Food Insecurity and Family Dynamics: A Systematic Review.

BACKGROUND: Undernutrition is related to numerous childhood outcomes. However, little research has investigated the relationship between food insecurity and family dynamics. This systematic review seeks to validate the evidence for a relationship between these 2 factors. METHODS: A systematic literature review was conducted in Embase, PubMed, and Scopus. Inclusion criteria include peer-reviewed research articles published during or after 1996 in English, using standardized measures of family function and food insecurity. Exclusion criteria include measurement of parent or child characteristics without assessing household or family characteristics or demographics. Two reviewers independently voted using Covidence, and Alpha agreement was determined at each phase. RESULTS: A total of 15 studies were included for data extraction after the initial search being completed in April 2022. All included studies were found to be appropriate in numerous categories for quality assessment. Primary findings from these studies show a potential relationship exists between food insecurity and family dynamics. DISCUSSION: The findings in this review suggest that effects of food insecurity expand to various aspects of healthy family functioning. Unhealthy family dynamics in childhood can also expose children to trauma and lead to increased physical and mental health disorders in the future.

Incorporating Anti-racist Principles Throughout the Research Lifecycle: A Position Statement from the Society of General Internal Medicine (SGIM).

Biomedical research has advanced medicine but also contributed to widening racial and ethnic health inequities. Despite a growing acknowledgment of the need to incorporate anti-racist objectives into research, there remains a need for practical guidance for recognizing and addressing the influence of ingrained practices perpetuating racial harms, particularly for general internists. Through a review of the literature, and informed by the Research Lifecycle Framework, this position statement from the Society of General Internal Medicine presents a conceptual framework suggesting multi-level systemic changes and strategies for researchers to incorporate an anti-racist perspective throughout the research lifecycle. It begins with a clear assertion that race and ethnicity are socio-political constructs that have important consequences on health and health disparities through various forms of racism. Recommendations include leveraging a comprehensive approach to integrate anti-racist principles and acknowledging that racism, not race, drives health inequities. Individual researchers must acknowledge systemic racism's impact on health, engage in self-education to mitigate biases, hire diverse teams, and include historically excluded communities in research. Institutions must provide clear guidelines on the use of race and ethnicity in research, reject stigmatizing language, and invest in systemic commitments to diversity, equity, and anti-racism. National organizations must call for race-conscious research standards and training, and create measures to ensure accountability, establishing standards for race-conscious research for research funding. This position statement emphasizes our collective responsibility to combat systemic racism in research, and urges a transformative shift toward anti-racist practices throughout the research cycle.

Building Climate Change into Medical Education: A Society of General Internal Medicine Position Statement.

Building expertise in climate and planetary health among healthcare professionals cannot come with greater urgency as the threats from climate change become increasingly apparent. Current and future healthcare professionals-particularly internists-will increasingly need to understand the interconnectedness of natural systems and human health to better serve their patients longitudinally. Despite this, few national medical societies and accreditation bodies espouse frameworks for climate change and planetary health-related education at the undergraduate (UME), graduate (GME), and continuing (CME) medical education level. As a community of medical educators with an enduring interest in climate change and planetary health, the Society of General Internal Medicine (SGIM) recognizes the need to explicitly define structured educational opportunities and core competencies in both UME and GME as well as pathways for faculty development. In this position statement, we build from the related SGIM Climate and Health position statement, and review and synthesize existing position statements made by US-based medical societies and accreditation bodies that focus on climate change and planetary health-related medical education, identify gaps using Bloom's Hierarchy, and provide recommendations on behalf of SGIM regarding the development of climate and planetary health curricula development. Identified gaps include (1) limited systematic approach to climate and planetary health medical education at all levels; (2) minimal emphasis on learner-driven approaches; (3) limited focus on physician and learner well-being; and (4) limited role for health equity and climate justice. Recommendations include a call to relevant accreditation bodies to explicitly include climate change and planetary health as a competency, extend the structural competency framework to climate change and planetary health to build climate justice, proactively include learners in curricular development and teaching, and ensure resources and support to design and implement climate and planetary health-focused education that includes well-being and resiliency.

Incorporating Health Policy and Advocacy Curricula Into Undergraduate Medical Education in the United States.

Physicians serve as crucial advocates for their patients. Undergraduate medical education (UME) must move beyond the biomedical model, built upon the perception that health is defined purely in the absence of illness, to also incorporate population health through health policy, advocacy, and community engagement to account for structural and social determinants of health. Currently, the US guidelines for UME lack structured training in health policy or advocacy, leaving trainees ill-equipped to assume their role as physician-advocates or to engage with communities. There is an undeniable need to educate future physicians on legislative advocacy toward improving the social determinants of health through the creation of evidence-based health policy, in addition to training in effective techniques to engage in partnership with the communities in which physicians serve. The authors of this article also present curricular case studies around two programs at their institution that could be used to implement similar programs at other US medical schools.

