Stopping Elderly Accidents, Deaths, and Injuries (STEADI) initiative to help providers talk to their patients about falls. Specifically, CDC’s new STEADI-based fall prevention program, the Coordinated Care Plan to Prevent Older Adult Falls (CCP) and Evaluation Guide for Older Adult Clinical Fall Prevention Programs can assist healthcare providers in integrating and evaluating new fall prevention programs that screen older adults for fall risk, assess patients’ modifiable fall risk factors, and implement evidenced-based fall prevention interventions . The CCP offers guidance for incorporating a STEADI-based fall prevention program including how to engage leadership, integrate with existing clinic workflow and electronic health records, and strategies on how to obtain reimbursement for fall prevention. The Evaluation Plan offers details on how to engage stakeholders, collect data, interpret findings and how to share results for maximum impact. Both documents were based on lessons learned from successful implementation of STEADI-based programs in primary care. A STEADI-based program in New York found fewer fall-related hospitalizations among at-risk patients who received a fall prevention care plan compared to at-risk patients who did not receive a care plan.


Undernutrition affects millions of children in low- and middle-income countries (LMIC) and underlies almost half of all deaths among children under 5 years old. The growth deficits that characterize childhood undernutrition (stunting and wasting) result from simultaneous underlying defects in multiple physiological processes, and current treatment regimens do not completely normalize these pathways. Most deaths among undernourished children are due to infections, indicating that their anti-pathogen immune responses are impaired. Defects in the body's first-line-of-defense against pathogens, the innate immune system, is a plausible yet understudied pathway that could contribute to this increased infection risk. In this review, we discuss the evidence for innate immune cell dysfunction from cohort studies of childhood undernutrition in LMIC, highlighting knowledge gaps in almost all innate immune cell types. We supplement these gaps with insights from relevant experimental models and make recommendations for how human and animal studies could be improved. A better understanding of innate immune function could inform future tractable immune-targeted interventions for childhood undernutrition to reduce mortality and improve long-term health, growth and development. In low- and middle-income countries (LMIC) childhood undernutrition manifests as growth deficits which can result in a child being too short for their age  score <-2), and/or too thin for their height  score <-2), which are both associated with a greater risk of all-cause mortality . Severe Stunting and wasting are the most readily measurable indicators of undernutrition, but these anthropometric deficits result from underlying defects in multiple physiological processes . The mosIn this review we will discuss the current evidence for the role of innate immune cell dysfunction in undernutrition, focusing on children living in LMIC. We will draw on population studies and supplement knowledge gaps from existing undernutrition research with insights from experimental models. Our goal is to highlight the potential for innate immune cell dysfunction to shape clinical outcomes of undernutrition and outline how future studies could be used to improve our understanding of these pathways.in utero: a principal predictor of postnatal growth is maternal nutritional status during pregnancy, and length and weight at birth  recurrent symptomatic infections and sub-clinical pathogen carriage; (2) chronic systemic inflammation and immune activation; (3) impaired gut function, enteropathy and dysbiosis of the gut microbiome , 13; (4)at birth . These iat birth . The resat birth . Immune at birth . For exaat birth . Micronuat birth . The comat birth .In the past decade, substantial advances in experimental approaches to study the microbiome have been used to demonstrate a causal association between dysbiosis in the gut and malnutrition . Hoin vitro. Addition of Vitamin A to monocyte cultures treated with BCG led to an inhibitory histone methylation mark (H3K9me3) that suppressed monocyte cytokine responses upon re-stimulation relative to monocytes treated with BCG alone  is present and associated with colonization with pathogenic microorganisms, dysbiosis, innate leukocyte recruitment, and reduced gut functional capacity . Not allStudies among children hospitalized with SAM suggest that systemic and intestinal inflammation independently contribute to mortality , 43, 44.Inclusion of functional analysis of immune cells in cohort studies of children in LMIC is uncommon. Of the studies conducted, many demonstrate innate and adaptive immune cell dysfunction during undernutrition [summarized in a systematic review by Rytter et al. ]. HowevePlasmodium parasites has shaped a distinct myelopoietic niche in the bone marrow resulting in a characteristic neutropenia among the majority of people of African ancestry . The interaction between HIV, inflammation and undernutrition was demonstrated in a recent study of children starting antiretroviral therapy in Uganda and Zimbabwe . A propory alone . CarefulNo studies to our knowledge have assessed innate immune cell function in stunting in LMIC beyond soluble inflammatory biomarkers (discussed above). There has also been limited assessment of innate immune cell function in undernourished tissues, with an understandable majority of studies focusing on more readily accessible innate immune cells in peripheral blood. Despite the limitations of existing studies, a number demonstrate innate immune cell dysfunction in undernutrition  and basal (from the lamina propria) signaling via polarized expression of receptors and tight regulation of membrane permeability. Immunohistochemical analysis of intestinal biopsy specimens indicates that this regulation by epithelial cells is disrupted in children with SAM  in gut biopsy specimens from severely undernourished Gambian children compared to adequately-nourished controls from the same community . Epithelsphatase —a mechansphatase . Murine nfection . Intestinfection . After enfection . Defectsnfection . Thus, bDisrupted epithelial cell responses have also been observed in enteropathy associated with other health conditions. For example, diabetic enteropathy in adults causes defects in colonic epithelial stem cell mobilization due to reduced levels of circulating IGF-1 and IGFBP3 , both ofper se . In a sin vitro ; both dein vitro . Interfein vitro . The assin vitro , 8 and din vitro , suggestin vitro, even when NK-to-tumor cell ratios were high  or antibody ligation of NK1.1 surface antigens relative to NK cells isolated from ad libitum-fed controls  share some of the functions of adaptive T cells, but respond to challenges with the rapid kinetics of innate immune cells [reviewed by Eberl et al. ]. NK celIn this review we have outlined knowledge gaps in the function of all innate immune cell types during childhood undernutrition. A concerted effort is needed to translate immunological paradigms from animal models into human cohort studies. Furthermore, whilst assays of soluble immune biomarkers, proteome, transcriptome, epigenome, and metabolome profiling in peripheral samples provide insights into immune and immune-metabolic derangement, direct measurements of immune function will rely on cell- and tissue-based assays. In the long-term, developing high-quality assays of innate immune cell function for well-powered population studies in LMIC will rely on leveraging existing laboratory capacity for immunology research and developing capacity where it is not currently available. Such efforts would be accelerated by adaptation of existing technologies for assessing immune cell function in high-income settings to affordable standardized field-deployable formats. Cohort studies of innate immune function should be: (i) powered adequately to detect differences in highly heterogeneous immune responses; (ii) longitudinal in design to distinguish short-term fluctuations from persistent functional defects; and, (iii) ideally nested within studies that also characterize concurrent immunological stimuli , which are necessary to accurately interpret immune cell behavior. To identify localized changes in innate immune cells and learn more about the function of tissue-resident cells during undernutrition, sampling from a more diverse range of anatomical sites will be necessary. For example, despite respiratory tract infections being a frequent cause of mortality among undernourished children , we knowBeyond understanding the basic immunology of childhood undernutrition, developing novel therapies targeting innate immune dysfunction will require cohort studies to assess whether innate immune cell function is associated with clinical outcomes, and identify the pathways that lead to dysfunction. Identifying immune biomarkers of prognostic value for stunting, wasting and infectious mortality has proven challenging to-date due to the multiple mediators that are simultaneously altered , 10, 12.vice versa has been bolstered by studies of nutrient deprivation in animals  Environmental toxin exposure, such as exposure to mycotoxins derived from molds that contaminate staple crops, which is extremely common amongst pregnant mothers and children in some settings . SeveralExisting studies have been critical to our understanding of innate immune cell function in childhood undernutrition, but considerable knowledge gaps remain. Studies among undernourished children demonstrate impairments in a range of innate immune responses, but the pathways underlying these defects are unclear. Experimental animal models provide a clearer picture of how individual features of the undernourished state  can drive changes in innate immune cell function, but do not recapitulate the multiple simultaneous immune challenges that are typical during childhood undernutrition in LMIC. It is increasingly apparent that novel therapeutic approaches are required to improve health outcomes for children with undernutrition, given the complex pathology that underlies wasting and stunting. Since infections are the leading cause of death , a betteCB wrote the manuscript with input and critical commentary from KJ and AP.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.


Family caregivers of persons with dementia experience guilt for various reasons when placing their family member into residential long-term care (RLTC). Research has shown a relationship between guilt and overall caregiver burden; however, literature on predictors of guilt related to caregiving following RLTC placement is limited. The Residential Care Transition Module (RCTM) provides counseling and psychoeducation to family caregivers who have recently moved their family member with Alzheimer’s disease or a related dementias into RLTC. This semi-structured intervention provides counseling on various topics including guilt, grief, and family dynamics. Using treatment group data (N=87) from the parent RCTM randomized controlled trial, we identified the impact of caregiver status , sense of caregiver competence, and relationship closeness on baseline measures of guilt status and magnitude. Preliminary analyses showed that adult child status was associated with greater prevalence of guilt (37.5%) compared to spousal caregivers (26.7%). In addition, qualitative case notes were coded to identify common themes of experiences of guilt to inform practice. Examples include: Guilt related to no longer being able to care for the family member at home; not meeting self-dictated expectations ; and feeling guilted into being a caregiver in the first place. The current analyses aim to help practitioners better predict risk for placement-related guilt and highlight specific issues practitioners should consider to help mitigate such feelings. Specific opportunities for intervention are discussed.


