A longitudinal study of social, religious, and spiritual capital and physical and emotional functioning in a national sample of African-Americans.

The present study builds on prior research by examining the moderating relationships between different types of capital on physical functioning, emotional functioning, and depressive symptoms using a 2.5-year longitudinal design with a national sample of African-American adults. Results indicated a significant T1 social capital × T1 religious capital interaction such that among low T1 religious capital participants, those with high T1 social capital had lower T2 physical functioning than those with lower T1 social capital. There was also a marginally significant T1 social capital × T1 spiritual capital interaction suggesting that among low T1 spiritual capital participants, those with higher T1 social capital reported a decline in depressive symptoms compared to those with lower T1 social capital. Future research and implications for intervention and policy development are discussed.

Heterozygous GBA D409V and ATP13a2 mutations do not exacerbate pathological α-synuclein spread in the prodromal preformed fibrils model in young mice.

Autophagic dysregulation and lysosomal impairment have been implicated in the pathogenesis of Parkinson's disease, partly due to the identification of mutations in multiple genes involved in these pathways such as GBA, SNCA, ATP13a2 (also known as PARK9), TMEM175 and LRRK2. Mutations resulting in lysosomal dysfunction are proposed to contribute to Parkinson's disease by increasing α-synuclein levels, that in turn may promote aggregation of this protein. Here, we used two different genetic models-one heterozygous for a mutated form of the GBA protein (D409V), and the other heterozygous for an ATP13a2 loss-of-function mutation, to test whether these mutations exacerbate the spread of α-synuclein pathology following injection of α-synuclein preformed fibrils in the olfactory bulb of 12-week-old mice. Contrary to our hypothesis, we found that mice harboring GBA D409V+/- and ATP13a2+/- mutations did not have exacerbated behavioral impairments or histopathology (α-synuclein, LAMP2, and Iba1) when compared to their wildtype littermates. This indicates that in the young mouse brain, neither the GBA D409V mutation or ATP13a2 loss-of-function mutation accelerate the spread of α-synuclein pathology. As a consequence, we postulate that these mutations increase Parkinson's disease risk only by acting in one of the initial, upstream events in the Parkinson's disease pathogenic process. Further, the mutations, and the molecular pathways they impact, appear to play a less important role once the pathogenic process has been triggered and therefore do not specifically influence α-synuclein pathology spread.

A longitudinal examination of social support as a mediator of the personality-health relationship in a national sample of African Americans.

The present study investigates whether social support mediates the relationship between personality traits and health among African Americans over a five-year period, filling a gap in the literature on longitudinal tests of the personality-health association. Data were collected from a national probability sample of African American adults (N = 200). Personality was assessed at Time 1 (T1), social support was assessed 2.5 years later (T2), and physical functioning was examined 5 years (T3) after T1. Telephone surveys included measures of the Five Factor Model personality traits (T1), social support (T2), and physical functioning (T3). Results suggested that relationships between the T1 personality traits and T3 physical functioning were not mediated by T2 social support. Secondary analyses found that among all T1 personality traits, higher openness and lower neuroticism uniquely predicted higher T2 social support. Further, among T1 personality traits, higher conscientiousness uniquely predicted better T3 physical functioning. This information may be useful to healthcare providers and community members in developing prevention and intervention strategies for African Americans.

Meaning in Life Predicts Decreased Depressive Symptoms and Increased Positive Affect over Time but Does Not Buffer Stress Effects in a National Sample of African-Americans.

Few studies have specifically focused on meaning in life in African Americans and many important questions remain, including whether effects of meaning in life are direct or moderated by levels of stress. In a national sample of 909 African Americans, we tested meaning in life as a prospective predictor of changes in depressive symptoms and positive affect over a 2.5-year period. Controlling for demographics and hassles, meaning in life predicted decreased depressive symptoms and increased positive affect across the span of 2.5 years. Moderation effects were not found for hassles, age, or income. Gender moderated the effect of meaning on positive affect such that effects were stronger for women than for men. These results suggest that, for African Americans, meaning in life appears to robustly protect against future depressive symptoms and promote positive affect over time unaffected by amount of stress experienced or most demographic factors.

Unique contribution of education to behavioral and psychosocial antecedents of health in a national sample of African Americans.

