Data harmonization methods facilitate further use of existing studies and research resources. Most statistical harmonization methods require pooling data across studies, which is complex and requires careful scrutiny of source data. Most methods  require datasets to have common items for linking a common construct across studies: this necessitates the qualitative process of pre-statistical harmonization. Here, we document pre-statistical harmonization of items measuring behavioral and psychological symptoms  which represent problematic behaviors among people with dementia administered in a national survey (ADAMS), evaluations conducted at Alzheimer’s Disease Research Centers (NACC), and in six randomized trials . We describe our approach to review question content and scoring procedures to establish comparability across items prior to data pooling. We identified 327 items from 15 instruments across these eight studies. We found considerable cross-study heterogeneity in administration and coding procedures for items that measure the same domain. For example, eight items were coded as count variables in some studies but as categorical variables in others. Moreover, of the 359 items, 191 are conditionally dependent on values of another item. These issues around item response heterogeneity and conditional dependency needed to be resolved prior to estimation of item response theory models for statistical co-calibration. We leveraged several rigorous data transformation procedures to address these issues, including re-coding and winsorization. This study provides guidelines for how future research may acknowledge and address similar issues in pooling behavioral and related instruments.


The Arabidopsis genome encodes ten Argonautes proteins showing distinct expression pattern as well as intracellular localisation during sexual reproduction. Dear Editor,Small RNAs (sRNAs) are key regulators of gene expression. The importance of reproduction-specific sRNAs has been recognized in plants . Beyond Arabidopsis AGOs are detected in mature ovules before fertilization. Within the female gametophyte, their accumulation seems to be particularly enriched in the egg cell compared with the central cell. Preferential AGO expression in the egg cell was confirmed using previously published female gametophyte transcriptome data obtained by laser-capture microdissection , we could detect expression of 8 out of 10 on limit . mCherryon limit . GFP-AGOon limit . Based oon limit . This dion limit  and suggWe then analyzed AGO accumulation patterns in the differentiated zygote at the heart-stage  As previArabidopsis AGO1 and AGO4 have been shown to shuttle between the cytoplasm and the nucleus although their respective steady-state subcellular localizations seem to reflect their involvement in either PTGS  or TGS   . In agreArabidopsis, yet they are often marred by biological incongruities such as the use of overexpression promoters or C-terminal fusions known to affect AGO functions. The uniform set of tools presented in this study might help bridging this gap across the plant RNA silencing community.To conclude, our study reveals a clear asymmetry of AGO expression between the gametes and accessory cells before fertilization and between the embryo and endosperm lineage after fertilization. A summary of their expression pattern in reproductive tissue can be found in  Schematic representation of the constructs used in this study. RT-qPCR results assessing AGOs expression levels in inflorescence of wild-type and complemented lines. Complementation of ago mutants. Additional channels and LUTs corresponding to the pictures of  Additional pictures. Arabidopsis AGO transcription patterns extracted from microarray data of LCM-dissected female gametophytes (tophytes  confirmi Additional pictures of AGOs expression pattern in mature pollen counter stained with DAPI. AGO accumulation in germinating pollen tube. Paternal expression in the early zygote of AGOs expressed in sperm cells. Additional channels and LUT corresponding to the pictures of  Arabidopsis AGO transcription patterns extracted from microarray data of LCM-dissected seeds at the pre-globular stage (ar stage  confirmi Primers used in this study. Materials and Methods.kiab474_Supplementary_DataClick here for additional data file.


Pulmonary vein stenosis (PVS) is a known complication after radiofrequency ablation of atrial fibrillation (RAAF) and is often misdiagnosed owing to lack of awareness regarding PVS among noncardiologists. Misdiagnosis results in unnecessary treatment; therefore, greater understanding of PVS can improve the management of these patients.We report the case of a 38-year-old man with a history of RAAF who presented with massive hemoptysis. His symptoms persisted despite undergoing transcatheter bronchial artery embolization on two occasions.Pulmonary computed tomography angiography revealed a completely occluded left superior pulmonary vein. Considering the patient’s history of RAAF, we diagnosed him with RAAF-induced PVS and performed left superior lobectomy after which hemoptysis did not recur.Unexplained massive hemoptysis should alert clinicians regarding the possibility of RAAF-induced PVS. Balloon angioplasty and stent placement are used to treat PVS; however, their efficacy is controversial considering the high recurrence rates associated with these interventions. Hemoptysis is an important clinical manifestation of respiratory diseases. Common causes of hemoptysis observed in clinical practice include bronchitis, bronchogenic carcinoma, bronchiectasis, infections, and tuberculosis.. Additionally, a high-density stripe observed in the left upper lobe suggested chronic inflammation . Medical treatment with vasopressin and hemagglutinin was ineffective. Left bronchial artery angiography revealed an enlarged bronchial artery showing an extensive branching pattern, and contrast agent extravasation was observed in the left upper lung field . We performed transcatheter bronchial artery embolization using polyvinyl alcohol embolization particles , gelatin sponge particle embolic agent  and fibered platinum coils . Hemoptysis was controlled immediately after the procedure; however, massive hemoptysis recurred on the second day. Repeat angiography revealed that an ectopic bronchial artery originating from the left internal thoracic artery was the source of hemorrhage ; therefore, we performed transcatheter embolization of the ectopic bronchial artery. Unfortunately, hemoptysis was controlled only for 2 days after the procedure and recurred thereafter.The patient was referred to the emergency department at our hospital because of massive hemoptysis. He reported a history of catheter ablation performed for atrial fibrillation, 10 days prior to presentation. Chest radiography did not reveal any positive findings. Thoracic computed tomography (CT) scan revealed scattered ground-glass opacities in the left upper lobe, suggesting alveolar hemorrhage A. Additiammation B. Medicang field A. We permorrhage B; theref. Based on his history of RAAF, hemoptysis was attributed to RAAF-induced PVS in this patient. The patient underwent left superior lobectomy after which hemoptysis did not recur.Pulmonary CT angiography was performed to detect potential ectopic bronchial arteries, and complete occlusion of the left superior pulmonary vein was accidently discovered during this examination A and B. ,Since it was first reported in 1998,Most patients with PVS present with dyspnea, recurrent cough, expectoration, chest pain, flu-like symptoms and hemoptysis. Recurrent hemoptysis was the predominant symptom in our patient, and although hemoptysis is not rare in patients with PVS, hemoptysis associated with RAAF-induced PVS is relatively rare when considering the overall common causes of hemoptysis. The pathophysiological mechanism contributing to hemoptysis in patients with PVS remains unclear. We concluded that hemoptysis was attributable to increased pulmonary vascular resistance secondary to PVS. Magnetic resonance imaging and pulmonary vein CT angiography are valuable noninvasive diagnostic tools for PVS. Both modalities provide useful information regarding the site and extent of PVS, but the low spatial resolution associated with these modalities is a limitation; therefore, cardiac catheterization and pulmonary artery angiography remain the gold standard for the diagnosis of PVS.Transcatheter bronchial artery embolization is widely used as a safe and effective treatment to prevent hemoptysis; however, it is ineffective in patients with RAAF-induced PVS because these patients develop hemoptysis secondary to elevated pulmonary vein pressure and reduced venous backflow. Therefore, treatment in these patients is primarily aimed at relieving the obstruction and increasing blood flow through the pulmonary veins. The main treatment modalities for PVS include balloon angioplasty and/or stent implantation. Both methods are known to successfully alleviate symptoms; however, high rates of restenosis have been observed over the long-term follow-up. Compared with balloon dilation, stent implantation is associated with a relatively low restenosis rate, particularly with the use of stents measuring >10 mm in diameter. Long-term anticoagulant therapy is necessary after the procedure to avoid pulmonary vein thrombosis. A recent study has reported the use of drug-eluting stents to reduce the restenosis rate,In conclusion, PVS is a complication of RAAF that is often misdiagnosed owing to lack of adequate awareness regarding this condition among noncardiologists. Unexplained massive hemoptysis should alert clinicians regarding the possibility of RAAF-induced PVS in patients with such a clinical presentation. Pulmonary vein CT angiography is a valuable noninvasive method to diagnose PVS. Minimally invasive treatments, such as balloon dilation and pulmonary vein stenting have been used to treat PVS; however, their efficacy remains controversial owing to the relatively high recurrence rates associated with these interventions.Written informed consent was obtained from patients for publication of this case reports and any accompanying images.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.


