Altered DNA repair creates novel Alu/Alu repeat-mediated deletions.

Alu elements are the most abundant source of nonallelic homology that influences genetic instability in the human genome. When there is a DNA double-stranded break, the Alu element's high copy number, moderate length and distance and mismatch between elements uniquely influence recombination processes. We utilize a reporter-gene assay to show the complex influence of Alu mismatches on Alu-related repeat-mediated deletions (RMDs). The Alu/Alu heteroduplex intermediate can result in a nonallelic homologous recombination (HR). Alternatively, the heteroduplex can result in various DNA breaks around the Alu elements caused by competing nucleases. These breaks can undergo Alt-nonhomologous end joining to cause deletions focused around the Alu elements. Formation of these heteroduplex intermediates is largely RAD52 dependent. Cells with low ERCC1 levels utilize more of these alternatives resolutions, while cells with MSH2 defects tend to have more RMDs with a specific increase in the HR events. Therefore, Alu elements are expected to create different forms of deletions in various cancers depending on a number of these DNA repair defects.

Alu insertion variants alter mRNA splicing.

RNA splicing is a highly regulated process dependent on sequences near splice sites. Insertions of Alu retrotransposons can disrupt splice sites or bind splicing regulators. We hypothesized that some common inherited polymorphic Alu insertions are responsible for splicing QTLs (sQTL). We focused on intronic Alu variants mapping within 100 bp of an alternatively used exon and screened for those that alter splicing. We identify five loci, 21.7% of those assayed, where the polymorphic Alu alters splicing. While in most cases the Alu promotes exon skipping, at one locus the Alu increases exon inclusion. Of particular interest is an Alu polymorphism in the CD58 gene. Reduced CD58 expression is associated with risk for developing multiple sclerosis. We show that the Alu insertion promotes skipping of CD58 exon 3 and results in a frameshifted transcript, indicating that the Alu may be the causative variant for increased MS risk at this locus. Using RT-PCR analysis at the endogenous locus, we confirm that the Alu variant is a sQTL for CD58. In summary, altered splicing efficiency is a common functional consequence of Alu polymorphisms including at least one instance where the variant is implicated in disease risk. This work broadens our understanding of splicing regulatory sequences around exons.

Home but still engaged: participation in social activities among the homebound.

PURPOSE: Participation in social and community activities that require leaving one's home is important to older adults; however, many older adults have difficulty or are unable to leave their dwellings, and little is known from national samples about issues related to remaining active outside the home or the barriers faced by these older adults. DESIGN AND METHODS: We used the National Health and Aging Trends Study, a nationally representative study of older adults (n = 7197), to understand the following: (1) the importance that homebound and semi-homebound adults place on involvement in social or community activities, (2) their current level of involvement, and (3) reported barriers to participation. RESULTS: Despite the heavy burden of functional limitations, depression, pain, and falls, homebound adults reported that activities outside the home were important to them ranging from 25.2 % (attend clubs) to 70.0 % (visit family). Similarly, semi-homebound older adults had a strong interest in such participation, including visiting friends and family (81.8 %), attending religious services (72.6 %), and going out for enjoyment (72.5 %). Many homebound adults reported health (42.9-64.1 % depending on the activity) and transportation (12.2-18.2 %) as barriers to participation. Semi-homebound adults also identified health (23.8-41.0 %) and transportation (6.5-10.2 %) as participation barriers. IMPLICATIONS: This information can be useful in designing community programs that will foster meaningful social and community engagement for older adults, which may improve their quality of life.

The Effects of Social Support on Physical Functioning in Older African Americans: Longitudinal Results from the Baltimore Study of Black Aging.