Education has demonstrated consistent links with many aspects of physical health and is theorized to relate to a variety of behavioral and psychosocial antecedents of health that may ultimately account for these associations. However, many of these associations and the extent to which they manifest specifically for African Americans have not been thoroughly tested. We examined associations of education-distinct from income-with established behavioral and psychosocial antecedents of health in a national sample of African Americans. Education favorably related to many behavioral (e.g., fruit/vegetable intake, lifetime smoking) and psychosocial (e.g., self-efficacy, personality traits, self-esteem, psychological well-being) antecedents of health, but not to all. Some evidence of stronger salutary relations of education for women was found. Results suggest that, for African Americans, education is generally favorably associated with an array of behavioral and psychosocial antecedents of physical health, partially explaining health disparities and providing a point of intervention moving forward.

Biochemical Profiling of the Brain and Blood Metabolome in a Mouse Model of Prodromal Parkinson's Disease Reveals Distinct Metabolic Profiles.

Parkinson's disease is the second most common neurodegenerative disease. In the vast majority of cases the origin is not genetic and the cause is not well understood, although progressive accumulation of α-synuclein aggregates appears central to the pathogenesis. Currently, treatments that slow disease progression are lacking, and there are no robust biomarkers that can facilitate the development of such treatments or act as aids in early diagnosis. Therefore, we have defined metabolomic changes in the brain and serum in an animal model of prodromal Parkinson's disease. We biochemically profiled the brain tissue and serum in a mouse model with progressive synucleinopathy propagation in the brain triggered by unilateral injection of preformed α-synuclein fibrils in the olfactory bulb. In total, we accurately identified and quantified 71 metabolites in the brain and 182 in serum using 1H NMR and targeted mass spectrometry, respectively. Using multivariate analysis, we accurately identified which metabolites explain the most variation between cases and controls. Using pathway enrichment analysis, we highlight significantly perturbed biochemical pathways in the brain and correlate these with the progression of the disease. Furthermore, we identified the top six discriminatory metabolites and were able to develop a model capable of identifying animals with the pathology from healthy controls with high accuracy (AUC (95% CI) = 0.861 (0.755-0.968)). Our study highlights the utility of metabolomics in identifying elements of Parkinson's disease pathogenesis and for the development of early diagnostic biomarkers of the disease.

Personality, Social Capital, and Depressive Symptomatology Among African Americans.

The present study examined the relationship between social capital and depressive symptoms and the moderating role of the Big Five personality constructs in a national sample of African American adults. Data were collected from a national probability sample of 803 African American men and women using a telephone survey including measures of the Big Five personality traits, social capital, and depressive symptomatology. Most interestingly, there was evidence for Personality X Social Capital interactions on depressive symptoms. Higher social capital was related to lower depressive symptomology among persons with low conscientiousness, low extraversion, or high neuroticism. However, social capital was significantly but not as strongly related to depressive symptoms among those with high conscientiousness, high extraversion, or low neuroticism. This study reinforces the importance of personality traits when considering potential protective health effects of social capital in understanding depressive symptoms. This information may be useful to practitioners and community members in prevention and treatment.

Intrastriatal injection of pre-formed mouse α-synuclein fibrils into rats triggers α-synuclein pathology and bilateral nigrostriatal degeneration.

Previous studies demonstrate that intrastriatal injections of fibrillar alpha-synuclein (α-syn) into mice induce Parkinson's disease (PD)-like Lewy body (LB) pathology formed by aggregated α-syn in anatomically interconnected regions and significant nigrostriatal degeneration. The aim of the current study was to evaluate whether exogenous mouse α-syn pre-formed fibrils (PFF) injected into the striatum of rats would result in accumulation of LB-like intracellular inclusions and nigrostriatal degeneration. Sprague-Dawley rats received unilateral intrastriatal injections of either non-fibrillized recombinant α-syn or PFF mouse α-syn in 1- or 2- sites and were euthanized at 30, 60 or 180 days post-injection (pi). Both non-fibrillized recombinant α-syn and PFF α-syn injections resulted in phosphorylated α-syn intraneuronal accumulations (i.e., diffuse Lewy neurite (LN)- and LB-like inclusions) with significantly greater accumulations following PFF injection. LB-like inclusions were observed in several areas that innervate the striatum, most prominently the frontal and insular cortices, the amygdala, and the substantia nigra pars compacta (SNpc). α-Syn accumulations co-localized with ubiquitin, p62, and were thioflavin-S-positive and proteinase-k resistant, suggesting that PFF-induced pathology exhibits properties similar to human LBs. Although α-syn inclusions within the SNpc remained ipsilateral to striatal injection, we observed bilateral reductions in nigral dopamine neurons at the 180-day time-point in both the 1- and 2-site PFF injection paradigms. PFF injected rats exhibited bilateral reductions in striatal dopaminergic innervation at 60 and 180 days and bilateral decreases in homovanillic acid; however, dopamine reduction was observed only in the striatum ipsilateral to PFF injection. Although the level of dopamine asymmetry in PFF injected rats at 180 days was insufficient to elicit motor deficits in amphetamine-induced rotations or forelimb use in the cylinder task, significant disruption of ultrasonic vocalizations was observed. Taken together, our findings demonstrate that α-syn PFF are sufficient to seed the pathological conversion and propagation of endogenous α-syn to induce a progressive, neurodegenerative model of α-synucleinopathy in rats.