Modifying neighborhood environments to target well-established risk factors for cardiovascular disease may reduce health disparities by complementing clinical services. Prior research, however, includes limited measures of neighborhoods and does not adequately account for individual-level processes known to mediate health outcomes. We combine baseline data from the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) dataset with neighborhood-level data to yield a diverse sample of Black and white middle-aged and older residents of Baltimore City (N=2707). We use structural equation modeling to examine associations between neighborhood environments and obesity (BMI>=30), focusing on individual-level mediators. Initial direct associations between neighborhoods and obesity  are mediated by healthcare access and health behaviors. Additional indirect pathways exist through health behaviors . These findings highlight the importance of considering indirect pathways to cardiovascular health promotion among aging adults in different neighborhood contexts.


OBJECTIVES/SPECIFIC AIMS: Incomplete spinal cord injury typically results in life-long disability, often in the form of profound loss of locomotion capability. Individuals who have experienced incomplete spinal cord injury exhibit persistent eccentric motor deficits, which are particularly prevalent in the weight acceptance phase of gait and emphasized in sagittal plane knee motion and frontal plane hip motion. METHODS/STUDY POPULATION: Motion analysis can capture the kinematic and joint-level deficits of these individuals, but it is impossible to directly calculate the contributions of individual muscles to weight acceptance due to the complexity of the musculoskeletal system. Instead, those muscle contributions must be simulated in order to approximate muscle power during locomotion. RESULTS/ANTICIPATED RESULTS: The traditional method for driving these simulations with electromyography readings is unavailable for individuals who have neuromuscular deficits , due to the need to generate reliable maximum voluntary isometric contractions for baseline purposes. Instead, this research develops a novel method for using resting electromyography data to drive musculoskeletal simulations using a muscle activation threshold paradigm. DISCUSSION/SIGNIFICANCE OF IMPACT: The simulation results of this method more closely resemble experimental results, but further simulation refinement is needed to fully capture the true muscle activity.


A 69-year-old man presented with precordial pain and a dilated ascending aorta with the suspicion of an intramural hematoma. At emergency operation, the aorta appeared grossly thickened with diffuse intimal scarring. Retrospectively, the patient tested positive to serologic screening for syphilis with histologic findings also compatible with a syphilitic aortitis. A 69-year-old man, previously asymptomatic and with an unremarkable clinical history, presented with dyspnea and precordial pain at our emergency unit. He denied any risky sexual behavior and did not show any signs or symptoms related to secondary syphilis. An angio computed tomographic (CT) scan showed a fusiform aneurysm of the ascending aorta with a maximum diameter of 65 mm, with a thickened wall raising the suspicion of an intramural hematoma . Other Histology of the aortic wall showed full-thickness infiltrates involving all layers with adventitial fibrosis surrounding thickened vasa vasorum ,B witAortitis is the main manifestation of a syphilitic cardiovascular infection, but aortic aneurysms due to tertiary infection are substantially uncommon in the modern era;Syphilitic aortitis is usually diagnosed combining histologic and laboratory data, although cases of negative laboratory testing have been reported.Our experience demonstrates that luetic infection still remains a potential cause of ascending aortic aneurysms.


One consequence of modern longevity is the growing number of older adults with very old parents. While family members are often interdependent in their development and aging, less is known about how intergenerational relationships may influence individuals’ attitudes toward their own aging in later life. Using 70 dyads of oldest-old parents (Mage = 93) and their children (Mage = 67) from the Boston Aging Together Study, we examined the dyadic concordance in positive attitudes toward own aging, and how perceptions of giving and receiving care are associated with attitudes toward own aging for parents and children. On average, parents reported more negative attitudes toward own aging than did children. In less than half of all dyads (46%), both parents and children reported positive  attitudes toward own aging. T-test results showed that the dyads with positive attitudes toward own aging had more within-dyad age difference, better average self-rated health, fewer depressive symptoms and less loneliness than others. For children, higher level of caregiver’s burden was associated with more negative attitudes toward own aging. For parents, perception of received support was not associated with their attitudes toward own aging. This study sheds light on how both individual and family characteristics may influence individuals’ aging perceptions. Findings suggest the context of parent-child ties may particularly be relevant to those older adults who may have to deal with their own aging- related challenges as well as those of their parents.


When students from two or more professions learn about, from, and with one another in joint learning activities, interdisciplinary perceptions and attitudes improve and collaborative knowledge and skills increase.3 Most, more or less, hinge on the development of competencies deemed necessary for effective collaborative practice, such as communication and ethical values.The contribution of these skill sets to the positive and productive function of patient care teams is both apparent and universal. For example, abilities to listen and constructively consult, discuss, and debate are obvious elements for collegial interactions. Respecting patient dignity and maintaining confidentiality reflects a commitment to professional conduct and engenders trusting relationships. Such behaviours and attitudes are further recognized as collective competencies given they have been adopted by many North American health professional training programs as discipline-specific educational outcomes. By both accounts, these principles also apply to the scholar competency role.Different frameworks exist to guide integration of IPE programming into health professional curricula worldwide.4Similarly, the American Association of Medical Colleges outlines an entrustable professional activity milestone whereby trainees ‘form clinical questions and retrieve evidence to advance patient care’.5Albarqouni et al recently enlisted over 200 multidiscipline clinicians and academics from 28 countries to agree upon a set of evidence-based practice competencies for health professional teaching and learning.6 Through Delphi survey and consensus processes,they arrived at a set of 68 core competencies further organized into introductory concepts and five main evidence-based practicesteps including: ask, acquire, appraise and interpret, apply, and evaluate.While the authors acknowledge somecompetencies likely require modification to suit specific needs of any given discipline, most are indeed fundamental skills broadly applicable across professions. Examples include converting clinical questions into structured, answerable formats; constructing and carrying out an appropriate search strategy; distinguishing evidence-based from opinion-based clinical practice guidelines; explaining the evidence to patients and integrating their preferences into decision-making processes; and managing clinical decision-making uncertainty in practice. The consensus statement represents an important step towards unifying expectations of evidence-based practice. The details can guide instructional and assessment design and delivery in health professional curricula and for a number of programs, these may fall within the scholar competency role  .From 50 years agowhen McMaster University launched a novel medical program where students first learned about patient problems concurrent with epidemiology and biostatistics, Canadian physicians-in-training today are meant to ‘identify pertinent evidence, evaluate it using specific criteria, and apply it in their practice’ as part of the scholar competency role.nt care) .7 That is, how are these competencies truly interprofessional in nature and not simply common skills expected by many different professions? First, this set of competencies is an acknowledgement that a majority of professionals employ evidence-based practice in patient care. Although decision-making may occur within the discrete scope of a profession’s practice, we can be assured of a common language when this care is informed by reported literature, such as randomized controlled trials, meta-analyses, or clinical practice guidelines. Like the fundamental aspects of interprofessional communication  these competencies represent an opportunity for standardization of practice principles across patient care providers. Furthermore, when teams of various disciplines convene to develop treatment protocols or care pathways, there is a shared understanding of how the evidence under consideration may be interpreted.Clinicians may enlist similar approaches to navigate incomplete available data or ambiguous study findings to make treatment choices.If as Nandiwada&Kormos further contend, this work substantiates the existence and importance of evidence-based practice competencies across health professions, howdo they expressly promote shared or collaborative care?Interprofessional competencies are meant to promote collaborative care that ultimately improves patient outcomes. Integration of evidence-based competencies into shared decision-making clearly has the potential to do so. Patient adherence may be enhanced when care providers can clearly explain the data underpinning the rationale for the selected treatment and offer realistic estimates of potential risk. Clinicians who can interpret and synthesize a wide array of literature may have greater abilities to individualize care while also incorporating patient preferences. In this regard, optimal evidence-based practice must be enabled by the communication and collaboration skills endorsed by both profession-specific and interprofessional competency frameworks. Just as effective team-based care must draw upon the collective contributions of its diverse members, quality healthcare also relies on this complement of a clinician’s knowledge, skills, and behaviors.


Aortic dissection is the most devastating sequelae of aortopathy other than aortic rupture. However, aortic dissection can be asymptomatic in the acute phase with delayed symptomatic presentation or incidental diagnosis upon chest imaging. We report a case of a 63-year-old male who was diagnosed with pericardial effusion upon preoperative workup for elective cholecystectomy. Further investigations confirmed hemorrhagic pericardial effusion secondary to a chronic dissecting ascending aortic aneurysm. The patient condition was successfully managed with open surgical repair with an uneventful postoperative course. This case demonstrates an extremely rare presentation of incidental hemorrhagic pericardial effusion caused by a chronic dissecting ascending aortic aneurysm. A 63-year-old male with a history of hypertension, 20 pack-years of smoking, thyroid cancer in remission with partial thyroidectomy, and chronic obstructive lung disease (COPD) presented to the emergency department (ED) with acute abdominal pain. Abdominal ultrasound showed gallstones with no evidence of cholecystitis or biliary obstruction. The patient was diagnosed with biliary colic and discharged home with a plan to perform an elective cholecystectomy. Computed tomography (CT) scan of the abdomen was performed as an outpatient as part of the preoperative workup which showed evidence of gallstones, small bilateral pleural effusions, and moderate pericardial effusion with high density suggestive of hemorrhage . ConsequAcute Stanford type A aortic dissection (AD) is a life-threatening condition that serves as an impetus to immediate surgical repair aiming to prevent dissection-associated complications such as acute aortic regurgitation, aortic rupture, myocardial or cerebral ischemia, and pericardial tamponade . HoweverThe first clue for CTAD diagnosis was the detection of high-density pericardial effusion note on abdominal CT scan before elective cholecystectomy. Given the lake of symptoms, transudation of fluid across the wall of the false lumen into the pericardial cavity is the most plausible mechanisms. Also, hemopericardium in our case could be a sign of silent contained rupture.All patients with aortic dissections will need immediate surgical evaluation independent of location . PatientOur patient had an aorta diameter of 7.5 cm; furthermore, his dissection was complicated by hemorrhagic pericardial effusion and moderate aortic regurgitation. Thus, the open surgical repair was the chosen approach. According to a recent review of a 696 type A patients, following open repair, patients with CTAD had lower in-hospital mortality and longer five- and ten-year survival compared to the acute type A dissection patients [Chronic type A aortic dissection is a challenging diagnosis with a wide range of clinical presentations including incidental hemorrhagic pericardial effusion. Pericardial puncture in pericarial effusion complicating type A dissection can result in the propagation of the rupture. Accordingly, obtaining a CT scan of the chest prior to any diagnostic pericardial puncture is highly recommended. Surgical repair is the treatment of choice for complicated chronic type A aortic dissection.


