Deciphering the role of a SINE-VNTR-Alu retrotransposon polymorphism as a biomarker of Parkinson's disease progression.

SINE-VNTR-Alu (SVA) retrotransposons are transposable elements which represent a source of genetic variation. We previously demonstrated that the presence/absence of a human-specific SVA, termed SVA_67, correlated with the progression of Parkinson's disease (PD). In the present study, we demonstrate that SVA_67 acts as expression quantitative trait loci, thereby exhibiting a strong regulatory effect across the genome using whole genome and transcriptomic data from the Parkinson's progression markers initiative cohort. We further show that SVA_67 is polymorphic for its variable number tandem repeat domain which correlates with both regulatory properties in a luciferase reporter gene assay in vitro and differential expression of multiple genes in vivo. Additionally, this variation's utility as a biomarker is reflected in a correlation with a number of PD progression markers. These experiments highlight the plethora of transcriptomic and phenotypic changes associated with SVA_67 polymorphism which should be considered when investigating the missing heritability of neurodegenerative diseases.

You Cannot Function in "Overwhelm": Helping Primary Care Navigate the Slow End of the Pandemic.

GOAL: This study was developed to explicate underlying organizational factors contributing to the deterioration of primary care clinicians' mental health during the COVID-19 pandemic. METHODS: Using data from the Larry A. Green Center for the Advancement of Primary Health Care for the Public Good's national survey of primary care clinicians from March 2020 to March 2022, a multidisciplinary team analyzed more than 11,150 open-ended comments. Phase 1 of the analysis happened in real-time as surveys were returned, using deductive and inductive coding. Phase 2 used grounded theory to identify emergent themes. Qualitative findings were triangulated with the survey's quantitative data. PRINCIPAL FINDINGS: The clinicians shifted from feelings of anxiety and uncertainty at the start of the pandemic to isolation, lack of fulfillment, moral injury, and plans to leave the profession. The frequency with which they spoke of depression, burnout, and moral injury was striking. The contributors to this distress included crushing workloads, worsening staff shortages, and insufficient reimbursement. Consequences, both felt and anticipated, included fatigue and demoralization from the inability to manage escalating workloads. Survey findings identified responses that could alleviate the mental health crisis, namely: (1) measuring and customizing workloads based on work capacity; (2) quantifying resources needed to return to sufficient staffing levels; (3) promoting state and federal support for sustainable practice infrastructures with less administrative burden; and (4) creating patient visits of different lengths to rebuild relationships and trust and facilitate more accurate diagnoses. PRACTICAL APPLICATIONS: Attention to clinicians' mental health should be rapidly directed to on-demand, confidential mental health support so they can receive the care they need and not worry about any stigma or loss of license for accepting that help. Interventions that address work-life balance, workload, and resources can improve care, support retention of the critically important primary care workforce, and attract more trainees to primary care careers.

Exploring SVA Insertion Polymorphisms in Shaping Differential Gene Expressions in the Central Nervous System.

Transposable elements (TEs) are repetitive elements which make up around 45% of the human genome. A class of TEs, known as SINE-VNTR-Alu (SVA), demonstrate the capacity to mobilise throughout the genome, resulting in SVA polymorphisms for their presence or absence within the population. Although studies have previously highlighted the involvement of TEs within neurodegenerative diseases, such as Parkinson's disease and amyotrophic lateral sclerosis (ALS), the exact mechanism has yet to be identified. In this study, we used whole-genome sequencing and RNA sequencing data of ALS patients and healthy controls from the New York Genome Centre ALS Consortium to elucidate the influence of reference SVA elements on gene expressions genome-wide within central nervous system (CNS) tissues. To investigate this, we applied a matrix expression quantitative trait loci analysis and demonstrate that reference SVA insertion polymorphisms can significantly modulate the expression of numerous genes, preferentially in the trans position and in a tissue-specific manner. We also highlight that SVAs significantly regulate mitochondrial genes as well as genes within the HLA and MAPT loci, previously associated within neurodegenerative diseases. In conclusion, this study continues to bring to light the effects of polymorphic SVAs on gene regulation and further highlights the importance of TEs within disease pathology.