Participant Retention in a Longitudinal National Telephone Survey of African American Men and Women.

OBJECTIVE: The purpose of this article is to describe participant demographic factors related to retention, and to report on retention strategies in a national study of African Americans re-contacted 2.5 years after an initial baseline telephone interview. DESIGN & SETTING: The Religion and Health in African Americans (RHIAA) study was originally developed as a cross-sectional telephone survey to examine relationships between religious involvement and health-related factors in a national sample of African Americans. The cohort was re-contacted on average of 2.5 years later for a follow-up interview. PARTICIPANTS: RHIAA participants were 2,803 African American men (1,202) and women (1,601). INTERVENTIONS: RHIAA used retention strategies consistent with recommendations from Hunt and White. Participants also received a lay summary of project findings. MAIN OUTCOME MEASURES: Retention at the follow-up interview. RESULTS: Retention rates ranged from 39%- 41%. Retained participants tended to be older and female. In age- and sex-adjusted analyses, retained participants were more educated, single, and in better health status than those not retained. There was no difference in religious involvement in adjusted analyses. CONCLUSIONS: Although overall retention rates are lower than comparable longitudinal studies, RHIAA was not originally designed as a longitudinal study and so lacked a number of structures associated with long-term studies. However, this project illustrates the feasibility of conducting lengthy cold call telephone interviews with an African American population and helps to identify some participant factors related to retention and study strategies that may aid in retention.

Social integration and health insurance status among African American men and women.

Using 2010 national data, we investigate the relationship between social integration and health insurance for African American adults. During the previous year 21.6% of men and 19.8% of women lacked continuous health insurance. The effect of marital status, income, and employment on insurance coverage differed by age and gender. Additionally, frequency of church attendance was positively associated with continuous health insurance for women aged 51-64. Spiritual/religious identity was marginally associated with insurance status for men aged 36-50. As provisions of the Affordable Care Act take effect, implementation programs should expand enrollment efforts to include the conjugal unit and the church.

Decreasing tropomyosin phosphorylation rescues tropomyosin-induced familial hypertrophic cardiomyopathy.

Studies indicate that tropomyosin (Tm) phosphorylation status varies in different mouse models of cardiac disease. Investigation of basal and acute cardiac function utilizing a mouse model expressing an α-Tm protein that cannot be phosphorylated (S283A) shows a compensated hypertrophic phenotype with significant increases in SERCA2a expression and phosphorylation of phospholamban Ser-16 (Schulz, E. M., Correll, R. N., Sheikh, H. N., Lofrano-Alves, M. S., Engel, P. L., Newman, G., Schultz Jel, J., Molkentin, J. D., Wolska, B. M., Solaro, R. J., and Wieczorek, D. F. (2012) J. Biol. Chem. 287, 44478-44489). With these results, we hypothesized that decreasing α-Tm phosphorylation may be beneficial in the context of a chronic, intrinsic stressor. To test this hypothesis, we utilized the familial hypertrophic cardiomyopathy (FHC) α-Tm E180G model (Prabhakar, R., Boivin, G. P., Grupp, I. L., Hoit, B., Arteaga, G., Solaro, R. J., and Wieczorek, D. F. (2001) J. Mol. Cell. Cardiol. 33, 1815-1828). These FHC hearts are characterized by increased heart:body weight ratios, fibrosis, increased myofilament Ca(2+) sensitivity, and contractile defects. The FHC mice die by 6-8 months of age. We generated mice expressing both the E180G and S283A mutations and found that the hypertrophic phenotype was rescued in the α-Tm E180G/S283A double mutant transgenic animals; these mice exhibited no signs of cardiac hypertrophy and displayed improved cardiac function. These double mutant transgenic hearts showed increased phosphorylation of phospholamban Ser-16 and Thr-17 compared with the α-Tm E180G mice. This is the first study to demonstrate that decreasing phosphorylation of tropomyosin can rescue a hypertrophic cardiomyopathic phenotype.

Tropomyosin dephosphorylation results in compensated cardiac hypertrophy.

