Association between genetic polymorphisms and risk of adolescent idiopathic scoliosis in case-control studies: a systematic review.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is a structural lateral spinal curvature of ≥10° with rotation. Approximately 2%-3% of children across populations are affected with AIS, and this condition is responsible for ~$3 billion in costs within the USA. Although AIS is believed to have a strong genetic contribution, clinical translation of identified genetic variants has stalled. METHODS: The databases MEDLINE (via PubMed), Embase, Google Scholar and Ovid MEDLINE were searched and limited to articles in English. Title and abstract, full-text and data extraction screening was conducted through Covidence, followed by data transfer to a custom REDCap database. Studies containing variant-level data using genome-wide methodology as well as validation studies of genome-wide methods were considered. Quality assessment was conducted using Q-Genie. RESULTS: 33 studies were included, including 9 genome-wide association studies, 4 whole exome sequencing and 20 validation studies. Combined, these studies included data from >35,000 cases and >67,000 controls, not including validation cohorts. Additionally, results from six meta-analyses containing novel cohorts were also reported. All included study cohorts were from populations of primarily East Asian or Caucasian descent. Quality assessment found that overall study quality was high and control group selection was moderate. The highest number of reported associations were in single nucleotide polymorphisms (SNPs) in or near LBX1, LBX1-AS1, GPR126/ADGRG6 or BNC2. CONCLUSION: AIS risk may be influenced by specific SNPs, particularly those in/near LBX1 and GPR126. Translatability of study findings is unknown due to an underrepresentation of most ethnic groups as well as few identified genome-wide studies. Further studies may benefit from increased cohort diversity and thorough evaluation of control cohort groups.

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 .

The (in)visible Brazilians: A perspective review on the need for brain health and dementia research with Brazilian immigrants in the United States.

Introduction: The Brazilian population in the United States (U.S.), a Latinx subgroup, is rapidly growing and aging but remains underrepresented in U.S. health research. In addition to group-specific genetic and environmental risks, Brazilian immigrants and their offspring in the U.S. likely have cumulative risks for health inequities.It is estimated that 71% of Brazilian immigrants in the U.S. are undocumented, which may limit healthcare access/utilization. Furthermore, mental health is reported as a health priority by Brazilian immigrants in the U.S., and there is a lack of research on Alzheimer's disease and related dementia (AD/ADRD) in this population. Methods: We reviewed the scientific literature using traditional (e.g., PubMed) sources and databases generated by U.S. and Brazilian governments, as well as international organizations, and press articles. Results: This perspective review lists recommendations for researchers, health providers, and policymakers to promote greater inclusion of U.S. Brazilian populations in health research and care. The review identifies research areas in need of attention to address health inequities and promote mental/brain health in Brazilian immigrants and their offspring living in the U.S. These research areas are: 1) epidemiological studies to map the prevalence and incidence of mental/brain health conditions; 2) research on aging and AD/ADRD risk factors among Brazilian populations in the U.S.; and 3) the need for greater representation of U.S-residing Brazilian population in other relevant research areas involving genetics, neuropathology, and clinical trials. Conclusions: The recommendation and research efforts proposed should help to pave the way for the development of community-engagement research and to promote mental/brain health education, improvement of mental/brain health and AD/ADRD services, and the development of culturally-informed intervention to the U.S.-residing Brazilian communities. HIGHLIGHTS: The Brazilian population in the United States is growing but is underrepresented in U.S. health research.Approximately 71% of Brazilian immigrants in the United States are undocumented, with an increased risk for health inequities.Mental health is reported as a central health priority by Brazilian immigrants in the United States.There is a lack of research on Alzheimer's disease and other dementias (ADRD) in Brazilian immigrants in the United States.Epidemiological research is needed to map the prevalence/incidence of mental health conditions and ADRD risk factors among Brazilian immigrants in the United States.

Depletion of pyruvate kinase (PK) activity causes glycolytic intermediate imbalances and reveals a PK-TXNIP regulatory axis.