Declines of large-bodied herbivorous reptiles are well documented, but the consequences for ecosystem function are not. Understanding how large-bodied herbivorous reptiles engineer ecosystems is relevant given the current interest in restoration of tropical islands where extinction rates are disproportionately high and reptiles are prominent as herbivores.Conolophus subcristatus), large-bodied herbivores known to feed on many plant species. We characterized plant communities on each island by developing high-resolution (<1 cm2) aerial imagery and delineating extent of plant associations and counting individual plants on each.In this study, we measured the ecosystem-level outcomes of long-term quasi-experiment represented by two adjacent islands within the Galapagos Archipelago, one with and the other without Galapagos land iguanas (In the presence of iguanas there was dramatically less woody plant cover, more area with seasonal grasses, and many fewer cacti. Cacti had a more clumped distribution where iguanas were absent than where iguanas were present.This study provided strong evidence that Galapagos land iguanas can substantially engineer the structure of terrestrial plant communities; therefore, restoration of large-bodied reptilian herbivores, such as land iguanas and giant tortoises, should be regarded as an important component of overall ecosystem restoration, especially for tropical islands from which they have been extirpated. ReptileConolophus subcristatus, C. marthae and C. pallidus) and giant tortoises (Chelonoidis spp.) once dominated as the only large-bodied herbivores present in the Galapagos Islands  reproduction while enhancing sexual reproduction via seed dispersal away from adult plants where bird predation on seeds is intense  aerial imagery and delineating extent of plant associations on each. Our study provided an opportunity to ask questions about the role of reptilian herbivores on structuring the plant communities of islands, including impacts on keystone plants, as well as to explore the ramifications of restoring reptile populations on islands to promote ecosystem recovery , Bouteloua disticha (Poaceae), Cyperus anderssonii (Cyperaceae), Panicum laxum (Poaceae), Sporobolus pyramidatus (Poaceae); woody plants—Acacia rorudiana (Mimosaceae), Bursera graveolens (Burseraceae), Maytenus octogona (Celastraceae), Parkinsonia aculeata , and Scutia spicata (Rhamnaceae); succulents—Sesuvium edmonstonei (Aizoaceae), and cactus—Opuntia echios (Cactaceae).The Galapagos Islands are a volcanic archipelago straddling the equator 1000 km west of continental Ecuador . ClimateZalophus wollebaeki) to enter the island for resting. A final biotic difference known to occur between the islands other than presence/absence of land iguanas was the former existence of a small cohort of goats  using the Geospatial Data Abstraction Library for geo encoding, warping and tiling supported with Python 3.4 and Imagemagick software  in R  in R . To measge) in R .versus its extent in the eight neighboring grid cells  and 1,777 grid cells on South Plaza island (iguanas present) . Vegetatid cells  indicateid cells  revealedThis study provides evidence that large-bodied, herbivorous reptiles can substantially engineer the structure of terrestrial plant communities. Not only was woody vegetation far less extensive on the island with land iguanas, the spatial pattern of woody vegetation also differed insofar as it tended to be surrounded by more woody vegetation in the presence of iguanas than in their absence. Land iguana impacts on cactus—a keystone species for the entire vertebrate community—were also substantial, reducing cactus abundance and altering spatial distribution of cactus.We suspect the dramatic contrasts in vegetation between islands were due primarily to herbivory by iguanas. Land iguanas consume fruits, flowers, leaves and shoots of woody plants, including those of species that dominated on the Plazas Islands . TargeteLand iguana herbivory might well have a cascading effect on the biotic community of small oceanic islands, by influencing other terrestrial vertebrates through changes in habitat structure and composition. One important interaction likely resulting from iguana herbivory with impacts on many other species on the Plazas Islands involves marine mammals. Sea lions cannot navigate through woody vegetation when seeking basking sites, and occupy more sparsely vegetated areas facilitated by iguanas. Sea lions deposit prolific amounts of guano with attendant changes in the soil chemistry . Notablyvia trampling and altering soil chemistry through deposition of feces sea lions affecting vegetation. This said, many parts of South Plaza Island remain inaccessible to sea lions and those areas still evidence the general differences observed in vegetation  between North and South Plazas Islands.A primary limitation of our study is that it represents a pseudo-replicated design with one replicate within each treatment. Unfortunately given the widespread extinctions of island forms of large-bodied reptilian herbivores elsewhere in Galapagos and around the world , there aWhy land iguanas do not occur on North Plaza Island is not clear. The species’ habitat is characterized as “dry areas with low growing shrubs and Opuntia cactus”  which deversus absence of land iguanas. We provide evidence that land iguanas substantially engineer the structure of plant communities. This study suggests that the widespread extinction of reptile herbivores, which once served as the dominant herbivore in many tropical oceanic ecosystems, might have profound implications for the status of these ecosystems, and the species that comprise them, today. Restoration of large-bodied reptilian herbivores, such as land iguanas and giant tortoises, should be regarded as an important component of restoration in ecosystems where they have been extirpated.Understanding how large-bodied herbivores engineer ecosystems is relevant today given widespread, current interest in reintroducing extant species back to places from which they were extirpated in historical times . With ma10.7717/peerj.12711/supp-1Supplemental Information 12) aerial imagery and delineating extent of plant associations and counting individual plants on each .Plant communities characterized on each island by developing high-resolution  and North Plaza Island (iguanas absent).Click here for additional data file.


ABSTRACT IMPACT: This qualitative study describes health system barriers to high-quality care for Latino older adults with Alzheimer’s Disease and Related Dementias OBJECTIVES/GOALS: Compared to non-Latino Whites, Latino older adults are more likely to receive low-quality dementia care such as high-risk medications or services. Caregivers play a critical role in managing medical care for persons with dementia (PWD). Yet little is known about the perceptions and knowledge of dementia quality of care among Latino caregivers of PWD. METHODS/STUDY POPULATION: We used a qualitative research design and conducted interviews with Latino caregivers of PWD and caregiver advocates. We recruited both from community organizations, senior centers, and clinics. Our interview guide focused on experiences of caregiving, interactions with medical system, and knowledge and experiences managing behavioral and eating problems. We used Grounded Theory methodology for coding and analysis, focusing on contrasting and comparing experiences within and between caregivers and caregiver advocates. RESULTS/ANTICIPATED RESULTS: Preliminary results from interviews with two caregivers and two caregiver advocates illustrate that caregivers of persons with dementia have a difficult time receiving high quality care from primary care clinicians. All participants noted that many primary care doctors didn’t know how to diagnose ADRD and dismissed critical symptoms as part of old age. Caregivers also reported that they wished they had more information on what to expect with ADRD disease progression, noting they received little information from the formal medical care system. With respect to behavioral problems, caregiver advocates noted that primary care doctors often did not provide non-pharmacological alternatives to behavioral problems. DISCUSSION/SIGNIFICANCE OF FINDINGS: Findings from our pilot study demonstrate that there is a clear need to train primary care physicians who serve Latino older adults on ADRD care. Improved diagnosis and management could improve outcomes among Latino older adults with dementia.


COVID-19 upended in-person educational programming in areas such as classroom instruction within academic institutions, engagement of adult learners, and training of direct care workers. In-person educational offerings were forced, as a result of health restrictions, to pivot into either asynchronous or synchronous web-based instruction. This panel discussion will discuss lessons-learned in cyber-pedagogy in three areas: 1) Faculty Consultation: Faculty who teach online regularly and have completed training in quality online educational practices are experts who were called upon to assist others with transitioning courses to an online format. This presentation outlines the ways in which certified online instructors, at one academic center, tutored and assisted faculty in the health sciences with online instruction. 2) Adult Learning: The rapid transition to online learning has implications for adult learners pertaining to accessibility, diverse learning and technology abilities, and course and peer engagement. This presentation will explore strategies that faculty can utilize to offer adult learners differentiated learning and engagement opportunities. This discussion will also highlight the nexus among these pedagogical strategies and the Age-Friendly University Global Network, providing guidance for how universities can connect online learning methods to the Age-Friendly University principles. 3) Workforce Training: The direct care workforce employed in community-based services and support programs and long-term care settings tend to receive little or no training in geriatric care. This presentation will discuss how educational trainings offered through a Geriatric Workforce Enhancement Program transitioned onto web-based platforms in order to accommodate these ongoing educational needs throughout the pandemic.


Existing research has identified significant risk factors for experiencing social isolation in later life including chronic health conditions, mobility impairments, and living alone among others. Although many older people who live alone maintain active social lives, living alone remains a top predictor of social isolation. Less is known about other types of risk factors, such as place-based risks and social exclusion. Despite calls to examine the role of place and social exclusion in social isolation risk, few studies have investigated the links. Models of isolation risk have often omitted place-based factors and social exclusion and focused largely on individual-level risks. In order to address these gaps, this paper presents the findings of 17 in-depth, qualitative interviews with community-dwelling older people who live alone (aged 65-93). Participants were recruited using a theoretical sampling strategy to ensure that a diverse range of neighbourhood types were represented among the participants . Interview transcripts were analyzed using a constructivist grounded approach resulting in several major themes. Participants described aspects of their local environments as shaping their risk of isolation including infrastructure and amenities delivered in place, and neighbourhood makeup, among others. These themes are further examined through the lens of place-based exclusion and used to conceptualize how dimensions of both place and social exclusion fit into the model of known isolation risk factors. An adapted model of risk is presented to guide future research and intervention planning.


As COVID-19 lockdowns began in Canada last spring, family caregivers (FCGs) of people living with dementia (PLWD) found themselves facing a catch-22: they and their family members were often most at risk of severe outcomes should they contract the virus, yet the public health measures put in place also detrimentally affected their ability to continue providing care. To understand the nuances of caregiver experiences during the pandemic, we conducted 9 focus groups with 19 FCGs of PLWD in the Calgary region in summer 2020. Caregivers reported negative outcomes resulting from decreased services for both themselves and the PLWD, including increased isolation, poor mental health, and accelerated dementia progression. Caregivers also emphasized the importance thinking beyond the binary of either locking down or opening up; rather, we must find creative solutions to safely continue providing supports to caregivers. This presentation explores FCG suggestions for balancing COVID-19 risk against caregiver needs.


