The Need to Appear Healthy: Concealment of Chronic Illness, Privacy, and Self-Sufficiency Among Chronically Ill Older Nigerians.

Background and Objectives: Prior research has highlighted the beneficial impact of social networks and social support on older adults' physical and psychosocial well-being. However, the impact of the relationship between chronic illness and social networks on the psychosocial well-being of older Nigerians remains understudied. This study explored how older Nigerians with chronic illnesses navigate the physical, mental, and emotional changes due to their chronic disease diagnosis within their social contexts. Research Design and Methods: The current qualitative study used semistructured in-depth interviews with 19 purposively sampled older adults, aged 50 years and over, chronically ill, and receiving clinical care to examine the role of social networks in how chronically ill older Nigerians cope with their diagnosis. Results: Three main themes reflecting participants' experiences emerged from the findings: (1) closely knit circles, (2) privacy and self-sufficiency, and (3) body image. Results show that chronically ill older Nigerians prefer to keep the knowledge of their conditions strictly within their close family circles. It was considered horrific to inform friends, community members, and religious groups about one's chronic illness. Findings further reveal that the need to appear healthy to one's social network stems from the fear of being discriminated against and attempts to maintain some level of normalcy when interacting with others. Additionally, feelings of inferiority and shame limited their participation in social activities and social network maintenance. Discussion and Implications: We discuss the implications of the results for the mental well-being and quality of life of chronically ill older Nigerians and make recommendations for policies and resources that can improve the well-being of chronically ill Nigerians.

The ATR inhibitor ceralasertib potentiates cancer checkpoint immunotherapy by regulating the tumor microenvironment.

The Ataxia telangiectasia and Rad3-related (ATR) inhibitor ceralasertib in combination with the PD-L1 antibody durvalumab demonstrated encouraging clinical benefit in melanoma and lung cancer patients who progressed on immunotherapy. Here we show that modelling of intermittent ceralasertib treatment in mouse tumor models reveals CD8+ T-cell dependent antitumor activity, which is separate from the effects on tumor cells. Ceralasertib suppresses proliferating CD8+ T-cells on treatment which is rapidly reversed off-treatment. Ceralasertib causes up-regulation of type I interferon (IFNI) pathway in cancer patients and in tumor-bearing mice. IFNI is experimentally found to be a major mediator of antitumor activity of ceralasertib in combination with PD-L1 antibody. Improvement of T-cell function after ceralasertib treatment is linked to changes in myeloid cells in the tumor microenvironment. IFNI also promotes anti-proliferative effects of ceralasertib on tumor cells. Here, we report that broad immunomodulatory changes following intermittent ATR inhibition underpins the clinical therapeutic benefit and indicates its wider impact on antitumor immunity.

A pre-existing Toxoplasma gondii infection exacerbates the pathophysiological response and extent of brain damage after traumatic brain injury in mice.

Traumatic brain injury (TBI) is a key contributor to global morbidity that lacks effective treatments. Microbial infections are common in TBI patients, and their presence could modify the physiological response to TBI. It is estimated that one-third of the human population is incurably infected with the feline-borne parasite, Toxoplasma gondii, which can invade the central nervous system and result in chronic low-grade neuroinflammation, oxidative stress, and excitotoxicity-all of which are also important pathophysiological processes in TBI. Considering the large number of TBI patients that have a pre-existing T. gondii infection prior to injury, and the potential mechanistic synergies between the conditions, this study investigated how a pre-existing T. gondii infection modified TBI outcomes across acute, sub-acute and chronic recovery in male and female mice. Gene expression analysis of brain tissue found that neuroinflammation and immune cell markers were amplified in the combined T. gondii + TBI setting in both males and females as early as 2-h post-injury. Glutamatergic, neurotoxic, and oxidative stress markers were altered in a sex-specific manner in T. gondii + TBI mice. Structural MRI found that male, but not female, T. gondii + TBI mice had a significantly larger lesion size compared to their uninfected counterparts at 18-weeks post-injury. Similarly, diffusion MRI revealed that T. gondii + TBI mice had exacerbated white matter tract abnormalities, particularly in male mice. These novel findings indicate that a pre-existing T. gondii infection affects the pathophysiological aftermath of TBI in a sex-dependent manner, and may be an important modifier to consider in the care and prognostication of TBI patients.