INTRODUCTION: Compared with other racial/ethnic groups, African Americans have higher rates of chronic conditions and suffer a disproportionate burden of disability. We aimed to examine the effects of social support on physical functioning among older African Americans. METHODS: We analyzed a sample of 448 urban, community-dwelling, older African Americans (aged 48-98 years) from the Baltimore Study of Black Aging. Baseline physical functioning was collected between 2006 and 2008 (wave 1), and change in physical functioning was collected between 2009 and 2011 (wave 2), physical functioning was assessed by self-reported limitations in 7 activities of daily living-eating, dressing, grooming, walking, bathing, using the toilet, and transferring in and out of bed-using a binary variable to indicate whether the individual had difficulty performing each specific activity. Social support was measured by how frequently participants provided/received goods and services, financial assistance, transportation, companionship, advice, or encouragement (never [0], rarely [1], sometimes [2], frequently [3]). Negative binomial regression models were used to test the effects of social support given, received, and a ratio (support received/support given) on physical functioning for those who improved and those who declined in physical functioning. RESULTS: Participants reported physical functioning at wave 1 (1.24, standard deviation [SD] = 1.98) and at wave 2 (0.34, SD = 0.83). Average social support given was 7.49 (SD = 3.26), and average social support received was 7.81 (SD = 3.17). Those who improved in physical function gave less social support and had lower social support ratios; social support received had no effect. Those who remained stable or declined in physical function gave more social support; neither social support received nor social ratio had an effect. CONCLUSION: Social support given and social support received as well as the ratio should be considered when seeking to understand how physical functioning changes over time among older African Americans.

Relationship Between Chronic Conditions and Disability in African American Men and Women.

BACKGROUND: Race differences in chronic conditions and disability are well established; however, little is known about the association between specific chronic conditions and disability in African Americans. This is important because African Americans have higher rates and earlier onset of both chronic conditions and disability than white Americans. METHODS: We examined the relationship between chronic conditions and disability in 602 African Americans aged 50 years and older in the Baltimore Study of Black Aging. Disability was measured using self-report of difficulty in activities of daily living (ADL). Medical conditions included diagnosed self-reports of asthma, depressive symptoms, arthritis, cancer, diabetes, cardiovascular disease (CVD), stroke, and hypertension. RESULTS: After adjusting for age, high school graduation, income, and marital status, African Americans who reported arthritis (women: odds ratio (OR)=4.87; 95% confidence interval(CI): 2.92-8.12; men: OR=2.93; 95% CI: 1.36-6.30) had higher odds of disability compared to those who did not report having arthritis. Women who reported major depressive symptoms (OR=2.59; 95% CI: 1.43-4.69) or diabetes (OR=1.83; 95% CI: 1.14-2.95) had higher odds of disability than women who did not report having these conditions. Men who reported having CVD (OR=2.77; 95% CI: 1.03-7.41) had higher odds of disability than men who did not report having CVD. CONCLUSIONS: These findings demonstrate the importance of chronic conditions in understanding disability in African Americans and how it varies by gender. Also, these findings underscore the importance of developing health promoting strategies focused on chronic disease prevention and management to delay or postpone disability in African Americans. PUBLICATION INDICES: Pubmed, Pubmed Central, Web of Science database.

The Relationship between Pain, Disability, and Sex in African Americans.

Older African Americans consistently report diminished capacities to perform activities of daily living (ADL) compared with other racial groups. The extent to which bodily pain is related to declining abilities to perform ADL/ADL disability in African Americans remains unclear, as does whether this relationship exists to the same degree in African American men and women. For nurses to provide optimal care for older African Americans, a better understanding of the relationship between bodily pain and ADL disability and how it may differ by sex is needed. The aim of this study was to examine whether pain, age, education, income, marital status and/or comorbid conditions were associated with ADL disabilities in older African American women and men. This was a cross-sectional descriptive study. The sample included 598 participants (446 women, 152 men) from the first wave of the Baltimore Study on Black Aging. African American women (odds ratio [OR] = 4.06; 95% confidence interval [CI] 2.63-6.26) and African American men (OR = 6.44; 95% CI = 2.84-14.57) who reported bodily pain had greater ADL disability than those who did not report bodily pain. Having two or more comorbid conditions also was significantly associated with ADL disability in African American women (OR = 3.95; 95% CI: 2.09-7.47). Further work is needed to understand pain differences between older African American women and men to develop interventions that can be tailored to meet the individual pain needs of both groups.