Axons in the adult mammalian nervous system can extend over formidable distances, up to one meter or more in humans. During development, axonal and dendritic growth requires continuous addition of new membrane. Of the three major kinds of membrane lipids, phospholipids are the most abundant in all cell membranes, including neurons. Not only immature axons, but also severed axons in the adult require large amounts of lipids for axon regeneration to occur. Lipids also serve as energy storage, signaling molecules and they contribute to tissue physiology, as demonstrated by a variety of metabolic disorders in which harmful amounts of lipids accumulate in various tissues through the body. Detrimental changes in lipid metabolism and excess accumulation of lipids contribute to a lack of axon regeneration, poor neurological outcome and complications after a variety of central nervous system (CNS) trauma including brain and spinal cord injury. Recent evidence indicates that rewiring lipid metabolism can be manipulated for therapeutic gain, as it favors conditions for axon regeneration and CNS repair. Here, we review the role of lipids, lipid metabolism and ectopic lipid accumulation in axon growth, regeneration and CNS repair. In addition, we outline molecular and pharmacological strategies to fine-tune lipid composition and energy metabolism in neurons and non-neuronal cells that can be exploited to improve neurological recovery after CNS trauma and disease. Developing axons in the mammalian nervous system can extend very long distances . After rContinuous addition of new membrane is required during axon and dendrite growth ,24, streA schematic representation of membrane expansion during axonal and dendritic growth, stretch growth of integrated axons, myelin formation and repair, sealing of membrane ruptures and axon regeneration. PPV: plasmalemmal precursor vesicles.Membrane expansion in developing axons is mediated by polarized exocytosis of plasmalemmal precursor vesicles that are anterogradely transported to the growth cone ,36. New A schematic representation of the assembly of the exocyst octameric protein complex that controls the tethering of secretory vesicles to the plasma membrane prior to SNARE-mediated fusion. Soluble N-ethylmaleamide attachment proteins (SNAP), vesicle associated membrane proteins (VAMP) and syntaxis form the core machinery of vesicle fusion also known as the SNARE  complex . WhereasAfter axotomy, rapid sealing of disrupted membranes is necessary to restore boundary integrity of the axonal compartment, to equilibrate ion concentration and to counteract osmotic stress . These sFormation of a new growth cone at the axonal stump also requires insertion of new membrane into the neurolemma ,59. A prAnother recent study in adult CNS neurons has shed light on the specific changes in lipid metabolism that contribute to axon regeneration. After axotomy, expression of the phosphatidic acid phosphatase enzyme lipin 1 increase in retinal ganglion cells . MechaniProm1, which encodes the membrane glycoprotein Prominin-1, acts as a positive regulator of peripheral nerve regeneration in adulthood [Prom1 forced expression enhances axon regeneration via Smad2-dependent signaling and inhibits the expression of genes related to cholesterol biosynthesis [During early stages of development, immature neurons exhibit an extraordinary axon growth and regenerative capacity ,62,63. Adulthood . Prom1 fynthesis . In the adult CNS, the vast majority of cholesterol is present in myelin sheaths and plasma membranes. After SCI, disruption of cellular membranes and myelin sheaths cause an excess of cholesterol to accumulate in the extracellular space. Of interest, cholesterol depletion has been shown to promote axon growth in vitro and regeneration of peripheral nerves in vivo . By loweThe neuronal cell bodies in sensory, sympathetic and parasympathetic ganglia are wrapped by satellite glial cells . The impTogether, experimental evidence suggests that rewiring lipid metabolism can be manipulated for therapeutic gain as it favors axon regeneration both in the central and peripheral nervous systems. Whether pharmacological and molecular strategies lowering cholesterol synthesis promote neurological recovery after SCI is unknown and deserves further attention in future investigations. Drosophila have shown that dendrite expansion in larva neurons relies on cell-autonomous production of lipids [srebp mutant. SREBP acts as a basic helix–loop–helix leucine zipper transcription factor that binds to sterol regulatory elements to control the expression of genes that encode key enzymes of both fatty acid and cholesterol metabolism [srebp mutant larvae. In turn, cell-autonomous production of fatty acids is necessary for correct dendritic development and function. A genetic screen in dendritic arborization sensory neurons of the Drosophila larval peripheral nervous system has identified the easily shocked (eas) gene, which encodes the ethanolamine kinase , as a c mutants , causing mutants . Eas mut neurons ,86. ThusMyelin is constituted by multiple overlapping layers of a specialized membrane spiraling around axons . Myelin During normal brain development, astrocyte-derived fatty acids constitute a significant portion of lipids incorporated into CNS myelin . RemarkaAs result of CNS trauma and disease, myelin sheaths along the axon can be severely damaged. De novo fatty acid synthesis via fatty acid synthase is critical for CNS myelin formation after demyelination injury. Genetic depletion of fatty acid synthase from OPC has no effect on proliferation and differentiation along the oligodendrocyte lineage, yet is necessary for accurate CNS myelination . TreatmeIn mammals, the ability to regenerate and repair the CNS declines with age ,117. In Recent evidence suggests that a delicate balance in lipid synthesis and homeostasis is crucial during myelin formation and remyelination during CNS development, as well as after injury or disease. Strategies targeting lipid composition of the myelin membrane may exert contradictory responses where a lipid-enriched diet may rescue myelination defects while excess lipids trigger oligodendrocyte death and inflammation. Learning how to fine tune lipid composition in myelin membranes via extracellular lipid supply, lowering cholesterol levels or promoting its clearance with spatial precision without causing adverse effects represent important areas of future investigation. As discussed above, lipids are necessary for proper sealing of the plasma membrane, formation of a new growth cone and regeneration after axonal injury. These energy demanding processes require optimal mitochondrial transport and adenosine triphosphate (ATP) production ,122,123.As axons reach their target field during late stages of development, formation of collateral branches and synaptic contacts allow neurons to establish complex connectivity patterns ,131,132.Mitochondria trafficking and anchoring along the axons needs to be tightly regulated to respond to altered energy requirements . To meetMitochondrial positioning along the axon is important as it enables local energy supply . AccumulO-linked β-N-acetylglucosamine (O-GlcNAc) post-translational modification of serine and threonine residues of proteins acts as a nutrient sensor and metabolic mediator [worms, a decrease in O-GlcNAc levels promotes axon regeneration by adopting glycolysis as the primary source of energy [O-GlcNAc levels fail to regenerate after blocking glucose transport or inhibiting glycolysis, increasing O-GlcNAc levels act on mitochondrial function and enhance axon regeneration in Caenorhabditis elegans through FOXO/DAF-16–dependent mechanisms [O-GlcNAc levels drive distinct branches of the insulin pathway to promote regeneration in worms may help explain these seemingly contradictory results. How does cellular metabolism contribute to neuron repair after axotomy? By linking glucose metabolism to the hexosamine biosynthetic pathway, mediator . One dayf energy . Whilst chanisms . The facAs glial cells are metabolically coupled to axons, they may provide energy metabolites to support axon survival and function ,156,157.Together, the above examples underscore the importance of achieving optimal mitochondrial transport and glial metabolism as they are necessary for energy production to fuel axon growth and regeneration. Whether mitochondrial transport may be linked to nutrient and energy sensing is not known. It is also not clear whether mitochondria have memories, allowing them to respond rapidly to changes in environmental nutrient and energy levels. The extent to which boosting energy metabolism and mitochondria trafficking may be sufficient to promote functionally relevant regeneration and CNS repair under different experimental conditions awaits confirmation. After CNS trauma and disease, altered lipid metabolism and lipid accumulation in neurons and various tissues in the body can be harmful, as it causes permanent cellular damage . To undeUnder normal physiological conditions, excess energy is stored in depots of white adipose tissue (WAT) in the form of triacylglycerides. WAT depots include abdominal and subcutaneous fat ,163 Fig. To mobiGeneration of body heat by external stimuli like temperature or food is called adaptive thermogenesis and is further classified as either shivering or non-shivering thermogenesis. By controlling the non-shivering thermogenic function, brown adipose tissue (BAT) plays a crucial role in maintaining whole-body energy balance. BAT’s unique ability to produce heat relies on the mitochondrial uncoupling protein 1 (UCP1), which disengages oxidative phosphorylation from the electron transport chain to produce heat instead of energy in the form of ATP . IncreasRecent evidence suggests that innervation of adipose tissue may play a critical role in lipid mobilization and endocrine signaling ,170,171.More than 100 years ago, Dogiel reported neurons of unknown origin innervate WAT . DecadesSensory neurons also innervate WAT. In fact, T13-L3 neuronal cell bodies can be visualized upon retrograde tracing in WAT . SimilarUnlike WAT, BAT segments bilaterally . As noreLipolysis and adaptive thermogenesis are necessary to control a healthy energy balance. Neurons that connect the hypothalamic regions and innervate WAT and BAT form a ‘leptin sensitive’ closed loop. The arcuate nucleus in the hypothalamus is one such CNS region that critically senses leptin levels  to promoIndividuals that sustained an injury to the brain or spinal cord may have lower life expectancy due to chronic secondary complications that develop months and years after injury. Bladder and bowel dysfunction can cause anxiety, social isolation and depression after SCI . SympathIt is important to note that adiposity in SCI individuals and healthy individuals is not exactly the same. Within a year after injury, SCI individuals lose bodyweight, mostly in lean muscle mass . The draAt least half of individuals with SCI has >30% of their total body mass as adipose tissue, indicating SCI individuals are at high risk of developing metabolic syndrome  Figure . AdiposeA rise in triglycerides in the liver may be caused by increased storage after de novo synthesis, reduced breakdown, or impaired secretion in the form of very-low-density lipoproteins (VLDL). Under pathological conditions like obesity, fatty acids are converted into triglycerides. These are stored as neutral lipid droplets as they no longer get converted into energy substrates by oxidation. With more incoming fatty acids adding to the pool of stored lipid droplets in the liver, the de novo synthesis of lipids increases, thereby causing lipid accumulation within the liver ,225. As Proper insulin signaling in the liver orchestrates the critical steps of VLDL secretion . HoweverMore than half of the triglycerides deposited in the liver originates from circulating fatty acids and ~25% of the triglycerides comes from de novo lipogenesis . Given tA gradual rise in whole-body adiposity compromises the balance between fatty acid uptake and secretion with negative impacts on the liver metabolic profile. Despite recent progress, a thorough mechanistic understanding of liver pathology after SCI is still lacking. As the liver represents the primary site for drug metabolism, reducing hepatic metabolic dysfunction may boost efficacy of SCI medications and repair strategies. As circulating free fatty acid levels increase due to adiposity, the glucose-fatty acid cycle, also known as the ‘Randle’ cycle , destabiCardiovascular complications represent the leading cause of death in chronic SCI individuals ,242,243.We have discussed evidence suggesting that reprogramming lipid metabolism, boosting mitochondrial transport and neuron-glia metabolic coupling promote survival and regeneration of injured axons. Whereas large amounts of lipids are necessary during development to grow axons, dendrites and myelin sheaths, dysregulation of lipid metabolism, impaired mitochondrial functions and excess lipid accumulation through the body including in non-adipose organs can be harmful as they cause lipotoxicity and increased levels of fatty acids. Not only do such detrimental conditions contribute to axon regeneration failure, but also to insulin resistance, cardiovascular disease and metabolic syndrome, thus leading to poor neurological outcomes and a diminished quality of life. In addition, spatial and temporal alteration of circulating fatty acids may compromise CNS function and repair under pathological conditions including CNS trauma and neurodegenerative diseases. Correct positioning of organelles for membrane trafficking, lipid exchange and energy production requires a complex interplay between various organelles and molecular motors . The fab


Strong social relationships and social engagement are crucial for both successful aging and successful community re-entry after incarceration. Here, we utilized a mixed methods approach to understand the impact of incarceration on social relationships and social engagement among formerly incarcerated community-dwelling African-American adults aged >50. Participants in the 2012 or 2014 waves of the Health and Retirement Study answered questions regarding prior incarceration, social relationships, and participation in social activities. Additionally, we utilized key informant interviews to further explore how incarceration might impact relationships and social engagement. This presentation will describe quantitative associations between prior incarceration and social relationship structure & function. Further, we will use our qualitative interview data to further explore possible explanations for our findings. Finally, we will describe how MCUAAAR Scientist/Faculty interactions facilitated this work.


