The National Institutes of Health INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Project: Accelerating research discoveries for people with Down syndrome across the lifespan.

The National Institutes of Health (NIH) has a long-standing history of support for research in Down syndrome (DS). In response to a 2018 congressional directive for a trans-NIH initiative to address medical issues in DS, NIH launched the INCLUDE Project (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE). Reflecting the three INCLUDE components of basic science research, cohort development, and clinical trials, the Project has published funding opportunities to address conditions such as immune disorders and Alzheimer's disease. Due to a steady expansion in dedicated funding over its first 5 years, INCLUDE has invested $258 M in over 250 new research projects. INCLUDE also supports training initiatives to expand the number and diversity of investigators studying DS. NIH has funded an INCLUDE Data Coordinating Center that is collecting de-identified clinical information and multi-omics data from research participants for broad data sharing and secondary analyses. Through the DS-Connect® registry, INCLUDE investigators can access recruitment support. The INCLUDE Research Plan articulates research goals for the program, with an emphasis on diversity of research participants and investigators. Finally, a new Cohort Development Program is poised to increase the impact of the INCLUDE Project by recruiting a large DS cohort across the lifespan.

Differences in the longitudinal change of behaviours related to dementia in long-term care: a growth mixture modelling approach.

BACKGROUND: There is still a need for more information about the different trajectories of responsive behaviours that people living with dementia present in long-term care homes (LTC). OBJECTIVE: This study identified subgroups of individuals with similar trajectories of responsive behaviours related to dementia in LTC and evaluated the role of demographic variables, depressive symptomatology, social engagement, cognitive functioning, and activities of daily living (ADL) on class membership. METHODS: Growth mixture models were run using data from the Continuing Care Reporting System. RESULTS: Results suggest that change in responsive behaviours is best represented by seven classes of trajectories. The largest class was composed of individuals who presented the lowest frequency of behaviours upon entry in LTC that increased at a slow linear rate. The other classes were composed of individuals who presented different frequencies of behaviours upon entry in LTC and varying rates of change (e.g., individuals who presented a low frequency of behaviours upon entry in LTC that increased at a linear rate followed by a decrease in the later months, individuals who presented a high frequency of responsive behaviours upon entry in LTC and that remained stable). Cognitive functioning, social engagement, depressive symptomatology, and ADL were markers of class membership. CONCLUSIONS: These findings can help identify individuals at increased risk of presenting a high frequency of responsive behaviours and highlight interventions that could decrease behaviours in LTC.

Mass Testing for SARS-CoV-2 in 16 Prisons and Jails - Six Jurisdictions, United States, April-May 2020.

Preventing coronavirus disease 2019 (COVID-19) in correctional and detention facilities* can be challenging because of population-dense housing, varied access to hygiene facilities and supplies, and limited space for isolation and quarantine (1). Incarcerated and detained populations have a high prevalence of chronic diseases, increasing their risk for severe COVID-19-associated illness and making early detection critical (2,3). Correctional and detention facilities are not closed systems; SARS-CoV-2, the virus that causes COVID-19, can be transmitted to and from the surrounding community through staff member and visitor movements as well as entry, transfer, and release of incarcerated and detained persons (1). To better understand SARS-CoV-2 prevalence in these settings, CDC requested data from 15 jurisdictions describing results of mass testing events among incarcerated and detained persons and cases identified through earlier symptom-based testing. Six jurisdictions reported SARS-CoV-2 prevalence of 0%-86.8% (median = 29.3%) from mass testing events in 16 adult facilities. Before mass testing, 15 of the 16 facilities had identified at least one COVID-19 case among incarcerated or detained persons using symptom-based testing, and mass testing increased the total number of known cases from 642 to 8,239. Case surveillance from symptom-based testing has likely underestimated SARS-CoV-2 prevalence in correctional and detention facilities. Broad-based testing can provide a more accurate assessment of prevalence and generate data to help control transmission (4).

Ageism and COVID-19: what does our society's response say about us?