Promoting healthy aging does not end when people enter skilled nursing facilities (SNF) where the demands for clinical and psychosocial care are likely to be greatest. Many chronic conditions present opportunities for better SNF care and thus, healthier aging. Such conditions cannot wait for the often-long path to discovery that is typical of most traditional randomized controlled clinical trials. Conversely, pragmatic clinical trials are real-world investigations that offer the possibility of immediate benefit while answering important research questions. Depression and disrupted sleep are two examples of treatable conditions with opportunities for immediate benefit through pragmatic trials and applied best practices. How best to support best-practice integration has received increasing attention but identifying the most effective strategies continues to evolve. We report two different SNF-mentorship models utilizing Minimum Data Set (MDS) data for depression and environmental (noise-level) data for disrupted sleep, which have supported better SNF practices and presumably, healthier aging.


Although CGRP has been implicated in numerous physiological processes , the precise physiological roles of CGRP remain to be elucidated. To provide a better understanding of the physiological role(s) mediated by this peptide neurotransmitter, we have generated aCGRP-null mice by targeted modification in embryonic stem cells.


A 54-year-old man presented to the emergency department with confusion and Parkinsonian features after suspected heroin snorting. He had magnetic resonance imaging of the brain demonstrating isolated symmetric bilateral globus pallidus (GP) restricted diffusion and edema consistent with hypoxic ischemic encephalopathy. In contrast to other anoxic/ischemic insults, where the GP is preferentially spared, autopsy reports on intravenous heroin users have found the GP to be specifically affected, often demonstrating symmetric bilateral lesions. Opioid toxicity should be considered in patients presenting with Parkinsonian features on examination or pallidal lesions on imaging, especially in younger adults where infarction is less common. On arrival to the ED he was awake but confused and noted to have bilateral upper and lower extremity rigidity along with sustained clonus, hyperreflexia in upper and lower extremities, and complained of “foot cramping.” A non-contrast computed tomography of the brain was normal (A 54-year-old man presented to the emergency department (ED) after receiving naloxone for a suspected opioid overdose. He was found in bed unresponsive, hypoxemic to SpOs normal . Brain ms normal .In autopsies on patients with heroin use disorder, bilateral GP lesions were noted to be frequently encountered.The patient was admitted to the hospital where he admitted to snorting heroin powder. He had resolution of his symptoms by hospital day five. Hypoxic ischemic insult, including opioid toxicity, should be considered in patients with Parkinsonian features on exam and/or isolated pallidal lesions on imaging without history of overt cardiorespiratory arrest, especially in adolescents and younger adults where infarction is less common.What do we already know about this clinical entity?Bilateral Globus Pallidus (GP) lesions have been noted in autopsies of patients with heroin use disorder. The etiology is unclear as anoxic-ischemic insults typically affects other brain areas.What is the major impact of the image(s)?Toxin induced Globus pallidus injury is a recognized finding in carbon monoxide, methanol, and cyanide poisoning. This magnetic resonance imaging finding should prompt a differential that includes opioid use.How might this improve emergency medicine practice?Recognition of GP lesions may identify a patient at high risk of future opioid related injury or death; who would benefit from counseling, substance use referral, and other resources.


RESULTS/ANTICIPATED RESULTS: Results: The symptom of auditory hallucination was significantly more endorsed in AA bipolar patients than EA bipolar patients . Conversely, the symptom of elevated or euphoric mood was significantly less endorsed in AA bipolar patients than in EA patients . AA, in comparison to EA bipolar patients, had a significantly higher prevalence of lifetime exposure to haloperidol  and fluphenazine . In contrast, AA, in comparison to EA bipolar patients, had a significantly lower prevalence rate of lifetime exposure to lithium , and lamotrigine . DISCUSSION/SIGNIFICANCE OF IMPACT: Conclusion: The higher rate of psychotic symptom endorsement and lower rate of core manic symptom endorsement represent differential illness presentation that may contribute to misdiagnosis in African-American bipolar patients. The higher rate of high potency typical antipsychotic treatment and lower rate of classic mood stabilizing treatment may also contribute poorer bipolar treatment outcome. While structured diagnostic interviews are the gold standard in diagnostic confirmation, this study is limited by lack of knowledge of clinician/expert interviewer interpretation of symptom endorsement which may contribute to symptom misattribution and misdiagnosis. Incorporation of additional African American participants in research is a critical future direction to further delineate symptom presentation and diagnosis to serve as validation for these results.OBJECTIVES/SPECIFIC AIMS: Learning Objectives of this session: Identify possible reasons for misdiagnosis of bipolar patients of African ancestry by reviewing differences in symptom presentation between African American (AA) and European American (EA) bipolar individuals. Introduction: Bipolar disorder is a chronic mental illness with a prevalence rate up to 5.5% of the US population and is associated with substantial personal and economic morbidity/mortality. Misdiagnosis is common in bipolar disorder, which can impact treatment and outcome. Misdiagnosis disproportionally affects racial/ethnic minorities; in particular, AAs are often misdiagnosed with schizophrenia. There is interest in better understanding the contribution of differential illness presentation and/or racial bias to misdiagnosis. METHODS/STUDY POPULATION: Patients and Methods Utilizing the Genetic Association Information Network (GAIN) public database, this study compared clinical phenomenology between bipolar patients of African Versus European ancestry (AA=415 vs. EA=1001). The semi-structured Diagnostic Interview for Genetic Studies (DIGS) was utilized to evaluate individual symptom endorsement contributing to diagnostic confirmation. A χ


OBJECTIVES/SPECIFIC AIMS: Modulation of autophagy has the potential to treat inflammatory bowel disease (IBD). IBD is characterized by dysregulated inflammatory pathways and a defective intestinal epithelial barrier. We sought to better understand how autophagy can be utilized to regulate both inflammation and the intestinal barrier. METHODS/STUDY POPULATION: We examined mice with an autophagy defect in only macrophages in an animal model of IBD. To understand the phenotype, we utilized macrophages to investigate the mechanism behind autophagy and proinflammatory cytokine secretion. In addition, we analyzed the development of colonoids in a co-culture system with macrophages with or without a functional autophagy pathway. Lastly, pharmacological modulation of autophagy to control inflammation was assessed. RESULTS/ANTICIPATED RESULTS: Mice with autophagy-deficient macrophages were highly susceptible to intestinal barrier disruption. Susceptibility was due to enhanced proinflammatory cytokine secretion and intestinal permeability. Furthermore, proinflammatory macrophages (due to an autophagy defect) co-cultured with colonoids, significantly decreased the number of mucus producing goblet cells. Finally, pharmacologically modulation of autophagy reduced the secretion of proinflammatory cytokine by macrophages and reduced intestinal permeability. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results strongly suggest autophagy modulation can dampen inflammation and enhance the intestinal epithelial barrier.


Older adults are at risk for altered nutritional status and functional impairment due to physiological  and psychosocial factors . Those with alterations in nutritional and/or functional status are at risk for poor health outcomes-including delayed healing of chronic wounds. We will discuss our lessons learned when devising nutrition assessment protocols from our ongoing double-blind randomized control clinical trial testing the effectiveness of ultrasound treatment on healing chronic leg wounds. The discussion will focus on the following measures: the Mini-Nutritional Assessment, hand-grip strength assessment, and inflammatory biomarkers.


Oral history narratives of nine childless centenarians  from the Oklahoma 100 Year Life Project were reviewed to investigate loneliness. Oral history narratives were assessed qualitatively, using content analysis to determine themes. We predicted that childless centenarians would feel lonely due to “elder orphanhood.” Findings revealed little indication of loneliness. Centenarians admitted they voluntarily chose to remain childless due to raising siblings earlier in life or delaying marriage. However, most remained socially well-adjusted and connected to extended family, particularly nieces. When confronted by social network losses due to death or relocation, most adapted by actively seeking and forming new relationships. In some cases, childless centenarians remained gainfully employed and working. Childlessness does not appear to make centenarians lonely. Rather, purposeful pursuit of intrapersonal and interpersonal sources of lifelong emotional contentment may render childless centenarians immune from conditions of loneliness.


Foreign body ingestion is an important problem in adult with psychological disorders. In literature ingestion such as fish bone, fork and several metallic elements were reported. The first attempt, after diagnosis, is endoscopic removalA 25-year-old male deaf patient was admitted in emergency department with complaint of abdominal pain and unable to communicate anything of his clinical history. Physical examination was normal except an epigastric tenderness. Laboratory results were normal. Direct radiography revealed a circular shaped metallic object in stomach and other several metallic objects in gastrointestinal tract A. An emeA delay in the diagnosis an dextraction of sharp or large sized foreign objects can lead to severe complications including mucosal laceration, obstruction, hemorrhage, and perforation. Therapeutic esophagogastroduodenoscopy with an esophageal overtube should be the first choice retrieval of large sized foreign bodies to avoid mucosal laceration, perforation and the surgical treatment.