OBJECTIVES/GOALS: People engaging in high-risk substance use or experiencing food insecurity or housing instability are at increased risk to develop end-stage kidney disease. This study will examine associations between these risk factors, patient indicators of socioeconomic position, and hospitalization rates and quality of life after initiation of hemodialysis. METHODS/STUDY POPULATION: The proposed study will leverage a prospective cohort design. We will enroll a convenience sample of 330 participants from the same large dialysis organization. Participants will complete measures of socioeconomic position ; substance use; food insecurity; housing instability; and quality of life at baseline. We will follow participants for 6 months and extract hospitalization counts from the dialysis facility medical record. RESULTS/ANTICIPATED RESULTS: We will generate risk scores  from measures of substance use, food insecurity and housing instability. We will conduct multiple logistic regression to generate odds ratios comparing risk group membership by indicators of socioeconomic position. We anticipate that low or medium-risk groups will differ from high risk groups by indicators of socioeconomic position. We will conduct Poisson regression to generate incidence rate ratios for 6-month hospitalization rates comparing low or medium-risk and high-risk groups. Lastly, we will conduct multiple linear regression to generate beta coefficients for changes in quality of life scores comparing low or medium-risk and high-risk groups. We anticipate that high-risk groups will have higher hospitalization rates and lower quality of life scores. DISCUSSION/SIGNIFICANCE OF IMPACT: As the prevalence of end-stage kidney disease continues to increase, there is a need for tertiary prevention interventions that reduce costly inpatient utilization and improve health-related quality of life. The proposed study will lay groundwork for the development of interventions to improve patient outcomes and reduce Medicare spending.


Oral health is a global public health concern. The four papers in this symposium capture various understudied risk and protective factors in oral health and dental care among older adults in China. The first paper examined the relationship between social isolation, loneliness, and tooth loss among Chinese older adults, using the Chinese Longitudinal Healthy Longevity Survey. The findings suggest that higher levels of social isolation, rather than loneliness, were associated with fewer remaining teeth and accelerated tooth loss over time. The second paper investigated urban-rural disparities in dental care utilization among Chinese adults aged 18 to 65 years old, using the 2019 New Era and Living Conditions in Megacities Survey. The findings demonstrate urban residents were more likely to visit dentists than rural residents. Besides socioeconomic status, health attitudes/behaviors, and oral health needs, health insurance coverage was considered an important enabling factor to promote dental care use in this population. The third paper examined the relationship between denture use and cognitive decline among Chinese older adults, using data from the Chinese Longitudinal Healthy Longevity Survey. The findings indicate that denture use is protective against cognitive decline over time in later life. The fourth paper examined the prevalence of self-reported orofacial pain symptoms and their correlates at the last year of life among Chinese older adults. Low socioeconomic status, smoking, chronic conditions, oral hygiene practice, and natural teeth condition were associated with such symptoms. This symposium offers valuable insights to improve oral health and dental care in older adults in China.


ABSTRACT IMPACT: This project aims to better understand mechanisms of sensory and motor deficits in individuals with ASD with the goal of informing diagnosis and treatment development. OBJECTIVES/GOALS: Over-reliance on both visual and proprioceptive feedback have both been observed during motor behavior in persons with Autism Spectrum Disorders (ASD), suggesting that separate sensory feedback processes may be selectively altered during different behaviors. The objective of this study is to clarify sensory mechanisms of fine motor control in ASD. METHODS/STUDY POPULATION: Participants with ASD (N=43) and controls (N=23) matched on age (10-20 yrs) and non-verbal IQ completed tests of precision gripping. Participants were instructed to press on force sensors with their index finger and thumb so that a moving bar corresponding to their force output reached and stayed as stable as possible at the level of a stationary target bar. Visual feedback was manipulated by changing the visual gain of the force bar . The force bar moved more per change in force output at higher gains. Proprioceptive feedback was manipulated by applying 80 Hz tendon vibration at the wrist to induce an illusion of muscle contraction. This was compared to a condition with the tendon vibrator turned off. Force variability (standard deviation) and regularity (sample entropy) were examined. RESULTS/ANTICIPATED RESULTS: Controls showed increased force variability with the tendon vibration on compared to off ; however, the ASD group showed no difference in force variability between the tendon vibration conditions . Individuals with ASD had stronger age-associated reductions in force variability relative to controls across tendon vibrator and gain conditions . The ASD group also had greater age-associated increases in force regularity relative to controls, especially at higher gain levels . Unlike the ASD group for whom regularity increased with age in both tendon vibration conditions, controls only showed these age-related gains when the tendon vibrator was off . DISCUSSION/SIGNIFICANCE OF FINDINGS: Our findings indicate that while controls integrate proprioceptive and visual feedback online to accurately adjust fine motor behavior, persons with ASD rely mostly on visual feedback. Our results suggest delayed development of sensory integration and reduced reliance on multisensory feedback during online fine motor control in persons with ASD.


Although cognitive decline has previously been associated with mobility limitations and frailty, the relationship between sustained attention and gait speed is incompletely characterized. To better quantify the specificity of the sustained attention and gait speed association, we examined the extent to which this relationship is unique rather than accounted for by executive functioning and physical health characteristics. 58 middle-to-older-aged community-dwelling adults without overt illness or diseases  participated in the study. Each participant completed a 4-meter gait speed assessment and validated neuropsychological tests to examine various domains of executive functions including working memory , inhibitory control , and task switching . Multiple physical and vascular risk factors were also evaluated. Sustained attention was assessed using the gradual onset continuous performance task (gradCPT), a well validated go/no-go sustained attention task. A series of linear regression models were created to examine how different aspects of cognition, including sustained attention and traditional measures of executive functioning, related to gait speed while controlling for a variety of physical and vascular risk factors. Among all predictors, gradCPT accuracy explained the most variance in gait speed  and was the only significant predictor  when accounting for executive functioning and other physical and vascular risk factors. The present results indicate that sustained attention may be uniquely sensitive and mechanistically linked to mobility limitations in middle-to-older adults.


Inflammaging characterized with increased low grade inflammation in older adults is common determinant of unhealthy aging; and is a major risk factor of morbidity and mortality in older adults. The precise origin of inflammation in older adults is not known, however, emerging evidence indicate that increased intestinal epithelial permeability (leaky gut) and abnormal (dysbiotic) gut microbiota could be one of the key source. However, no preventive and treatment therapies are available to reverse the leaky gut and microbiome dysbiosis in older adults. Here, we presented the evidence that a human-origin probiotics cocktail containing 5 Lactobacillus and 5 Enterococcus strains isolated from healthy human infant gut can ameliorate aging-related metabolic, physical and cognitive dysfunctions in older mice. We show that the Feeding this probiotic cocktail prevented high-fat diet–induced (HFD-induced) abnormalities in glycose metabolism and physical functions in older mice and reduced microbiota dysbiosis, leaky gut, inflammation. Probiotic-modulated gut microbiota reduced leaky gut by increasing tight junctions on intestinal epithelia, which in turn reduced inflammation. Mechanistically, probiotics increased bile salt hydrolase activity in older microbiota, which in turn increased taurine deconjugation from bile acids to increase free taurine abundance in the gut. We further show that taurine stimulated tight junctions and suppressed gut leakiness. Further, taurine increased life span, reduced adiposity and leaky gut, and enhanced physical function in Caenorhabditis elegans. Whether this novel human origin probiotic therapy could prevent or treat aging-related leaky gut and inflammation in the elderly by reversing microbiome dysbiosis requires evaluation.


Function by Roy et al.“Choose your parents wisely” is a popular adage coined by the British Philosopher Bertrand Russell, and often used when discussing issues such as socioeconomic position and genetic contributions to disease risk. When it comes to vascular function, a predictor of cardiovascular disease risk, the recent study in HCR) and vice versa (HCR-mtLCR). Specifically, HCR female offspring were backcrossed with male LCR  via inbreeding, and this backcross procedure was repeated over several generations to generate the LCR-mtHCR and HCR-mtLCR. The investigators performed echocardiography to assess cardiac function and left ventricular mass, wire, and pressure myography to assess arterial vasodilatory function (with and without PVAT) and mechanics, macroscopic tissue imaging of PVAT, and bioenergetic assays with vascular smooth muscle cells (VSMCs).The investigators studied rats artificially selected (within-family) for intrinsic aerobic endurance running capacity to generate LCR and HCR male rats.HCR) but decreased left ventricular mass and several indices of cardiac performance in HCR-mtLCR relative to HCR.Compared to HCR, LCR rats had higher body mass, epididymal fat mass, and blood pressure. Regarding cardiac measures, HCR rats presented higher left ventricular mass than LCR rats see . CompareHCR), however, it did not reduce vascular function in HCR-mtLCR. Using mesenteric arterioles and plotting internal lumen and external diameters with intraluminal pressure curves, the authors revealed that the arterioles from LCR rats exhibited hypotrophic remodeling . Moreover, mitochondrial swap did not have an effect on either the LCR or HCR phenotype.The key findings were that compared to HCR, LCR rats presented with lower endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitroprusside) vasodilation in mesenteric resistance arteries. Mitochondrial swap rescued endothelium-dependent and endothelium-independent vasodilation in LCR  to what extent intrinsic exercise capacity and mitochondrial DNA influence vascular function in female and older rodents, (2) if the reduced endothelium-dependent vasodilation in LCR rats is mediated by reduced NO synthesis and/or bioavailability or a combination of NO and/or other vasodilators  or prostacyclin), (3) the role of mitochondrial ROS and other vascular sources of ROS  in contributing to the vascular phenotypes associated with HCR and LCR, and (4) determining whether exercise, similar to mitochondrial swapped conplastic strains, can also rescue endothelial dysfunction in LRC rodents .,HCR on LCR rodents demonstrates that mitochondrial DNA is an essential oddment to the protective phenotype conferred by high CRF. These findings will hopefully pave the way for exciting future research to determine mitochondrial-based targets to help prevent and treat cardiovascular disease.At the population level, we cannot do much to improve an individual’s intrinsic CRF. Indeed, the HERITAGE family study established that intrinsic capacity and trainability are genetically heritable in humans.