Social genomics, cognition, and well-being during the COVID-19 pandemic.

INTRODUCTION: Adverse psychosocial exposure is associated with increased proinflammatory gene expression and reduced type-1 interferon gene expression, a profile known as the conserved transcriptional response to adversity (CTRA). Little is known about CTRA activity in the context of cognitive impairment, although chronic inflammatory activation has been posited as one mechanism contributing to late-life cognitive decline. METHODS: We studied 171 community-dwelling older adults from the Wake Forest Alzheimer's Disease Research Center who answered questions via a telephone questionnaire battery about their perceived stress, loneliness, well-being, and impact of COVID-19 on their life, and who provided a self-collected dried blood spot sample. Of those, 148 had adequate samples for mRNA analysis, and 143 were included in the final analysis, which including participants adjudicated as having normal cognition (NC, n = 91) or mild cognitive impairment (MCI, n = 52) were included in the analysis. Mixed effect linear models were used to quantify associations between psychosocial variables and CTRA gene expression. RESULTS: In both NC and MCI groups, eudaimonic well-being (typically associated with a sense of purpose) was inversely associated with CTRA gene expression whereas hedonic well-being (typically associated with pleasure seeking) was positively associated. In participants with NC, coping through social support was associated with lower CTRA gene expression, whereas coping by distraction and reframing was associated with higher CTRA gene expression. CTRA gene expression was not related to coping strategies for participants with MCI, or to either loneliness or perceived stress in either group. DISCUSSION: Eudaimonic and hedonic well-being remain important correlates of molecular markers of stress, even in people with MCI. However, prodromal cognitive decline appears to moderate the significance of coping strategies as a correlate of CTRA gene expression. These results suggest that MCI can selectively alter biobehavioral interactions in ways that could potentially affect the rate of future cognitive decline and may serve as targets for future intervention efforts.

Entrapment of fractured balloon after angioplasty in an AV access using a covered stent.

Fracture of the angioplasty balloon is a known complication during endovascular procedures in arteriovenous (AV) fistulas and grafts. We describe a case of a patient with end-stage renal disease (ESRD) on dialysis with a brachiocephalic AV fistula that had become dysfunctional. After a percutaneous angioplasty procedure during balloon withdrawal, a portion of the balloon fractured and separated due to the balloon being caught in the struts of a previously placed bare metal stent. A covered stent was used to contain the segment of the fractured balloon to the wall of the fistula. The use of a covered stent in jailing the fractured balloon to prevent further complications is not well described. This strategy may be implemented in some circumstances such as this case to avoid surgical interventions.

When prion disease Isn't suspected: prion disease as the cause of terminal decline in chronic mixed dementia.

Alzheimer's Disease (AD) is the most common cause of dementia, although multiple pathologies are found in nearly half of the cases with clinically diagnosed AD. Prion diseases, such as Creutzfeldt-Jakob disease (CJD), are rare causes of dementia and typically manifest as a rapidly progressive dementia, where symptom onset to dementia most often occurs over the course of months. In this brief report, we describe a patient's typically progressive dementia with a precipitous decline at the end of their life who, on neuropathological evaluation, was found to have multiple neurodegenerative proteinopathies as well as spongiform encephalopathy due to CJD. This case of unsuspected CJD highlights a rare, but epidemiologically important, cause of sudden decline in well-established neurodegenerative dementias.

Aberrant Expression of ACO1 in Vasculatures Parallels Progression of Idiopathic Pulmonary Fibrosis.