Negative affect (NA) and positive affect (PA) vary from moment-to-moment and these variations are associated with cognitive health. Past work has primarily focused on valence (negative/positive), however, largely ignoring the potential import of arousal (high/low). We address this gap by assessing the impact of high and low arousal NA and PA on daily cognition. A sample of 238 older adults  completed mobile surveys up to four times daily for 14 days. Participants reported current levels of high and low arousal NA and PA and performed processing speed and working memory tasks. For processing speed, there were significant within-person affect by age interactions. Moments when low arousal NA was higher than usual were associated with slower processing speed , and this effect was amplified in older participants . Moments when high arousal PA was higher than usual were associated with faster processing speed , and this effect was amplified in younger participants . For working memory, a significant within-person high arousal PA by age interaction emerged  such that moments when high arousal PA was higher than usual were marginally associated with worse working memory performance only among older participants . Results suggest momentary increases in low arousal NA and high arousal PA may confer greatest risk to daily cognitive health among older adults with more limited capacity and/or cognitive resources, whereas affective influences may be more facilitative among comparatively younger adults.


Carpopedal spasm have various causes ranging from dsyselecrolytemia, syndromic, metabolic or endocrine causes. Any of these could cause a decrease in ionized calcium and tetany. Excessive vomiting leading to alkalosis, hypokaleamia and decreased ionised calcium should be kept in mind for early etiological diagnosis of carpopedal spasm. We report a case of 4-year-old boy presenting with a history of recurrent painful spasm and flexion of bilateral hands following excessive vomiting and electrolyte derangement. Carpopedalspasms are frequent and involuntary muscle contractions in the hands and feet with associated pain. Hypocalcemia, low calcium levels can cause carpopedal spasms as a warning sign . It occu2. Abdomen is flat, soft and moves with respiration. Vital signs are normal and physical examination revealed mild dehydration as evidenced by dry oral mucosa, and tender bilateral carpopedal spasm (A 4-year-old boy was brought to the children emergency department of Wesley Guild Hospital Ilesa with painful spasm and flexion of bilateral hands . He had al spasm . LaboratIonized calcium was the active form responsible for tetany . AlkalosExcessive vomiting leads to alkalosis, hypokaleamia and decreased ionised calcium and carpopedal spasm. Hence, serum electrolyte including serum calcium, magnesium, potassium and bicarbonate should be done promptly in all patients with persistent vomiting from any cause to detect dyselectrolytemia early and forestall late complication such as carpopedal spasm and tetany.The authors declare no competing interests.


The term, ageism, refers to any form of personal or institutional prejudice or discrimination based on chronological age. Ageism may encompass attitudes and prejudices, as well as behaviors, highlighting the complex nature of ageist behaviors observed among students and professionals alike . We examined the prevalence of self-reported ageist behaviors in a sample of college students who ranged in age from 18 to 44 years to test the hypothesis that aging knowledge would be associated with self-reported ageist behaviors (positive and negative). The study sample was comprised of adults who were enrolled in classes at Louisiana State University (n = 110). Most of these students were traditional aged college students (18-25 years old). Participants completed the Relating to Older People Evaluation , the Facts on Aging Quiz , and the Knowledge of Memory Aging Questionnaire . Results indicated that positive ageist behaviors were more frequent than negative ageist behaviors. Men endorsed positive and negative ageism items more than women reported. Follow-up analyses on participants’ responses to the two aging knowledge questionnaires showed that increased knowledge of aging was significantly correlated with diminished reports of negative ageist behaviors, after controlling for age and gender. These results imply that self-reported ageist behaviors are associated with aging knowledge. Strengthening college curricula by including course offerings in adult development and aging may improve self-reported ageist behaviors among college students.


Receptor-mediated gene delivery capitalises on the presence of specific cell surface molecules for DNA uptake into cells and represents a particularly appealing approach for targeting vector DNA to specific cell types in vivo and in vitro. Various ligand/DNA and antibody/DNA transfer complexes were generated that, following binding to cells, are internalised and reach the endosomal compartment. Vector complexes contain endosomolytic components that ensure vector release from the endosome and translocation of vector DNA into the nucleus where transcription occurs. Thus, receptor-mediated gene delivery encompasses several critical steps that must be considered when designing and applying such vector systems.


Magnetotactic bacteria biomineralize intracellular magnetic nanocrystals surrounded by a lipid bilayer called magnetosomes. Due to their unique characteristics, magnetite magnetosomes are promising tools in Biomedicine. However, the uptake, persistence, and accumulation of magnetosomes within mammalian cells have not been well studied. Here, the endocytic pathway of magnetite magnetosomes and their effects on human cervix epithelial (HeLa) cells were studied by electron microscopy and high spatial resolution nano-analysis techniques. Transmission electron microscopy of HeLa cells after incubation with purified magnetosomes showed the presence of magnetic nanoparticles inside or outside endosomes within the cell, which suggests different modes of internalization, and that these structures persisted beyond 120 h after internalization. High-resolution transmission electron microscopy and electron energy loss spectra of internalized magnetosome crystals showed no structural or chemical changes in these structures. Although crystal morphology was preserved, iron oxide crystalline particles of approximately 5 nm near internalized magnetosomes suggests that minor degradation of the original mineral structures might occur. Cytotoxicity and microscopy analysis showed that magnetosomes did not result in any apparent effect on HeLa cells viability or morphology. Based on our results, magnetosomes have significant biocompatibility with mammalian cells and thus have great potential in medical, biotechnological applications. C) STEM-HAADF image of magnetosomes inside endosome, showing crystalline structures near the magnetosome (white square) displayed with greater exposure on the inset. D) Higher magnification of the region indicated by the square in (C) showing a crystalline structure near the magnetosome; inset shows FFT corresponding to the white square area, with a plane lattice distance of (TIF)Click here for additional data file.


Aging the detrimental molecular changes that occur in lymphatics with age [The diverse etiologies of age-related diseases, from osteoarthritis to Alzheimer’s disease, all share an impairment, or slow loss, of tissue function. Aging tissue homeostasis shifts towards progressive, low-grade inflammation and a dampened immune response. The lymphatic vasculature is the key regulator of tissue homeostasis in health and disease. Lymphatics transport antigens and other macromolecules, excess interstitial fluid, and activated immune cells during inflammation. Shang and colleagues recently reviewed for with age . Here weAging review “Pathophysiology of aged lymphatic vessels”, Shang and authors have summarized research focused on lymphatic collecting vessels finding that lymphatic muscle contractions are reduced in amplitude and frequency and can become irregular with age [Lymphatic vessels are structurally quite different from blood vessels, beginning with blind-ended capillaries possessing leaf-like cell junctions that lead to large, unidirectionally-valved collecting vessels. These larger vessels are surrounded by lymphatic muscle cells that provide intrinsic pumping to maintain lymph flow. In their with age . The Gaswith age ,2. They Chronic tissue degeneration is a common feature of age-associated disorders like osteoarthritis (OA). A series of collaborative studies from the Schwarz and Xing groups have extensively detailed lymphatic involvement in several models of arthritis. They have demonstrated that inflammatory lymphangiogenesis and increased pumping initially facilitate the removal of immune cells and fluid to the draining lymph nodes, but that over time lymphatics regress and collecting lymphatic vessels lose contractility . In theiRecently mapped pathways by which fluid and immune cells enter lymphatic vessels may play important roles in neurological decline, notably in Alzheimer’s disease (AD). The Proulx laboratory used near infrared dynamic imaging of macromolecule transport to identify several outflow pathways for the egress of cerebral spinal fluid (CSF) to lymphatics . FurtherCardiovascular (CV) disease and diabetes are progressive pathologies whose diagnoses increase with age, and the side effects, treatment, and recovery are more difficult to manage in older patients. Lymphatic vessels have demonstrated a critical role and therapeutic potential in several CV pathologies including atherosclerosis, myocardial infarction, hypertension, and diabetes . AtherosIn conclusion, the pathophysiology of aging lymphatic vessels reviewed by Shang and colleagues reduces lymphatic fluid clearance, immune migration, and inflammatory responsiveness. Research in several disease models including osteoarthritis, Alzheimer’s disease, and CV disease has identified that enhancing lymphatic function may provide therapeutic benefit. Understanding the mechanisms of lymphatic decline and identifying maintenance or therapeutic regimens targeting lymphatic physiology is therefore important in addressing age-related disease.