CRISPR deletion of a SINE-VNTR-Alu (SVA_67) retrotransposon demonstrates its ability to differentially modulate gene expression at the MAPT locus.

Background: SINE-VNTR-Alu (SVA) retrotransposons are hominid-specific elements which have been shown to play important roles in processes such as chromatin structure remodelling and regulation of gene expression demonstrating that these repetitive elements exert regulatory functions. We have previously shown that the presence or absence of a specific SVA element, termed SVA_67, was associated with differential expression of several genes at the MAPT locus, a locus associated with Parkinson's Disease (PD) and frontotemporal dementia. However, we were not able to demonstrate that causation of differential gene expression was directed by the SVA due to lack of functional validation. Methods: We performed CRISPR to delete SVA_67 in the HEK293 cell line. Quantification of target gene expression was performed using qPCR to assess the effects on expression in response to the deletion of SVA_67. Differences between CRISPR edit and control cell lines were analysed using two-tailed t-test with a minimum 95% confidence interval to determine statistical significance. Results: In this study, we provide data highlighting the SVA-specific effect on differential gene expression. We demonstrate that the hemizygous deletion of the endogenous SVA_67 in CRISPR edited cell lines was associated with differential expression of several genes at the MAPT locus associated with neurodegenerative diseases including KANSL1, MAPT and LRRC37A. Discussion: This data is consistent with our previous bioinformatic work of differential gene expression analysis using transcriptomic data from the Parkinson's Progression Markers Initiative (PPMI) cohort. As SVAs have regulatory influences on gene expression, and insertion polymorphisms contribute to interpersonal differences in expression patterns, these results highlight the potential contribution of these elements to complex diseases with potentially many genetic components, such as PD.

Few Primary Care Physicians Lead Hospitals, Despite Their Immense Value: Systems Change and Delivery System Evolution Can Reverse This Trend.

Primary care physicians (PCPs) inherently offer a tremendous range of skills that would serve them well as chief executive officers in hospitals. Despite their immense value, very few serve in these top posts for a variety of reasons. Making changes in how we train, mentor, and support PCPs throughout their careers can reverse this trend.

In pursuit of high-quality primary care: A call to action to implement the objectives of the 2021 NASEM report.

A seminal National Academies of Sciences, Engineering, and Medicine consensus report released in May 2021-Implementing High-Quality Primary Care: Rebuilding the Foundation of Health Care-emphasizes the importance of ensuring that high-quality primary care is accessible to all people, regardless of whether they have paid for it and in spite of its limited availability. This report outlines five recommendations for primary care stakeholders seeking to transform the health care landscape. This article summarizes these recommendations; identifies progress made toward high-quality primary care implementation since the report's publication; and outlines examples of policies, operational approaches, and advocacy strategies we believe are necessary to implement high-quality primary care. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Strengthening Primary Care to Improve Health Outcomes in the US-Creating Oversight to Address Invisibility.

This Viewpoint discusses how the lack of a comprehensive national primary care approach creates gaps and confusion in federal policy and proposes solutions.

Uniting Public Health and Primary Care for Healthy Communities in the COVID-19 Era and Beyond.

The Coronavirus disease 2019 (COVID-19) pandemic has laid bare the dis-integrated health care system in the United States. Decades of inattention and dwindling support for public health, coupled with declining access to primary care medical services have left many vulnerable communities without adequate COVID-19 response and recovery capacity. "Health is a Community Affair" is a 1966 effort to build and deploy local communities of solution that align public health, primary care, and community organizations to identify health care problem sheds, and activate local asset sheds. After decades of independent effort, the COVID-19 pandemic offers an opportunity to reunite and align the shared goals of public health and primary care. Imagine how different things might look if we had widely implemented the recommendations from the 1966 report? The ideas and concepts laid out in "Health is a Community Affair" still offer a COVID-19 response and recovery approach. By bringing public health and primary care together in community now, a future that includes a shared vision and combined effort may emerge.