The goal of this commentary is to highlight the ageism that has emerged during the COVID-19 pandemic. Over 20 international researchers in the field of ageing have contributed to this document. This commentary discusses how older people are misrepresented and undervalued in the current public discourse surrounding the pandemic. It points to issues in documenting the deaths of older adults, the lack of preparation for such a crisis in long-term care homes, how some 'protective' policies can be considered patronising and how the initial perception of the public was that the virus was really an older adult problem. This commentary also calls attention to important intergenerational solidarity that has occurred during this crisis to ensure support and social-inclusion of older adults, even at a distance. Our hope is that with this commentary we can contribute to the discourse on older adults during this pandemic and diminish the ageist attitudes that have circulated.

Clinical markers to predict progression from acute to chronic kidney disease in Mesoamerican nephropathy.

An epidemic of chronic kidney disease (CKD) of unknown etiology, known as Mesoamerican Nephropathy (MeN), has been ongoing in Latin America for at least two decades. MeN primarily affects young adults without traditional CKD risk factors, and agricultural workers are disproportionately afflicted. We previously identified an acute phase of MeN that involves acute kidney injury (AKI) with tubulointerstitial nephritis and systemic inflammation. Because clinical disease progression in MeN is not yet understood, we sought to determine clinical predictors for progression from acute MeN to CKD. Through ongoing surveillance in Nicaragua, local physicians reported cases of acute MeN and CKD among agricultural workers. We analyzed clinical data collected during the acute MeN encounter to identify factors associated with progression to CKD. From February 2015 to May 2017, 586 agricultural workers (median age 27.8 years, 90% male) presented with acute MeN. The majority had a normal baseline creatinine, and leukocyturia (98.8%) and peripheral leukocytosis (80.7%) were common. Ultimately, 49 (8.4%) progressed to CKD, the majority of those within 6 months. CKD was attributed to MeN in all cases, and none had diabetes or hypertension. The strongest predictors of CKD progression were anemia and paresthesias at presentation, while leukocytosis was associated with renal recovery. Clinical markers of acute MeN may help clinicians identify patients at high risk for rapid progression to CKD, which in turn can inform early clinical management. Future studies should seek to determine the underlying etiology of disease and identify optimal interventions to interrupt the pathophysiologic process of MeN.

Intraocular Penetration of a vNAR: In Vivo and In Vitro VEGF165 Neutralization.

Variable new antigen receptor domain (vNAR) antibodies are novel, naturally occurring antibodies that can be isolated from naïve, immune or synthetic shark libraries. These molecules are very interesting to the biotechnology and pharmaceutical industries because of their unique characteristics related to size and tissue penetrability. There have been some approved anti-angiogenic therapies for ophthalmic conditions, not related to vNAR. This includes biologics and chimeric proteins that neutralize vascular endothelial growth factor (VEGF)165, which are injected intravitreal, causing discomfort and increasing the possibility of infection. In this paper, we present a vNAR antibody against human recombinant VEGF165 (rhVEGF165) that was isolated from an immunized Heterodontus francisci shark. A vNAR called V13, neutralizes VEGF165 cytokine starting at 75 µg/mL in an in vitro assay based on co-culture of normal human dermal fibroblasts (NHDFs) and green fluorescence protein (GFP)-labeled human umbilical vein endothelial cells (HUVECs) cells. In the oxygen-induced retinopathy model in C57BL/6:Hsd mice, we demonstrate an endothelial cell count decrease. Further, we demonstrate the intraocular penetration after topical administration of 0.1 µg/mL of vNAR V13 by its detection in aqueous humor in New Zealand rabbits with healthy eyes after 3 h of application. These findings demonstrate the potential of topical application of vNAR V13 as a possible new drug candidate for vascular eye diseases.

Provision of dementia-related services in Canada: a comparative study.