Pinus ponderosa) forests. However, the extent, characteristics, and predictability of ponderosa pine fire refugia are largely unknown. Within 23 fires in ponderosa pine-dominated forests of the Colorado Front Range (1996–2013), we evaluated the spatial characteristics and predictability of refugia: first using Monitoring Trends in Burn Severity (MTBS) burn severity metrics, then using landscape variables . Using 1-m resolution aerial imagery, we created a binary variable of post-fire conifer presence (‘Conifer Refugia’) and absence (‘Conifer Absence’) within 30-m grid cells. We found that maximum patch size of Conifer Absence was positively correlated with fire size, and 38% of the burned area was ≥ 50m from a conifer seed source, revealing a management challenge as fire sizes increase with warming further limiting conifer recovery. In predicting Conifer Refugia with two MTBS-produced databases, thematic burn severity classes (TBSC) and continuous Relative differenced Normalized Burn Ratio (RdNBR) values, Conifer Absence was high in previously forested areas of Low and Moderate burn severity classes in TBSC. RdNBR more accurately identified post-fire conifer survivorship. In predicting Conifer Refugia with landscape variables, Conifer Refugia were less likely during burn days with high maximum temperatures: while Conifer Refugia were more likely on moister soils and closer to higher order streams, homes, and roads; and on less rugged, valley topography. Importantly, pre-fire forest canopy cover was not strongly associated with Conifer Refugia. This study further informs forest management by mapping post-fire patches lacking conifer seed sources, validating the use of RdNBR for fire refugia, and detecting abiotic and topographic variables that may promote conifer refugia.Forested fire refugia (trees that survive fires) are important disturbance legacies that provide seed sources for post-fire regeneration. Conifer regeneration has been limited following some recent western fires, particularly in ponderosa pine ( We determined connectivity of Conifer Refugia and Conifer Absence patches by grouping contiguous pixels of the same classification using an eight-cell neighborhood . To determine whether the proportion of Conifer Refugia within fires changed over the study period, we analyzed the percent area of Conifer Refugia in each fire and used ordinary least squares regression to test the significance of a temporal trend 1996–2014 (α = 0.05) . To deteTo inform local management plans for potential post-fire recovery programs, we evaluated the reliability of two readily available MTBS databases to represent the locations of post-fire surviving conifers. We calculated the TBSC  and RdNBR values for pixels of Conifer Refugia and Conifer Absence across all fires. We graphed the percent of Conifer Refugia and Conifer Absence in different thematic burn severity classes. We assessed the power of TBSC and RdNBR to predict Conifer Refugia and Conifer Absence in a Classification and Regression Tree model (CART) in R ,70. CARTTo examine factors influencing patterns of Conifer Refugia and Conifer Absence, we first constructed spatial overlays with Pre-fire Forest Cover and daily fire weather variables and compared the distributions in the two classes across equal interval bins of each predictor variable. These descriptive statistics aided in interpretation of subsequent predictive models and associated predictor importance.To assess how well weather, anthropogenic, abiotic, and biotic factors predict the locations of Conifer Refugia and Conifer Absence, we used Random Forests  in R R ,73. We tOver 147,000 ha were mapped within the 23 fire perimeters in ponderosa pine-dominated forests of the CFR from 1996–2013 . For all2 = 0.85, p ≤0.0001, The proportion of Conifer Refugia within fire perimeters did not significantly decrease or increase over time between 1996 and 2013 p ≥0.05, . We founBoth TBSC and RdNBR maps showed relationships with the locations of Conifer Refugia and Conifer Absence across the study area . Within Overlays of fires with Pre-fire Forest Cover reveal that 95% of the total burned area had pre-fire forest cover (>1%), with over half (55%) of the total area having dense pre-fire forests  aerial imagery to map post-fire Conifer Refugia within 23 fires that burned ponderosa pine-dominated forests of the CFR from 1996–2013 allowed us to thoroughly examine the spatial characteristics and predictability of Conifer Refugia in this region. Our study of post-fire surviving trees found that over one-third of the area burned in the CFR resulted in large contiguous patches without surviving trees at distances greater than the common dispersal distance of ponderosa pine seeds, presenting a potential forest recovery challenge. We generally found that abiotic and topographic landscape variables, many indicative of moister microsites, were the most important predictors of conifer refugia, except under high maximum temperatures and the most extreme fire weather, in which case conifers were generally less likely to survive. The lack of a strong relationship between pre-fire forest cover and post-fire Conifer Refugia may have strong implications for forest management aimed at increasing the resilience of ponderosa pine to wildfire through tree thinning. We recommend prioritizing RdNBR over TBSC as a management tool to more accurately identify post-fire conifer refugia, evaluate patch metrics of surviving post-fire conifers, and plan for post-fire recovery.Post-fire forested refugia are important disturbance legacies providing seed sources and microsites for recovery of ponderosa pine forests ,22,24,75Evaluating both the spatial and temporal trends in Conifer Refugia proved critical to understanding the potential effectiveness of these legacies in promoting post-fire recovery. We found a consistent proportion of Conifer Refugia across time in the CFR, similar to findings during the last two decades in the northern Rockies . AlthougIn the Southern Rockies, from 1984 to 2006 there was a trend of increasing area burned , which mLimited long-distance dispersal into high-severity patches has been documented . Such diThe use of high-resolution imagery allowed us to accurately map conifers at very low densities and thoroughly evaluate the ability of coarser scale burn severity indices to detect these conifer refugia. We found that post-fire conifer refugia are not consistently detected by MTBS TBSC and that these classes generally under-estimated conifer loss in the ponderosa pine cover type in our region. Although thematic burn severity metrics typically capture changes in all organic matter above and below ground, such as soil, understory vegetation, and canopy mortality , we focuRdNBR provided a more robust method for detecting post-fire surviving conifers and we recommend its use in post-fire recovery planning in ponderosa pine-dominated forests. RdNBR is more consistent in classifying burn severity in areas with low forest cover and has identified fire refugia in other regions ,78. Our Conifer refugia were least likely to survive wildfires occurring under the highest temperatures, highest wind speeds, and driest conditions. Higher daily maximum temperature was the highest ranked variable in the primary random forest model predicting higher tree mortality. Our findings generally corroborate other studies showing the decreased importance of topographic variables in predicting fire severity and fire refugia under warmer, drier, and more extreme burning conditions ,30,31,78Our hypothesis that abiotic factors have an influential role in providing post-fire refugia across the CFR was generally supported. The most important landscape variables in predicting Conifer Refugia were related to soil characteristics, proximity to higher order streams, less rugged terrain, valley landforms, and lower elevation in drainages. The partial dependence plots of the Random Forest model suggest that post-fire conifer survivorship in ponderosa pine dominated forests is generally predicted in moister or less steep sites. Conifer survivorship in locations near the floodplain or watershed drainage is most likely influenced by soil properties, microclimates, and topography. Wetlands, stream confluences, riparian areas, valley bottoms and cold air drainages can have decreased fire severities ,89–92. ASoil properties in the top five centimeters heavily influenced the presence of Conifer Refugia. Quantitative studies of ponderosa pine densities and soil texture in the Southwest have shown that soils with a high clay content are less favorable for ponderosa pine and more favorable for competing grasses ,94,95. AAnthropogenic influences also promoted conifer survivorship within our study area. Both proximate distance to homes and distance to roads were consistently ranked in the top ten predictors of Conifer Refugia. Roads may serve as natural fuel breaks or be used to strategically locate active fire suppression efforts, both promoting survivorship of trees in the area. Homes are also actively protected from oncoming wildfires with wildfire suppression tactics and numerous private land owners in the CFR treat fuels adjacent to their homes ,97. TreeBiotic variables, distance to savanna and pre-fire forest cover, were not strong predictors of Conifer Refugia. Overlays showed that forest cover under 60% was only slightly more likely to survive these wildfires and half of the area with forest cover between 20% and 50% had no surviving conifers. Although forest cover overall had a very weak relationship with tree survivorship, the proximate distance to savannas (open areas and forest cover ≤ 20%) had a stronger influence. While elevation is historically the single most important predictor of low-severity fire within the CFR , forestsThe importance and decline of small meadows in ponderosa pine has been documented in Colorado . BetweenIn addition to the decline in area of meadows along the CFR, there appears to be a surprising lack of resistance to recent fire in the remaining savannas. Nearly half of the canopy cover of the savannas within the fire perimeters did not survive. The maintenance and protection of large, old trees is important for both ecosystem services and carbon storage . The higOur analysis highlights specific opportunities regarding forest management to enhance forest resilience in the face of increased wildfires under a warming climate –109: 1) Although 42% of the total burned area contained surviving post-fire conifers in our study of 23 fires, mechanisms of resilience of ponderosa pine systems to wildfire may be declining along the CFR. We highlight four general findings that underscore the potential declining resilience of ponderosa pine forests in Colorado with a continued trend of increasing area burned under a warming climate: 1) large fires are expected to have large patches approximately a third the size of the fire area that lack surviving conifers and therefore seed sources for regeneration; 2) wetter areas and topographic low points generally have a higher likelihood of conifer presence following wildfires; 3) forest cover was not a strong predictor of conifers surviving wildfire; and 4) conifers are less likely to survive under extreme fire weather and burning conditions. Research in the CFR and elsewhere has reported decreased ponderosa pine regeneration in response to warmer drier climates following wildfires. These same climate conditions are promoting large wildfires with extensive treeless patches, further compromising post-fire resilience to wildfire. For ponderosa pine forests in the CFR, the combination of larger fires and warmer-drier burning conditions poses a potentially great threat of forest loss with a lack of post-fire recovery due to lack of seed sources alone. Even patches of the lowest tree cover in ponderosa pine forests suffered high mortality in recent fires along the CFR. Our results suggest numerous management implications including: the preference of RdNBR over TBSC to evaluate post-fire surviving seed sources, the importance of including soil and topographic variables into management planning to promote post-fire conifer refugia, the increased use of prescribed fire in existing meadows and woodlands to potentially increase the survivorship of conifer trees, and a reprioritization that may include wide-scale planting of seedlings for this forest type in areas lacking seed sources but at sites where they are more likely to survive future fires.S1 TablePercent cover of forest and woodlands in the 2001 LANDFIRE Existing Vegetation Types within 23 fires that burned ponderosa pine-dominated forests along Colorado’s Front Range 1996–2013.(DOCX)Click here for additional data file.S2 TableTotal percent cover and area of forest and woodlands in the 2001 LANDFIRE Existing Vegetation Types across 23 fires that burned ponderosa pine-dominated forests along Colorado’s Front Range 1996–2013.(DOCX)Click here for additional data file.S3 TableImportance and data sources for landscape variables generated for the random forest model meant to classify Conifer Refugia and Conifer Absence. Selected variables in more than six of 11 Random forest models are indicated by *. An expected positive relationship between the variable and Conifer Refugia is denoted with (+) and an expected negative relationship with (-). All variables are at 30-m resolution.(DOCX)Click here for additional data file.S4 TableMaximum, mean, and standard deviation of distance to potential pre- and post-fire seed source for the 23 fires that burned ponderosa pine-dominated forests along Colorado’s Front Range 1996–2013.(DOCX)Click here for additional data file.S1 FigThree examples of Conifer Refugia within 23 fires that burned ponderosa pine-dominated forests along Colorado’s Front Range 1996–2013 as shown by 2015 NAIP aerial imagery.(TIF)Click here for additional data file.S1 Text(DOCX)Click here for additional data file.