Associations among pain, depression, and functional limitation in low-income, home-dwelling older adults: An analysis of baseline data from CAPABLE.

A complex relationship exists between pain, depression, and functional limitation. These conditions, which substantially impact health care spending and quality of life, remain under-addressed in the current system of health care delivery, particularly among low-income and minority populations. This analysis uses baseline assessment data from CAPABLE, an ongoing randomized controlled trial (RCT), to examine associations between pain, depression, and functional limitation among a sample of low-income, community-dwelling elders with functional limitations. Linear regression revealed close associations between depression, pain, and activity of daily living (ADL) limitation. Mediation analyses indicated that depression fully mediated the relationship between pain intensity and functional limitation and partially mediated the relationship between pain interference and depression. Past research has shown that these conditions may be easily identified using validated assessment tools and effectively addressed through the introduction of interdisciplinary interventions. Several recommendations are presented for clinicians and health care organizations.

Measuring gender satisfaction among women aging with paralytic polio.

In this study we tested the Gendered Outcome Scale as a measure of gender satisfaction among 295 women aging with the disabling effects of paralytic polio. Principal components analysis, reliability analyses, and content validity were analyzed on the scale. The scale had a Cronbach's alpha of.90. Younger women had more gender satisfaction (r =.181, p <.01), and women who had greater disability had greater gender satisfaction. (r = -.127, p <.05). The results support that the scale is a valid and reliable measure for determing gender satisfaction. Further work is needed to test the scale in diversified samples.

Work related injury among aging women.

This article reports the experiences of women aged 55 to 75 with mobility impairments who attributed aspects of their limitations to workplace injuries and provides insight into worker's compensation policies. The study sample includes Mexican American (MA) and non-Hispanic White (NHW) women aged 55 to 75 who participated in a 4-year ethnographic study of disablement. Ninety-two of the 122 participants in the study attributed aspects of their functional limitations to employment, and their experiences were analyzed using data from 354 meetings. Using Lipscomb and colleagues' conceptual model of work and health disparities, the women's experiences were grouped into three categories according to type of injury, assistance gained, and the consequences of a workplace injury; the results have broad implications for policies that influence aging outcomes. Workplace injuries causing permanent functional limitations compound the effects of age and gender on employment outcomes. Policies addressing health disparities should consider work related influences.

Discrimination, acculturation and other predictors of depression among pregnant Hispanic women.

OBJECTIVE: The purpose of our study was to examine the effects of socioeconomic status, acculturative stress, discrimination, and marginalization as predictors of depression in pregnant Hispanic women. DESIGN: A prospective observational design was used. SETTING: Central and Gulf coast areas of Texas in obstetrical offices. PARTICIPANTS: A convenience sample of 515 pregnant, low income, low medical risk, and self-identified Hispanic women who were between 22-24 weeks gestation was used to collect data. MEASURES: The predictor variables were socioeconomic status, discrimination, acculturative stress, and marginalization. The outcome variable was depression. RESULTS: Education, frequency of discrimination, age, and Anglo marginality were significant predictors of depressive symptoms in a linear regression model, F (6, 458) = 8.36, P<.0001. Greater frequency of discrimination was the strongest positive predictor of increased depressive symptoms. CONCLUSIONS: It is important that health care providers further understand the impact that age and experiences of discrimination throughout the life course have on depressive symptoms during pregnancy.

The use of saturation in qualitative research.

Understanding qualitative research is an important component of cardiovascular nurses' practice and allows them to understand the experiences, stories, and perceptions of patients with cardiovascular conditions. In understanding qualitative research methods, it is essential that the cardiovascular nurse understands the process of saturation within qualitative methods. Saturation is a tool used for ensuring that adequate and quality data are collected to support the study. Saturation is frequently reported in qualitative research and may be the gold standard. However, the use of saturation within methods has varied. Hence, the purpose of this column is to provide insight for the cardiovascular nurse regarding the use of saturation by reviewing the recommendations for which qualitative research methods it is appropriate to use and how to know when saturation is achieved. In understanding saturation, the cardiovascular nurse can be a better consumer of qualitative research.