Rationale: Idiopathic pulmonary fibrosis (IPF) is characterized by mitochondrial dysfunction. However, details about the non-mitochondrial enzymes that sustain the proliferative nature of IPF are unclear. Aconitases are a family of enzymes that sustain metabolism inside and outside mitochondria. It is hypothesized that aconitase 1 (ACO1) plays an important role in the pathogenesis of IPF given that ACO1 represents an important metabolic hub in the cytoplasm. Objectives: To determine if ACO1 expression in IPF lungs shows specific patterns that may be important in the pathogenesis of IPF. To determine the similarities and differences in ACO1 expression in IPF, bleomycin-treated, and aging lungs. Methods: ACO1 expression in IPF lungs were characterized and compared to non-IPF controls by western blotting, immunostaining, and enzymatic activity assay. ACO1-expressing cell types were identified by multicolor immunostaining. Using similar methods, the expression profiles of ACO1 in IPF lungs versus bleomycin-treated and aged mice were investigated. Measurements and main results: Lower lobes of IPF lungs, unlike non-IPF controls, exhibit significantly high levels of ACO1. Most of the signals colocalize with von Willebrand factor (vWF), a lineage marker for vascular endothelial cells. Bleomycin-treated lungs also show high ACO1 expressions. However, most of the signals colocalize with E-cadherin and/or prosurfactant protein C, representative epithelial cell markers, in remodeled areas. Conclusions: A characteristic ACO1 expression profile observed in IPF vasculatures may be a promising diagnostic target. It also may give clues as to how de novo angiogenesis contributes to the irreversible nature of IPF.

Pursuing Pharmacoequity: Determinants, Drivers, and Pathways to Progress.

The United States pays more for medical care than any other nation in the world, including for prescription drugs. These costs are inequitably distributed, as individuals from underrepresented racial and ethnic groups in the United States experience the highest costs of care and unequal access to high-quality, evidence-based medication therapy. Pharmacoequity refers to equity in access to pharmacotherapies or ensuring that all patients, regardless of race and ethnicity, socioeconomic status, or availability of resources, have access to the highest quality of pharmacotherapy required to manage their health conditions. Herein the authors describe the urgent need to prioritize pharmacoequity. This goal will require a bold and innovative examination of social policy, research infrastructure, patient and prescriber characteristics, as well as health policy determinants of inequitable medication access. In this article, the authors describe these determinants, identify drivers of ongoing inequities in prescription drug access, and provide a framework for the path toward achieving pharmacoequity.

Matrix Metalloproteinase 7 Expression and Apical Epithelial Defects in Atp8b1 Mutant Mouse Model of Pulmonary Fibrosis.

Abnormalities in airway epithelia and lung parenchyma are found in Atp8b1 mutant mice, which develop pulmonary fibrosis after hyperoxic insult. Microarray and ingenuity pathway analysis (IPA) show numerous transcripts involved in ciliogenesis are downregulated in 14-month (14 M) -old Atp8b1 mouse lung compared with wild-type C57BL/6. Lung epithelium of Atp8b1 mice demonstrate apical abnormalities of ciliated and club cells in the bronchial epithelium on transmission electron microscopy (TEM). Matrix metalloproteinase 7 (MMP7) regulates of ciliogenesis and is a biomarker for idiopathic pulmonary fibrosis (IPF) in humans. Mmp7 transcript and protein expression are significantly upregulated in 14 M Atp8b1 mutant mouse lung. MMP7 expression is also increased in bronchoalveolar lavage fluid (BAL). Immunohistochemistry is localized MMP7 to bronchial epithelial cells in the Atp8b1 mutant. In conclusion, MMP7 is upregulated in the aged Atp8b1 mouse model, which displays abnormal ciliated cell and club cell morphology. This mouse model can facilitate the exploration of the role of MMP7 in epithelial integrity and ciliogenesis in IPF. The Atp8b1 mutant mouse is proposed as a model for IPF.

A geroscience motivated approach to treat Alzheimer's disease: Senolytics move to clinical trials.

The pathogenic processes driving Alzheimer's disease (AD) are complex. An incomplete understanding of underlying disease mechanisms has presented insurmountable obstacles for developing effective disease-modifying therapies. Advanced chronological age is the greatest risk factor for developing AD. Intervening on biological aging may alter disease progression and represents a novel, complementary approach to current strategies. Toward this end, cellular senescence has emerged as a promising target. This complex stress response harbors damaged cells in a cell cycle arrested, apoptosis-resistant cell state. Senescent cells accumulate with age where they notoriously secrete molecules that contribute to chronic tissue dysfunction and disease. Thus, benefits of cell survival in a senescent fate are countered by their toxic secretome. The removal of senescent cells improves brain structure and function in rodent models at risk of developing AD, and in those with advanced Aß and tau pathology. The present review describes the path to translating this promising treatment strategy to AD clinical trials. We review evidence for senescent cell accumulation in the human brain, considerations and strategies for senescence-targeting trials specific to AD, approaches to detect senescent brain cells in biofluids, and summarize the goals of the first senolytic trials for the treatment of AD (NCT04063124 and NCT04685590). This article is part of the Special Issue - Senolytics - Edited by Joao Passos and Diana Jurk.

The Cellular Senescence Stress Response in Post-Mitotic Brain Cells: Cell Survival at the Expense of Tissue Degeneration.