BACKGROUND: Dementia is common, particularly among older adults, and is one of the major causes of dependency later in life. We sought to provide an overview and comparison of key services related to dementia care as the disease progresses in three large Canadian healthcare centres. METHODS: We identified family physicians, geriatric specialists, and dementia case managers from three major population centres in Canada with universal healthcare coverage. Using a standardized longitudinal dementia case vignette, participants were interviewed on services they would provide at each stage of the disease. We used principles of content analysis to generate codes and identify themes; appropriate time frames from the vignette fitting the necessary provision of services were derived from the Canadian consensus statement and determined in consultation with clinical experts. Proportions of participants that identified dementia-related care services were analyzed at each time point of the vignette using chi-square tests. RESULTS: Thirty-four healthcare providers from Calgary (Alberta), Edmonton (Alberta), and Ottawa (Ontario) participated. Review of our data identified seven overarching themes of dementia-related care services. Services provided in the community setting include future planning and related services, educational and social support services, and home care and respite services. Although all providers consistently identified educational and social support services (e.g. the Alzheimer Society) within the appropriate time frame, the provision of other services was variable. The proportion of providers reporting potential access of future planning services was significantly different across the three sites (Calgary, 91.7 %; Edmonton; 58.3 %; and Ottawa, 30.0 %), p = 0.012. Also, the proportion of providers that identified day program services were significantly different across the three sites (Calgary, 100.0 %; Edmonton, 91.7 %; and Ottawa, 60.0 %), p = 0.023 according to a chi-square test. CONCLUSIONS: We found important types of variability in service delivery among different regions in Canada for a typical patient with dementia and their family caregiver. Health systems can be calibrated by aligning services from different settings to appropriate time points in the vignette, which illustrates the dynamic course of service delivery and opportunities for improvement throughout the disease trajectory.

Perceptions of family and staff on the role of the environment in long-term care homes for people with dementia.

BACKGROUND: Disruptive behaviors are frequent and often the first predictor of institutionalization. The goal of this multi-center study was to explore the perceptions of family and staff members on the potential contribution of environmental factors that influence disruptive behaviors and quality of life of residents with dementia living in long-term care homes. METHODS: Data were collected using 15 nominal focus groups with 45 family and 59 staff members from eight care units. Groups discussed and created lists of factors that could either reduce disruptive behaviors and facilitate quality of life or encourage disruptive behaviors and impede the quality of life of residents. Then each participant individually selected the nine most important facilitators and obstacles. Themes were identified from the lists of data and operational categories and definitions were developed for independent coding by four researchers. RESULTS: Participants from both family and staff nominal focus groups highlighted facility, staffing, and resident factors to consider when creating optimal environments. Human environments were perceived to be more important than physical environments and flexibility was judged to be essential. Noise was identified as one of the most important factors influencing behavior and quality of life of residents. CONCLUSION: Specialized physical design features can be useful for maintaining quality of life and reducing disruptive behaviors, but they are not sufficient. Although they can ease some of the anxieties and set the stage for social interactions, individuals who make up the human environment are just as important in promoting well-being among residents.

Using the performance arts to address a "methods gap" in dementia research.

INTRODUCTION: Traditional methods of research have frequently failed to accommodate the communication difficulties experienced by a significant proportion of residents living in long-term care. In dementia research, specifically, there is cause for more collaborative, creative ways of working. METHODS: The Linking Lives Through Care study is a performance-based narrative inquiry that will take place in a long-term care setting and will bring together all three members of the care triad - residents who are living with dementia, family members and personal support workers - to explore relational care from multiple positions and perspectives. DISCUSSION: In this article, we discuss the design choices and creative measures taken to ensure a more inclusive research environment, specifically for those participants who are cognitively frail and/or may find it difficult to express their views using just words.

Caring for the caregiver: Why policy must shift from addressing needs to enabling caregivers to flourish.

Policies supporting caregivers ("caregiver policies") are limited in the extent to which they meet the needs of those who care for others. Where policies do exist, they focus on relieving the burdens associated with caring or the needs of the person they care for, rather than consider the holistic needs of the caregiver that would enable them to flourish. We argue that the established approach to caregiver policies reflects a policy failure, requiring a reassessment of current practice related to caregiver support. Often, caregiver policies target the care recipient rather than the caregiver's needs. Through a consultative exercise, we identified five areas of need that existing caregiver policies touch upon. Yet current approaches remain piecemeal and inadequate in a global context. Caregiver policies should not just relieve burden to the extent that caregivers can continue in the role, but they should support caregivers to flourish, and future work may benefit from drawing on related frameworks from positive psychology, such as the PERMA™ model; this is important for both policymakers and researchers.