The coexistence of expiratory central airway collapse and diaphragmatic paralysis presents a diagnostic and treatment challenge. Both entities are underrecognized causes of dyspnea, cough, sputum production, and orthopnea. Optimal treatment must be individualized and is best achieved by a multidisciplinary team. We present a case of a patient with profound functional impairment from dyspnea and hypoxemia due to expiratory central airway collapse, complicated by bronchiectasis from recurrent respiratory infections, and diaphragmatic paralysis. There are a myriad of causes of dyspnea, hypoxemia, and excessive sputum production. Identifying the relevant contributors to patient's presenting concerns is critical for appropriate management. Expiratory central airway collapse (ECAC) involving either the cartilaginous tracheal wall or the posterior membranous portion may be suggested by computed tomography imaging of the chest obtained during forced expiration and confirmed by dynamic bronchoscopy. Fluoroscopy and diaphragm ultrasound are used to diagnose diaphragmatic paralysis. Surgical management includes tracheobronchoplasty and diaphragmatic plication. ECAC and diaphragm paralysis both compromise gas exchange during surgery but the effect can be mitigated by the use of intraoperative extracorporeal membrane oxygenation (ECMO).A 54-year-old man presented with progressive shortness of breath, cough, and recurrent pneumonia. Chest examination was notable for reduced bilateral lung excursion, coarse breath sounds diffusely, and paradoxical breathing in the supine position. Pulmonary function testing suggested severe restriction with FVC of 27% predicted, FEV 1 28% predicted, normal FEV1/FVC ratio, and respiratory muscle strength < 10% predicted.Computed tomography (CT) of the chest revealed basilar bronchiectasis and bilateral diaphragmatic elevation with associated atelectasis. Dynamic CT showed anterior displacement of the posterior tracheal wall at the distal trachea, bilateral main stem bronchi, and bronchus intermedius. Electromyogram demonstrated bilateral phrenic neuropathy and left brachial plexus neuropathy. Ultrasound confirmed the absence of diaphragm movement bilaterally. He had progressive clinical decline requiring near constant noninvasive positive pressure ventilation (NPPV). Dynamic bronchoscopy showed severe expiratory central airway collapse (ECAC) with >90% collapse of the trachea, main stem bronchi, and bronchus intermedius . A stentThe initial surgery was aborted due to the inability to maintain adequate oxygenation during single lung ventilation. One week later, the procedure was successfully completed through right thoracotomy under venous-venous extra-corporeal membrane oxygenation (VV ECMO) support. Central airway stabilization was achieved by suturing a knitted polypropylene mesh to the posterior membrane of the trachea and bilateral main bronchi. Due to persistent ventilator dependency, left diaphragm plication through a left thoracotomy was performed 5 days postoperatively. He was discharged home on postoperative day #23.At follow-up evaluation, he no longer required NPPV and regained independence in activities of daily living. Pulmonary function testing showed improvement with FVC of 53% predicted, FEV1 42% predicted, and respiratory muscle strength 13% predicted. CT of the chest demonstrated improved lung volumes . DynamicAlthough diagnostic parsimony encourages identifying a single unifying explanation for one's symptoms, this case illustrates the veracity of Hickam's dictum: “A man may have as many diseases as he damn well pleases .” We hypUnilateral or bilateral dysfunction of the diaphragm can result from phrenic nerve dysfunction, neuromuscular junction disease, or myopathy. Paradoxical respiratory efforts and decline in FVC while supine suggest DP with confirmation achieved with fluoroscopy, ultrasound, or phrenic nerve EMG. Symptomatic unilateral disease that cannot be explained by another underlying disease process may be amenable to plication. Bilateral DP can be managed by noninvasive positive-pressure ventilation and treatment, if available, of the underlying cause. Diaphragmatic pacing may be beneficial if phrenic nerve function is intact. The goal of plication is at eliminating the paradoxical upward motion of the paralyzed diaphragm and decreasing the basilar parenchymal compression. Although historically performed via a thoracotomy, plication can also be performed effectively with minimally invasive robotic, thoracoscopic, or laparoscopic techniques . SurgicaRecognition of large airway dysfunction during expiration as a cause of chronic respiratory symptoms is gradually increasing. Two patterns have been described in ECAC: (1) tracheobronchomalacia (TBM) in which the cartilaginous component of the anterolateral tracheal wall collapses on forced expiration and (2) excessive dynamic airway collapse (EDAC) in which there is anterior displacement of the posterior (membranous) tracheal wall during expiration . When clWhen the degree of airway collapse is severe, surgical repair should be considered. A preoperative stent trial with uncovered self-expandable metallic stents is strongly advised to estimate the potential surgical benefit prior to surgical intervention . In our Our technique for tracheobronchoplasty involves plication of the redundant posterior membrane of the trachea and mainstem bronchi and fixation to a semirigid permanent (polypropylene) permeable mesh. The standard approach is through a right thoracotomy, although minimally invasive robotic and thoracoscopic approaches have also been reported to be feasible but with unknown long-term results .We hypothesize that basilar bronchiectasis in this patient was due to inadequate airway clearance from both ECAC and DP resulting in recurrent lower respiratory infections. Medical management of bronchiectasis to improve airway mucous clearance was limited due to compromised large airways from ECAC and weak cough from DP.VV ECMO is used most commonly in acute respiratory distress syndrome and in patients with advanced lung disease requiring transplant either intraoperatively or as a bridge to lung transplantation. As the use of ECMO increases, understanding the surgical implications of this therapy is critical. In a review of 563 patients on ECMO, 269 required noncardiac surgery. There was no difference in outcomes between those needing or not needing surgery . AnticipBoth ECAC and bilateral diaphragmatic dysfunction, with associated bronchiectasis, synergistically lead to dyspnea, cough, respiratory infections, and severe functional impairment in this patient. Demonstration of the improvement in clinical outcomes with an airway stent trial before entertaining surgical correction of ECAC is critical to optimize patient selection. As demonstrated, surgical intervention for both ECAC and diaphragm paralysis can dramatically improve the quality of life and functional capability. Intraoperative ECMO may permit definitive surgical treatment of ECAC in patients with gas exchange abnormalities that would otherwise preclude surgery.This case elucidates three critical concepts to comprehensive patient-centered care. The importance of thoroughly investigating all the relevant contributors to a patient's symptoms, with specific attention to those for which therapy can be offered, is illustrated. Additionally, the novel use of ECMO demonstrates the need to embrace unconventional surgical approaches as mandated by the patient's clinical scenario. Finally, it was only the multidisciplinary team-based approach to care, involving pulmonologists, interventionalists, thoracic surgeons, anesthesiologists, and intensivists that allowed successful management of this patient's complex presentation.


Racial minorities and educationally disadvantaged experienced more housing loss, unemployment, and financial strain during the 2007-2009 Great Recession. These hardships may heighten stress and amplify persistent and growing health inequities, which were further worsened by the recent COVID-19 pandemic. It is therefore essential to identify factors that contribute to individual differences in vulnerability so that more effective interventions can be implemented, especially in older adult populations who may face unique economic hardships tied to age discrimination. According to the reserve capacity model, higher levels of psychosocial resources, including psychological well-being, can protect against the negative health outcomes related to heightened stress exposure. This study tested the intersections between recession hardship, pre-existing vulnerability defined as racial and educational disadvantage, and psychological well-being as predictors of biological indicators of chronic allostatic load. Chronic allostatic load was assessed with cardiovascular reactivity and recovery to acute mental stress and systemic inflammation . Biological data came from a national sample of adults known as the Midlife in the US Study  that completed assessments after the recession. Multiple regression models revealed that more widespread recession hardship predicted greater biological dysregulation. Tests of three-way interactions revealed that the association between recession hardship and biological dysregulation was strongest among respondents with combined disadvantages of low educational status and low levels of psychological well-being. This study connected a major economic event to individual variation in health vulnerability and identified potential biological pathways to future disease outcomes.


Compared to non-dementia caregivers, family/friend caregivers of individuals with dementia experience more negative caregiving consequences. One reason is the myriad of negatively impacted life domains including: managing symptoms; family communication; financial and legal matters; and finding and coordinating services. Few psychometrically tested measures exist for assessing the range of potential unmet needs of dementia caregivers. Such a measure would describe the frequency and correlates of unmet needs and provide a key outcome for intervention research. This study tested the psychometric properties of a comprehensive measure of unmet needs, the BRI Unmet Need Instrument. Data from 192 family/friend dementia caregivers was used to test reliability and four validity types. Results showed total unmet needs, as well as its nine subscales, had good reliability . Discriminant validity was confirmed through factor analyses of the 45 unmet needs and items in measures of depression and care-related strain. Unmet need items loaded on separate factors that were deemed acceptable (.72-.38). Predictive validity was assessed by the association with depression, which was significant and an acceptable range . Convergent validity was confirmed by significant associations with three caregiver strain measures, mastery , emotional strain , and relationship strain . Good structural validity for nine predetermined unmet needs subscales was found using principal component analysis (loadings = .82-.39). Results suggest the BRI Unmet Needs Instrument is a ready-to-use, reliable and valid comprehensive measure.