Engaging With Communities - Lessons (Re)Learned From COVID-19.

Coronavirus disease 2019 (COVID-19) has underscored longstanding societal differences in the drivers of health and demonstrated the value of applying a health equity lens to engage at-risk communities, communicate with them effectively, share data, and partner with them for program implementation, dissemination, and evaluation. Examples of engagement - across diverse communities and with community organizations; tribes; state and local health departments; hospitals; and universities - highlight the opportunity to apply lessons from COVID-19 for sustained changes in how public health and its partners work collectively to prevent disease and promote health, especially with our most vulnerable communities.

A Systematic Approach to Understanding and Implementing Patient-Centered Care.

In 2014, Family Medicine for America's Health (FMAHealth) began implementing a specialty-wide strategic plan. The FMAHealth Board of Directors created an Engagement Tactic Team and charged the team with two major objectives: (1) to engage patients as partners in transforming primary care, and (2) to strengthen working alliances with other primary care professions and key stakeholders to speak with a unified voice for primary care. The team's first objective sought to engage patients as partners to achieve the triple aim. The second objective required the team to explore how best to collaborate with others to align on core values of high-functioning primary care.When it comes to realizing the promise of patient-centered care, aspirational strategic objectives are often easier to declare than to implement. As the team grappled with its charge, it discovered that the approach to achieving each objective became as important as the actions required to accomplish them. The team recognized the value of taking ample time to build an approach to delivering patient-centered care that could be sustained and scaled over time to achieve the two objectives.The team ultimately settled on three projects that leveraged collaborative partnerships with organizations inside and outside the specialty to better understand and advance patient-centered care at three levels: practice transformation, organizational governance, and policy making.

The Persistence of Specialty Disrespect: Student Perspectives.

PURPOSE: One aspect of the hidden curriculum of medicine is specialty disrespect (SD)-an expressed lack of respect among medical specialties that occurs at all levels of training and across geographic, demographic, and professional boundaries, with quantifiable impacts on student well-being and career decision making. This study sought to identify medical students' perceptions of and responses to SD in the learning environment. METHODS: We conducted quantitative and content analysis of an annual survey collected between 2008 and 2012 from 702 third- and fourth-year students at the University of Washington School of Medicine. We describe the frequency of reported SD, its self-rated impact on student specialty choice, and major descriptive categories. RESULTS: Nearly 80% of respondents reported experiencing SD in the previous year. A moderate or strong impact on specialty choice was reported by 25.9% of respondents. In our sample, students matching into family medicine, obstetrics/gynecology, and emergency medicine were most likely to report exposure. Content analysis identified two new concepts not previously reported. Internecine strife describes students distancing themselves from both disrespecting and disrespected specialties, while legitimacy questions the validity of the targeted specialty. CONCLUSIONS: SD is a consistent and ubiquitous part of clinical training that pushes students away from both disrespecting and disrespected specialties. These results emphasize the need for solutions aimed at minimizing disrespect and mitigating its effects upon students.

National network television news coverage of contraception - a content analysis.

OBJECTIVE: The objective was to describe and analyze national network television news framing of contraception, recognizing that onscreen news can influence the public's knowledge and beliefs. STUDY DESIGN: We used the Vanderbilt Television News Archives and LexisNexis Database to obtain video and print transcripts of all relevant national network television news segments covering contraception from January 2010 to June 2014. We conducted a content analysis of 116 TV news segments covering contraception during the rollout of the Affordable Care Act. Segments were quantitatively coded for contraceptive methods covered, story sources used, and inclusion of medical and nonmedical content (intercoder reliability using Krippendorf's alpha ranged 0.6-1 for coded categories). RESULTS: Most (55%) news stories focused on contraception in general rather than specific methods. The most effective contraceptive methods were rarely discussed (implant, 1%; intrauterine device, 4%). The most frequently used sources were political figures (40%), advocates (25%), the general public (25%) and Catholic Church leaders (16%); medical professionals (11%) and health researchers (4%) appeared in a minority of stories. A minority of stories (31%) featured medical content. CONCLUSIONS: National network news coverage of contraception frequently focuses on contraception in political and social terms and uses nonmedical figures such as politicians and church leaders as sources. This focus deemphasizes the public health aspect of contraception, leading medical professionals and health content to be rarely featured. IMPLICATIONS: Media coverage of contraception may influence patients' views about contraception. Understanding the content, sources and medical accuracy of current media portrayals of contraception may enable health care professionals to dispel popular misperceptions.