Treatment with the vascular endothelial growth factor-A antibody, bevacizumab, has sex-specific effects in a rat model of mild traumatic brain injury.

Mild traumatic brain injury (mTBI) involves damage to the cerebrovascular system. Vascular endothelial growth factor-A (VEGF-A) is an important modulator of vascular health and VEGF-A promotes the brain's ability to recover after more severe forms of brain injury; however, the role of VEGF-A in mTBI remains poorly understood. Bevacizumab (BEV) is a monoclonal antibody that binds to VEGF-A and neutralises its actions. To better understand the role of VEGF-A in mTBI recovery, this study examined how BEV treatment affected outcomes in rats given a mTBI. Adult Sprague-Dawley rats were assigned to sham-injury + vehicle treatment (VEH), sham-injury + BEV treatment, mTBI + VEH treatment, mTBI + BEV treatment groups. Treatment was administered intracerebroventricularly via a cannula beginning at the time of injury and continuing until the end of the study. Rats underwent behavioral testing after injury and were euthanized on day 11. In both females and males, BEV had a negative impact on cognitive function. mTBI and BEV treatment increased the expression of inflammatory markers in females. In males, BEV treatment altered markers related to hypoxia and vascular health. These novel findings of sex-specific responses to BEV and mTBI provide important insights into the role of VEGF-A in mTBI.

A progressive agenda toward equity in pain care.

Background: There are inconsistencies documenting the pain experience of Black adults and other racially minoritized populations. Often disregarded, pain among these groups is characterized by misconceptions, biases, and discriminatory practices, which may lead to inequitable pain care. Methods: To address this issue, this professional commentary provides an overview of pain reform and the need to declare chronic pain as a critical public health issue, while requiring that equity be a key focus in providing comprehensive pain screening and standardizing epidemiological surveillance to understand the prevalence and incidence of pain. Results and Conclusions: This roadmap is a call to action for all sectors of research, practice, policy, education, and advocacy. More importantly, this progressive agenda is timely for all race and other marginalized groups and reminds us that adequate treatment of pain is an obligation that cannot be the responsibility of one person, community, or institution, but rather a collective responsibility of those willing to service the needs of all individuals.

Definitions, terminology, and related concepts of "racial health equity": a scoping review protocol.

BACKGROUND: In the USA, access to quality healthcare varies greatly across racial and ethnic groups, resulting in significant health disparities. A new term, "racial health equity" (RHE), is increasingly reported in the medical literature, but there is currently no consensus definition of the term. Additionally, related terms such as "health disparities," "health inequities," and "equality" have been inconsistently used when defining RHE. METHODS: The primary purpose of this scoping review is to investigate the current use and underlying concepts used to define racial health equity. The study will address two key questions: (1) "What terminology and definitions have been used to characterize RHE?" and (2) "What knowledge gaps and challenges are present in the current state of RHE research and theory?" The review will collect and analyze data from three sources: (1) websites from key national and international health organizations, (2) theoretical and narrative published articles, and (3) evidence synthesis studies addressing interventions targeting racial health equity and minority stakeholder engagement. DISCUSSION: Defining "racial health equity" and related terminology is the first step to advancing racial health equity within the USA. This review aims to offer an improved understanding of RHE constructs and definitions, bringing greater unity to national racial health equity research efforts across disciplines. SYSTEMATIC REVIEW REGISTRATION: This protocol is registered with the Open Science Framework at https://osf.io/7pvzq .

Sociocultural and Economic Disparities in Physical Therapy Utilization Among Insured Older Adults With Rheumatoid Arthritis.

OBJECTIVE: To examine influences of sociocultural and economic determinants on physical therapy (PT) utilization for older adults with rheumatoid arthritis (RA). METHODS: In these annual cross-sectional analyses between 2012 and 2016, we accessed Medicare enrollment data and fee-for-service claims. The cohort included Medicare beneficiaries with RA based on 3 diagnosis codes or 2 codes plus a disease-modifying antirheumatic drug medication claim. We defined race and ethnicity and dual Medicare/Medicaid coverage (proxy for income) using enrollment data. Adults with a Current Procedural Terminology code for PT evaluation were classified as utilizing PT services. Associations between race and ethnicity and dual coverage and PT utilization were estimated with logistic regression analyses. Potential interactions between race and ethnicity status and dual coverage were tested using interaction terms. RESULTS: Of 106,470 adults with RA (75.1% female; aged 75.8 [SD 7.3] years; 83.9% identified as non-Hispanic White, 8.8% as non-Hispanic Black, 7.2% as Hispanic), 9.6-12.5% used PT in a given year. Non-Hispanic Black (adjusted odds ratio [aOR] 0.77, 95% CI 0.73-0.82) and Hispanic (aOR 0.92, 95% CI 0.87-0.98) individuals had lower odds of PT utilization than non-Hispanic White individuals. Adults with dual coverage (lower income) had lower odds of utilization than adults with Medicare only (aOR 0.44, 95% CI 0.43-0.46). There were no significant interactions between race and ethnicity status and dual coverage on utilization. CONCLUSION: We found sociocultural and economic disparities in PT utilization in older adults with RA. We must identify and address the underlying factors that influence these disparities in order to mitigate them.