Immune checkpoint blockade (ICB) has elicited durable therapeutic responses across a number of cancer types. However, the impact of ICB on mCRPC has been disappointing, which may signal the need to combine mechanistically-distinct ICB agents and/or override immunosuppression in the tumor microenvironment. Our objective is to determine if robust immunotherapy responses in mCRPC may be elicited by the combined actions of ICB agents together with targeted agents that neutralize MDSCs yet preserve T cell function. METHODS/STUDY POPULATION: We created a novel embryonic stem cell-based chimeric mouse model of mCRPC engineered with signature mutations to study the response to single and combination immunotherapy. The efficacy studies were followed with detailed mechanistic investigation and clinical validation. RESULTS/ANTICIPATED RESULTS: Consonant with early stage clinical trials experience, anti-CTLA4 or anti-PD1 monotherapy failed to impact disease progression. Similarly, modest anti-tumor activity was observed with combination ICB as well as monotherapy with targeted agents including Cabozantinib (tyrosine kinase inhibitor), Dactolisib (PI3K/mTOR inhibitor), and Dasatinib (tyrosine kinase inhibitor). In contrast, mCRPC primary and metastatic disease showed robust responses to dual ICB treatment together with either Cabozantinib or Dactolisib, but not with Dasatinib which impaired T cell infiltration in the tumor. Detailed intratumoral immune profiling with mass cytometry (CyTOF) showed that combined ICB and Cabozantinib or Dactolisib was associated with significant depletion of MDSCs. Cabozantinib and Dactolisib blocked the PI3K signaling activity in MDSCs and reduced their immunosupppresive activity. Mechanistically, the combination efficacy was due to the upregulation of IL-1RA and suppression of MDSC-promoting cytokines secreted by mCRPC cells. DISCUSSION/SIGNIFICANCE OF IMPACT: We demonstrated that an antibody cocktail targeting CTLA4 and PD1 was insufficient to generate effective anti-tumor response, but combination of ICB with targeted therapy that inactivates PI3K signaling displayed superior synergistic efficacy through impairing MDSCs in the tumor microenvironment. These observations illuminate a clinical path hypothesis for combining ICB with MDSC-targeted therapies in the treatment of mCRPC. Importantly, conclusions from the study on PCa may have implications in combination immunotherapy for aggressive breast cancer which is also largely resistant to immune checkpoint blockade and replete with immunosuppressive myeloid cells.OBJECTIVES/SPECIFIC AIMS: Prostate cancer (PCa) is the most common noncutaneous malignancy in men in the United States. A significant fraction of advanced PCa treated with androgen deprivation therapy experience relentless progression to lethal metastatic castration-resistant prostate cancer (mCRPC). The PCa tumor microenvironment is comprised of a complex mixture of epithelial and stroma cell types engaged in multifaceted heterotypic interactions functioning to maintain tumor growth and immune evasion. We recently uncovered the important role played by myeloid-derived suppressor cells (MDSCs) to mediate tumor immune evasion in aggressive PCa (Wang, Lu


Cicatricial organizing pneumonia is an uncommon form of organizing pneumonia, which may manifest as persisting linear opacities on computerized tomography (CT) scan mimicking a fibrosing interstitial pneumonia. It may also manifest with pulmonary ossification, which is a metaplastic bone formation within the lung tissue. The latter presentation could be either nodular or dendriform, both secondary to underlying lung disease and rarely idiopathic. Dendriform pulmonary ossification (DPO) has rarely been described as a cause of spontaneous pneumothorax. We present a case of a 55-year-old male with history of recurrent pneumothoraces and worsening dyspnea on exertion. A CT of the chest revealed progressive bilateral sub-pleural and peribronchovascular reticular opacities associated with densely ossified branching and nodular opacities. Video-assisted thoracoscopic biopsy of the lung demonstrated cicatricial organizing pneumonia with areas of marked diffuse DPO. The case highlights that dendriform pulmonary ossification arising from cicatricial organizing pneumonia should be considered in the differential diagnosis of recurrent pneumonias among patients with lower lobe sub-pleural reticular opacities. The case highlights that dendriform pulmonary ossification rarely can cause spontaneous pneumothorax and can be associated with cicatricial organizing pneumonia and reticular opacities on imaging. Organizing pneumonia (OP) is characterized by the presence of organizing fibromyxoid proliferations within the lumens of respiratory bronchioles and alveolar ducts. Peripheral and /or peribronchiolar consolidations are the most frequent findings of OP on a computerized tomography (CT) scan. These opacities could be migratory in nature. OP is often steroid-responsive and reversible with total resolution of radiological opacities, but occasionally may recur , 2.Cicatricial OP (OPc) is a newly described entity in the pathology literature , 4 and dA 55 year-old, nonsmoker male presented with a recurrent large left pneumothorax requiring a chest tube placement. He had a same side pneumothorax three and six years earlier, also requiring a chest tube placement. The patient also reported dyspnea on exertion with stairs and inclines, which had progressed over last three years along with a dry cough.He had a remote exposure to quails while training hunting dogs. He was known to have hypertension and suffered with symptoms of gastroesophageal reflux disorder (GERD). His physical examination was unremarkable. A review of his pulmonary function revealed gradual decline in his FEV1, FVC and diffusion capacity over the past seven years .Review of serial chest CT imaging revealed progressive bilateral sub-pleural and peribronchovascular branching dense opacities suggestive of DPO . He undeOrganizing pneumonia is usually steroid-responsive and pathologically characterized by presence of loose fibromyxoid plugs within the lumens of the respiratory bronchioles and alveolar ducts , 2. CicaOn CT, conventional OP presents as patchy bilateral peribronchial and subpleural consolidations –19, whicPulmonary ossification is a metaplastic process where mature bone is present in the alveolar interstitium and/or alveolar spaces. Pulmonary ossification is classified into DPO and NPO. NPO is usually a localized process of lamellar bone and can occur in the setting of chronic congestion as seen in mitral valve stenosis. Unlike DPO, NPO usually does not contain bone marrow (fat or hematopoietic cells) . On CT, DPO manifests on CT as small  nodules, which are seen predominantly in the peripheral interstitium . These nodules form contiguous and branching pattern resembling tree branches. In most instances these nodules are of high attenuation, reflecting the underlying ossification. The detection of small high-attenuation foci is improved using thin slices and maximum-intensity-projection images. DPO has tendency to affect lower lobes and posterior aspect of upper lobes. Association with recurrent aspiration and DPO has been suggested . The preSpontaneous pneumothorax has been reported in several cases of DPO –14 incluThe case we present showed evidence of radiographic progression and worsening restrictive pattern on PFT over several years. The reported cases of cicatricial OP by Churg and his colleagues  have beeIn summary, we present a case of cicatricial OP with DPO presenting with recurrent pneumothoraces and slow progressive pulmonary physiologic restrictive impairment. Cicatricial OP should be considered in the differential diagnosis of peribronchial or subpleural reticular opacities with DPO. Radiologists and clinicians alike should be aware of this newly described entity as distinct from other classical fibrosing processes, its potential association with DPO, and the presumed association between subpleural DPO and spontaneous pneumothorax.


Rapid changes in family structures have expanded caregiving boundaries beyond the level of lineal kin to include extended and fictive kin. Guided by stress process and health behavior models, we analyzed semi-structured interviews with 120 family caregivers of persons with dementia (PWD) in rural Appalachia to explore personal/family circumstances that influence the responsibilities nonlineal kin assumed to meet the needs of PwD. Compared to spouse and adult children caregivers, nonlineal caregivers reported that PWD had similar behavioral problems, but greater ADL limitations. They also expressed greater burden, overload and role captivity; yet, they reported higher personal mastery, and perseverance. Although sisters and nieces did not report using any paid services to care for PwD, grandchildren and fictive kin used paid services such as meal delivery, personal care, and respite services. Findings provide new insights into a more elaborated conception of caregiving that considers the transformations occurring in family life today.


Correction to: Antimicrob Resist Infect Control (2019) 8:77https://doi.org/10.1186/s13756-019-0524-4The original article  containsAs such, the authors would like to clarify that in the context of this manuscript, LCMV needlestick injuries may only lead to life-threatening infections in immunosuppressed persons.The Conclusions sub-section of the Abstract should instead state:“This is the first case report of a PCR-documented LCMV meningitis, coupled with seroconversion, following needlestick injury. It highlights the importance of infection prevention practices that comprise particularly well established safety precaution protocols in research laboratories handling this pathogenic virus, because exposure to LCMV can lead to a severe infection.”The latter part of the penultimate paragraph of the Background section should instead state:“Therefore, prevention of stab wounds with contaminated sharp objects, bite of infected mice and inhalation of contagious droplets, is indispensable to protect laboratory worker from occupational infection.”The final paragraph of the Background section should instead state:“This highlights the importance of infect prevention strategies that comprise particularly well established safety precaution protocols in research laboratories handling this pathogenic virus, because exposure to LCMV can lead to a severe infection.”A middle sentence in the Discussion and conclusion section should instead only state:“Prevention of stab wounds with contaminated sharp objects, bite of infected mice and inhalation of contagious droplets, is crucial to protect laboratory worker from iatrogenic infection.”The latter half of the penultimate paragraph of the Discussion and conclusion section should instead state the following:“When working with LCMV in research laboratories, standard biosafety 2 laboratory practices are mandatory. This includes an appropriate ventilation system as well as wearing high quality gloves and protective gowns when working with LCMV. Surfaces should be routinely disinfected using a registered compound active against LCMV. In addition, a standard operating procedure should be available for the management of unintentional exposure to the virus. Pregnant women and immunosuppressed persons must be taught that exposure to this virus can lead to a severe, life-threatening infection.”The final paragraph of the Discussion and conclusion section should instead only state:“In conclusion, this well-documented case of LCMV-meningitis after needlestick injury highlights the importance of infection prevention practices in research laboratories and the need of safe handling of this virus.”The affected statements in the manuscript and their corrected version can be viewed ahead:


The dentate gyrus continually produces new neurons throughout life. Behavioral studies in rodents and network models show that new neurons contribute to normal dentate functions, but there are many unanswered questions about how the relatively small population of new neurons alters network activity. Here we discuss experimental evidence that supports multiple cellular mechanisms by which adult-born neurons contribute to circuit function. Whereas past work focused on the unique intrinsic properties of young neurons, more recent studies also suggest that adult-born neurons alter the excitability of the mature neuronal population via unexpected circuit interactions. Thus, GCs integrate sensory and spatial information to help generate a neural representation of a context5. Interestingly, resident neural stem cells produce new GCs throughout adulthood, and these adult-born GCs receive synapses from cortical neurons via the perforant path and form output synapses with downstream neurons to participate in hippocampal network activity. Although the majority of neuroblasts undergo programmed cell death, surviving neurons are permanently incorporated into the DG and acquire properties similar to GCs generated early in development8. While adult-born GCs may replace a fraction of the developmentally generated population that is lost over time10, their continuous addition accounts for the substantial increase in GC number across the first year of life in rodents12. How this process contributes to hippocampal learning and memory is an intriguing neurobiological question. Current insight into this question relies on experimentally tractable rodent models, but evidence of DG neurogenesis in healthy humans across the lifespan14 suggests that it could have implications for human cognition.The dentate gyrus (DG) is viewed as the main entry point for neural activity into the hippocampus, a brain region essential for learning and memory. The principal neurons, the dentate granule cells (GCs), are innervated by neurons of the entorhinal cortex that encode information about objects, spatial location, and details of the environment16. Brain regions involved in associative learning, such as the cerebellum and hippocampus, use circuits that perform pattern separation as a “pre-processing” step to help discriminate input patterns carrying sensory or contextual cues17. Sparse population activity, wherein only a small fraction of principal neurons are active at a given time, is thought to be a critical component of pattern separation17. In the DG, sparse activity is predicted to allow distinct GC ensembles to encode similar  patterns of afferent activity, with a large capacity to transform overlapping patterns in the cortex into non-overlapping patterns in CA319. Interestingly, selective manipulations of adult-born GCs are sufficient to alter behavior paradigms thought to rely on DG pattern separation ergic interneurons that inhibit mature GCs, a circuit motif called feedback inhibition. Consistent with this idea, reducing neurogenesis with focal X-irradiation generated bursts of GC activityin vivo35 and hypersensitivity to a chemoconvulsant52. While these studies assayed excitability across the population of GCs, subsequent work acutely silencing young GCsin vivo andex vivo using designer receptors exclusively activated by designer drugs (DREADDs) also revealed enhanced excitability of individual mature GCs consistent with feedback inhibition53.Some of the first evidence that adult-born GCs alter the excitability of mature GCs came from voltage-sensitive dye imaging of hippocampal slices from mice with enhanced or ablated neurogenesis56 58. Whereas feedback inhibition generated by 8-week-old GCs suppressed perforant path-induced spiking, inhibition evoked by the same number of 4-week-old GCs had little effect -mediated currents in mature GCs even when polysynaptic activity was blocked by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) antagonists. Such recurrent connectivity contrasts sharply with the conventional view that GCs provide a unidirectional glutamatergic projection, except in pathological conditions like epilepsy62. Yet the possibility that young GCs release both GABA and glutamate is consistent with a long-standing literature showing a transient dual-neurotransmitter phenotype, although the nature and prevalence of GABAergic signaling from young GCs has been controversial65.The plot thickened as subsequent work proposed that ChR2 activation of adult-born GCs younger than 7 weeks old provides strong inhibitory responses in neighboring GCs66 first showed that silencing adult-born GCs increased mature GC responses evoked by stimulation of the lateral perforant path (LPP), whereas it reduced mature GC responses evoked by stimulation of the medial perforant path (MPP). Since the LPP carries sensory information and the MPP carries spatial information3, adult-born GCs might selectively gate different forms of information during the creation of DG contextual representations in mature GCs. This unexpected pathway-specific regulation was attributed to activation of postsynaptic glutamate receptors on mature GCs rather than feedback inhibition. In fact, blocking GABAA receptors did not block the responses evoked by new GCs, suggesting that feedback inhibition generated by young GCs is not a major circuit function in this paradigm.Even as the efficacy of GABAergic feedback inhibition recruited by young GCs remains debated, a recent study further expands the potential repertoire of adult-born GC circuit functions by focusing on the direct glutamatergic signaling from young GCs to mature GCs . Luna an68. Luna and colleagues showed that optogenetic activation of young GCs evoked NMDAR-mediated excitatory postsynaptic potentials (EPSPs) in mature GCs as well as slow inhibitory postsynaptic potentials (IPSPs) driven by mGluRs. Such NMDAR- and mGluR-driven responses are characteristic of spillover signaling, wherein receptors located outside of synapses are activated by glutamate acting at a distance from the release site. Spillover transmission can occur in the absence of anatomically defined synaptic junctions or in addition to conventional point-to-point synaptic transmission71. The authors suggest that when a small number of young GCs are activated by LPP stimulation, the relatively low level of glutamate spillover favors mGluR-mediated inhibition, whereas a larger population of young GCs activated by MPP stimulation recruit stronger NMDAR-mediated depolarization that overrides mGluR inhibition. Thus, the number of young GCs recruited will affect their circuit function  coupled to potassium channels that cause hyperpolarizationunction . In thiset al.66 described circuit interactions that enable adult-born GCs to rapidly modify mature GC excitability in response to network activity, neurogenesis also changes synaptic structure and function of existing GCs over a longer time window as young GCs integrate into the circuit. The possibility that newborn GCs compete for synaptic input with existing GCs was implied by evidence that the survival of newborn GCs is competitively regulated by NMDAR activation72. Subsequent anatomical analysis showed that immature dendritic spines transiently receive a high proportion of synapses from multiple-synapse boutons that could represent an intermediate structure in the transfer of cortical synapses from old to new GCs74 (but see77. In accordance with a redistribution of available presynaptic and postsynaptic elements, ablating GCs enhances the density of GABAergic somatic synapses on remaining GCs78 and increasing the number of new GCs does not appear to alter the density of spines and synapses in the molecular layer79. Recent support for the hypothesis that new GCs integrate into the circuit by competing for pre-existing synapses was provided by complementary studies showing that reducing the spine density of mature GCs enhanced the integration of new GCs80 and that manipulating the number of newborn GCs inversely regulated synaptic connectivity of mature GCs81. Thus, synaptic competition and subsequent redistribution of cortical connectivity may provide an additional mechanism for neurogenesis to contribute to sparsity and decorrelation of mature GC activity20.Whereas Luna but see. Whetheret al.66 propose that dual signaling allows young GCs to differentially regulate mature GC excitability depending on the strength of LPP versus MPP activity that differs between behavioral states and in the superior and inferior blade. Another possibility is that direct excitation/inhibition exerts local effects on neighboring GCs, whereas feedback influences GCs over a larger spatial domain as dictated by the extensive axonal arbors of GABAergic interneurons. Untangling the consequences of these multifaceted circuit interactions on hippocampal encoding and behavior will be an interesting challenge.The possibility that young GCs influence mature GC excitability by direct glutamatergic excitation and inhibition suggests an unexpectedly complex regulation layered upon additional secondary influences including feedback inhibition and synaptic competition. On the surface, it is difficult to envision the purpose of simultaneous direct excitation and inhibition. Luna82? Finally, what is the temporal relationship and relative efficacy of direct glutamatergic signaling in comparison with feedback inhibition and synaptic competition at each stage of new GC maturation? While the existing evidence indicates that the integration of new GCs has complex consequences for the local circuit, there is still a long way to go to understand how a few cells affect the many. The multi-layered complexity of the circuit interactions, in combination with activity-dependent regulation of adult neurogenesis, implies that continual neurogenesis provides extraordinary flexibility for adaptation to environmental changes and cognitive demands. Further exploring the cellular mechanisms by which adult-born GCs modify DG excitability and downstream hippocampal activity, along with cell-type-specific manipulations in behaving rodents to test their influence on behavior (reviewed inMany questions also remain about the mechanisms of these interactions at the cellular and synaptic level. For example, how is glutamate released from young GCs in a manner that generates receptor activation reminiscent of spillover signaling and where does this signaling occur? What is the efficiency of this novel signaling mechanism in controlling mature GC spiking, especially considering the stimulation of a single or small number of young GCs is insufficient to engage these interactions? How does the MPP recruit a larger population of young GCs than the LPP in light of evidence that the LPP preferentially innervates young GCsAMPAR, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; ChR2, channelrhodopsin-2; DG, dentate gyrus; EPSP, excitatory postsynaptic potential; GABA, gamma-aminobutyric acid; GC, granule cell; IPSP, inhibitory postsynaptic potential; LPP, lateral perforant path; mGluR, metabotropic glutamate receptor; MPP, medial perforant path; NMDAR, N-methyl-D-aspartate receptor.