Group Randomized Trial of Healthy Eating and Gardening Intervention in Navajo Elementary Schools (Yéego!).

Introduction: Few healthy eating, school-based interventions have been rigorously evaluated in American Indian communities. Gardening and healthy eating are priorities in the Navajo Nation. Collaborations between researchers and local partners supported the design and implementation of this project. Design: The Yéego! Healthy Eating and Gardening Study was a group-randomized controlled trial to evaluate a school-based healthy eating and gardening intervention in 6 schools in the Navajo Nation. Schools were randomized 1:2 to intervention or comparison. Setting/participants: The Shiprock and Tsaile/Chinle areas in the Navajo Nation were selected. Elementary schools were screened for eligibility. All students in third and fourth grades were invited to participate in the assessments. Intervention: Delivered during 1 school year in the intervention schools, the intervention included a culturally relevant nutrition and gardening curriculum and a school garden. Main outcome measures: Student self-efficacy for eating fruits and vegetables, student self-efficacy for gardening, and student healthy foods score from a modified Alternative Healthy Eating Index were assessed in third and fourth graders at the beginning and end of a school year affected by the COVID-19 pandemic. Primary analyses used repeated measures linear mixed models accounting for students nested within schools to estimate the intervention effect and 95% CIs. Results: Students in the intervention schools had self-efficacy scores for eating fruits and vegetables that were 0.22 points greater (95% CI=0.04, 0.41) than those in the comparison schools, although the student healthy foods score increased in the intervention schools by 2.0 (95% CI=0.4, 3.6); the differential change was modest at 1.7 (95% CI=-0.3, 3.7). The self-efficacy to grow fruits and vegetables in the school garden increased among those in the intervention schools (OR=1.92; 95% CI=1.02, 3.63) but not significantly more than it increased in the comparison schools (OR=1.29; 95% CI=0.60, 2.81). Conclusions: The intervention was efficacious in improving self-efficacy for eating fruits and vegetables among third- and fourth-grade students over a school year. The findings warrant further evaluation of the intervention in larger-group randomized trials with schools in Navajo communities. Trial registration: This study is registered at clinicaltrials.gov NCT03778021.

Potential Therapeutic Applications of Synthetic Conotoxin s-cal14.2b, Derived from Californiconus californicus, for Treating Type 2 Diabetes.

The FDA's approval of peptide drugs such as Ziconotide or Exendin for pain relief and diabetes treatment, respectively, enhanced the interest to explore novel conotoxins from Conus species venom. In general, conotoxins can be used in pathologies where voltage-gated channels, membrane receptors, or ligands alter normal physiological functions, as in metabolic diseases such as Type 2 diabetes. In this study, the synthetic cal14.2b (s-cal14.2b) from the unusual Californiconus californicus demonstrated bioactivity on NIT-1 insulinoma cell lines stimulating insulin secretion detecting by high performance liquid chromatography (HPLC). Accordingly, s-cal14.2b increased the CaV1.2/1.3 channel-current by 35 ± 4% with a recovery τ of 10.3 ± 4 s in primary cell culture of rat pancreatic ß-cells. The in vivo results indicated a similar effect of insulin secretion on mice in the glucose tolerance curve model by reducing the glucose from 500 mg/dL to 106 mg/dL in 60 min, compared to the negative control of 325 mg/dL at the same time. The PET-SCAN with radiolabeling 99mTc-s-cal14.2b demonstrated biodistribution and accumulation in rat pancreas with complete depuration in 24 h. These findings show the potential therapeutic use of s-cal14.2b in endocrinal pathologies such as early stages of Type 2 Diabetes where the pancreas's capability to produce insulin is still effective.

Meanings, functions, and experiences of living at home for individuals with dementia at the critical point of relocation.

The sociophysical home environment is an integral component of everyday coping, self-identity, and well-being for individuals with dementia; however, residential discontinuity is a common experience for many of these individuals. This article examined the meanings, functions, and experiences associated with living at home for individuals with dementia at the critical point of relocation to a residential care facility. Qualitative research methods were used to analyze in-depth interviews with 16 individuals with dementia at their homes within 2 months prior to relocation. At the time of relocation, living at home had become a paradoxical experience for most participants. The findings inform practice and policy interventions at both individual and societal levels to help individuals with dementia age in place for as long as possible and to maximize their efforts to "place" themselves in their new living environments after relocation.