Phosphorylation of tropomyosin (Tm) has been shown to vary in mouse models of cardiac hypertrophy. Little is known about the in vivo role of Tm phosphorylation. This study examines the consequences of Tm dephosphorylation in the murine heart. Transgenic (TG) mice were generated with cardiac specific expression of α-Tm with serine 283, the phosphorylation site of Tm, mutated to alanine. Echocardiographic analysis and cardiomyocyte cross-sectional area measurements show that α-Tm S283A TG mice exhibit a hypertrophic phenotype at basal levels. Interestingly, there are no alterations in cardiac function, myofilament calcium (Ca(2+)) sensitivity, cooperativity, or response to ß-adrenergic stimulus. Studies of Ca(2+) handling proteins show significant increases in sarcoplasmic reticulum ATPase (SERCA2a) protein expression and an increase in phospholamban phosphorylation at serine 16, similar to hearts under exercise training. Compared with controls, the decrease in phosphorylation of α-Tm results in greater functional defects in TG animals stressed by transaortic constriction to induce pressure overload-hypertrophy. This is the first study to investigate the in vivo role of Tm dephosphorylation under both normal and cardiac stress conditions, documenting a role for Tm dephosphorylation in the maintenance of a compensated or physiological phenotype. Collectively, these results suggest that modification of the Tm phosphorylation status in the heart, depending upon the cardiac state/condition, may modulate the development of cardiac hypertrophy.

Tropomyosin de-phosphorylation in the heart: what are the consequences?

The focus of this review is on the very recent work we have conducted that addresses the molecular, morphological, and physiological significance of cardiac tropomyosin phosphorylation in the heart. We employ transgenic mice to address questions of how cardiomyocytes and the whole heart respond when the tropomyosin phosphorylation site (Ser283) is converted to a non-phosphorylatable amino acid (Ala). We address the phenotype of these mice during normal development and in response to acute cardiac stress (transaortic coarctation). In addition, we also examined how transgenic mice encoding the altered tropomyosin phosphorylation site (Ser283Ala) would respond to chronic cardiac stress through an encoded hypertrophic cardiomyopathy mutation (Glu180Gly). These studies are the first to address the in vivo significance of tropomyosin phosphorylation in the heart. In this review manuscript, we report the recent findings of these investigations.

Development of the men's prostate awareness church training: church-based workshops for African American men.

This article describes the development of a spiritually based intervention to increase informed decision making for prostate cancer screening through African American churches. The intervention used spiritually themed health messages, incorporated women as supportive health partners, and included a health information technology component. The Men's Prostate Awareness Church Training Project followed a community-based participatory research process to develop educational materials, and training for 40 community health advisors to implement the 4-part prostate health workshop series that will be implemented in 20 churches. Implications are discussed for designing culturally relevant interventions to reduce prostate cancer disparities impacting African American men.

Air pollution nanoparticle and alpha-synuclein fibrils synergistically decrease glutamate receptor A1, depending upon nPM batch activity.

Background: Epidemiological studies have variably linked air pollution to increased risk of Parkinson's disease (PD). However, there is little experimental evidence for this association. Alpha-synuclein (α-syn) propagation plays central roles in PD and glutamate receptor A1 (GluA1) is involved in memory and olfaction function. Methods: Each mouse was exposed to one of three different batches of nano-particulate matter (nPM) (300 µg/m3, 5 h/d, 3 d/week), collected at different dates, 2017-2019, in the same urban site. After these experiments, these nPM batches were found to vary in activity. C57BL/6 female mice (3 mo) were injected with pre-formed murine α-synuclein fibrils (PFFs) (0.4 µg), which act as seeds for α-syn aggregation. Two exposure paradigms were used: in Paradigm 1, PFFs were injected into olfactory bulb (OB) prior to 4-week nPM (Batch 5b) exposure and in Paradigm 2, PFFs were injected at 4th week during 10-week nPM exposure (Batches 7 and 9). α-syn pSer129, microglia Iba1, inflammatory cytokines, and Gria1 expression were measured by immunohistochemistry or qPCR assays. Results: As expected, α-syn pSer129 was detected in ipsilateral OB, anterior olfactory nucleus, amygdala and piriform cortex. One of the three batches of nPM caused a trend for elevated α-syn pSer129 in Paradigm 1, but two other batches showed no effect in Paradigm 2. However, the combination of nPM and PFF significantly decreased Gria1 mRNA in both the ipsi- and contra-lateral OB and frontal cortex for the most active two nPM batches. Neither nPM nor PFFs alone induced responses of microglia Iba1 and expression of Gria1 in the OB and cortex. Conclusion: Exposures to ambient nPM had weak effect on α-syn propagation in the brain in current experimental paradigms; however, nPM and α-syn synergistically downregulated the expression of Gria1 in both OB and cortex.