Gastric outlet obstruction can be caused by various pathologies, including peptic ulcer disease, gastric polyps, and malignancies. The incidence rate of breast cancer metastasis to the stomach is only 0.3%. We describe a rare case of an 83-year-old female with a remote history of breast cancer who presented with symptoms of nausea and vomiting. She underwent an upper endoscopy, and biopsies revealed chronic gastritis. However, when she presented for the second time with similar symptoms, she underwent endoscopic ultrasound (EUS)-guided biopsies, which clinched the diagnosis of breast cancer metastasis causing gastric outlet obstruction. This case describes the importance of keeping a wide differential diagnosis for the causes of gastric outlet obstruction and the significance of deeper EUS-guided biopsies if initial endoscopic biopsies are inconclusive. Gastric outlet obstruction (GOO) has multiple etiologies, including peptic ulcer disease, malignancies, and gastric polyps. With the identification of Helicobacter pylori and the use of proton pump inhibitors, the etiology of gastric outlet obstructions has changed over the years with malignancy now being the most common cause . The mosAn 83-year-old female presented to our emergency department with complaints of nausea and vomiting for four days. She had been diagnosed with right-sided, multicentric, infiltrating lobular carcinoma of the breast , progesterone receptor positive (PR+), human epidermal growth factor receptor 2 negative (HER2-) 10 years ago. She had undergone a right mastectomy, and her sentinel lymph nodes, which were sampled during surgery, were negative for metastases. Previously, she had been treated with adjuvant anastrozole for five years, and yearly mammograms had been negative for recurrence.One year prior to this presentation, she was evaluated at our hospital for similar complaints of nausea and vomiting. A computed tomography (CT) scan of her abdomen and pelvis on admission revealed a mass-like thickening of the gastric antrum and distension of the proximal stomach, as illustrated in Figure An upper endoscopy (EGD) was performed, which revealed esophagitis and gastric stenosis. This was dilated using a through-the-scope controlled radial expansion (CRE) balloon  to a maximum balloon size of 12 mm without fluoroscopic guidance. Biopsy of the gastric stenosis revealed gastric mucosa of antral type with minimal chronic inactive gastritis. No morphologic evidence of a Helicobacter pylori infection was detected. The patients’ symptoms of nausea and vomiting improved following balloon dilation. She was subsequently discharged on a daily proton pump inhibitor.The patient underwent endoscopic ultrasound (EUS) 12 weeks later. Gastric stenosis was found at the pylorus and duodenal bulb, which was dilated again with a CRE balloon to a maximum dilation of 13.5 mm. Diffuse wall thickening of the antrum of the stomach was visualized endosonographically. The gastric wall measured up to 11 mm in thickness. Thickening within the deep mucosa, submucosa, and muscularis propria was noted. EUS-guided biopsies were taken, which revealed invasive poorly differentiated metastatic breast adenocarcinoma, as shown in Figure Tumor immunohistochemistry and morphology revealed ER+, PR+, and HER2- negative lobular breast adenocarcinoma as demonstrated in Figure This case highlights the importance of keeping a broad differential diagnosis for cases presenting with gastric outlet obstruction, especially in patients with a history of cancer. A diagnosis of breast cancer metastases to the gastrointestinal tract is often challenging because of its low incidence. Distinguishing between metastatic breast carcinoma and primary gastric adenocarcinoma cannot always be done using histological examination alone, and superficial biopsies may not be sufficient. Invasive lobular breast carcinoma and primary gastric cancer can have similar histopathology, as both can show signet ring cells. Immunohistochemistry is needed to make a distinction between the two, based on staining for estrogen and progesterone receptors . As in oAn important differential diagnosis for patients with concurrent gastric and breast adenocarcinoma includes hereditary diffuse gastric cancer (HDGC), which is an inherited cancer syndrome associated with an increased risk for primary gastric cancer and lobular breast carcinoma and is characterized by a poor prognosis. CDH1 gene mutations are frequently associated with HDGC and patients with this syndrome may benefit from genetic counseling.Ulmer et al. described a similar case to ours where previous gastric mucosal biopsies had been negative; however, a EUS-guided fine needle aspiration clinched the final diagnosis of metastatic lobular breast carcinoma causing gastric outlet obstruction . Of noteAlthough case reports of breast cancer metastasis causing GOO do exist in the literature, our case emphasizes the need to be diligent and thorough with a low threshold for EUS-guided biopsies if the initial endoscopic biopsy is inconclusive. This is critical in order to avoid delay in care for a patient with metastatic carcinoma.


Nursing homes that fostered open communication and teamwork were more likely to change their practices and adopt the “It’s Not OK to Fall” program. This pilot study evaluated the feasibility and acceptance of a team-building approach for developing leadership skills to three groups of coworkers: Administrators/Directors of Nursing, charge nurses, and certified nursing assistants (CNA) employed by nursing homes in Oklahoma. Each coworker group received one day of job specific leadership training, with another one half-day session where all levels engaged in team-building exercises. Participant satisfaction with course content ranged from agree-to-strongly agree. All stated that they could apply the leadership strategies at their facility. Administrators/Directors of Nursing found tools for tracking turnover/retention and strategies for improving staff communication helpful. Charge nurses and certified nursing assistants seldom viewed themselves as leaders, found coworker group communication very fragmented, and felt least knowledgeable about nursing home care best practices.


Widespread changes to the epigenome occur with aging. DNA methylation is one of the most commonly studied epigenetic mechanisms, reflects lifetime exposures that impact aging, and is associated with age-related disease risk. Many longitudinal cohort studies have existing cross-sectional or longitudinal DNA methylation data along with genotype and expression data permitting investigation of relationships between DNA methylation markers, exposures, and disease. The data can be leveraged to conduct large epigenome-wide association studies (EWAS) of aging and age-related disease to identify DNA methylation biomarkers and lead to insights into novel biologic pathways for development of interventions to delay aging. DNA methylation age measures robustly predict chronologic age and associate with both healthspan and lifespan. During the workshop, examples from cohort studies and the CHARGE consortium will be presented.


The Diverse Elders Coalition, in partnership with its six member organizations and the Benjamin Rose Institute on Aging, completed a national survey of 840 family and friend caregivers from diverse racial, ethnic, and sexual orientation communities to understand their unique caregiving issues and challenges. Data from a subsample of 404 caregivers identifying as Hispanic/Latino, Asian, Southeast Asian or from multiple ethnicities were examined to determine the relationship between difficulties performing culture-related care tasks  and a variety of caregiver outcomes. Regression analysis controlling for background and context characteristics showed caregivers experiencing more culture-related task difficulties had significantly higher levels of several negative caregiving consequences, including health strain , relationship strain , work strain,  isolation , and symptoms of depression . Moreover, higher levels of strain and depression among caregivers who reported high levels of culture-related task difficulties ranged from 26%-54%. More difficulties with culture-related tasks also were significantly related to dissatisfaction with support resources, including lower ratings of the quality of care receivers’ healthcare , and lower satisfaction with support they and their care receivers received from family and friends . Results suggest caregivers from diverse communities struggling with culture-related tasks experience more negative consequences of caregiving and less helpful social support. Service providers working with caregivers from diverse communities should assess for culture-related task difficulties, recognizing these problems may be a window into a variety of adverse caregiving effects.


The 1.7 million older adults receiving long-term services often do not receive end of life care consistent with their wishes. Advance directives (ADs) can help, yet only one-third of Americans have completed ADs. The limited effectiveness of traditional interventions to increase AD completion may be because they do not address the behavioral aspects of advance care planning. Behavioral Design is an innovative approach that combines design thinking and behavioral economics to identify predictable behavioral bottlenecks and create real-time solutions. This study used Behavioral Design to address low AD completion rates of long-term care residents. Consistent with the Behavioral Design process, an interdisciplinary team compiled evidence from 10 diverse data sources to identify behavioral bottlenecks to AD completion. These barriers were analyzed using the cognitive bias codex to determine behavioral levers for intervention. Informed by these findings, the study team designed multicomponent interventions to address behavioral aspects of AD completion. Four behavioral bottlenecks incorporating ten behaviorally mediated causes for lack of AD completion were identified. For example, AD completion is affected by complexity mediated by hassle factor, choice overload, and ambiguity effect. Three interventions were designed to address these behaviorally mediated causes. For example, the intervention HeAD Start would provide a simple, easy to read AD (addressing choice overload) to residents upon admission (addressing hassle factor) with scheduled follow-up by trained staff (addressing ambiguity effect). Behavioral Design incorporates design thinking and leverages behavioral economic principles to create behaviorally mediated AD interventions. Next steps include testing behaviorally informed designs in practice.


Background and Objectives: The relationship between objective and subjective cognitive function and depressive symptoms is complex and potentially multidirectional. This longitudinal prospective study examined the directionality of their relationship among a community sample of older people with no known diagnosis or treatment for dementia or depression. Research Design and Methods: We examined the temporal relationship between objective cognitive functioning, subjective cognitive complaints, and depressive symptoms in 1,814 community-dwelling older people at baseline and one-year follow-up using regression and two-wave cross-lagged panel analyses, after controlling for demographic and health confounders. Results: Cross-lagged analysis showed that depressive symptoms at follow-up were directly predicted by baseline subjective cognitive complaints, but not baseline objective cognitive functioning. The effect differed across objective cognitive functioning levels. In people with clinically significant cognitive impairment at baseline, objective cognitive decline but not baseline subjective cognitive complaints predicted depressive symptoms. In people with mild objective cognitive impairment at baseline, baseline subjective complaints but not objective cognitive decline predicted depressive symptoms. Discussion and Implications: The effects of objective and subjective cognitive decline on depressive symptoms varied across older people with different levels of cognitive impairment. Awareness and insight of one’s cognitive status may contribute to the development/progression in depressive symptom in people with mild cognitive impairment. Mechanisms unrelated to appraisal may be involved in increased depressive symptoms among older persons with significant objective cognitive impairment.