A historical review of pain disparities research: Advancing toward health equity and empowerment.

BACKGROUND AND PURPOSE: This theory-guided review draws on 30 years of published data to examine and interrogate the current and future state of pain disparities research. METHODS: Using the Hierarchy of Health Disparity Research framework, we synthesize and present an overview of "three generations" of pain disparities scholarship, while proposing directions for adopting a "fourth generation" that redefines, explains, and theorizes future pain disparities research in a diverse society. DISCUSSION: Prior research has focused on describing the scope of disparities, and throughout the historical context of human existence, racialized groups have been subjected to inadequate pain care. It is imperative that research not only illuminates existing problems but also provides solutions that can be implemented and sustained across varying social milieus. CONCLUSION: We must invest in new theoretical models that expand on current perspectives and ideals that position all individuals at the forefront of justice and equity in their health.

A biopsychosocial approach assessing pain indicators among Black men.

Introduction: The lack of empirical evidence documenting the pain experience of Black men may be the result of social messaging that men are to project strength and avoid any expression of emotion or vulnerability. This avoidant behavior however, often comes too late when illnesses/symptoms are more aggressive and/or diagnosed at a later stage. This highlights two key issues - the willingness to acknowledge pain and wanting to seek medical attention when experiencing pain. Methods: To better understand the pain experience in diverse raced and gendered groups, this secondary data analysis aimed to determine the influence identified physical, psychosocial, and behavioral health indicators have in reporting pain among Black men. Data were taken from a baseline sample of 321 Black men, >40 years old, who participated in the randomized, controlled Active & Healthy Brotherhood (AHB) project. Statistical models were calculated to determine which indicators (somatization, depression, anxiety, demographics, medical illnesses) were associated with pain reports. Results: Results showed that 22% of the men reported pain for more than 30 days, with more than half of the sample being married (54%), employed (53%), and earning an income above the federal poverty level (76%). Multivariate analyses showed that those reporting pain were more likely to be unemployed, earn less income, and reported more medical conditions and somatization tendencies (OR=3.28, 95% CI (1.33, 8.06) compared to those who did not report pain. Discussion: Findings from this study indicate that efforts are needed to identify the unique pain experiences of Black men, while recognizing its impact on their identities as a man, a person of color, and someone living with pain. This allows for more comprehensive assessments, treatment plans, and prevention approaches that may have beneficial impacts throughout the life course.

Interrupting Biases in the Experience and Management of Pain Nurses can help address challenges faced by racially and ethnically diverse patients and caregivers.

This article is part of a series, Supporting Family Caregivers: No Longer Home Alone, published in collaboration with the AARP Public Policy Institute. Results of focus groups, conducted as part of the AARP Public Policy Institute's No Longer Home Alone video project, supported evidence that family caregivers aren't given the information they need to manage the complex care regimens of family members. This series of articles and accompanying videos aims to help nurses provide caregivers with the tools they need to manage their family member's health care at home. The articles in this new installment of the series provide practical information nurses can share with family caregivers of persons living with pain. To use this series, nurses should read the articles first, so they understand how best to help family caregivers. Then they can refer caregivers to the informational tear sheet-Information for Family Caregivers-and instructional videos, encouraging them to ask questions. For additional information, see Resources for Nurses. Cite this article as: Booker, S.Q., et al. Interrupting Biases in the Experience and Management of Pain. Am J Nurs 2022; 122(9): 48-54.

Treatment with vascular endothelial growth factor-A worsens cognitive recovery in a rat model of mild traumatic brain injury.