The meaning of gender while aging with paralytic polio.

The purpose of this article is to report the influence of gender on aging with childhood onset paralytic polio. The hermeneutic phenomenological exploration of gender was done using multiple qualitative interviews with 25 women, age 55 to 75 years of age, who had polio since before 14 years of age. We noted three themes: (a) the movement of her body, (b) integrating body and gender, and (c) gender discrepancies. Findings are discussed in the context of gendered expectations and the women's bodies.

Factors Associated With Physical Activity in Latina Women: A Systematic Review.

The purpose of this systemic literature review is to unveil a greater understanding of Physical Activity in Latinas. We used PubMed and PsycInfo databases to search for articles published between 1991 and August 2016, examining physical activity and its correlates exclusively in adult Latinas. Only 21 primary studies met the inclusion criteria. Although physical activity derives from body movements in various domains, the leisure domain led the focus of research interest. The use of self-reports, cross-sectional design, and the ecological framework predominated. Only one study included examining the occupational domain, albeit as disaggregate in studies with a general physical activity approach. Occupational physical activity showed negative associations with education and acculturation. Positive associations were found between leisure-time physical activity, education, acculturation, and perceived health status. Despite the limited evidence to reach overall conclusions, this review uncovered methodological challenges and opportunities to advance knowledge about physical activity in Latinas.

Ethnic Differences in the Effects of Naloxone on Sustained Evoked Pain: A Preliminary Study.

Ethnic differences in pain response have been well documented, with non-Hispanic Black (NHB) participants reporting enhanced clinical pain and greater laboratory-evoked pain sensitivity to a variety of quantitative sensory testing (QST) methods compared to non-Hispanic Whites (NHW). One potential mechanism that may contribute to these disparities is differential functioning of endogenous pain-regulatory systems. To evaluate endogenous opioid (EO) mechanisms in pain responses, we examined group differences in response to tonic capsaicin pain following double-blinded crossover administration of saline and the opioid antagonist, naloxone. Ten percent topical capsaicin cream and a thermode were applied to the dorsum of the non-dominant hand, maintaining a constant temperature of 40°C for 90 min. Naloxone (0.1 mg/kg) or saline placebo was administered at the 25 min mark and post-drug pain intensity ratings were obtained every 5 min thereafter. As an index of EO function, blockade effects were derived for each participant, reflecting the difference between mean post-drug pain intensity ratings under the saline versus naloxone conditions, with higher positive scores reflecting greater EO inhibition of pain. Thirty-nine healthy, young individuals (19 non-Hispanic Black [NHB], 20 non-Hispanic White [NHW]) participated. Group difference in EO function were identified, with NHB participants displaying lower EO function scores (mean=-10.8, SD=10.1) as compared to NHW participants (mean=-0.89, SD=11.5; p=0.038). NHB participants experienced significant paradoxical analgesia with naloxone. Thirty five percent of the NHW participants showed a positive blockade effect indicating EO analgesia (i.e., an increase in pain with naloxone), while only 10% of the NHB participants exhibited evidence of EO analgesia. These findings suggest differential functioning of the endogenous opioid pain regulatory system between NHB and NHW participants. Future research is warranted to examine whether these differences contribute to the disparities observed in clinical pain between groups.

Factors associated with disability among middle-aged and older African American women with osteoarthritis.

BACKGROUND: Middle-aged and older African American women experience disproportionate rates of functional limitations and disability from osteoarthritis (OA) compared to other racial ethnic groups; however, little is known about what factors contribute to this disparity within African American women. OBJECTIVE: To examine factors associated with physical function and disability among African American women ages 50-80 with OA using the disablement process model. METHODS: This descriptive study included 120 African American women with OA from the Southwestern region of the United States. Regression techniques were used to model the correlates of physical function and disability and to test a mediation model. RESULTS: BMI and pain severity were significantly related to functional limitations. Depressive symptoms mediated the relationship between racial discrimination and disability. CONCLUSION: Biological, intra-individual, and extra-individual factors are related to disablement outcomes in this sample of African American women, which is consistent with theory suggesting the need for treatment coupled with environmental modifications. This study can inform the development of future bio-behavioral interventions.