OBJECTIVE: Cancer cells convert more glucose into lactate than healthy cells, what contributes to their growth advantage. Pyruvate kinase (PK) is a key rate limiting enzyme in this process, what makes it a promising potential therapeutic target. However, currently it is still unclear what consequences the inhibition of PK has on cellular processes. Here, we systematically investigate the consequences of PK depletion for gene expression, histone modifications and metabolism. METHODS: Epigenetic, transcriptional and metabolic targets were analysed in different cellular and animal models with stable knockdown or knockout of PK. RESULTS: Depleting PK activity reduces the glycolytic flux and causes accumulation of glucose-6-phosphate (G6P). Such metabolic perturbation results in stimulation of the activity of a heterodimeric pair of transcription factors MondoA and MLX but not in a major reprogramming of the global H3K9ac and H3K4me3 histone modification landscape. The MondoA:MLX heterodimer upregulates expression of thioredoxin-interacting protein (TXNIP) - a tumour suppressor with multifaceted anticancer activity. This effect of TXNIP upregulation extends beyond immortalised cancer cell lines and is applicable to multiple cellular and animal models. CONCLUSIONS: Our work shows that actions of often pro-tumorigenic PK and anti-tumorigenic TXNIP are tightly linked via a glycolytic intermediate. We suggest that PK depletion stimulates the activity of MondoA:MLX transcription factor heterodimers and subsequently, increases cellular TXNIP levels. TXNIP-mediated inhibition of thioredoxin (TXN) can reduce the ability of cells to scavenge reactive oxygen species (ROS) leading to the oxidative damage of cellular structures including DNA. These findings highlight an important regulatory axis affecting tumour suppression mechanisms and provide an attractive opportunity for combination cancer therapies targeting glycolytic activity and ROS-generating pathways.

The association between isometric strength and cognitive function in adults with cerebral palsy.

Background: The literature supports quantifying the maximum force/tension generated by one's forearm muscles such as the hand grip strength (HGS) to screen for physical and cognitive frailty in older adults. Thus, we postulate that individuals with cerebral palsy (CP), who are at higher risk for premature aging, could benefit from tools that objectively measure muscle strength as a functional biomarker to detect frailty and cognitive decline. This study assesses the clinical relevancy of the former and quantifies isometric muscle strength to determine its association with cognitive function in adults with CP. Methods: Ambulatory adults with CP were identified from a patient registry and were enrolled into this study. Peak rate of force development (RFD) and maximum voluntary isometric contraction of the quadriceps were measured using a commercial isokinetic machine, while HGS was collected with a clinical dynamometer. Dominant and non-dominant side were identified. Standardized cognitive assessments, including the Wechsler Memory and Adult Intelligence Scales IV, Short Test of Mental Status, and the Patient-Reported Outcomes Measurement Information System (PROMIS®) were used to evaluate cognitive function. Results: A total of 57 participants (32 females; mean age 24.3 [SD 5.3]; GMFCS levels I-IV) were included in the analysis. Although dominant and non-dominant RFD and HGS measures were associated with cognitive function, non-dominant peak RFD showed the strongest associations with cognitive function. Conclusion: RFD capacity may reflect age-related neural and physical health and could be a better health indicator than HGS in the CP population.

Global rural health disparities in Alzheimer's disease and related dementias: State of the science.

INTRODUCTION: Individuals living in rural communities are at heightened risk for Alzheimer's disease and related dementias (ADRD), which parallels other persistent place-based health disparities. Identifying multiple potentially modifiable risk factors specific to rural areas that contribute to ADRD is an essential first step in understanding the complex interplay between various barriers and facilitators. METHODS: An interdisciplinary, international group of ADRD researchers convened to address the overarching question of: "What can be done to begin minimizing the rural health disparities that contribute uniquely to ADRD?" In this state of the science appraisal, we explore what is known about the biological, behavioral, sociocultural, and environmental influences on ADRD disparities in rural settings. RESULTS: A range of individual, interpersonal, and community factors were identified, including strengths of rural residents in facilitating healthy aging lifestyle interventions. DISCUSSION: A location dynamics model and ADRD-focused future directions are offered for guiding rural practitioners, researchers, and policymakers in mitigating rural disparities. HIGHLIGHTS: Rural residents face heightened Alzheimer's disease and related dementia (ADRD) risks and burdens due to health disparities. Defining the unique rural barriers and facilitators to cognitive health yields insight. The strengths and resilience of rural residents can mitigate ADRD-related challenges. A novel "location dynamics" model guides assessment of rural-specific ADRD issues.

Using an academic-community partnership model to deliver evidence-based falls prevention programs in a metropolitan setting: A community case study.