In 1960, Rita Levi-Montalcini and Barbara Booker made an observation that transformed neuroscience: as neurons mature, they become apoptosis resistant. The following year Leonard Hayflick and Paul Moorhead described a stable replicative arrest of cells in vitro, termed "senescence". For nearly 60 years, the cell biology fields of neuroscience and senescence ran in parallel, each separately defining phenotypes and uncovering molecular mediators to explain the 1960s observations of their founding mothers and fathers, respectively. During this time neuroscientists have consistently observed the remarkable ability of neurons to survive. Despite residing in environments of chronic inflammation and degeneration, as occurs in numerous neurodegenerative diseases, often times the neurons with highest levels of pathology resist death. Similarly, cellular senescence (hereon referred to simply as "senescence") now is recognized as a complex stress response that culminates with a change in cell fate. Instead of reacting to cellular/DNA damage by proliferation or apoptosis, senescent cells survive in a stable cell cycle arrest. Senescent cells simultaneously contribute to chronic tissue degeneration by secreting deleterious molecules that negatively impact surrounding cells. These fields have finally collided. Neuroscientists have begun applying concepts of senescence to the brain, including post-mitotic cells. This initially presented conceptual challenges to senescence cell biologists. Nonetheless, efforts to understand senescence in the context of brain aging and neurodegenerative disease and injury emerged and are advancing the field. The present review uses pre-defined criteria to evaluate evidence for post-mitotic brain cell senescence. A closer interaction between neuro and senescent cell biologists has potential to advance both disciplines and explain fundamental questions that have plagued their fields for decades.

Evidence of the Cellular Senescence Stress Response in Mitotically Active Brain Cells-Implications for Cancer and Neurodegeneration.

Cellular stress responses influence cell fate decisions. Apoptosis and proliferation represent opposing reactions to cellular stress or damage and may influence distinct health outcomes. Clinical and epidemiological studies consistently report inverse comorbidities between age-associated neurodegenerative diseases and cancer. This review discusses how one particular stress response, cellular senescence, may contribute to this inverse correlation. In mitotically competent cells, senescence is favorable over uncontrolled proliferation, i.e., cancer. However, senescent cells notoriously secrete deleterious molecules that drive disease, dysfunction and degeneration in surrounding tissue. In recent years, senescent cells have emerged as unexpected mediators of neurodegenerative diseases. The present review uses pre-defined criteria to evaluate evidence of cellular senescence in mitotically competent brain cells, highlights the discovery of novel molecular regulators and discusses how this single cell fate decision impacts cancer and degeneration in the brain. We also underscore methodological considerations required to appropriately evaluate the cellular senescence stress response in the brain.

NAD+ supplementation prevents STING-induced senescence in ataxia telangiectasia by improving mitophagy.

Senescence phenotypes and mitochondrial dysfunction are implicated in aging and in premature aging diseases, including ataxia telangiectasia (A-T). Loss of mitochondrial function can drive age-related decline in the brain, but little is known about whether improving mitochondrial homeostasis alleviates senescence phenotypes. We demonstrate here that mitochondrial dysfunction and cellular senescence with a senescence-associated secretory phenotype (SASP) occur in A-T patient fibroblasts, and in ATM-deficient cells and mice. Senescence is mediated by stimulator of interferon genes (STING) and involves ectopic cytoplasmic DNA. We further show that boosting intracellular NAD+ levels with nicotinamide riboside (NR) prevents senescence and SASP by promoting mitophagy in a PINK1-dependent manner. NR treatment also prevents neurodegeneration, suppresses senescence and neuroinflammation, and improves motor function in Atm-/- mice. Our findings suggest a central role for mitochondrial dysfunction-induced senescence in A-T pathogenesis, and that enhancing mitophagy as a potential therapeutic intervention.

Soluble ACE2 as a potential therapy for COVID-19.

Soluble angiotensin-converting enzyme 2 (sACE2) could be a therapeutic option to treat coronavirus disease 2019 (COVID-19) infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes ACE2 receptors on cell surfaces to gain intracellular entry, making them an ideal target for therapy. High-affinity variants of sACE2, engineered using high-throughput mutagenesis, are capable of neutralizing COVID-19 infection as decoy receptors. These variants compete with native ACE2 present on cells by binding with spike (S) protein of SARS-CoV-2, making native ACE2 on cell surfaces available to convert angiotensin II to angiotensin-1,7, thus alleviating the exaggerated inflammatory response associated with COVID-19 infection. This article explores the use of sACE2 as potential therapy for COVID-19 infection.