Mild traumatic brain injury (mTBI) is a common and unmet clinical issue, with limited treatments available to improve recovery. The cerebrovascular system is vital to provide oxygen and nutrition to the brain, and a growing body of research indicates that cerebrovascular injury contributes to mTBI symptomatology. Vascular endothelial growth factor-A (VEGF-A) is a potent promoter of angiogenesis and an important modulator of vascular health. While indirect evidence suggests that increased bioavailability of VEGF-A may be beneficial after mTBI, the direct therapeutic effects of VEGF-A in this context remains unknown. This study therefore aimed to determine whether intracerebroventricular administration of recombinant VEGF-A could improve recovery from mTBI in a rat model. Male and female Sprague-Dawley rats were assigned to four groups: sham + vehicle (VEH), sham + VEGF-A, mTBI + VEH, mTBI + VEGF-A. The mTBI was induced using the lateral impact model, and treatment began at the time of the injury and continued until the end of the study. Rats underwent behavioral testing between days 1 and 10 post-injury, and were euthanized on day 11 for post-mortem analysis. In males, the mTBI + VEGF-A group had significantly worse cognitive recovery in the water maze than all other groups. In females, the VEGF treatment worsened cognitive performance in the water maze regardless of mTBI or sham injury. Analysis of hippocampal tissue found that these cognitive deficits occurred in the presence of gene expression changes related to neuroinflammation and hypoxia in both male and female rats. These findings indicate that the VEGF-A treatment paradigm tested in this study failed to improve mTBI outcomes in either male or female rats.

AZD4625 is a Potent and Selective Inhibitor of KRASG12C.

AZD4625 is a potent, selective, and orally bioavailable inhibitor of oncogenic KRASG12C as demonstrated in cellular assays and in vivo in preclinical cell line-derived and patient-derived xenograft models. In vitro and cellular assays have shown selective binding and inhibition of the KRASG12C mutant isoform, which carries a glycine to cysteine mutation at residue 12, with no binding and inhibition of wild-type RAS or isoforms carrying non-KRASG12C mutations. The pharmacology of AZD4625 shows that it has the potential to provide therapeutic benefit to patients with KRASG12C mutant cancer as either a monotherapy treatment or in combination with other targeted drug agents.

Interrupting Biases in the Experience and Management of Pain.

This article is part of a series, Supporting Family Caregivers: No Longer Home Alone, published in collaboration with the AARP Public Policy Institute. Results of focus groups, conducted as part of the AARP Public Policy Institute's No Longer Home Alone video project, supported evidence that family caregivers aren't given the information they need to manage the complex care regimens of family members. This series of articles and accompanying videos aims to help nurses provide caregivers with the tools they need to manage their family member's health care at home. The articles in this new installment of the series provide practical information nurses can share with family caregivers of persons living with pain. To use this series, nurses should read the articles first, so they understand how best to help family caregivers. Then they can refer caregivers to the informational tear sheet-Information for Family Caregivers-and instructional videos, encouraging them to ask questions. For additional information, see Resources for Nurses.

Targeting the Cerebrovascular System: Next-Generation Biomarkers and Treatment for Mild Traumatic Brain Injury.

The diagnosis, prognosis, and treatment of mild traumatic brain injuries (mTBIs), such as concussions, are significant unmet medical issues. The kinetic forces that occur in mTBI adversely affect the cerebral vasculature, making cerebrovascular injury (CVI) a pathophysiological hallmark of mTBI. Given the importance of a healthy cerebrovascular system in overall brain function, CVI is likely to contribute to neurological dysfunction after mTBI. As such, CVI and related pathomechanisms may provide objective biomarkers and therapeutic targets to improve the clinical management and outcomes of mTBI. Despite this potential, until recently, few studies have focused on the cerebral vasculature in this context. This article will begin by providing a brief overview of the cerebrovascular system followed by a review of the literature regarding how mTBI can affect the integrity and function of the cerebrovascular system, and how this may ultimately contribute to neurological dysfunction and neurodegenerative conditions. We then discuss promising avenues of research related to mTBI biomarkers and interventions that target CVI, and conclude that a clinical approach that takes CVI into account could result in substantial improvements in the care and outcomes of patients with mTBI.

The Intersection of Pain Outcomes and Social Isolation Among African Americans.