Accelerating Momentum Toward Improved Health for Patients and Populations: Family Medicine as a Disruptive Innovation-A Perspective from the Keystone IV Conference.

This paper was prepared in follow up to the G. Gayle Stephens Keystone IV Conference by authors who attended the conference and are also members of the Family Medicine for America's Health board of directors (FMAHealth.org). It connects the aspirations of the current strategic and communications efforts of FMAHealth with the ideas developed at the conference. The FMAHealth project is sponsored by 8 national family medicine organizations and seeks to build on the work of the original Future of Family Medicine project. Among its objectives are a robust family physician workforce practicing in a continually improving medical home model, supported by a comprehensive payment model sufficient to sustain the medical home and enable the personal physician relationship with patients.

A Countercultural Heritage: Rediscovering the Relationship-Centered and Social Justice Roots of Family Medicine-A Perspective from the Keystone IV Conference.

The 2015 G. Gayle Stephens Keystone conference convened a cohort of primary care professionals to discuss what promises personal physicians will make to their patients going forward. New physicians were prompted to rediscover the foundational values of and historic context for family medicine. At the heart of this rediscovery was learning of the writings and teachings of Dr. G. Gayle Stephens, a founder of family medicine who emphasized the essentiality of relationship-centered care and social justice to the new specialty. Dr. Stephens viewed family medicine as being in a countercultural relationship to mainstream medicine, as family medicine fought for justice and equity in an inequitable and fragmented health care system. Here we argue that by reaffirming and renewing this countercultural heritage the new generation of family physicians will have better clarity in approaching the many challenges in health care today. Particularly for trainees and new physicians, the historic lens offered by Dr. Stephens's writing and other foundational documents allows us to better see ourselves in a trajectory of ongoing health care reform.

Social Determinants of Health and Primary Care: Intentionality Is Key to the Data We Collect and the Interventions We Pursue.

Social determinants of health (SDOHs)-the conditions where we live, learn, work, and play-often influence the lives of patients much more than health care services. Family physicians in particular witness the impact of these factors on a daily basis in clinical practice, and they have begun to screen for SDOHs and intervene when appropriate to mitigate their effects. This issue of the Journal of the American Board of Family Medicine focuses on SDOH data collection and analysis that informs patient care, population health, and policy interventions. Collectively, this series of articles establishes the foundation for a robust SDOH research agenda for primary care.

Community Vital Signs: Taking the Pulse of the Community While Caring for Patients.

In 2014 both the Institute of Medicine and the National Quality Forum recommended the inclusion of social determinants of health data in electronic health records (EHRs). Both entities primarily focus on collecting socioeconomic and health behavior data directly from individual patients. The burden of reliably, accurately, and consistently collecting such information is substantial, and it may take several years before a primary care team has actionable data available in its EHR. A more reliable and less burdensome approach to integrating clinical and social determinant data exists and is technologically feasible now. Community vital signs-aggregated community-level information about the neighborhoods in which our patients live, learn, work, and play-convey contextual social deprivation and associated chronic disease risks based on where patients live. Given widespread access to "big data" and geospatial technologies, community vital signs can be created by linking aggregated population health data with patient addresses in EHRs. These linked data, once imported into EHRs, are a readily available resource to help primary care practices understand the context in which their patients reside and achieve important health goals at the patient, population, and policy levels.