Development and Evaluation of a Cancer Literacy Intervention to Promote Mammography Screening Among Navajo Women: A Pilot Study.

PURPOSE: Develop and evaluate a mammography intervention that provides hope about cancer prevention and treatment. DESIGN: Pilot randomized controlled trial. SETTING: Two communities on the Navajo Nation. PARTICIPANTS: Navajo women and support persons. INTERVENTION: Both groups received standard care: one home visit discussing mammography pros/cons and barriers. The treatment group received an intervention based on Navajo language via an additional home visit with health education materials (written and oral) in English and Navajo, including a Navajo Cancer Glossary with a new descriptive phrase for cancer. ANALYSIS: Between control and intervention conditions, we compared baseline sociodemographics; changes from baseline to 3 months on mammography completion and breast cancer literacy scores. MEASURES: (1) intervention feasibility; (2) self- and clinic-reported mammography screening completion; (3) breast cancer literacy. RESULTS: A total of 25 participants were randomly assigned (13 treatment, 12 control), with 7 support persons in each arm. Mean age was 53 years, 90% had a high school degree or higher, 86% spoke Navajo and English. At 3 months, 44% had a clinically verified mammogram. Mammography completion was 57% among those with a support person and 27% among those without (P = .14). Intervention women reported more breast cancer beliefs consistent with mammography (P = .015). CONCLUSIONS: Increases in breast cancer beliefs consistent with mammography show promise. Findings highlight a need to tailor education materials to Navajo culture/language and focus on enhancing support.

Symbolic meaning of relocation to a residential care facility for persons with dementia.

OBJECTIVES: This study explored the perspectives of persons with dementia (PWD) on the meanings and experiences associated with relocation to a residential care facility (RCF). METHODS: A qualitative design was employed, which involved in-depth interviews with 16 PWD at their homes within two months prior to relocation. The work of Strauss and Corbin guided the analysis process. RESULTS: Participants viewed relocation to an RCF as a major residential change and life transition requiring significant adaptive efforts. The experience clearly had a profound personal meaning for the participating PWD, shaped by their unique personal identities, psycho-environmental histories and current living circumstances. However, despite individual variations, four major themes captured the common perspectives and experiences in the sample. Relocation to an RCF: (a) symbolized the end of an era and a long-established way of life; (b) signaled the inevitable downward trajectory of old age; (c) meant living a more protected, dependent, structured and communal lifestyle in a place that is associated with 'hospitality' and 'rest'; and (d) presented a life course challenge that could be dealt with by drawing on one's sense of identity as a 'survivor'. CONCLUSION: The findings raise awareness of the subjective meanings of residential transitions in the experience of aging with dementia, and inform supportive interventions to optimize housing decisions for PWD in order to promote successful adaptation to their new living environments.

Assessing Determinants of Perceived Quality in Transitions for People with Dementia: a Prospective Observational Study.

BACKGROUND: The trajectory of dementia through time is characterized by common transitions which are difficult for persons with dementia (PWDs) and their families and friends. Our study sought to identify determinants for the quality of transition outcomes. METHOD: A 24-month, prospective, longitudinal design identified specific transitions as they occurred in 108 person-with-dementia/caregiver dyads, and assessed the perceived transition quality from the perspective of the caregiver and what we denote as the 'summative' transition quality outcome variable (as explained in the Data Processing section under Methods). RESULTS: Among caregivers and during the authors' deliberations of the summative transition quality outcomes, good transition quality was associated with the PWD's baseline Disability Assessment for Dementia (OR 1.04, 95% CI 1.02-1.06 per increase in percent score based on summative assessments), and with the PWD's higher baseline quality of life scores (OR 1.11, 95% CI 1.05-1.18 per increase in unit of score in QOL-AD based on summative assessments). Caregiver-perceived better outcome quality was associated with lower caregiver burden, (OR 0.97, 95% CI 0.95-0.99 per unit CBI score increase). CONCLUSION: Identifying determinants of successful transitions is feasible and may be translated into practical guidance for use in clinical encounters. Those with worse prior quality of life or worse performance in activities of daily living appear to require specific support during transitions, as do those whose caregivers report higher levels of burden.