There is increasing evidence suggesting the influence social isolation has on health outcomes and mental well-being. Chronic medical conditions, such as pain, have been shown to impact social relationships and isolation among majority populations, but there is little evidence documenting this relationship among African Americans. To address this lack of scholarly work, the current study aimed to examine subjective and objective social isolation, pain interference with daily life, and problems with pain in a sample of African American adults 18 + years of age. Taken from the National Survey of American Life: Coping with Stress in the 21st Century (NSAL), results showed that participants who were objectively isolated from family only were more likely to have a chronic health problem that was associated with increased pain. Data further showed that those reporting subjective isolation from both family and friends experienced greater interference from pain than those who were not isolated from family and friends. Findings from this study acknowledge a larger issue that addresses the impact social isolation has on health, quality of life, and general well-being. Recognizing the influence of such may allow systems to acknowledge the determinants that perpetuate social isolation, while still recognizing the needs of marginalized groups.

Pre-existing Toxoplasma gondii infection increases susceptibility to pentylenetetrazol-induced seizures independent of traumatic brain injury in mice.

Introduction: Post-traumatic epilepsy (PTE) is a debilitating chronic outcome of traumatic brain injury (TBI), and neuroinflammation is implicated in increased seizure susceptibility and epileptogenesis. However, how common clinical factors, such as infection, may modify neuroinflammation and PTE development has been understudied. The neurotropic parasite, Toxoplasma gondii (T. gondii) incurably infects one-third of the world's population. Thus, many TBI patients have a pre-existing T. gondii infection at the time of injury. T. gondii infection results in chronic low-grade inflammation and altered signaling pathways within the brain, and preliminary clinical evidence suggest that it may be a risk factor for epilepsy. Despite this, no studies have considered how a pre-existing T. gondii infection may alter the development of PTE. Methods: This study aimed to provide insight into this knowledge gap by assessing how a pre-existing T. gondii infection alters susceptibility to, and severity of, pentylenetetrazol (PTZ)-induced seizures (i.e., a surrogate marker of epileptogenesis/PTE) at a chronic stage of TBI recovery. We hypothesized that T. gondii will increase the likelihood and severity of seizures following PTZ administration, and that this would occur in the presence of intensified neuroinflammation. To test this, 6-week old male and female C57BL/6 Jax mice were intraperitoneally injected with 50,000 T. gondii tachyzoites or with the PBS vehicle only. At 12-weeks old, mice either received a severe TBI via controlled cortical impact or sham injury. At 18-weeks post-injury, mice were administered 40 mg/kg PTZ and video-recorded for evaluation of seizure susceptibility. Fresh cortical tissue was then collected for gene expression analyses. Results: Although no synergistic effects were evident between infection and TBI, chronic T. gondii infection alone had robust effects on the PTZ-seizure response and gene expression of markers related to inflammatory, oxidative stress, and glutamatergic pathways. In addition to this, females were more susceptible to PTZ-induced seizures than males. While TBI did not impact PTZ responses, injury effects were evident at the molecular level. Discussion: Our data suggests that a pre-existing T. gondii infection is an important modifier of seizure susceptibility independent of brain injury, and considerable attention should be directed toward delineating the mechanisms underlying this pro-epileptogenic factor.

Examining the Association of Pain and Financial Hardship Among Older Men by Race in the United States.

Pain associated with financial hardship among older men varies by race. The purpose of this study was to examine the association of financial hardship with the presence of pain in men 50 years and older by race. Using the Health and Retirement Study (HRS) 2010 wave, bivariate and multivariate logistic regression models were used to assess the association between four financial hardship indicators and total financial hardship as a composite score, and the presence of pain by race. Among White men, the association between the presence of pain and hardship controlling for demographic factors was statistically significant across four indicators and one composite score: ongoing financial hardship (OR = 1.29, 95% CI [1.02, 1.64]), food insecurity (OR = 2.55, 95% CI [1.51, 4.31]), taking less medication due to cost (OR = 2.12, 95% CI [1.40, 3.22]), difficulty paying bills (OR = 1.36, 95% CI [1.07, 1.73]), and total financial hardship (OR = 1.27, 95% CI [1.12, 1.44]). Among African American men, the association between the presence of pain and taking less medication due to cost (OR = 2.99, 95% CI [1.31, 6.85]) was significant. With increasing comorbidities among older adults, particularly African Americans, it is imperative to fully understand the mechanisms of this underexplored area in both the pain and financial hardship literature.