The extant literature highlights the physiological and psychological benefits of active lifestyles among older adults, though there is a considerable gap in scholarship for sexual minority groups. Utilizing the Social Integration Model, we hypothesize that social activities enhance individual psychological well-being, but those effects differ by one’s social identities. Using a national AARP foundation survey of adults (45+), this study examines whether individuals’ activities predict loneliness and depressive symptoms of heterosexual (n=2905) and LGBTQ adults (n=318). We utilize an index of diverse activities, which includes, social technology use, meeting with friends, and volunteer activities. Multiple linear regression is used to study cross-sectional associations of loneliness and depressive symptoms on the diverse activity index. Results show that a wider array of activities correspond with higher psychological well-being and lower loneliness, and this association is higher for LGBTQ older adults. We discuss implications for counseling and wellness programming for LGBT older adults.


Although insurance companies are increasingly paying for home-based palliative care (HBPC), enrollment remains low. To identify patient and caregiver perceived barriers to HBPC and their recommendations for overcoming these barriers, we conducted semi-structured individual interviews. Our interview protocol elicited participants’ perspectives on HBPC services; positive and negative aspects of the palliative program explanation; and suggestions for improving HBPC messaging. Seventeen patients and eight caregivers who were eligible for a randomized controlled trial of HBPC were interviewed. Themes related to HBPC referral barriers included reluctance to have home visits, enrollment timing, lack of palliative care knowledge, and patients’ self-perceived health condition. Themes related to recommendations for overcoming these obstacles included ensuring that HBPC referrals come from healthcare providers or insurance companies and presenting HBPC more clearly. Findings reinforce the need for palliative care education among seriously ill patients and the importance of delivering palliative care information and referrals from trusted sources.


Maternofetal stress induces fetal programming that restricts skeletal muscle growth capacity and metabolic function, resulting in intrauterine growth restriction (IUGR) of the fetus. This thrifty phenotype aids fetal survival but also yields reduced muscle mass and metabolic dysfunction after birth. Consequently, IUGR-born individuals are at greater lifelong risk for metabolic disorders that reduce quality of life. In livestock, IUGR-born animals exhibit poor growth efficiency and body composition, making these animals more costly and less valuable. Specifically, IUGR-associated programming causes a greater propensity for fat deposition and a reduced capacity for muscle accretion. This, combined with metabolic inefficiency, means that these animals produce less lean meat from greater feed input, require more time on feed to reach market weight, and produce carcasses that are of less quality. Despite the health and economic implications of IUGR pathologies in humans and food animals, knowledge regarding their specific underlying mechanisms is lacking. However, recent data indicate that adaptive programing of adrenergic sensitivity in multiple tissues is a contributing factor in a number of IUGR pathologies including reduced muscle mass, peripheral insulin resistance, and impaired glucose metabolism. This review highlights the findings that support the role for adrenergic programming and how it relates to the lifelong consequences of IUGR, as well as how dysfunctional adrenergic signaling pathways might be effective targets for improving outcomes in IUGR-born offspring. Intrauterine growth restriction (IUGR) is the result of fetal developmental programming aimed at increasing the chances of surviving poor intrauterine conditions by promoting thrifty growth and metabolism. Unfortunately, these same developmental changes also diminish metabolic health and quality of life after birth . The linLow birthweight in livestock due to IUGR is a barrier to the economic sustainability of meat production, as these animals exhibit greater early-life mortality and lifelong performance deficits . Severe The establishment and characterization of several animal models for IUGR provides the opportunity to study the fetal programming mechanisms underlying IUGR pathologies in livestock and humans . CurrentThere is a broad range of causes for IUGR in livestock and humans that result in varying degrees of fetal growth restriction, which have been reviewed in greater detail elsewhere . In liveIUGR is necessitated by the increase in nutrient requirements to support normal fetal growth and the inability of the compromised placenta to meet them. Peak placental development occurs from the mid-1st trimester to the late 2nd trimester, which is from approximately day 30 to 100 of gestation in sheep and day 50 to 90 in humans . Most ma2 by the placenta creates chronic fetal hypoxemia and hypoglycemia  muscles from near-term IUGR fetal sheep exhibited 20–50% reductions in the proportion of oxidative fibers  relative to glycolytic fibers   . Changestrations . This imtrations .Glucose homeostasis in the IUGR fetus and offspring is further impeded by reductions in pancreatic islet mass and function . β cellsgreater-than-normal fat deposition as juveniles , which are expressed in tissue-specific combinations throughout the body  modestly reduces glucose uptake but increases glycogen breakdown, glucose oxidation, and protein synthesis  described in earlier sections. Additional work is warranted to more thoroughly characterize the observed adrenergic programming, but existing evidence indicates that it almost certainly contributes to the persistent deficits in muscle mass and glucose oxidation exhibited by IUGR-born offspring . By 60 days of age, these lambs exhibited substantial improvements in growth, muscle mass, and body symmetry (In vivo and ex vivo metabolic studies showed that daily clenbuterol injections at least partially recovered glucose-stimulated insulin secretion and skeletal muscle glucose oxidation, which was reflected by improvements in early-life whole-body O2 consumption rates (The identification and characterization of adrenergic programming mechanisms in IUGR tissues provides a target for potential treatment and intervention strategies. Indeed, animal studies have begun to provide the fundamental basis for adrenergic manipulation as a strategy to improve growth and metabolic outcomes in IUGR fetuses and offspring. In IUGR fetal sheep, pharmaceutical blockade of elevated adrenergic activity ecretion . Althougecretion . Moreovexidation . Althougon rates . Howeversymmetry . Greateron rates , 2021.2 supplementation was used to improve fetal oxemic status in sheep, metabolic improvements exceeded the impact on apparent adrenergic tone. Specifically, acute fetal normoxia improved insulin secretion in the IUGR fetus prior to reductions in circulating norepinephrine (2 content (The complexity of IUGR programming means that targeting adrenergic dysfunction alone is unlikely to fully recover growth and metabolic deficits in their entirety. For example, adrenal demedullation of IUGR fetal sheep did not improve deficits in pancreatic islet development and only partially corrected insulin secretion . Moreovenephrine , and dai content . Recent  content , glucoco content , and poo content  in the d