Background: Prevention is an effective approach for mitigating the negative health outcomes associated with falls in older adults. The Administration for Community Living (ACL) has sponsored the implementation of evidence-based falls prevention programs (EBFPPs) across the United States through cooperative agreement grants to decrease the health and economic burden of falls. Marymount University received two of these grants to deliver three EBFPPs into the northern Virginia region. This community case study describes the development of a collaboration between a university and community-based organizations to adopt and implement multiple evidence-based programming in an area where none previously existed. Methods: Through an academic-community partnership, EBFPPs were introduced to and implemented by senior-focused organizations. Target adopters were senior and community centers, multi-purpose senior services organizations, recreational organizations, and residential facilities serving older adults. The three EBFPPs were (1) Stay Active and Independent for Life (SAIL), (2) a Matter of Balance (MOB) and (3) Otago Exercise Program (OEP). Key interdependent project elements included: (1) fostering ongoing community organization collaboration, (2) introducing programs in the community, (3) growing and sustaining delivery sites, (4) preparing trained program leaders, and (5) building community demand for the programs. Results: From August 2016-June 2022, 5,857 older adults participated in one of the three EBFPPs. SAIL classes were offered at 33 sites and MOB workshops at 31 with over 70% of them occurring at community or senior centers. OEP was offered at 4 sites. Factors that influenced the implementation of these programs included having: key advocates at host organizations, programs embedded into site workflows, sufficient capacity and workforce, engaged invested partners, and flexibility in working with a complex set of agencies and systems with different administrative structures. Conclusion: By connecting academic faculty with various community members from multiple sectors, new initiatives can be successfully implemented. Results from this ACL-funded project indicate that using an academic-community partnership model to build relationships and capacity for ongoing delivery of health promotion programming for older adults is feasible and effective in delivering EBFPPs. In addition, academic-community partnerships can develop a strong network of invested partners to foster continued support of fall prevention activities.

The structural and social determinants of Alzheimer's disease related dementias.

INTRODUCTION: The projected growth of Alzheimer's disease (AD) and AD-related dementia (ADRD) cases by midcentury has expanded the research field and impelled new lines of inquiry into structural and social determinants of health (S/SDOH) as fundamental drivers of disparities in AD/ADRD. METHODS: In this review, we employ Bronfenbrenner's ecological systems theory as a framework to posit how S/SDOH impact AD/ADRD risk and outcomes. RESULTS: Bronfenbrenner defined the "macrosystem" as the realm of power (structural) systems that drive S/SDOH and that are the root cause of health disparities. These root causes have been discussed little to date in relation to AD/ADRD, and thus, macrosystem influences, such as racism, classism, sexism, and homophobia, are the emphasis in this paper. DISCUSSION: Under Bronfenbrenner's macrosystem framework, we highlight key quantitative and qualitative studies linking S/SDOH with AD/ADRD, identify scientific gaps in the literature, and propose guidance for future research. HIGHLIGHTS: Ecological systems theory links structural/social determinants to AD/ADRD. Structural/social determinants accrue and interact over the life course to impact AD/ADRD. Macrosystem is made up of societal norms, beliefs, values, and practices (e.g., laws). Most macro-level determinants have been understudied in the AD/ADRD literature.

The Impact of Complementary and Integrative Medicine Following Traumatic Brain Injury: A Scoping Review.

OBJECTIVE: To examine the evidence levels, study characteristics, and outcomes of nonpharmacologic complementary and integrative medicine (CIM) interventions in rehabilitation for individuals with traumatic brain injury (TBI). DATA SOURCES: MEDLINE (OvidSP), PubMed (NLM), EMBASE ( Embase.com ), CINAHL (EBSCO), PsycINFO (OvidSP), Cochrane Library (Wiley), and National Guidelines Clearinghouse databases were evaluated using PRISMA guidelines. The protocol was registered in INPLASY (protocol registration: INPLASY202160071). DATA EXTRACTION: Quantitative studies published between 1992 and 2020 investigating the efficacy of CIM for individuals with TBI of any severity, age, and outcome were included. Special diets, herbal and dietary supplements, and counseling/psychological interventions were excluded, as were studies with mixed samples if TBI data could not be extracted. A 2-level review comprised title/abstract screening, followed by full-text assessment by 2 independent reviewers. DATA SYNTHESIS: In total, 90 studies were included, with 57 001 patients in total. This total includes 2 retrospective studies with 17 475 and 37 045 patients. Of the 90 studies, 18 (20%) were randomized controlled trials (RCTs). The remainder included 20 quasi-experimental studies (2-group or 1-group pre/posttreatment comparison), 9 retrospective studies, 1 single-subject study design, 2 mixed-methods designs, and 40 case study/case reports. Guided by the American Academy of Neurology evidence levels, class II criteria were met by 61% of the RCTs. Included studies examined biofeedback/neurofeedback (40%), acupuncture (22%), yoga/tai chi (11%), meditation/mindfulness/relaxation (11%), and chiropractic/osteopathic manipulation (11%). The clinical outcomes evaluated across studies included physical impairments (62%), mental health (49%), cognitive impairments (39%), pain (31%), and activities of daily living/quality of life (28%). Additional descriptive statistics were summarized using narrative synthesis. Of the studies included for analyses, 97% reported overall positive benefits of CIM. CONCLUSION: Rigorous and well experimentally designed studies (including RCTs) are needed to confirm the initial evidence supporting the use of CIM found in the existing literature.