How to accommodate women with mobility limitations in biological studies.

People with disabilities should be routinely included in research studies if there is no specific reason for their exclusion. Regardless, they may be inadvertently excluded because of the procedures of the study. By conducting a community-based biological study with women aging with mobility limitations, these authors gained further understanding of their accommodation needs during research participation. The women aging with mobility limitations offered specific physical, cultural, or environmental needs that could have influenced the methods, procedures, and possible outcomes involved when conducting a biological study with this community living population. The authors and participants identified methodological challenges for women with mobility impairments within three key areas: recruitment procedures, laboratory procedures, and community-based data collection. The authors propose possible solutions to these identified challenges. It is our hope that this will begin a larger dialogue on how to routinely accommodate people with disabilities in biological research studies.

The pain and suffering of a Mexican American woman with mobility impairment.

There is a dearth of literature examining how adversity shapes the experiences of pain and/or suffering in middle-aged Mexican American women. The purpose of this qualitative descriptive study was to understand pain and suffering from a life course perspective as described by a Mexican American woman aging with early-onset mobility impairment. This Hispanic woman experienced episodes of abuse and rejection over the life course, which may have significantly influenced her pain and suffering experience in adulthood. This adds to the literature on how adversity influences later life pain experience and provides insight on why pharmacological treatment alone may not be as successful as a holistic intervention.

A qualitative analysis of life course adjustment to multiple morbidity and disability.

The accumulation of limitations over the life course requires that women readapt to environmental barriers they encounter over time. The purpose of this qualitative case study was to detail the life experiences associated with living with mobility, cognitive, and sensory loss experienced by a woman and her sister who participated in an ongoing ethnographic study of mobility impairment in women. In-depth interviews were subjected to thematic, life course analysis. A family case study was interpreted as an exemplar for aging with early-onset disability into multiple morbidity, which was described as a series of loss, recovery, and reengagement. Within the case study, the participant suggested that because her functional limitations were not accommodated earlier in life due to societal and family-level disadvantage, these limitations were more difficult to adjust to in later years.

A study of the health literacy needs of people with visual impairments.

The purpose of this mixed methods study was to understand preferences surrounding health literacy for 18 men and women with permanent and severe visual impairment (VI). Participants completed demographic questions--the National Eye Institute Visual Function Questionnaire (NEI-VFQ)--and 1 semi-structured interview to ascertain views on obtaining, processing, and understanding health information. Overall, the sample had low total eye health scores on the NEI-VFQ--indicating that the sample represented a group with severe visual impairments. The sample mentioned multiple health promotion topics of interest and types of devices used to gain information. They also described multiple barriers to health information, which could be eliminated. Implications for intervention development and technology use are provided.

End of life and women aging with a disability.

Approximately 21 million noninstitutionalized Americans with physical disabilities will ultimately face end-of-life [EOL] issues. Studies have documented disparate care and poorer outcomes for persons with preexisting disabilities who have life-limiting illnesses, which raises the question of how EOL experiences may differ for these individuals. The aim of this qualitative, descriptive study was to explore how EOL issues might emerge within the life stories of women aging with functional disabilities. Interview data were obtained from a larger, ongoing ethnographic study focused on the creation of an explanatory model of health disparities of disablement in women with mobility impairment. Each participant was interviewed three to four times using a life-course perspective that captures life trajectories and transitions experienced over time. For this analysis, 41 interviews were selected from 20 participants who discussed issues related to death and dying. Content analysis of the data revealed five analytic categories: death as a signpost, impact of others' deaths, deaths that affected personal insights and choice, EOL possibilities, and a personal brush with death. EOL issues were manifested in a variety of ways that revealed both determination to remain as independent as possible within the context of declining functional ability and uncertainty regarding the future.