Polymeric hydrogels are fascinating platforms as 3D scaffolds for tissue repair and delivery systems of therapeutic molecules and cells. Among others, methacrylated gelatin (GelMA) has become a representative hydrogel formulation, finding various biomedical applications. Recent efforts on GelMA-based hydrogels have been devoted to combining them with bioactive and functional nanomaterials, aiming to provide enhanced physicochemical and biological properties to GelMA. The benefits of this approach are multiple: i) reinforcing mechanical properties, ii) modulating viscoelastic property to allow 3D printability of bio-inks, iii) rendering electrical/magnetic property to produce electro-/magneto-active hydrogels for the repair of specific tissues , iv) providing stimuli-responsiveness to actively deliver therapeutic molecules, and v) endowing therapeutic capacity in tissue repair process . The nanomaterial-combined GelMA systems have shown significantly enhanced and extraordinary behaviors in various tissues  that are rarely observable with GelMA. Here we systematically review these recent efforts in nanomaterials-combined GelMA hydrogels that are considered as next-generation multifunctional platforms for tissue therapeutics. The approaches used in GelMA can also apply to other existing polymeric hydrogel systems.  •Physicochemical properties of GelMA hydrogel.•Role of nanomaterials for engineering bio-functional GelMA hydrogel.•Diverse biomedical applications of nanostructured GelMA hydrogel.•Promising directions for nano-inspired GelMA bioink formulation.•Applications and challenges of advanced GelMA-nanomaterial platforms. Compared to other biomaterial platforms used for regenerative purposes, hydrogels have an increasing demand owing to their close resemblance to the cellular microenvironment . These mBulcke et al. synthesized one such representative hydrogel formulation in the year 2000 popularly known as Gelatin methacryloyl or GelMA . GelMA oIn this review we emphasize multifunctional GelMA platforms with nanomaterials from different aspects, including its fabrication, crosslinking, polymeric–nanophase interactions, and its application as tissue therapeutics with future perspectives. The key objective is to provide critical analysis of multifunctional GelMA-nanomaterial platforms as versatile substrates and insights about their current challenges and future directions from a biomaterial point of view to their regenerative applications. Even though, many conceivable applications of these multi-functional materials are known, we focus more on its biomedical applications highlighting its current trends in regenerating tissues.  shows th2Hydrogel formation occurs by the cross-linking of polymer chains dispersed in an aqueous medium through numerous mechanisms, including physical gelation, ionic interactions, and chemical crosslinking . Most of2) and hydroxyl (-OH) groups are mainly involved in this substitution reaction where methacryloyl groups are introduced onto gelatin. The polymerization of GelMA occurs in an aqueous state by a free radical mechanism in presence of a photoinitiator. The UV irradiation of the photoinitiator causes the generation of free radicals by homolytic cleavage which initiates chain-growth polymerization. In the second step chain propagation occurs between methacryloyl groups present on the polymeric chain and finally terminates between a propagating chain and another free radical . M. M83]. Mractions . Polar ac groups ,22,24. Bc groups . Other ic groups . The BGnc groups . This hy3.3The hydrogels integrated with metallic nanomaterials have become an evolving area in developing customized multi-responsive constructs for tissue repair. Nano-biomaterials based on metals and their oxides have been shown to possess desired physical properties such as conductivity of electricity (gold-based) , magnetiNavaei and colleagues reported a photopolymerizable hybrid platform based on GNR encapsulated within GelMA hydrogels . This na3.4Among the multitude of GelMA platforms developed for tissue engineering, polymeric nanomaterial incorporated ones have attained a remarkable interest. These structures are similar to the macromolecule-centered components in the human body and are often considered to be good candidates for drug delivery purposes since they offer spatial and sequential control over drug/gene/growth factor release owing to the tailored physical properties, manageable degradation as well as their capability to resist the degradation of labile biomolecules .Such delivery systems can impact therapeutically advantageous properties of drug delivery and are set to possess clinical importance . CompareSeveral polymeric nanomaterials such as hyperbranched polymers, dendrimers, nanopolysaccharides, proteins like ferritin, etc. have various hydrophobic or hydrophilic units available for conjugation with the functional groups of hydrogels . These pI) acted as the delivery system for VEGF which efficiently transfect myocardial tissues which could facilitate local myocardial neovascularization at the injected sites, reduces fibrosis, and potentially improve cardiac function in an in-vivo AMI model as indicated in (N-isopropylacrylamide-co-acrylamide) nanogels loaded with DOX by entangling it within the GelMA prepolymer before photocrosslinking [A biocompatible injectable hydrogel gene delivery system developed by Paul and colleagues also showed its efficacy in specific delivery of vascular endothelial growth factor (VEGF), a signaling protein that supports angiogenesis that is necessary for the regeneration of damaged cardiac tissues for acute myocardial therapy (AMI) . GelMA icated in . This naslinking . This naslinking ,261,262.4Tissue repair and reconstruction using nano-engineered hydrogels have been developed as a promising medical strategy to the existing replacement therapies for the healing of damaged tissues . Tissue 4.1Many new developments have been made in engineering bone tissues by using hydrogel as a multifunctional platform during the last decade. Even though hydrogel-based materials display excellent bio functionality it possesses demerits such as poor mechanical stability and low processability making it unsuitable for bone tissue regeneration ,290,291.. However, single-layered GelMA hydrogels often fail to regenerate multiple tissue defects such as osteochondral defects possibly due to the mismatched stiffness of the hydrogels relative to cartilage and subchondral bones. On the other hand, bilayered GelMA hydrogels based on mussel-inspired chemistry without nanomaterial engineering have been shown to restore such defects [Owing to many fascinating potential uses of multicomponent GelMA-based materials, their design and synthesis have been a focus of substantial research over the last few years defects ,297.ve and gram −ve bacterial contamination both in-vitro and in-vivo rat cranial bone defects. The overall results show the effective role of nAg/HNTs/GelMA hybrid hydrogels in dealing with infected bone defects. In another study, Xin and co-workers embedded MBGN into GelMA hydrogel by an amide reaction to construct a hybrid membrane that can act as a substitute for periosteum [GelMA-nanomaterial interfaces provide an appropriate matrix environment and facilitate controlled growth factor delivery at different points of bone regeneration. In an early attempt studies using GNP encapsulated GelMA hydrogels (GNP/GelMA) revealed that the presence of GNP might promote cell spreading, osteogenic differentiation, and basic phosphatase activities of ADSCs . In respriosteum . This Geriosteum . The higNaturally occurring hydroxyapatite (HA) incorporated microfabricated GelMA platforms were exploited for modular tissue engineering to mimic native osteons, which are basic structural units of mature bones . These bPrevious studies thus highlight the vital role of inorganic components in regenerating bones by regulating mechanical properties and cellular differentiation. Except for inorganic components, some biodegradable organic components have also been introduced to impart specific functions into the GelMA hydrogel. For instance polylactic acid, a biodegradable polyester was introduced into 3D printed GelMA constructs consists of bioactive GNPs through filament freeform fabrication technique for regenerating diseased bones . It was Many nanocomposites were examined actively for their potential use in soft tissue engineering but these hydrogels cannot often mineralize thereby limiting their usage in engineering bone tissues . Recent 4.2The hydrogel wound dressing is considered as best wound treatment technique because of its excellent biocompatibility, moisture resistance, and ability to activate immune cells to promote wound healing . PolymerMany GelMA-based materials were reported to show tissue adhesiveness. However, due to the poor mechanical properties of GelMA, various functional nanomaterials were mainly added to improve the mechanical properties. Assmann and colleagues developed a highly elastic adhesive hydrogel that could act as tissue sealants . The dev+ released from the hydrogel also concurrently exhibits antibacterial activity. It was shown that the NIH 3T3 fibroblasts cultured on these substrates grow and multiply extensively on soft 15% GelMA hydrogels compared to other sets. AgNPs incorporated within the GelMA matrix even at a higher concentration of 150 μg/ml showed no significant toxicity, which agrees to the optimum Ag+ ion concentration required to destroy both gram +ve and gram -ve bacterial strains  also possess enhanced electrical conductivity and superior mechanical properties ,264,360.4.4Nerve tissue regeneration is an advanced and fast-developing area that assures replacement or repairment of injured, diseased nerve tissues or treating major neurological disorders that are difficult to rectify employing a normal clinical approach . Among tDifferent approaches to fabricate NGCs have been introduced in recent years to overcome the typical limitations related to nerve grafting . Differe5The 3D bioprinting arose as an innovative approach that utilizes a computer-aided process to fabricate cell-laden constructs of defined geometries that support soft or hard tissue regeneration or alternate for organ replacements . Self-he. The presence of two independent entwined polymer chains in this bio-ink conjugated themselves via a distinct cross-linking mechanism allows precise control over its characteristics. The presence of nSi enhances the mechanical stiffness and tissue adhesiveness by exerting reversible electrostatic interactions within the hydrogel chains. Being a printable hydrogel formulation this could be utilized for the fabrication of various mechanically robust cellularized structures [Nanoengineered ionic covalent entanglement bio-ink (NICE), a novel smart bio-ink developed by Chimene and colleagues for 3D bone bioprinting is one of a kind . This biructures . Furtherructures . These iructures . The ostructures . This syImproved cytocompatibility and bioactivity are the most essential requirements in nanomaterials intended to be used in developing new bio-ink. Many inorganic ions are capable of inducing cellular differentiation. So there exists massive promise for these ions for effective use in bone regeneration. The role of strontium (Sr) in the remodeling and engineering of bone tissues has been reported in recent years . A low cThe regeneration of cardiac tissues using nanoengineered hydrogels also profusely progressed due to the new insights of converging microscale technologies with stem cell biology. Even though a lot of noteworthy studies have been done focused on developing bio-engineered cardiac constructs or patches for functional tissue replacement, a clinically applicable engineered cardiac structure representing the morphological, physiological, and functional properties of natural myocardium remains the challenge . Surfact3D bioprinting of soft tissue constructs was always a challenge for biomedical researchers since it lacks the desired mechanical properties . Advance6The nano-structured hydrogels of succeeding generations have got potential to transform or replace the existing systems for various tissue engineering applications. The superior characteristics owned by multi-functional hybrid systems, which lack in their hydrogel counterparts enable them for various applications. Being a dominant hydrogel formulation of recent times, the future direction on GelMA-nanomaterial platforms certainly includes balanced optimization in all aspects says physical, chemical as well as biological. Next-generation nano-engineered GelMA is being progressively evaluated for its various clinical applications. Even though the non-functionalized nanomaterial and GelMA interactions could result in useful material characteristics, the resultant hybrid composites lack control over many key properties including stimuli responsiveness and physiological degradation. To overcome these drawbacks different strategies have been introduced in which modifying GelMA hydrogel network by incorporating multifaceted nanomaterials of various types is the most common approach. Our research group also recently focused on developing similar systems by functionalizing antioxidant nanomaterials such as cerium oxide (CeO2) using macromolecules such as dendrimers which would interact with the hydrogel physically or chemically and resulted in multi-responsive scaffolds of better stiffness and microarchitecture. Nowadays more efforts are also made in designing hydrogels with long-term biocompatibility that will aid desired biological behavior. The reviewed literature proposes that the development of novel synthetic routes, functionalizing strategies, and fabrication technologies for GelMA-nanomaterial hybrid systems will continue in the coming years and more priority will be given to research for its personalized applications. Microfabrication approaches for knowing the cell-nanophase communication is one such attempt. Microscale technologies are emerging as a prevailing technology to solve the many existing challenges in tissue engineering. Studies conducted using CNT reinforced hybrid microgels and hyperbranched polyesters have shown the effective utilization of microscale technologies for cell entrapping on pre-defined patterns resulting in different functional tissues of interest. Engineered GelMA hydrogel holds a groundbreaking role in hastening the progress in clinical therapeutics by converging biological and bio-fabrication approaches. Apart from the advances, there are many challenges linked to the clinical translation of photocrosslinkable hydrogels like GelMA. The most important factor is the conversion of various synthetic strategies towards successful regeneration methods and procedures by accepting good manufacturing practices (GMP) while conserving the envisioned capacity for tissue regeneration. Furthermore, evaluations on nano-functionalized constructs are mandatory before the clinical applications to limit the concerns related to biosafety. Certain nanocomposite hydrogels could be applicable only in culturing specific cell types  compared to non-functionalized GelMA hydrogel platforms, due to the intrinsic material characteristics. Consequently integrating universal functionalities is also important to attain tissue engineering applications in a broader range. GelMA-based hydrogel constructs have not been completely applied for clinical applications due to limitations concerning their biosafety associated with using UV radiations used for crosslinking which can damage cellular DNA by oxidation and also could result in sudden inheritable changes. Assessing the biosafety for both cell-free and cell encapsulated GelMA-nanomaterial platforms is thus of utmost importance to ensure safe and effective usage for its future biomedical applications.The authors declare no competing financial interest.