Learner-centered nutrition education improves folate intake and food-related behaviors in nonpregnant, low-income women of childbearing age.

BACKGROUND: Recent studies suggest low-income women of childbearing age may be at risk of suboptimal folate intake. OBJECTIVE: To evaluate the effect of learner-centered nutrition education on folate intake and food-related behaviors among nonpregnant, low-income women of childbearing age, compared to education unrelated to nutrition. DESIGN: Participants were randomly assigned by recruitment site to receive either the nutrition lesson or a control lesson about resource management. PARTICIPANTS: Nonpregnant, low-income (< or =185% federal poverty level) women of childbearing age (18 to 45 years, n=155) from five California counties. MAIN OUTCOME VARIABLES: Changes in folate intake and other food-related behaviors. STATISTICAL ANALYSIS: Analysis of covariance, adjusting for baseline responses and potential confounders. RESULTS: Adjusting for baseline, participants who received the nutrition education had greater increases in folate intake and use of the Nutrition Facts label than the control group. Change in intake of specific folate-rich foods differed by ethnicity. Participants in the Special Supplemental Nutrition Program for Women, Infants, and Children who received the nutrition education increased folate intake but had no significant changes in other food-related behaviors. Food stamp recipients who received the nutrition education had no significant changes in folate intake but did increase the frequency of eating more than one kind of vegetable each day, compared to controls. CONCLUSIONS: This study supports the use of learner-centered approaches to nutrition education for low-income audiences, compared to education unrelated to nutrition. Future work is needed to compare learner-centered techniques to traditional pedagogical nutrition education, and to determine whether observed changes from this study persist over the long term.

Folate intake and food-related behaviors in nonpregnant, low-income women of childbearing age.

Information about folate intake among low-income women of childbearing age remains limited. This report presents results from a cross-sectional study of folate intake and food-related behaviors in a sample of low-income, nonpregnant women of childbearing age in California. One hundred fifty-seven nonpregnant, low-income (

Qualitative investigation of factors contributing to effective nutrition education for Navajo families.

OBJECTIVES: Obesity rates in American Indian and Alaskan Native children are a major health threat, yet effective ways to address this remain elusive. Building on an earlier dietary assessment of Navajo Head Start families which indicated a gap in parental nutrition awareness despite a strong program emphasis, the aim of this project was to identify culturally relevant nutrition education strategies for Navajo parents and educators of young children. METHODS: Eight focus group interviews were conducted with 41 parents and early childhood education paraprofessionals to identify contributors to both healthful and unhealthy food ways of Navajo preschoolers. RESULTS: were presented in two community venues to verify the themes and discuss implications. Results Barriers to healthful eating included availability/cost, parenting/control, preferences/habits, time pressures, and knowledge/education. Enablers to healthful eating included the categories of schools/education, and support/modeling. Reactions to these findings during community forums suggested (1) the need for stronger parenting and parental control over the food environment; (2) community-level action to address these barriers; and (3) the need for knowledge and culturally relevant educational strategies for caregivers and children. CONCLUSIONS: Implications for interventions include building upon existing community resources to enhance culturally relevant and respectful parental, family, and community support for affordable and acceptable food experiences and choices for young children and their families.

The effect of a therapy dog on the communication skills of an adult with aphasia.

UNLABELLED: Little evidence-based research has been published within the field of communication disorders on the role of dogs as catalysts for human communication. This single participant study, a point of entry into this realm of research, explores the effects of a therapy dog on the communication skills of a patient with aphasia receiving intensive speech and language therapy within a rehabilitation setting. The researchers conclude that the presence of the dog does have the potential to stimulate both overt social-verbal and social-nonverbal communication. LEARNING OUTCOMES: As a result of this activity the reader will be able to (1) describe the beneficial role of dogs to serve as catalysts for human communication (2) describe ways in which a person with aphasia may be assisted by a therapy dog and (3) become familiar with an animal-assisted therapy (AAT) program set-up for patients with communication disorders within a rehabilitation setting.