Assessing the role of spirituality in coping among African Americans diagnosed with cancer.

Spirituality plays an important role in cancer coping among African Americans. The purpose of this study was to report on the initial psychometric properties of instruments specific to the cancer context, assessing the role of spirituality in coping. Items were developed based on a theoretical model of spirituality and qualitative patient interviews. The instruments reflected connections to self, others, God, and the world. One hundred African American cancer survivors completed the instruments by telephone. The instruments showed adequate internal reliability, mixed convergent validity, discriminant validity, and interpretable factor structures.

Assessment of religious and spiritual capital in African American communities.

African American faith communities are an important source of social capital. The present study adapted a theory-based social capital instrument to result in religious (e.g., from organized worship) and spiritual (e.g., from relationship with higher power) capital measures. Data from a national sample of 803 African Americans suggest the instruments have high internal reliability and are distinct from general religiosity. Measurement models confirmed factor structures. Religious capital was positively associated with self-rated health status. Religious and spiritual capital were negatively associated with depressive symptoms, but these associations largely became nonsignificant in multivariate models that controlled for demographic characteristics. An exception is for spiritual capital in the form of community participation, which retained a negative association with depressive symptoms. These instruments may have applied value for health promotion research and practice in African American communities.

Disability and Health in African Americans: Population Research and Implications for Occupational Therapy Community-Based Practice.

Background: Population-based research and community-based interventions are integral to occupational therapy's scope of practice, yet they are underdeveloped in actual implementation. Therefore, this paper focuses on some health challenges facing the African American population, guided by the Person-Environment-Occupation-Performance Model. Method: Using data from an observational cross-sectional nationwide telephone survey of African American adults, we examined differences between African Americans who are receiving disability payments (RDP) and those who are employed full time (FTE) on several physical health behaviors and psychosocial health indicators. We further compared the differences between African Americans RDP versus those FTE on those physical health behaviors and psychosocial health indicators across five US regions. Results: Findings suggest that African Americans RDP are engaging in fewer positive physical health behaviors and experiencing worse psychosocial health compared to their counterparts FTE. There are also nuanced regional variations in the differences between African Americans RDP and FTE in physical health behaviors and psychosocial health indicators. Conclusion: This research highlighted some health challenges of African Americans RDP and FTE using a regional lens, demonstrating the value of OT population-based research. There is a need for OT population-specific community-based practice to address the health disparities of underserved and minority populations, such as African Americans.

A novel automated morphological analysis of Iba1+ microglia using a deep learning assisted model.

There is growing evidence for the key role of microglial functional state in brain pathophysiology. Consequently, there is a need for efficient automated methods to measure the morphological changes distinctive of microglia functional states in research settings. Currently, many commonly used automated methods can be subject to sample representation bias, time consuming imaging, specific hardware requirements and difficulty in maintaining an accurate comparison across research environments. To overcome these issues, we use commercially available deep learning tools Aiforia® Cloud (Aifoira Inc., Cambridge, MA, United States) to quantify microglial morphology and cell counts from histopathological slides of Iba1 stained tissue sections. We provide evidence for the effective application of this method across a range of independently collected datasets in mouse models of viral infection and Parkinson's disease. Additionally, we provide a comprehensive workflow with training details and annotation strategies by feature layer that can be used as a guide to generate new models. In addition, all models described in this work are available within the Aiforia® platform for study-specific adaptation and validation.

Role of religious involvement and spirituality in functioning among African Americans with cancer: testing a mediational model.

The present study tested a mediational model of the role of religious involvement, spirituality, and physical/emotional functioning in a sample of African American men and women with cancer. Several mediators were proposed based on theory and previous research, including sense of meaning, positive and negative affect, and positive and negative religious coping. One hundred patients were recruited through oncologist offices, key community leaders and community organizations, and interviewed by telephone. Participants completed an established measure of religious involvement, the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-SP-12 version 4), the Positive and Negative Affect Schedule (PANAS), the Meaning in Life Scale, the Brief RCOPE, and the SF-12, which assesses physical and emotional functioning. Positive affect completely mediated the relationship between religious behaviors and emotional functioning. Though several other constructs showed relationships with study variables, evidence of mediation was not supported. Mediational models were not significant for the physical functioning outcome, nor were there significant main effects of religious involvement or spirituality for this outcome. Implications for cancer survivorship interventions are discussed.