Malignant paediatric nervous system tumours, such as Medulloblastoma, Neuroblastoma and ATRT commonly harbour tumour cells with stem-like features which are highly tumorigenic and resistant to conventional cancer therapies. These tumours can exhibit high lethality and may result in severe sequelae, including cognitive and motor deficits that significantly affect patients’ quality of life. Oncolytic virotherapy is a novel therapy class that exploits viruses that preferentially infect and destroy tumour cells. These viruses present a unique advantage in targeting highly heterogeneous cancers, such as nervous system tumours, as they possess a secondary mechanism of action through which they induce a tumour-specific immune response. Clinical studies employing oncolytic virotherapy have in general reported low toxicity and minimal adverse effects, deeming oncolytic virotherapy as a potentially attractive and safer intervention against paediatric tumours.The Zika virus (ZIKV) is capable of infecting and destroying neural stem-like cancer cells from human embryonal Central Nervous System (CNS) tumours in vitro and in vivo. Infection of CNS tumour cells with ZIKV effectively inhibits tumour metastasis in mice and, in some cases, induces complete tumour remission. Neuroblastoma arises from immature nerve cells and multiple Neuroblastoma cell lines are susceptible to ZIKV infection and oncolysis. These initial findings have demonstrated the potential for a ZIKV-based virotherapy against paediatric nervous system tumours and warrants examination into the molecular mechanisms through which ZIKV executes its oncolytic ability. My research goal is to elucidate the mechanisms which are of paramount importance for ZIKV-induced oncolysis of brain tumour and Neuroblastoma cells. Utilising global expression omics profiling of ZIKV infection and mapping of viral protein-host protein interactions will identify these mechanisms both at the cellular pathway and molecular levels. These collectively will inform our understanding of how we can employ a future ZIKV-based virotherapy against paediatric nervous system tumours.


Outpatient peer support groups have been demonstrated to help patients reintegrate with the community and improve self-acceptance following burn injury. Despite this, there is little data examining who desires participation. This is especially true for minority and socio-disadvantaged populations. The purpose of this study is to examine factors that influence desire to participate in burn survivor groups and actual participation rates.Patients attending outpatient clinic were asked about participation in burn survivor group, interest in joining a group, and administered National Institute of Health Patient-Reported Outcomes Measurement Information System (PROMIS) Managing Emotions (ME) and Managing Social Interactions (MSI) questionnaires. Patient demographics, total body surface area burned (TBSA), initial hospital length of stay (LOS), and surgical intervention were collected from the medical record. While controlling for age and gender, indicators of injury severity and scores on PROMIS questionnaires were each examined for associations with survivor group interest using Firth or standard binary logistic regression.70 patients completed surveys in English  and Spanish . Current or past participation in burn survivor group was low , with greater interest in joining burn survivor group . Most patients interested in burn survivor group were Spanish speaking . Interest in joining a burn survivor group was associated with all collected measures of injury severity (Table 1). Scores on ME and MSI were not significantly associated with burn survivor group interest .There is a gap between interest and participation in burn survivor group, particularly among Spanish speaking patients. Patients with increase in TBSA, LOS, and undergoing surgery were more likely to express interest in burn survivor group participation. Interestingly, patients’ self-reported outcomes on emotional distress and interactions with others were not related to interest in burn survivor group.


For couples affected by HIV, and serodifferent couples in particular, pregnancy desire is often juxtaposed against the risk of HIV transmission between the couple and the potential neonate leading to thinking about measures to minimize risk of HIV transmission. We assess the use of fertility awareness methods [FAM] and evaluate the drivers of alignment between indicators of fertility and sexual behavior among HIV-serodifferent couples desiring pregnancy.HIV-serodifferent couples from Thika, Kenya were enrolled into an open-label pilot evaluation of safer conception strategies. Women responded to daily 7-item short message service [SMS] surveys on FAM and sexual activity. Menstrual cycles were categorized as having condomless sex aligned, not aligned, or partially aligned to the predicted peak fertility. We used binomial logit models with generalized estimating equations to assess alignment between condomless sex during peak fertility days and FAM results. We used Cox proportional hazards to compare pregnancy incidence among months with sex and peak fertility aligned and mis-aligned.A total of 6929 SMS surveys across 252 menstrual cycles of 65 women were included. Reporting “sticky” cervical mucus  and positive ovulation prediction kit [OPK] result  were associated with increased likelihood of alignment of condomless sex during peak fertility. Pregnancy incidence was statistically similar among periods with sex aligned and not aligned with peak fertility.Among women engaged in a comprehensive safer conception program, a moderate percentage of women aligned condomless sex and predicted peak fertility days at least once. While FAM, particularly cervical mucus and OPK, are an inexpensive option for couples to consider using as a component of their safer conception strategies, antiretroviral-based strategies remain important to minimize risk. HIV-serodifferent couples are partnerships where one partner is living with HIV and the other is not. For these couples, the desire to become pregnant can be in contrast to the risk of transmitting HIV either to the baby or between the couple. Safer conception strategies can be used to reduce the risk of HIV transmission during pregnancy attempts, and they include fertility awareness methods [FAM] which involve timing condomless sex to the time when a woman is most likely to become pregnant during her menstrual cycle, called the peak fertility window. FAM include tracking menstrual cycles, monitoring cervical mucus, measuring daily body temperature, and using an ovulation prediction kit [OPK].Seventy-four HIV-serodifferent couples were enrolled in a clinical study in Kenya. Each wanted to become pregnant and all were trained to track FAM. Women reported their sexual activity and FAM indicators via text message every day.Sexual activity was better aligned to the peak fertility window when women found their cervical mucus to be “sticky” and if they had a positive OPK result. The use of these FAM indicators to align condomless sex with peak fertility did not affect pregnancy outcomes.While FAM indicators are an inexpensive option for HIV-serodifferent couples to consider using as a part of their safer conception strategies, other HIV prevention strategies remain important to minimize risk.For heterosexual couples who desire pregnancy, augmenting the probability of conception by estimating days with peak fertility and having sex on those days is an important method to achieve reproductive goals. Fertility awareness methods (FAM) are used to identify peak fertility days and optimally time condomless sex to these days to improve chances of conceiving . For peoFor couples affected by HIV, and serodifferent couples in particular, pregnancy desire is often juxtaposed against the risk of HIV transmission between the couple and the potential neonate leading to thinking about measures to minimize risk of HIV transmission. HIV-serodifferent couples can employ any number of “safer conception” strategies to reduce HIV risk during pregnancy attempts, including timing of condomless sex to peak fertility and use of condoms at all other times, antiretroviral therapy (ART), pre-exposure prophylaxis (PrEP), and/or reproductive assistance technologies when fertility may be compromised –10. TailSeveral studies have assessed the use of FAM indicators to improve the time-to-pregnancy , 13, andThe Safer Conception Intervention for Partners  was an open-label pilot evaluation of a comprehensive safer conception package that enrolled 74 heterosexual HIV-serodifferent couples between March 2016 to April 2018 in Thika, Kenya : 0–1), and were in their partnerships for 2 years (IQR: 1–3 years). Approximately half of the women were living with HIV (47.7% and 53.3% were HIV-negative and in a partnership with a person living with HIV) and, of these women, two-thirds were virally suppressed , similar pregnancy incidence rate pattern was observed across alignment categories Table . Across Among HIV-serodifferent couples engaged in a comprehensive safer conception program to minimize HIV transmission during pregnancy attempts, a moderate percentage (71%) of women aligned condomless sex to predicted peak fertility periods at least once. After training women and couples on the use of FAM indicators, there was high uptake of the use of FAM methods reported via SMS (65 of 74 couples). Across similar settings in Africa, couples and women desiring pregnancy are not often aware of safer conception methods or have low uptake of methods such as timed intercourse –23. TherSticky cervical mucus and positive OPK results allow women to self-estimate their peak fertility period and reporting these characteristics was associated with timing of condomless sex in our cohort. Other studies have found that cervical mucus status is the strongest indictor of upcoming fertility days and that self-tracking mucus characteristics reduces the time-to-pregnancy , 24. OurPrevious fecundity studies have demonstrated that tracking FAM improves fertility rates , 12, 13.Our analysis had several limitations including that this was a small sample of couples attempting pregnancy and may not be broadly generalizable. Further, there may be misclassification of the time-varying characteristics since study visits were not timed to menstrual cycles and most data points for time-varying confounding factors straddled two consecutive cycles. We conducted sensitivity analyses to assess whether there was a meaningful effect of misclassification when matching menstrual cycle data to in-clinic interviews, and we found a similar magnitude and same direction for all associations. Finally, the pregnancy incidence rates may indicate misreporting of sexual activity or misclassification of fertility periods since the aligned definition of sex only within the peak fertility period had a lower pregnancy incidence than partial or non-aligned.Safer conception interventions improve reproductive health outcomes of heterosexual HIV-serodifferent couples attempting pregnancy and uphold the reproductive rights of HIV-serodifferent couples to satisfy their desires to attempt pregnancy . The FAM


OBJECTIVES/GOALS: Parents’ empathy toward their children affects their parenting, which can in turn impact child outcomes. Although parental empathy is theoretically distinct from trait empathy, current literature relies on largely self-report measures of parents’ trait empathy. Thus, the current study evaluated new analog assessments of parental empathy. METHODS/STUDY POPULATION: One parental empathy analog measure  was created based on parents’ responses to open ended prompts describing scenarios that elicit different emotions  in children. These responses were used to create short scripts. A second analog task  was created using 20 sec audio clips of children expressing the different emotions wherein participants respond with how they feel hearing the emotions and separately, how they believe the child feels. After an initial pilot, both versions of the EMPAT-E were administered to 120 families enrolled in a prospective longitudinal study. Parents completed self-report measures of trait empathy and parental empathy, as well as the EMPAT-ES and EMPAT-EA analog tasks. RESULTS/ANTICIPATED RESULTS: Internal consistency of both the EMPAT-ES and EMPAT-EA tasks are expected to be robust, demonstrating the reliability of these novel assessments of parental empathy. Results are also expected to demonstrate the construct and convergent validity of both analog tasks. These new measures of parental empathy are expected to be significantly associated with measures of trait empathy. Specifically, parents’ responses indicating how they believe the child feels in the analog are expected to be strongly related to their reported emotion recognition abilities and responses indicating how analog items made parents feel are expected to be related to parents’ empathic concern. Finally, parents’ responses to the analog tasks are anticipated to be strongly associated with parents’ self-reported parental empathy. DISCUSSION/SIGNIFICANCE OF IMPACT: Valid, novel assessments of parental empathy can impact the parenting literature as well as community intervention and prevention efforts with parents. Such analog tasks can bolster parenting research but they may also be translated to the community setting as a training tool wherein parents are taught new skills that promote more positive parenting.